Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/dailymed/adverseReaction
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| dailymed-drugs:1703 |
None known.
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| dailymed-drugs:2351 |
None known.
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| dailymed-drugs:2746 |
None known.
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| dailymed-drugs:3122 |
None known.
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| dailymed-drugs:3589 |
None known.
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| dailymed-drugs:4127 |
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| dailymed-drugs:926 |
Please refer to the package insert for ProstaScint or Zevalin for
this information on the final drug product.
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| dailymed-drugs:432 |
None
known
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| dailymed-drugs:541 |
Please refer to the package insert for OncoScint CR/OV, ProstaScint, or Zevalin for this information on the final drug product.
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| dailymed-drugs:1262 |
None
known.
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| dailymed-drugs:1 |
Cefizox (ceftizoxime for injection, USP) is generally well tolerated. The most frequent adverse reactions (greater than 1% but less than 5%) are: Hypersensitivity--Rash, pruritus, fever. Hepatic--Transient elevation in AST (SGOT), ALT (SGPT), and alkaline phosphatase. Hematologic--Transient eosinophilia, thrombocytosis. Some individuals have developed a positive Coombs test. Local--Injection site--Burning, cellulitis, phlebitis with IV administration, pain, induration, tenderness, paresthesia. The less frequent adverse reactions (less than 1%) are: Hypersensitivity--Numbness and anaphylaxis have been reported rarely. Hepatic--Elevation of bilirubin has been reported rarely. Renal--Transient elevations of BUN and creatinine have been occasionally observed with Cefizox. Hematologic--Anemia, including hemolytic anemia with occasional fatal outcome, leukopenia, neutropenia, and thrombocytopenia have been reported rarely. Urogenital--Vaginitis has occurred rarely. Gastrointestinal--Diarrhea; nausea and vomiting have been reported occasionally. Symptoms of pseudomembranous colitis can appear during or after antibiotic treatment . In addition to the adverse reactions listed above which have been observed in patients treated with ceftizoxime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin���class antibiotics: Stevens���Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, serum���sickness like reaction, toxic nephropathy, aplastic anemia, hemorrhage, prolonged prothrombin time, elevated LDH, pancytopenia, and agranulocytosis. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
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| dailymed-drugs:2 |
The incidence of common adverse events in Table 1 is based upon 7 placebo-controlled US clinical trials in which 1,176 pediatric, adolescent, and adult patients (466 females and 710 males) previously treated with as-needed bronchodilators and/or inhaled corticosteroids were treated with FLOVENT DISKUS (doses of 50 to 500 mcg twice daily for up to 12 weeks) or placebo. Table 1 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in any of the groups treated with FLOVENT DISKUS and were more common than in the placebo group. In considering these data, differences in average duration of exposure should be taken into account. These adverse events were mostly mild to moderate in severity, with<2% of patients discontinuing the studies because of adverse events. Rare cases of immediate and delayed hypersensitivity reactions, including rash and other rare events of angioedema and bronchospasm, have been reported. Other adverse events that occurred in the groups receiving FLOVENT DISKUS in these studies with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo were:<br/>Cardiovascular: Palpitations.<br/>Drug Interaction, Overdose, and Trauma: Soft tissue injuries, contusions and hematomas, wounds and lacerations, postoperative complications, burns, poisoning and toxicity, pressure-induced disorders.<br/>Ear, Nose, and Throat: Ear signs and symptoms; rhinorrhea/postnasal drip; hoarseness/dysphonia; epistaxis; tonsillitis; nasal signs and symptoms; laryngitis; unspecified oropharyngeal plaques; otitis; ear, nose, throat, and tonsil signs and symptoms; ear, nose, and throat polyps; allergic ear, nose, and throat disorders; throat constriction.<br/>Endocrine and Metabolic: Fluid disturbances, weight gain, goiter, disorders of uric acid metabolism, appetite disturbances.<br/>Eye: Keratitis and conjunctivitis, blepharoconjunctivitis.<br/>Gastrointestinal: Diarrhea, gastrointestinal signs and symptoms, oral ulcerations, dental discomfort and pain, gastroenteritis, gastrointestinal infections, abdominal discomfort and pain, oral erythema and rashes, mouth and tongue disorders, oral discomfort and pain, tooth decay.<br/>Hepatobiliary Tract and Pancreas: Cholecystitis.<br/>Lower Respiratory: Lower respiratory infections.<br/>Musculoskeletal: Muscle pain, arthralgia and articular rheumatism, muscle cramps and spasms, musculoskeletal inflammation.<br/>Neurological: Dizziness, sleep disorders, migraines, paralysis of cranial nerves.<br/>Non-Site Specific: Chest symptoms; malaise and fatigue; pain; edema and swelling; bacterial infections; fungal infections; mobility disorders; cysts, lumps, and masses.<br/>Psychiatry: Mood disorders.<br/>Reproduction: Bacterial reproductive infections.<br/>Skin: Skin rashes, urticaria, photodermatitis, dermatitis and dermatosis, viral skin infections, eczema, fungal skin infections, pruritus, acne and folliculitis.<br/>Urology: Urinary infections. Three (3) of the 7 placebo-controlled US clinical trials were pediatric studies. A total of 592 patients 4 to 11 years were treated with FLOVENT DISKUS (dosages of 50 or 100 mcg twice daily) or placebo; an additional 174 patients 4 to 11 years received FLOVENT ROTADISK at the same doses. There were no clinically relevant differences in the pattern or severity of adverse events in children compared with those reported in adults. In the first 16 weeks of a 52-week clinical trial in adult patients with asthma who previously required oral corticosteroids (daily doses of 5 to 40 mg oral prednisone), the effects of FLOVENT DISKUS 500 mcg twice daily (n = 41) and 1,000 mcg twice daily (n = 36) were compared with placebo (n = 34) for the frequency of reported adverse events. Adverse events, whether or not considered drug related by the investigators, reported in more than 5 patients in the group taking FLOVENT DISKUS and that occurred more frequently with FLOVENT DISKUS than with placebo are shown below (percent FLOVENT DISKUS and percent placebo). In considering these data, theincreased average duration of exposure for patients taking FLOVENT DISKUS (105 days for FLOVENT DISKUS versus 75 days for placebo) should be taken into account.<br/>Ear, Nose, and Throat: Hoarseness/dysphonia (9% and 0%), nasal congestion/blockage (16% and 0%), oral candidiasis (31% and 21%), rhinitis (13% and 9%), sinusitis/sinus infection (33% and 12%), throat irritation (10% and 9%), and upper respiratory tract infection (31% and 24%).<br/>Gastrointestinal: Nausea and vomiting (9% and 0%).<br/>Lower Respiratory: Cough (9% and 3%) and viral respiratory infections (9% and 6%).<br/>Musculoskeletal: Arthralgia and articular rheumatism (17% and 3%) and muscle pain (12% and 0%).<br/>Non-Site Specific: Malaise and fatigue (16% and 9%) and pain (10% and 3%).<br/>Skin: Pruritus (6% and 0%) and skin rashes (8% and 3%).<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of fluticasone propionate in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate or a combination of these factors.<br/>Ear, Nose, and Throat: Aphonia, facial and oropharyngeal edema, and throat soreness.<br/>Endocrine and Metabolic: Cushingoid features, growth velocity reduction in children/adolescents, hyperglycemia, and osteoporosis.<br/>Eye: Cataracts.<br/>Psychiatry: Agitation, aggression, anxiety, depression, and restlessness. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.<br/>Non-Site Specific: Very rare anaphylactic reaction, very rare anaphylactic reaction in patients with severe milk protein allergy.<br/>Respiratory: Asthma exacerbation, bronchospasm, chest tightness, dyspnea, immediate bronchospasm, pneumonia, and wheeze.<br/>Skin: Contusions and ecchymoses.<br/>Eosinophilic Conditions: In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionateand these underlying conditions has not been established (see PRECAUTIONS: Eosinophilic Conditions).
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| dailymed-drugs:3 |
Most adverse effects have been mild and transient and have rarely required withdrawal of therapy.<br/>Cardiovascular: Bradycardia with heart rates of less than 60 beats per minute occurs commonly, and heart rates below 40 beats per minute and/or symptomatic bradycardia were seen in about 2 of 100 patients. Symptoms of peripheral vascular insufficiency, usually of the Raynaud type, have occurred in approximately 2 of 100 patients. Cardiac failure, hypotension, and rhythm/conduction disturbances have each occurred in about 1 of 100 patients. Single instances of first degree and third degree heart block have been reported; intensification of AV block is a known effect of beta blockers (see also CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).<br/>Central Nervous System: Dizziness or fatigue has been reported in approximately 2 of 100 patients; paresthesias, sedation, and change in behavior have each been reported in approximately 6 of 1000 patients.<br/>Respiratory: Bronchospasm has been reported in approximately 1 of 1000 patients (See CONTRAINDICATIONS and WARNINGS).<br/>Gastrointestinal: Nausea, diarrhea, abdominal discomfort, constipation, vomiting, indigestion, anorexia, bloating, and flatulence have been reported in 1 to 5 of 1000 patients.<br/>Miscellaneous: Each of the following has been reported in 1 to 5 of 1000 patients: rash; pruritus; headache; dry mouth, eyes, or skin; impotence or decreased libido; facial swelling; weight gain; slurred speech; cough; nasal stuffiness; sweating; tinnitus; blurred vision. Reversible alopecia has been reported infrequently. The following adverse reactions have been reported in patients taking nadolol and/or other beta-adrenergic blocking agents, but no causal relationship to nadolol has been established.<br/>Central Nervous System: Reversible mental depression progressing to catatonia; visual disturbances; hallucinations; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability with slightly clouded sensorium, and decreased performance on neuropsychometrics.<br/>Gastrointestinal: Mesenteric arterial thrombosis; ischemic colitis; elevated liver enzymes.<br/>Hematologic: Agranulocytosis; thrombocytopenic or nonthrombocytopenic purpura.<br/>Allergic: Fever combined with aching and sore throat; laryngospasm; respiratory distress.<br/>Miscellaneous: Pemphigoid rash; hypertensive reaction in patients with pheochromocytoma; sleep disturbances; Peyronie's disease. The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with nadolol.
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| dailymed-drugs:4 |
Please refer to the PRECAUTIONS: Potential for Stimulation of Tumor Growth and CLINICAL PHARMACOLOGY: Mechanism of Action sections regarding the potential for tumor stimulatory effects in KGF receptor-expressing tumors.<br/>Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Safety data are based upon 409 patients with hematologic malignancies (NHL, Hodgkin's disease, AML, ALL, CML, CLL, or multiple myeloma) who received Kepivance and 241 patients who received placebo in 3 randomized, placebo-controlled clinical studies and a pharmacokinetic study. Patients received Kepivance either before, or before and after, regimens of myelotoxic chemotherapy, with or without TBI, followed by PBPC support. The patients were predominantly between the ages of 41 and 60 years (median 48 yrs), male (62%), white(83%). NHL was the most common malignancy followed by Hodgkin's disease, multiple myeloma, and leukemia. The most common serious adverse reaction attributed to Kepivance was skin rash, which was reported in less than 1% (3/409) of patients treated with Kepivance. Grade 3 skin rashes occurred in 14 patients, 9 of 409 (3%) receiving Kepivance and 5 of 241 (2%) receiving placebo. In seven patients (5 Kepivance, 2 placebo), study drug was discontinued due to skin rash. Other serious adverse reactions occurred at a similar rate in patients who received Kepivance (20%) or placebo (21%). The most frequently reported serious adverse events in Kepivance and placebo-treated patients were fever, gastrointestinal events, and respiratory events. The most common adverse reactions attributed to Kepivance were skin toxicities (rash, erythema, edema, pruritus), oral toxicities (dysesthesia, tongue discoloration, tongue thickening, alteration of taste), pain arthralgias, and dysesthesia. The median time to onset of cutaneous toxicity was 6 days following the first of 3 consecutive daily doses of Kepivance, with a median duration of 5 days. In patients receiving Kepivance, dysesthesia (including hyperesthesia, hypoesthesia, and paresthesia) was usually localized to the perioral region, whereas in patients receiving placebo dysesthesias were more likely to occur in extremities. Adverse events occurring more frequently in Kepivance-treated patients as compared to placebo-treatedpatients (a higher incidence of���5%) are listed in Table 2. Hypertension: In a phase 1 placebo-controlled study in patients undergoing hematopoietic transplantation and receiving Kepivance (3 doses pre-myelotoxic therapy and 3 doses post-transplant), the proportion of Kepivance-treated patients reporting an adverse event of hypertension in the 60- and 80-mcg/kg/day Kepivance cohorts was greater than in the placebo group (2/15 patients [13%], 2/14 [14%], and 2/23 [9%], respectively). These events were transient and did not require treatment discontinuation in any patient. In an integrated analysis of adverse events across Kepivance studies in the hematology transplant setting, hypertensive events were reported in 30/409 Kepivance (7%) patients and 13/241 placebo (5%) patients. Proteinuria: In a placebo-controlled study conducted in 145 patients with metastatic colorectal cancer receiving multi-cycle chemotherapy (5-FU/leucovorin), serial urine specimens were collected for 27 placebo-treated and 54 Kepivance-treated patients. Among the 54 Kepivance-treated patients, 9 patients with a baseline urinalysis negative for protein subsequently developed 2+ or greater proteinuria after treatment with Kepivance. Among the 27 placebo-treated patients evaluated, none developed 2+ or greater proteinuria. Because of the study design, the number of cycles with urine analysis data collectedwas higher in the Kepivance- treated patients. In addition, for the 9 patients with proteinuria, underlying medical conditions known to be associated with proteinuria were present at baseline. A causal relationship between Kepivance and proteinuria has not been established. Laboratory Values: Reversible elevations in serum lipase and amylase, which did not require treatment intervention, are shown in Table 2. In general, peak increases were observed during the period of cytotoxic therapy and returned to baseline by the day of PBPC infusion. Fractionation of amylase revealed it to be predominantly salivary in origin.<br/>Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. The clinical significance of antibodies to Kepivance is unknown but may include lessened activity and/or cross reactivity with other members of the FGF family of growth factors. A sensitive electrochemiluminescence-based binding assay was performed on post-treatment sera from 645 patients treated with Kepivance in clinical studies. Twelve (2%) of these 645 patients tested positive for antibodies to Kepivance following treatment. None of the samples had evidence of neutralizing activity in a cell-based assay. The incidence of antibody positivity is highly dependent on the specific assay and its sensitivity. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Kepivance with the incidenceof antibodies to other products may be misleading.<br/>Postmarketing Experience: The following adverse reactions have been identified during postapproval of Kepivance. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during postmarketing use of Kepivance in the stem cell transplant setting: tongue disorder (e.g. redness, bumps, edema); face edema and mouth edema; vaginal edema and erythema; transient hyperpigmentation of the skin; Palmar-plantar Erythrodysaesthesia Syndrome (dysaesthesia, erythema, edema on the palms and soles) and anaphylactic / allergic reactions.
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| dailymed-drugs:5 |
Reactions to mepivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, inadvertent intravascular injection, or slow metabolic degradation.<br/>Systemic: The most commonly encountered acute adverse experiences which demand immediate countermeasures are related to the central nervous system and the cardiovascular system. These adverse experiences are generally dose related and due to high plasma levels which may result from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea (���Total or High Spinal���). Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia may occur. This may lead to secondary cardiac arrest if untreated. Factors influencing plasma protein binding, such as acidosis, systemic diseases which alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance.<br/>Central Nervous System Reactions: These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may be nausea, vomiting, chills, and constriction of the pupils. The incidence of convulsions associated with the use of local anesthetics varies with the procedure used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations.<br/>Cardiovascular Reactions: High doses or, inadvertent intravascular injection, may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, heart block, hypotension (or sometimes hypertension), bradycardia, ventricular arrhythmias, and possibly cardiac arrest.<br/>Allergic: Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients, such as the antimicrobial preservative methylparaben, contained in multiple-dose vials. These reactions are characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid-like symptomatology (including severe hypotension). Cross sensitivity among members of the amide-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established.<br/>Neurologic: The incidences of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient. Many of these effects may be related to local anesthetic techniques, with or without a contribution from the drug. In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter or needle may occur. Subsequent adverse effects may depend partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture. A high spinal is characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia. Neurologic effects following epidural or caudal anesthesia may include spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities, and loss of sphincter control all of which may have slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid. Neurologic effects following other procedures or routes of administration may include persistent anesthesia, paresthesia, weakness, paralysis, all of which may have slow, incomplete or no recovery.
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| dailymed-drugs:6 |
Clinical use of MUSTARGEN usually is accompanied by toxic manifestations.<br/>Local Toxicity: Thrombosis and thrombophlebitis may result from direct contact of the drug with the intima of the injected vein. Avoid high concentration and prolonged contact with the drug, especially in cases of elevated pressure in the antebrachial vein (e.g., in mediastinal tumor compression from severe vena cava syndrome).<br/>Systemic Toxicity:<br/>General:: Hypersensitivity reactions, including anaphylaxis, have been reported. Nausea, vomiting and depression of formed elements in the circulating blood are dose-limiting side effects and usually occur with the use of full doses of MUSTARGEN. Jaundice, alopecia, vertigo, tinnitus and diminished hearing may occur infrequently. Rarely, hemolytic anemia associatedwith such diseases as the lymphomas and chronic lymphocytic leukemia may be precipitated by treatment with alkylating agents including MUSTARGEN. Also, various chromosomal abnormalities have been reported in association with nitrogen mustard therapy. MUSTARGEN is given preferably at night in case sedation for side effects is required. Nausea and vomiting usually occur 1 to 3 hours after use of the drug. Emesis may disappear in the first 8 hours, but nausea may persist for 24 hours. Nausea and vomiting may be so severe as to precipitate vascular accidents in patients with a hemorrhagic tendency. Premedication with antiemetics, in addition to sedatives, may help control severe nausea and vomiting. Anorexia, weakness and diarrhea may also occur.<br/>Hematologic:: The usual course of MUSTARGEN (total dose of 0.4 mg/kg either given as a single intravenous dose or divided into two or four daily doses of 0.2 or 0.1 mg/kg, respectively) generally produces a lymphocytopenia within 24 hours after the first injection; significant granulocytopenia occurs within 6 to 8 days and lasts for 10 days to 3 weeks. Agranulocytosis appears to be relatively infrequent and recovery from leukopenia in most cases is complete within two weeks of the maximum reduction. Thrombocytopenia is variable but the time course of the appearance and recovery from reduced platelet counts generally parallels the sequence of granulocyte levels. In some cases severe thrombocytopenia may lead to bleeding from the gums and gastrointestinal tract, petechiae, and small subcutaneous hemorrhages; these symptoms appear to be transient and in most cases disappear with return to a normal platelet count. However, asevere and even uncontrollable depression of the hematopoietic system occasionally may follow the usual dose of MUSTARGEN, particularly in patients with widespread disease and debility and in patients previously treated with other antineoplastic agents or x-ray. Persistent pancytopenia has been reported. In rare instances, hemorrhagic complications may be due to hyperheparinemia. Erythrocyte and hemoglobin levels may decline during the first 2 weeks after therapy but rarely significantly. Depression of thehematopoietic system may be found up to 50 days or more after starting therapy.<br/>Integumentary:: Occasionally, a maculopapular skin eruption occurs, but this may be idiosyncratic and does not necessarily recur with subsequent courses of the drug. Erythema multiforme has been observed. Herpes zoster, a common complicating infection in patients with lymphomas, may first appear after therapy is instituted and on occasion may be precipitated by treatment. Further treatment should be discontinued during the acute phase of this illness to avoid progression to generalized herpes zoster.<br/>Reproductive:: Since the gonads are susceptible to MUSTARGEN, treatment may be followed by delayed catamenia, oligomenorrhea, or temporary or permanent amenorrhea. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs. In some instances spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued. Patients should be warned of the potential risk to their reproductive capacity.
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| dailymed-drugs:7 |
In Patients Receiving Multiple Doses for Infections Other Than Vaginal Candidiasis: Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities. Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similarin the two groups (1.5%). The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%. Hepatobiliary: In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with fluconazole. The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of fluconazole. In two comparative trials evaluating the efficacy of fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 lU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.<br/>Post-Marketing Experience: In addition, the following adverse events have occurred during post-marketing experience. Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported. Cardiovascular: QT prolongation, torsades de pointes. Central Nervous System: Seizures, dizziness. Dermatologic: Exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis , alopecia. Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia. Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia. Gastrointestinal: Dyspepsia, vomiting. Other Senses: Taste perversion.<br/>Adverse Reactions in Children: In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.
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| dailymed-drugs:8 |
Adverse reactions include, in decreasing order of frequency, elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing. Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids. Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. The development of secondary ocular infection (bacterial, fungal, and viral) have occurred. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used . Transient burning and stinging upon instillation and other minor symptoms of ocular irritation have been reported with the use of PRED FORTE suspension. Other adverse events reported with the use of PRED FORTE suspension include: visual disturbance (blurry vision); foreign body sensation; and allergic reactions.
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| dailymed-drugs:9 |
Clinical Trials: Estradiol levels
may increase during the first weeks following the initial injection
of LUPRON, but then decline to menopausal levels. This transient increase
in estradiol can be associated with a temporary worsening of signs
and symptoms . As would be expected with a drug that lowers serum estradiol levels,
the most frequently reported adverse reactions were those related
to hypoestrogenism. The monthly formulation of LUPRON DEPOT
3.75 mg was utilized in controlled clinical trials that
studied the drug in 166 endometriosis and 166 uterine fibroids patients.
Adverse events reported in���5% of patients in either of these
populations and thought to be potentially related to drug are noted
in the following table. In one controlled
clinical trial utilizing the monthly formulation of LUPRON DEPOT,
patients diagnosed with uterine fibroids received a higher dose (7.5
mg) of LUPRON DEPOT. Events seen with this dose that were thought
to be potentially related to drug and were not seen at the lower dose
included glossitis, hypesthesia, lactation, pyelonephritis, and urinarydisorders. Generally, a higher incidence of hypoestrogenic effects
was observed at the higher dose. Table 3 lists the potentially drug-related adverse events observed
in at least 5% of patients in any treatment group during the first
6 months of treatment in the add-back clinical studies. In the controlled clinical
trial, 50 of 51 (98%) patients in the LD group and 48 of 55 (87%)
patients in the LD/N group reported experiencing hot flashes on one
or more occasions during treatment. During Month 6 of treatment, 32
of 37 (86%) patients in the LD group and 22 of 38 (58%) patients in
the LD/N group reported having experienced hot flashes. The mean number
of days on which hot flashes were reported during this month of treatment
was 19 and 7 in the LD and LD/N treatment groups, respectively. The
mean maximum number of hot flashes in a day during this month of treatment
was 5.8 and 1.9 in the LD and LD/N treatment groups, respectively.<br/>Changes in Bone Density: In controlled
clinical studies, patients with endometriosis (six months of therapy)
or uterine fibroids (three months of therapy) were treated with LUPRON
DEPOT 3.75 mg. In endometriosis patients, vertebral bone density as
measured by dual energy x-ray absorptiometry (DEXA) decreased by an
average of 3.2% at six months compared with the pretreatment value.
Clinical studies demonstrate that concurrent hormonal therapy (norethindrone
acetate 5 mg daily) and calcium supplementation is effective in significantly
reducing the loss of bone mineral density that occurs with LUPRON
treatment, without compromising the efficacy of LUPRON in relieving
symptoms of endometriosis. LUPRON DEPOT 3.75 mg plus norethindrone acetate 5 mg daily was evaluated
in two clinical trials. The results from this regimen were similar
in both studies. LUPRON DEPOT 3.75 mg was used as a control group
in one study. The bone mineral density data of the lumbar spine from
these two studies are presented in Table 4. When
LUPRON DEPOT 3.75 mg was administered for three months in uterine
fibroid patients, vertebral trabecular bone mineral density as assessed
by quantitative digital radiography (QDR) revealed a mean decrease
of 2.7% compared with baseline. Six months after discontinuation of
therapy, a trend toward recovery was observed. Use of LUPRON DEPOT
for longer than three months (uterine fibroids) or six months (endometriosis)
or in the presence of other known risk factors for decreased bone
mineral content may cause additional bone loss and is not recommended.<br/>Changes in Laboratory Values During Treatment:<br/>Postmarketing: During postmarketing
surveillance, the following adverse events were reported. Like other
drugs in this class, mood swings, including depression, have been
reported. There have been rare reports of suicidal ideation and attempt.
Many, but not all, of these patients had a history of depression or
other psychiatric illness. Patients should be counseled on the possibility
of development or worsening of depression during treatment with LUPRON. Symptoms consistent with
an anaphylactoid or asthmatic process have been rarely reported. Rash,
urticaria, and photosensitivity reactions have also been reported. Localized reactions including
induration and abscess have been reported at the site of injection.
Symptoms consistent with fibromyalgia (eg: joint and muscle pain,
headaches, sleep disorder, gastrointestinal distress, and shortness
of breath) have been reported individually and collectively. Other
events reported are: Cardiovascular System���Hypotension, Pulmonary embolism; Hemic and Lymphatic System - Decreased
WBC; Central/Peripheral Nervous System - Convulsion, Peripheral neuropathy, Spinal fracture/paralysis; Musculoskeletal System - Tenosynovitis-like
symptoms; Urogenital System - Prostate pain.<br/>Pituitary apoplexy: During post-marketing
surveillance, rare cases of pituitary apoplexy (a clinical syndrome
secondary to infarction of the pituitary gland) have been reported
after the administration of gonadotropin-releasing hormone agonists.
In a majority of these cases, a pituitary adenoma was diagnosed, with
a majority of pituitary apoplexy cases occurring within 2 weeks of
the first dose, and some within the first hour. In these cases, pituitary
apoplexy has presented as sudden headache, vomiting, visual changes,
ophthalmoplegia, altered mental status, and sometimes cardiovascular
collapse. Immediate medical attention has been required. See other LUPRON
DEPOT and LUPRON Injection package inserts for other events reported
in different patient populations.
|
| dailymed-drugs:10 |
The most frequently reported ocular event in clinical trials was burning/stinging on instillation and was comparable between Betimol and timolol maleate (approximately one in eight patients). The following adverse events were associated with use of Betimol in frequencies of more than 5% in two controlled, double-masked clinical studies in which 184 patients received 0.25% or 0.5% Betimol:<br/>Ocular:: Dry eyes, itching, foreign body sensation, discomfort in the eye, eyelid erythema, conjunctival injection, and headache.<br/>Body As A Whole:: Headache. The following side effects were reported in frequencies of 1 to 5%:<br/>Ocular:: Eye pain, epiphora, photophobia, blurred or abnormal vision, corneal fluorescein staining, keratitis, blepharitis and cataract.<br/>Body As A Whole:: Allergic reaction, asthenia, common cold and pain in extremities.<br/>Cardiovascular:: Hypertension.<br/>Digestive:: Nausea.<br/>Metabolic/Nutritional:: Peripheral edema.<br/>Nervous System/Psychiatry:: Dizziness and dry mouth.<br/>Respiratory:: Respiratory infection and sinusitis. In addition, the following adverse reactions have been reported with ophthalmic use of beta blockers:<br/>Ocular:: Conjunctivitis, blepharoptosis, decreased corneal sensitivity, visual disturbances including refractive changes, diplopia and retinal vascular disorder.<br/>Body As A Whole:: Chest pain.<br/>Cardiovascular:: Arrhythmia, palpitation, bradycardia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure and cardiac arrest.<br/>Digestive:: Diarrhea.<br/>Endocrine:: Masked symptoms of hypoglycemia in insulin dependent diabetics .<br/>Nervous System/Psychiatry:: Depression, impotence, increase in signs and symptoms of myasthenia gravis and paresthesia.<br/>Respiratory:: Dyspnea, bronchospasm, respiratory failure and nasal congestion.<br/>Skin:: Alopecia, hypersensitivity including localized and generalized rash, urticaria.
|
| dailymed-drugs:11 |
Clinical experience with CHEMET has been limited. Consequently, the full spectrum and incidence of adverse reactions including the possibility of hypersensitivity or idiosyncratic reactions have not been determined. The most common events attributable to succimer, i.e., gastrointestinal symptoms or increases in serum transaminases, have been observed in about 10% of patients . Rashes, some necessitating discontinuation of therapy, have been reported in about 4% of patients. If rash occurs, other causes (e.g. measles) should be considered before ascribing the reaction to succimer. Rechallenge with succimer may be considered if lead levelsare high enough to warrant retreatment. One allergic mucocutaneous reaction has been reported on repeated administration of the drug . Mild to moderate neutropenia has been observed in some patients receiving succimer . Table I presents adverse events reported with the administration of succimer for the treatment of lead and other heavy metal intoxication.
|
| dailymed-drugs:12 |
Associated with Discontinuation
of Treatment: Approximately 16 percent of
the 453 patients who received REMERON' (mirtazapine) Tablets in US 6-week
controlled clinical trials discontinued treatment due to an adverse experience,
compared to 7 percent of the 361 placebo-treated patients in those studies. The
most common events (���1%) associated with discontinuation and considered to be
drug related (i.e., those events associated with dropout at a rate at least twice
that of placebo) included:<br/>Commonly Observed Adverse Events
in US Controlled Clinical Trials: The most commonly observed
adverse events associated with the use of REMERON' (mirtazapine) Tablets
(incidence of 5% or greater) and not observed at an equivalent incidence among
placebo-treated patients (REMERON' incidence at least twice that for placebo)
were:<br/>Adverse Events Occurring at an
Incidence of 1% or More Among REMERON'-Treated Patients: The table that follows
enumerates adverse events that occurred at an incidence of 1% or more, and were
more frequent than in the placebo group, among REMERON' (mirtazapine)
Tablets-treated patients who participated in short-term US placebo-controlled
trials in which patients were dosed in a range of 5 - 60 mg/day. This table shows
the percentage of patients in each group who had at least one episode of an event
at some time during their treatment. Reported adverse events were classified using
a standard COSTART-based dictionary terminology. The prescriber should be
aware that these figures cannot be used to predict the incidence of side effects
in the course of usual medical practice where patient characteristics and other
factors differ from those which prevailed in the clinical trials. Similarly, the
cited frequencies cannot be compared with figures obtained from other
investigations involving different treatments, uses and investigators. The cited
figures, however, do provide the prescribing physician with some basis for
estimating the relative contribution of drug and non-drug factors to the side
effect incidence rate in the population studied.<br/>ECG Changes: The electrocardiograms for
338 patients who received REMERON' (mirtazapine) Tablets and 261 patients who
received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation
in QTc���500 msec was not observed among mirtazapine-treated patients; mean change
in QTc was +1.6 msec for mirtazapine and���3.1 msec for placebo. Mirtazapine was
associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for
placebo. The clinical significance of these changes is unknown.<br/>Other Adverse Events Observed
During the Premarketing Evaluation of REMERON': During its premarketing
assessment, multiple doses of REMERON' (mirtazapine) Tablets were administered to
2796 patients in clinical studies. The conditions and duration of exposure to
mirtazapine varied greatly, and included (in overlapping categories) open and
double-blind studies, uncontrolled and controlled studies, inpatient and
outpatient studies, fixed dose and titration studies. Untoward events associated
with this exposure were recorded by clinical investigators using terminology of
their own choosing. Consequently, it is not possible to provide a meaningful
estimate of the proportion of individuals experiencing adverse events without
first grouping similar types of untoward events into a smaller number of
standardized event categories. In the tabulations that
follow, reported adverse events were classified using a standard COSTART-based
dictionary terminology. The frequencies presented, therefore, represent the
proportion of the 2796 patients exposed to multiple doses of REMERON' who
experienced an event of the type cited on at least one occasion while receiving
REMERON'. All reported events are included except those already listed in the
previous table, those adverse experiences subsumed under COSTART terms that are
either overly general or excessively specific so as to be uninformative, and those
events for which a drug cause was very remote. It is important to
emphasize that, although the events reported occurred during treatment with
REMERON', they were not necessarily caused by it. Events are further
categorized by body system and listed in order of decreasing frequency according
to the following definitions: frequent adverse events are those occurring on one
or more occasions in at least 1/100 patients; infrequent adverse events are those
occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer
than 1/1000 patients. Only those events not already listed in the previous table
appear in this listing. Events of major clinical importance are alsodescribed in
the WARNINGS and
PRECAUTIONS
sections. Body as a Whole: frequent: malaise, abdominal pain, abdominal
syndrome acute; infrequent: chills, fever,
face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen
enlarged; rare: cellulitis, chest pain
substernal. Cardiovascular System: frequent: hypertension, vasodilatation; infrequent: angina pectoris, myocardial
infarction, bradycardia, ventricular extrasystoles, syncope, migraine,
hypotension; rare: atrial arrhythmia,
bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly,
phlebitis, left heart failure. Digestive System: frequent: vomiting, anorexia; infrequent: eructation, glossitis, cholecystitis,
nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests
abnormal; rare: tongue discoloration,
ulcerative stomatitis, salivary gland enlargement, increased salivation,
intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver,
gastritis, gastroenteritis, oral moniliasis, tongue edema. Endocrine System: rare: goiter, hypothyroidism. Hemic and Lymphatic System: rare: lymphadenopathy, leukopenia, petechia,
anemia, thrombocytopenia, lymphocytosis, pancytopenia. Metabolic and Nutritional Disorders:
frequent: thirst; infrequent: dehydration, weight loss; rare: gout, SGOT increased, healing abnormal, acid
phosphatase increased, SGPT increased, diabetes mellitus. Musculoskeletal System: frequent: myasthenia, arthralgia; infrequent: arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture,
bone pain, myositis, tendon rupture, arthosis, bursitis. Nervous System: frequent: hypesthesia, apathy, depression,
hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia,
paresthesia; infrequent: ataxia, delirium,
delusions, depersonalization, dyskinesia, extrapyramidal syndrome, libido
increased, coordination abnormal, dysarthria, hallucinations, manic reaction,
neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria,
paranoid reaction; rare: aphasia,
nystagmus, akathisia, stupor, dementia, diplopia, drug dependence, paralysis,
grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal
syndrome. Respiratory System: frequent: cough increased, sinusitis; infrequent: epistaxis, bronchitis, asthma,
pneumonia; rare: asphyxia, laryngitis,
pneumothorax, hiccup. Skin and Appendages: frequent: pruritus, rash; infrequent: acne, exfoliative dermatitis, dry
skin, herpes simplex, alopecia; rare:
urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer. Special Senses: infrequent: eye pain, abnormality of
accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation
disorder, glaucoma, hyperacusis, ear pain; rare: blepharitis, partial transitory deafness, otitis media, taste
loss, parosmia. Urogenital System: frequent: urinary tract infection; infrequent: kidney calculus, cystitis, dysuria,
urinary incontinence, urinary retention, vaginitis, hematuria, breast pain,
amenorrhea, dysmenorrhea, leukorrhea, impotence; rare: polyuria, urethritis, metrorrhagia, menorrhagia, abnormal
ejaculation, breast engorgement, breast enlargement, urinary urgency.<br/>Other Adverse Events Observed
During Postmarketing Evaluation of REMERON': Adverse events reported
since market introduction, which were temporally (but not necessarily causally)
related to mirtazapine therapy, include four cases of the ventricular arrhythmia torsades de pointes. In three of the four cases, however, concomitant drugs were
implicated. All patients recovered.
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| dailymed-drugs:14 |
During clinical trials, the most frequently reported adverse event in the BenzaClin treatment group was dry skin (12%). The Table below lists local adverse events reported by at least 1% of patients in the BenzaClin and vehicle groups. The actual incidence of dry skin might have been greater were it not for the use of a moisturizer in these studies. Hypersensitivity/allergic reactions (including facial swelling and urticaria) have been reported in post-marketing use with BenzaClin Topical Gel. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
|
| dailymed-drugs:15 |
As with other penicillins, untoward reactions of
the sensitivity phenomena are likely to occur, particularly in individuals
who have previously demonstrated hypersensitivity to penicillins or
in those with a history of allergy, asthma, hay fever, or urticaria. As with other treatments for syphilis, the Jarisch-Herxheimer
reaction has been reported. The following have
been reported with parenteral penicillin G: General: Hypersensitivity
reactions including the following: skin eruptions (maculopapular to
exfoliative dermatitis), urticaria, laryngeal edema, fever, eosinophilia;
other serum sickness-like reactions (including chills, fever, edema,
arthralgia, and prostration); and anaphylaxis including shock and
death. Note: Urticaria, other skin rashes, and serum sickness-like
reactions may be controlled with antihistamines and, if necessary,
systemic corticosteroids. Whenever such reactions occur, penicillin
G should be discontinued unless, in the opinion of the physician,
the condition being treated is life-threatening and amenable only
to therapy with penicillin G. Serious anaphylactic reactions require
immediate emergency treatment with epinephrine. Oxygen, intravenous
steroids, and airway management, including intubation, should also
be administered as indicated. Gastrointestinal: Pseudomembranous colitis.
Onset of pseudomembranous colitis symptoms may occur during or after
antibacterial treatment. Hematologic: Hemolytic anemia,
leukopenia, thrombocytopenia. Neurologic: Neuropathy. Urogenital: Nephropathy. The following adverse events have been temporally associated
with parenteral administration of penicillin G benzathine: Body as a Whole: Hypersensitivity reactions including allergic vasculitis, pruritus,
fatigue, asthenia, and pain; aggravation of existing disorder; headache. Cardiovascular: Cardiac arrest; hypotension; tachycardia; palpitations; pulmonary
hypertension; pulmonary embolism; vasodilatation; vasovagal reaction;
cerebrovascular accident; syncope. Gastrointestinal: Nausea, vomiting;
blood in stool; intestinal necrosis. Hemic and Lymphatic: Lymphadenopathy. Injection Site: Injection site reactions including pain, inflammation, lump, abscess,
necrosis, edema, hemorrhage, cellulitis, hypersensitivity, atrophy,
ecchymosis, and skin ulcer. Neurovascular reactions including warmth,
vasospasm, pallor, mottling, gangrene, numbness of the extremities,
cyanosis of the extremities, and neurovascular damage. Metabolic: Elevated
BUN, creatinine, and SGOT. Musculoskeletal: Joint disorder; periostitis;
exacerbation of arthritis; myoglobinuria; rhabdomyolysis. Nervous System: Nervousness; tremors; dizziness; somnolence; confusion; anxiety;
euphoria; transverse myelitis; seizures; coma. A syndrome manifested
by a variety of CNS symptoms such as severe agitation with confusion,
visual and auditory hallucinations, and a fear of impending death
(Hoigne's syndrome), has been reported after administration of
penicillin G procaine and, less commonly, after injection of the combination
of penicillin G benzathine and penicillin G procaine. Other symptoms
associated with this syndrome, such as psychosis, seizures, dizziness,
tinnitus, cyanosis, palpitations, tachycardia, and/or abnormal perception
in taste, also may occur. Respiratory: Hypoxia; apnea; dyspnea. Skin: Diaphoresis. Special Senses: Blurred vision; blindness. Urogenital: Neurogenic bladder; hematuria;
proteinuria; renal failure; impotence; priapism.
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| dailymed-drugs:16 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:102 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:2056 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:3389 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:3513 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:4237 |
Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation, and
hypervolemia. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:17 |
The adverse reactions reported most frequently at the recommended dose of Amantadine Hydrochloride (5-10%) are: nausea, dizziness (lightheadedness), and insomnia. Less frequently (1-5%) reported adverse reactions are: depression, anxiety and irritability, hallucinations, confusion, anorexia, dry mouth, constipation, ataxia, livedo reticularis, peripheral edema, orthostatic hypotension, headache, somnolence, nervousness, dream abnormality, agitation, dry nose, diarrhea and fatigue. Infrequently (0.1-1%) occurring adverse reactions are: congestive heart failure, psychosis, urinary retention, dyspnea, fatigue, skin rash, vomiting, weakness, slurred speech, euphoria, thinking abnormality, amnesia, hyperkinesia, hypertension, decreased libido, and visual disturbance, including punctuate subepithelial or other corneal opacity, corneal edema, decreased visual acuity, sensitivity to light, and optic nerve palsy. Rare (less than 0.1%) occurring adverse reactions are: instances of convulsion, leukopenia, neutropenia, eczematoid dermatitis, oculogyric episodes, suicidal attempt, suicide, and suicidal ideation . Other adverse reactions reported during postmarketing experience with Amantadine Hydrochloride usage include:<br/>Nervous System/Psychiatric: coma, stupor, delirium, hypokinesia, hypertonia, delusions, aggressive behavior, paranoid reaction, manic reaction, involuntary muscle contractions, gait abnormalities, paresthesia, EEG changes, and tremor. Abrupt discontinuation may also precipitate delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression and slurred speech;<br/>Cardiovascular: cardiac arrest, arrhythmias including malignant arrhythmias, hypotension, and tachycardia;<br/>Respiratory: acute respiratory failure, pulmonary edema, and tachypnea;<br/>Gastrointestinal: dysphagia;<br/>Hematologic: leukocytosis;<br/>Special Senses: keratitis and mydriasis;<br/>Skin and Appendages: pruritus and diaphoresis;<br/>Miscellaneous: neuroleptic malignant syndrome , allergic reactions including anaphylactic reactions, edema, and fever;<br/>Laboratory Test: elevated: CPK, BUN, serum creatinine, alkaline phosphatase, LDH, bilirubin, GGT, SGOT, and SGPT.
|
| dailymed-drugs:18 |
Adverse reactions at therapeutic doses are usually minimal and transient. On long-term use of dipyridamole USP tablets initial side effects usually disappear. The following reactions in Table 1 were reported in two heart valve replacement trials comparing dipyridamole USP tablets and warfarin therapy to either warfarin alone or warfarin and placebo: Table 1: Adverse Reactions Reported in 2 Heart Valve Replacement Trials Other reactions from uncontrolled studies include diarrhea, vomiting, flushing and pruritus. In addition, angina pectoris has been reported rarely and there have been rare reports of liver dysfunction. On those uncommon occasions when adverse reactions have been persistent or intolerable, they have ceased on withdrawal of the medication. When dipyridamole USP tablets were administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone. In rare cases, increased bleeding during or after surgery has been observed. In post-marketing reporting experience, there have been rare reports of hypersensitivity reactions (such as rash, urticaria, severe bronchospasm, and angioedema), larynx edema, fatigue, malaise, myalgia, arthritis, nausea, dyspepsia, paresthesia, hepatitis, thrombocytopenia, alopecia, cholelithiasis, hypotension, palpitation, and tachycardia.
|
| dailymed-drugs:19 |
Allergic Reactions: Penicillin is a substance of low toxicity but does possess
a significant index of sensitization. The following hypersensitivity reactions
associated with use of penicillin have been reported: Skin rashes, ranging
from maculopapular eruptions to exfoliative dermatitis; urticaria; serum-sicknesslike
reactions, including chills, fever, edema, arthralgia, and prostration. Severe
and often fatal anaphylaxis has been reported . As with other treatments
for syphilis, the Jarisch-Herxheimer reaction has been reported. Procaine
toxicity manifestations and hypersensitivity reactions have been reported
.<br/>Gastrointestinal: Pseudomembranous colitis has been reported with the use of
penicillin G. Onset of pseudomembranous colitis symptoms may occur during
or after antibiotic treatment .
|
| dailymed-drugs:20 |
Hypertension: Quinapril hydrochloride has been evaluated for safety in 4960 subjects and patients. Of these, 3203 patients, including 655 elderly patients, participated in controlled clinical trials. Quinapril hydrochloride has been evaluated for long-term safety in over 1400 patients treated for 1 year or more. Adverse experiences were usually mild and transient. In placebo-controlled trials, discontinuation of therapy because of adverse events was required in 4.7% of patients with hypertension. Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 1563 patients in placebo-controlled hypertension trials who were treated with quinapril hydrochloride are shown below.<br/>Hypertension: Clinical adverse experiences probably, possibly, or definitely related, or of uncertain relationship to therapy occurring in 0.5% to 1.0% (except as noted) of the patients with hypertension treated with quinapril hydrochloride (with or without concomitant diuretic) in controlled or uncontrolled trials (N=4847) and less frequent, clinically significant events seen in clinical trials or post-marketing experience (the rarer events are in italics) include (listed by body system):<br/>General:: back pain, malaise, viral infections, anaphylactoid reaction.<br/>Cardiovascular:: palpitation, vasodilation, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, cardiac rhythm disturbances, cardiogenic shock.<br/>Hematology:: hemolytic anemia.<br/>Gastrointestinal:: flatulence, dry mouth or throat, constipation, gastrointestinal hemorrhage, pancreatitis, abnormal liver function tests, dyspepsia.<br/>Nervous/Psychiatric:: somnolence, vertigo, syncope, nervousness, depression, insomnia, paresthesia.<br/>Integumentary:: alopecia, increased sweating, pemphigus, pruritus, exfoliative dermatitis, photosensitivity reaction, dermatopolymyositis.<br/>Urogenital:: urinary tract infection, impotence, acute renal failure, worsening renal failure.<br/>Respiratory:: eosinophilic pneumonitis.<br/>Other:: amblyopia, edema, arthralgia, pharyngitis, agranulocytosis, hepatitis, thrombocytopenia.<br/>Fetal/Neonatal Morbidity and Mortality: See WARNINGS, Fetal/Neonatal Morbidity and Mortality.<br/>Angioedema: Angioedema has been reported in patients receiving quinapril hydrochloride (0.1%). Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis, and/or larynx occurs, treatment with quinapril hydrochloride should be discontinued and appropriate therapy instituted immediately. (See WARNINGS).<br/>Clinical Laboratory Test Findings:<br/>Hematology:: (See WARNINGS.)<br/>Hyperkalemia:: (See PRECAUTIONS.)<br/>Creatinine and Blood Urea Nitrogen:: Increases (>1.25 times the upper limit of normal) in serum creatinine and blood urea nitrogen were observed in 2% and 2%, respectively, of all patients treated with quinapril hydrochloride alone. Increases are more likely to occur in patients receiving concomitant diuretic therapy than those on quinapril hydrochloride alone. These increases often remit on continued therapy.
|
| dailymed-drugs:21 |
Cardiovascular Effects: Tachycardia, arrhythmias and hypertension have been reported with ocular administration of epinephrine. Local Effects: The most frequent side effects reported with dipivefrin hydrochloride alone were injection in 6.5% of patients and burning and stinging in 6%. Follicular conjunctivitis, mydriasis and allergic reactions to dipivefrin have been reported infrequently. Epinephrine therapy can lead to adrenochrome deposits in the conjunctiva and cornea.
|
| dailymed-drugs:22 |
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential. Hypernatremia may be associated with edema and exacerbation of congestive heart failure due to the retention of water, resulting in an expanded extracellular fluid volume. Reactions reported with the use of potassium-containing solutions include nausea, vomiting, abdominal pain and diarrhea. The signs and symptoms of potassium intoxication include paresthesias of the extremities, areflexia, muscular or respiratory paralysis, mental confusion, weakness, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities and cardiac arrest. Potassium deficits result in disruption of neuromuscular function, and intestinal ileus and dilatation. If infused in large amounts, chloride ions may cause a loss of bicarbonate ions, resulting in an acidifying effect. Abnormally high plasma levels of calcium can result in depression, amnesia, headaches, drowsiness, disorientation, syncope, hallucinations, hypotonia of both skeletal and smooth muscles, dysphagia, arrhythmias and coma. Calcium deficits can result in neuromuscular hyperexcitability, including cramps and convulsions. The physician should also be alert to the possibility of adverse reactions to drug additives. Prescribing information for drug additives to be administered in this manner should be consulted. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:23 |
The most common
adverse events reported by five to 14% of women using NuvaRing' in
clinical trials (n=2501) were the following: vaginitis, headache, upper
respiratory tract infection, vaginal secretion, sinusitis, weight gain,
and nausea. The most frequent
system-organ class adverse events leading to discontinuation in one to
2.5% of women using NuvaRing' in the trials included the following:
device-related events (foreign body sensation, coital problems, device
expulsion), vaginal symptoms (discomfort/vaginitis/vaginal secretion),
headache, emotional lability, and weight gain. Listed below are
adverse reactions that have been associated with the use of combination
hormonal contraceptives. These are also likely to apply to combination
vaginal hormonal contraceptives, such as NuvaRing'. An increased risk
of the following serious adverse reactions has been associated with the
use of combination hormonal contraceptives : There is evidence
of an association between the following conditions and the use of
combination hormonal contraceptives: The following
additional adverse reactions have been reported in users of combination
hormonal contraceptives and are believed to be drug-related: The following
additional adverse reactions have been reported in users of combination
hormonal contraceptives and a causal association has been neither
confirmed nor refuted:
|
| dailymed-drugs:24 |
Nystatin is virtually non-toxic and nonsensitizing and is well tolerated by all age groups including debilitated infants, even on prolonged administration. If irritation on topical application should occur, discontinue medication.
|
| dailymed-drugs:3449 |
Nystatin is virtually non-toxic and nonsensitizing and is well tolerated by all age groups including debilitated infants, even on prolonged administration. If irritation on topical application should occur, discontinue medication.
|
| dailymed-drugs:25 |
Note: The pharmacological similarities among the tricyclic antidepressants require that each of the reactions be considered when Surmontil is administered. Some of the adverse reactions included in this listing have not in fact been reported with Surmontil.<br/>Cardiovascular: Hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke.<br/>Psychiatric: Confusional states (especially the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.<br/>Neurological: Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alterations in EEG patterns; tinnitus; syndrome of inappropriate ADH (antidiuretic hormone) secretion.<br/>Anticholinergic: Dry mouth and, rarely, associated sublingual adenitis; blurred vision, disturbances of accommodation, mydriasis, constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.<br/>Allergic: Skin rash, petechiae, urticaria, itching, photosensitization, edema of face and tongue.<br/>Hematologic: Bone-marrow depression including agranulocytosis, eosinophilia; purpura; thrombo-cytopenia. Leukocyte and differential counts should be performed in any patient who develops fever and sore throat during therapy; the drug should be discontinued if there is evidence of pathological neutrophil depression.<br/>Gastrointestinal: Nausea and vomiting, anorexia, epigastric distress, diarrhea, peculiar taste, stomatitis, abdominal cramps, black tongue.<br/>Endocrine: Gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood-sugar levels.<br/>Other: Jaundice (simulating obstructive); altered liver function; weight gain or loss; perspiration; flushing; urinary frequency; drowsiness, dizziness, weakness, and fatigue; headache; parotid swelling; alopecia.<br/>Withdrawal Symptoms: Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.
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| dailymed-drugs:26 |
The following adverse reactions have been reported in patients treated with LACRISERT, but were in most instances mild and transient:Transient blurring of visionOcular discomfort or irritationMatting or stickiness of eyelashesPhotophobiaHypersensitivityEdema of the eyelidsHyperemia
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| dailymed-drugs:27 |
Incidence in Placebo-Controlled Trials:<br/>Associated with Discontinuation in Placebo-Controlled Clinical Trials:<br/>Male and Female Sexual Dysfunction with SSRIs:<br/>Other Adverse Events in Pediatric Patients:<br/>Other Events Observed During the Premarketing Evaluation of Sertraline Hydrochloride:<br/>Other Events Observed During the Post marketing Evaluation of Sertraline Hydrochloride:
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| dailymed-drugs:28 |
Sodium overload can occur with intravenous infusion of excessive
amounts of sodium-containing solutions. See WARNINGS and PRECAUTIONS.
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| dailymed-drugs:29 |
In a survey conducted in hospitalized patients, less than 1% of patients taking propoxyphene hydrochloride at recommended doses experienced side effects. The most frequently reported were dizziness, sedation, nausea, and vomiting. Some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, and minor visual disturbances. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Subacute painful myopathy has occurred following chronic propoxyphene overdosage.
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| dailymed-drugs:2140 |
In a survey conducted in hospitalized patients, less than 1% of patients taking propoxyphene hydrochloride at recommended doses experienced side effects. The most frequently reported were dizziness, sedation, nausea, and vomiting. Some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, and minor visual disturbances. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Subacute painful myopathy has occurred following chronic propoxyphene overdosage.
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| dailymed-drugs:30 |
PLAVIX has been evaluated
for safety in more than 42,000 patients, including over 9,000 patients
treated for 1 year or more. The clinically important adverse events
observed in CAPRIE, CURE, CLARITY and COMMIT are discussed below. The overall tolerability of PLAVIX
in CAPRIE was similar to that of aspirin regardless of age, gender
and race, with an approximately equal incidence (13%) of patients
withdrawing from treatment because of adverse reactions Hemorrhagic: In CAPRIE patients
receiving PLAVIX, gastrointestinal hemorrhage occurred at a rate of
2.0%, and required hospitalization in 0.7%. In patients receiving
aspirin, the corresponding rates were 2.7% and 1.1%, respectively.
The incidence of intracranial hemorrhage was 0.4% for PLAVIX compared
to 0.5% for aspirin. In CURE, PLAVIX use with aspirin was associated with an increase
in bleeding compared to placebo with aspirin (see Table 5). There was an excess in major
bleeding in patients receiving PLAVIX plus aspirin compared with placebo
plus aspirin, primarily gastrointestinal and at puncture sites. The
incidence of intracranial hemorrhage (0.1%), and fatal bleeding (0.2%),
were the same in both groups. The overall incidence of bleeding is described in Table 5 for patients
receiving both PLAVIX and aspirin in CURE. Ninety-two percent (92%)
of the patients in the CURE study received heparin/LMWH, and the rate
of bleeding in these patients was similar to the overall results. There was no excess in major
bleeds within seven days after coronary bypass graft surgery in patients
who stopped therapy more than five days prior to surgery (event rate
4.4% PLAVIX + aspirin; 5.3% placebo + aspirin). In patients who remained
on therapy within five days of bypass graft surgery, the event rate
was 9.6% for PLAVIX + aspirin, and 6.3% for placebo + aspirin. In CLARITY, the incidence of
major bleeding (defined as intracranial bleeding or bleeding associated
with a fall in hemoglobin>5 g/dL) was similar between groups (1.3%
versus 1.1% in the PLAVIX + aspirin and in the placebo + aspirin groups,
respectively). This was consistent across subgroups of patients defined
by baseline characteristics, and type of fibrinolytics or heparin
therapy. The incidence of fatal bleeding (0.8% versus 0.6% in the
PLAVIX + aspirin and in the placebo + aspirin groups, respectively)
and intracranial hemorrhage (0. 5% versus 0.7%, respectively) was
low and similar in both groups. The overall rate of noncerebral major bleeding or cerebral bleeding
in COMMIT was low and similar in both groups as shown in Table 6 below. Adverse events occurring
in���2.5% of patients on PLAVIX in the CAPRIE controlled clinical
trial are shown below regardless of relationship to PLAVIX. The median
duration of therapy was 20 months, with a maximum of 3 years. No additional clinically
relevant events to those observed in CAPRIE with a frequency���2.5%,
have been reported during the CURE and CLARITY controlled studies.
COMMIT collected only limited safety data. Other adverse experiences of potential importance occurring in 1%
to 2.5% of patients receiving PLAVIX (clopidogrel bisulfate) in the
controlled clinical trials are listed below regardless of relationship
to PLAVIX. In general, the incidence of these events was similar
to that in patients receiving aspirin (in CAPRIE) or placebo + aspirin
(in the other clinical trials). Autonomic
Nervous System Disorders: Syncope, Palpitation. Body as a Whole-general disorders:
Asthenia, Fever, Hernia. Cardiovascular
disorders: Cardiac failure. Central and peripheral nervous system disorders: Cramps
legs, Hypoaesthesia, Neuralgia, Paraesthesia, Vertigo. Gastrointestinal system disorders:
Constipation, Vomiting. Heart rate and
rhythm disorders: Fibrillation atrial. Liver and biliary system disorders:
Hepatic enzymes increased. Metabolic
and nutritional disorders: Gout, hyperuricemia, non-protein
nitrogen (NPN) increased. Musculo-skeletal
system disorders: Arthritis, Arthrosis. Platelet, bleeding&clotting disorders: GI hemorrhage, hematoma platelets decreased. Psychiatric disorders: Anxiety, Insomnia.Red blood cell disorders:
Anemia. Respiratory system disorders: Pneumonia, Sinusitis. Skin and appendage
disorders: Eczema, Skin ulceration. Urinary system disorders: Cystitis.Vision disorders: Cataract,
Conjunctivitis. Other
potentially serious adverse events which may be of clinical interest
but were rarely reported (<1%) in patients who received PLAVIX
in the controlled clinical trials are listed below regardless of relationship
to PLAVIX. In general, the incidence of these events was similar
to that in patients receiving aspirin (in CAPRIE) or placebo + aspirin
(in the other clinical trials). Body as a whole: Allergic reaction, necrosis ischemic. Cardiovascular disorders: Edema generalized.Gastrointestinal system disorders: Peptic, gastric or duodenal ulcer, gastritis, gastric ulcer perforated,
gastritis hemorrhagic, upper GI ulcer hemorrhagic. Liver and Biliary system disorders:
Bilirubinemia, hepatitis infectious, liver fatty. Platelet, bleeding and clotting disorders: hemarthrosis, hematuria, hemoptysis, hemorrhage intracranial, hemorrhage
retroperitoneal, hemorrhageof operative wound, ocular hemorrhage,
pulmonary hemorrhage, purpura allergic, thrombocytopenia. Red blood cell disorders: Anemia aplastic,
anemia hypochromic. Reproductive disorders,
female: Menorrhagia. Respiratory
system disorders: Hemothorax. Skin and appendage disorders: Bullous eruption, rash erythematous,
rash maculopapular, urticaria. Urinary
system disorders: Abnormal renal function, acute renal
failure. White cell and reticuloendothelial
system disorders: Agranulocytosis, granulocytopenia, leukemia,
leukopenia, neutropenia.<br/>Postmarketing Experience: The following events
have been reported spontaneously from worldwide postmarketing experience:
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| dailymed-drugs:31 |
The frequency of adverse events reported in patients using nystatin topical preparations is less than 0.1%. The more common events that were reported include allergic reactions, burning, itching, rash, eczema, and pain on application.
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| dailymed-drugs:32 |
In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received amiodarone for at least 1 week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more then 3 weeks, without an increased incidence of severe
adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days. The most important treatment-emergent adverse effects were hypotension, asystole/cardiac arrest/electromechanical dissociation (EMD), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse effects. The most common adverse effects leading to discontinuation of amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/EMD (1.2%), VT (1.1%), and cardiogenic shock (1%). The following table lists the most common (incidence���2%) treatment-emergent adverse events during amiodarone therapy considered at least possible drug-related. These data were collected from the Wyeth-Ayerst clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse events appeared to be dose-related. Other treatment-emergent possible drug-related adverse events reported in less than 2% of patients receiving amiodarone in Wyeth-Ayerst controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.<br/>Postmarketing Reports: In postmarketing surveillance, hypotension (sometimes fatal), sinus arrest, pseudotumor cerebri, syndrome of inappropriate antidiuretic hormone secretion (SIADH), toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, pancytopenia, neutropenia, erythema multiforme, angioedema, bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates, anaphylactic/anaphylactoid reaction (including shock), hallucination, confusional state, disorientation, and delirium also have been reported with amiodarone therapy. Also, in patients receiving recommended dosages, there have been postmarketing reports of the following injection site reactions: pain, erythema, edema, pigment changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing .
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| dailymed-drugs:33 |
Nystatin is well tolerated even with prolonged therapy. Oral irritation and sensitization have been reported. . Gastrointestinal: Diarrhea (including one case of bloody diarrhea), nausea, vomiting, gastrointestinal upset/disturbances. Dermatologic: Rash, including urticaria has been reported rarely. Stevens-Johnson syndrome has been reported very rarely. Other: Tachycardia, bronchospasm, facial swelling, and non-specific myalgia have also been rarely reported.
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| dailymed-drugs:3629 |
Nystatin is well tolerated even with prolonged therapy. Oral irritation and sensitization have been reported. . Gastrointestinal: Diarrhea (including one case of bloody diarrhea), nausea, vomiting, gastrointestinal upset/disturbances. Dermatologic: Rash, including urticaria has been reported rarely. Stevens-Johnson syndrome has been reported very rarely. Other: Tachycardia, bronchospasm, facial swelling, and non-specific myalgia have also been rarely reported.
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| dailymed-drugs:35 |
In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are: Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting. Other events including: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus. Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac capsules and tablets in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac. New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1000 mg/day). Incidence Greater Than or Equal To 1%���Probably Causally Related *Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac. Drug-related patient-complaints occurring in fewer than 3%, but more than 1%, are unmarked. Incidence Less Than 1%���Probably Causally Related (Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.) Incidence Less Than 1%���Causal Relationship Unknown (Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.) Additional Adverse Reactions Reported with NSAIDS
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| dailymed-drugs:36 |
The following adverse reactions have been reported as possibly related to Geocillin administration in controlled studies which include 344 patients receiving Geocillin.<br/>Gastrointestinal: The most frequent adverse reactions associated with Geocillin therapy are related to the gastrointestinal tract. Nausea, bad taste, diarrhea, vomiting, flatulence, and glossitis were reported. Abdominal cramps, dry mouth, furry tongue, rectal bleeding, anorexia, and unspecified epigastric distress were rarely reported.<br/>Dermatologic: Hypersensitivity reactions such as skin rash, urticaria, and less frequently pruritus.<br/>Hematologic: As with other penicillins, anemia, thrombocytopenia, leukopenia, neutropenia, and eosinophilia have infrequently been observed. The clinical significance of these abnormalities is not known.<br/>Miscellaneous: Other reactions rarely reported were hyperthermia, headache, itchy eyes, vaginitis, and loose stools.<br/>Abnormalities of Hepatic Function Tests: Mild SGOT elevations have been observed following Geocillin administration.
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| dailymed-drugs:37 |
Associated with Discontinuation of Treatment: Approximately 16 percent of the 453 patients who received mirtazapine in U.S. 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7 percent of the 361 placebo-treated patients in those studies. The most common events (���1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) included:<br/>Commonly Observed Adverse Events in U.S. Controlled Clinical Trials: The most commonly observed adverse events associated with the use of mirtazapine tablets (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (mirtazapine incidence at least twice that for placebo) were:<br/>Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine Treated Patients: The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among mirtazapine-treated patients who participated in short-term U.S. placebo-controlled trials in which patients were dosed in a range of 5 to 60 mg/day. This table shows the percentage of patients in each group who had at least one episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side effect incidence rate in the population studied.<br/>ECG Changes: The electrocardiograms for 338 patients who received mirtazapine and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation in QTc���500 msec was not observed among mirtazapine-treated patients; mean change in QTc was +1.6 msec for mirtazapine and -3.1 msec for placebo. Mirtazapine was associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The clinical significance of these changes is unknown.<br/>Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine: During its premarketing assessment, multiple doses of mirtazapine were administered to 2,796 patients in clinical studies. The conditions and duration of exposure to mirtazapine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first groupingsimilar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology. The frequencies presented, therefore, represent the proportion of the 2,796 patients exposed to multiple doses of mirtazapine who experienced an event of the type cited on at least one occasion while receiving mirtazapine. All reported events are included except those already listed in the previous table, those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, and those events for which a drug cause was very remote. It is important to emphasize that, although the events reported occurred during treatment with mirtazapine, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in the previous table appear in this listing. Events of major clinical importance are also described in the WARNINGS and PRECAUTIONS sections. Body as a Whole:frequent: malaise, abdominal pain, abdominal syndrome acute; infrequent: chills, fever, face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen enlarged; rare: cellulitis, chest pain substernal. Cardiovascular System:frequent: hypertension, vasodilatation; infrequent: angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, syncope, migraine, hypotension; rare: atrial arrhythmia, bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly, phlebitis, left heart failure. Digestive System:frequent: vomiting, anorexia; infrequent: eructation, glossitis, cholecystitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests abnormal; rare: tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver, gastritis, gastroenteritis, oral moniliasis, tongue edema. Endocrine System: rare: goiter, hypothyroidism. Hemic and Lymphatic System:rare: lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia. Metabolic and Nutritional Disorders:frequent: thirst; infrequent: dehydration, weight loss; rare: gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus. Musculoskeletal System:frequent: myasthenia, arthralgia; infrequent: arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthosis, bursitis. Nervous System:frequent: hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia, paresthesia; infrequent: ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidial syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare: aphasia, nystagmus, akathisia, stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome. Respiratory System:frequent: cough increased, sinusitis; infrequent: epistaxis, bronchitis, asthma, pneumonia; rare: asphyxia, laryngitis, pneumothorax, hiccup. Skin and Appendages:frequent: pruritus, rash; infrequent: acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia; rare: urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer. Special Senses:infrequent: eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, glaucoma, hyperacusis, ear pain; rare: blepharitis, partial transitory deafness, otitis media, taste loss, parosmia. Urogenital System:frequent: urinary tract infection; infrequent: kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence; rare: polyuria, urethritis, metrorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.<br/>Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine: Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to mirtazapine therapy, include four cases of the ventricular arrhythmia torsades de pointes. In three of the four cases, however, concomitant drugs were implicated. All patients recovered.
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| dailymed-drugs:38 |
Second-Line Single-Agent Therapy:<br/>Weekly Dosage Schedule: In three clinical studies evaluating the weekly dosage schedule, 304 patients with metastatic carcinoma of the colon or rectum that had recurred or progressed following 5-FU-based therapy were treated with Irinotecan Hydrochloride Injection. Seventeen of the patients died within 30 days of the administration of Irinotecan Hydrochloride Injection; in five cases (1.6%, 5/304), the deaths were potentially drug-related. These five patients experienced a constellation of medical events that included known effects of Irinotecan Hydrochloride Injection. One of these patients died of neutropenic sepsis without fever. Neutropenic fever occurred in nine (3.0%) other patients; these patients recovered with supportive care. One hundred nineteen (39.1%) of the 304 patients were hospitalized a total of 156 times because of adverse events; 81 (26.6%) patients were hospitalized for events judged to be related to administration of Irinotecan Hydrochloride Injection. The primary reasons for drug-related hospitalization were diarrhea, with or without nausea and/or vomiting (18.4%); neutropenia/leukopenia, with or without diarrhea and/or fever (8.2%); and nausea and/or vomiting (4.9%). Adjustments in the dose of Irinotecan Hydrochloride Injection were made during the cycle of treatment and for subsequent cycles based on individual patient tolerance. The first dose of at least one cycle of Irinotecan Hydrochloride Injection was reduced for 67% of patients who began the studies at the 125-mg/mstarting dose. Within-cycle dose reductions were required for 32% of the cycles initiated at the 125-mg/mdose level. The most common reasons for dose reduction were late diarrhea, neutropenia, and leukopenia. Thirteen (4.3%) patients discontinued treatment with Irinotecan Hydrochloride Injection because of adverse events. The adverse events in Table 5 are based on the experience of the 304 patients enrolled in the three studies described in the CLINICAL STUDIES, Studies Evaluating the Weekly Dosage Schedule, section.<br/>Once-Every-3-Week Dosage Schedule: A total of 535 patients with metastatic colorectal cancer whose disease had recurred or progressed following prior 5-FU therapy participated in the two phase 3 studies: 316 received irinotecan, 129 received 5-FU, and 90 received best supportive care. Eleven (3.5%) patients treated with irinotecan died within 30 days of treatment. In three cases (1%, 3/316), the deaths were potentially related to irinotecan treatment and were attributed to neutropenic infection, grade 4 diarrhea, and asthenia, respectively. One (0.8%, 1/129) patient treated with 5-FU died within 30 days of treatment; this death was attributed to grade 4 diarrhea. Hospitalizations due to serious adverse events (whether or not related to study treatment) occurred at least once in 60% (188/316) of patients who received irinotecan, 63% (57/90) who received best supportive care, and 39% (50/129) who received 5-FU-based therapy. Eight percent of patients treated with irinotecan and 7% treated with 5-FU-based therapy discontinued treatment due to adverse events. Of the 316 patients treated with irinotecan, the most clinically significant adverse events (all grades, 1-4) were diarrhea (84%), alopecia (72%), nausea (70%), vomiting (62%), cholinergic symptoms (47%), and neutropenia (30%). Table 6 lists the grade 3 and 4 adverse events reported in the patients enrolled to all treatment arms of the two studies described in the CLINICAL STUDIES, Studies Evaluating the Once-Every-3- Week Dosage Schedule, section.<br/>Overview of Adverse Events: Gastrointestinal: Nausea, vomiting, and diarrhea are common adverse events following treatment with Irinotecan Hydrochloride Injection and can be severe. When observed, nausea and vomiting usually occur during or shortly after infusion of Irinotecan Hydrochloride Injection. In the clinical studies testing the every 3-week-dosage schedule, the median time to the onset of late diarrhea was 5 days after irinotecan infusion. In the clinical studies evaluating the weekly dosage schedule, the median time to onset of late diarrhea was 11 days following administration of Irinotecan Hydrochloride Injection. For patientsstarting treatment at the 125-mg/mweekly dose, the median duration of any grade of late diarrhea was 3 days. Among those patients treated at the 125-mg/mweekly dose who experienced grade 3 or 4 late diarrhea, the median duration of the entire episode of diarrhea was 7 days. The frequenc of grade 3 or 4 late diarrhea was somewhat greater in patients starting treatment at 125 mg/mthan in patients given a 100-mg/mweekly starting dose (34% [65/193] versus 23% [24/102]; p=0.08). The frequency of grade 3 and 4 late diarrhea by age was significantly greater in patients���65 years than in patients<65 years (40% [53/133] versus 23% [40/171]; p=0.002). In one study of the weekly dosage treatment, the frequency of grade 3 and 4 late diarrhea was significantly greater in male than in female patients (43% [25/58] versus 16% [5/32]; p=0.01), but there were no gender differences in the frequency of grade 3 and 4 late diarrhea in the other two studies of the weekly dosage treatment schedule. Colonic ulceration, sometimes with gastrointestinal bleeding, has been observed in association with administration of Irinotecan Hydrochloride Injection. Hematology: Irinotecan Hydrochloride Injection commonly causes neutropenia, Leucopenia (including lymphocytopenia), and anemia. Serious thrombocytopenia is uncommon. When evaluated in the trials of weekly administration, the frequency of grade 3 and 4 neutropenia was significantly higher in patients who received previous pelvic/abdominal irradiation than in those who had not received such irradiation (48% [13/27] versus 24% [67/277]; p=0.04). In these same studies, patients with baseline serum total bilirubin levels of 1.0 mg/dL or more also had a significantly greater likelihood of experiencing first-cycle grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1.0 mg/dL (50% [19/38] versus 18% [47/266]; p<0.001). There were no significant differences in the frequency of grade 3 and 4 neutropenia by age or gender. In the clinical studies evaluating the weekly dosage schedule, neutropenic fever (concurrent NCI grade 4 neutropenia and fever of grade 2 or greater) occurred in 3% of the patients; 6% of patients received G-CSF for the treatment of neutropenia. NCI grade 3 or 4 anemia was noted in 7% of the patients receiving weekly treatment; blood transfusions were given to 10% of the patients in these trials. Body as a Whole: Asthenia, fever, and abdominal pain are generally the most common events of this type. Cholinergic Symptoms: Patients may have cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping and early diarrhea. If these symptoms occur, they manifest during or shortly after drug infusion. They are thought to be related to the anticholinesterase activity of the irinotecan parent compound and are expected to occur more frequently with higher irinotecan doses. Hepatic: In the clinical studies evaluating the weekly dosage schedule, NCI grade 3 or 4 liver enzyme abnormalities were observed in fewer than 10% of patients. These events typically occur in patients with known hepatic metastases. Dermatologic: Alopecia has been reported during treatment with Irinotecan Hydrochloride Injection. Rashes have also been reported but did not result in discontinuation of treatment. Respiratory: Severe pulmonary events are infrequent. In the clinical studies evaluating the weekly dosage schedule, NCI grade 3 or 4 dyspnea was reported in 4% of patients. Over half the patients with dyspnea had lung metastases; the extent to which malignant pulmonary involvement or other preexisting lung disease may have contributed to dyspnea in these patients is unknown. Interstitial pulmonary disease presenting as pulmonary infiltrates is uncommon during irinotecan therapy. Interstitial pulmonary disease can be fatal. Risk factors possibly associated with the development of interstitial pulmonary disease include pre-existing lung disease, use of pneumotoxic drugs, radiation therapy, and colony stimulating factors. Patients with risk factors should be closely monitored for respiratory symptoms before and during irinotecan therapy. Neurologic: Insomnia and dizziness can occur, but are not usually considered to be directly related to the administration of Irinotecan Hydrochloride Injection. Dizziness may sometimes represent symptomatic evidence of orthostatic hypotension in patients with dehydration. Cardiovascular: Vasodilation (flushing) may occur during administration of Irinotecan Hydrochloride Injection. Bradycardia may also occur, but has not required intervention. These effects have been attributed to the cholinergic syndrome sometimes observed during or shortly after infusion of Irinotecan Hydrochloride Injection. Thromboembolic events have been observed in patients receiving Irinotecan Hydrochloride Injection; the specific cause of these events has not been determined.<br/>Other Non-U.S. Clinical Trials: Irinotecan has been studied in over 1100 patients in Japan. Patients in these studies had a variety of tumor types, including cancer of the colon or rectum, and were treated with several different doses and schedules. In general, the types of toxicities observed were similar to those seen in U.S. trials with Irinotecan Hydrochloride Injection. There is some information from Japanese trials that Patients with considerable ascites or pleural effusions were at increased risk for neutropenia or diarrhea. A potentially life-threatening pulmonary syndrome, consisting of dyspnea, fever, and a reticulonodular pattern on chest x-ray, was observed in a small percentage of patients in early Japanese studies. The contribution of irinotecan to these preliminary events was difficult to assess because these patients also had lung tumors and some had preexisting nonmalignant pulmonary disease. As a result of these observations, however, clinical studies in the United States have enrolled few patients with compromised pulmonary function, significant ascites, or pleural effusions.<br/>Post-Marketing Experience: The following events have been identified during postmarketing use of Irinotecan Hydrochloride Injection in clinical practice. Infrequent cases of ulcerative and ischemic colitis have been observed. This can be complicated by ulceration, bleeding, ileus, obstruction, and infection, including typhlitis. Patients experiencing ileus should receive prompt antibiotic support . Rare cases of intestinal perforation have been reported. Rare cases of symptomatic pancreatitis or asymptomatic elevated pancreatic enzymes have been observed. Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have also been observed . Rare cases of hyponatremia mostly related with diarrhea and vomiting have been reported. Transient and mild to moderate increases in serum levels of transaminases (i.e., AST and ALT) in the absence of progressive liver metastasis; transient increase of amylase and occasionally transient increase of lipase have been very rarely reported. Infrequent cases of renal insufficiency including acute renal failure, hypotension or circulatory failure have been observed in patients who experienced episodes of dehydration associated with diarrhea and/or vomiting, or sepsis . Early effects such as muscular contraction or cramps and paresthesia have been reported.
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See BOXED WARNINGS, WARNINGS, and PRECAUTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximate rates. Endometrial Protection:Table 8 lists adverse experiences which were reported in���2% of patients (regardless of relationship to treatment) who received cyclic PROMETRIUM Capsules, 200 mg daily (12 days per calendar month cycle) with daily 0.625 mg conjugated estrogen, in a multicenter, randomized, double-blind, placebo-controlled clinical trial in 875 postmenopausal women. Secondary Amenorrhea:Table 9 lists adverse experiences which were reported in���5% of patients receiving PROMETRIUM Capsules, 400 mg/day, in a multicenter, randomized, double-blind, placebo-controlled clinical trial in estrogen-primed (6 weeks) postmenopausal women receiving conjugated estrogens 0.625 mg/day and cyclic (10 days per calendar month cycle) PROMETRIUM Capsules at a dose of 400 mg/day, for three cycles. The most common adverse experiences reported in���5% of patients in all PROMETRIUM Capsules dosage groups studied in this trial (100 mg/day to 400 mg/day) were: dizziness (16%), breast pain (11%), headache (10%), abdominal pain (10%), fatigue (9%), viral infection (7%), abdominal distention (6%), musculoskeletal pain (6%), emotional lability (6%), irritability (5%), and upper respiratory tract infection (5%). Other adverse events reported in<5% of patients taking PROMETRIUM Capsules include: Administration Site Conditions: edema, edema peripheral Blood and Lymphatic System: lymphadenopathy Cardiac Disorders: angina pectoris, palpitation Ear and Labyrinth Disorders: earache Eye Disorders: abnormal vision Gastrointestinal System Disorders: constipation, dry mouth, dyspepsia, gastroenteritis, hemorrhagic rectum, hiatus hernia, vomiting General Disorders: chest pain, fever Infections: abscess, herpes simplex Injury, Poisoning and Procedural Complications: accidental injury Musculoskeletal and Connective Tissue Disorders: arthritis, leg cramps, muscle disorder, myalgia Nervous System Disorders: hypertonia, impaired concentration, somnolence, speech disorder Psychiatric Disorders: anxiety, confusion, insomnia, personality disorder Renal and Urinary Disorders: urinary tract infection Reproductive System Disorders: fungal vaginitis, leukorrhea, uterine fibroid, vaginal dryness, vaginitis Respiratory System Disorders: bronchitis, nasal congestion, pharyngitis, pneumonitis, sinusitis Skin and Subcutaneous Tissue Disorders: acne, verruca, wound debridement Vascular Disorders: hypertension The following adverse experiences have been reported with PROMETRIUM Capsules in other U.S. clinical trials: increased sweating, asthenia, tooth disorder, anorexia, increased appetite, nervousness, and breast enlargement. In addition to the adverse events observed in clinical trials, the following spontaneous adverse events have been reported during the marketing of PROMETRIUM Capsules. Cardiac Disorders: circulatory collapse, tachycardia Congenital, Familial, and Genetic Disorders: cleft lip, cleft palate, congenital heart disease, patent ductus arteriosus, ventricular septal defect Ear and Labyrinth Disorders: tinnitus, vertigo Eye Disorders: blurred vision, diplopia, visual disturbance Gastrointestinal Disorders: acute pancreatitis, dysphagia, swollen tongue General Disorders and Administration Site Conditions: abnormal gait, difficulty walking, feeling abnormal, feeling drunk Hepatobiliary Disorders: cholestasis, cholestatic hepatitis, jaundice, hepatitis, hepatic failure, hepatic necrosis, increased liver function tests Immune System Disorders: anaphylactic reaction, hypersensitivity Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hepatic enzyme increased, blood glucose increased, weight decreased, weight increased Musculoskeletal Disorders: arthralgia, muscle cramp Neoplasms Benign, Malignant, and Unspecified: endometrial carcinoma Nervous System Disorders: convulsion, depressed consciousness, dysarthria, loss of consciousness, paresthesia, sedation, stupor, syncope (with and without hypotension), transient ischemic attack Pregnancy, Puerperium, and Perinatal Conditions: intra-uterine death, spontaneous abortion Psychiatric Disorders: aggression, depersonalization, disorientation, suicidal ideation, Reproductive System and Breast Disorders: menorrhagia, menstrual disorder, metrorrhagia, ovarian cyst Respiratory, Thoracic, and Mediastinal Disorders: asthma, choking, dyspnea, face edema, throat tightness Skin and Subcutaneous Tissue Disorders: alopecia, pruritus, urticaria Vascular Disorders: hypertension, hypotension The following additional adverse experiences have been observed in women taking estrogen and/or progestins in general: breakthrough bleeding, spotting, change in menstrual flow, amenorrhea, changes in weight (increase or decrease), changes in the cervical squamo-columnar junction and cervical secretions, cholestatic jaundice, anaphylactoid reactions and anaphylaxis, rash (allergic) with and without pruritus, melasma or chloasma, that may persist when drug is discontinued, dysmenorrhea, increase in size of uterine leiomyomata, ovarian cancer, endometrial hyperplasia, endometrial cancer, galactorrhea, nipple discharge, increased incidence of gallbladder disease, enlargement of hepatic hemangiomas, erythema multiforme, erythema nodosum, hirsutism, hemorrhagic eruption, intolerance to contact lenses, migraine, chorea, reduced carbohydrate tolerance, aggravation of porphyria, changes in libido, hypocalcemia, angioedema, exacerbation of asthma, increased triglycerides.
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The TIKOSYN clinical program involved approximately 8,600 patients in 130 clinical studies of normal volunteers and patients with supraventricular and ventricular arrhythmias. TIKOSYN was administered to 5,194 patients, including two large, placebo-controlled mortality trials (DIAMOND CHF and DIAMOND MI) in which 1,511 patients received TIKOSYN for up to three years. In the following section, adverse reaction data for cardiac arrhythmias and non-cardiac adverse reactions are presented separately for patients included in the supraventricular arrhythmia development program and for patients included in the DIAMOND CHF and MI mortality trials . In studies of patients with supraventricular arrhythmias a total of 1346 and 677 patients were exposed to TIKOSYN and placebo for 551 and 207 patient years, respectively. A total of 8.7% of patients in the dofetilide groups were discontinued from clinical trials due to adverse events compared to 8.0% in the placebo groups. The most frequent reason for discontinuation (>1%) was ventricular tachycardia (2.0% on dofetilide vs. 1.3% on placebo). The most frequent adverse events were headache, chest pain, and dizziness.<br/>Serious Arrhythmias and Conduction Disturbances: Torsade de pointes is the only arrhythmia that showed a dose-response relationship to TIKOSYN treatment. It did not occur in placebo treated patients. The incidence of torsade de pointes in patients with supraventricular arrhythmias was 0.8% (11/1346) . The incidence of torsade de pointes in patients who were dosed according to the recommended dosing regimen was 0.8% (4/525). Table 6 shows the frequency by randomized dose of serious arrhythmias and conduction disturbances reported as adverse events in patients with supraventricular arrhythmias. In the DIAMOND trials a total of 1511 patients were exposed to TIKOSYN for 1757 patient years. The incidence of torsade de pointes was 3.3% in CHF patients and 0.9% in patients with a recent MI. Table 7 shows the incidence of serious arrhythmias and conduction disturbances reported as adverse events in the DIAMOND subpopulation that had AF at entry to these trials.<br/>Other Adverse Reactions: Table 8 presents other adverse events reported with a frequency of>2% on TIKOSYN and reported numerically more frequently on TIKOSYN than on placebo in the studies of patients with supraventricular arrhythmias. Adverse events reported at a rate>2% but no more frequently on TIKOSYN than on placebo were: angina pectoris, anxiety, arthralgia, asthenia, atrial fibrillation, complications (application, injection, incision, insertion, or device), hypertension, pain, palpitation, peripheral edema, supraventricular tachycardia, sweating, urinary tract infection, ventricular tachycardia. The following adverse events have been reported with a frequency of���2% and numerically more frequently with TIKOSYN than placebo in patients with supraventricular arrhythmias: angioedema, bradycardia, cerebral ischemia, cerebrovascular accident, edema, facial paralysis, flaccid paralysis, heart arrest, increased cough, liver damage, migraine, myocardial infarct, paralysis, paresthesia, sudden death, and syncope. The incidences of clinically significant laboratory test abnormalities in patients with supraventricular arrhythmias were similar for patients on TIKOSYN and those on placebo. No clinically relevant effects were noted in serum alkaline phosphatase, serum GGT, LDH, AST, ALT, total bilirubin, total protein, blood urea nitrogen, creatinine, serum electrolytes (calcium, chloride, glucose, magnesium, potassium, sodium) or creatine kinase. Similarly, no clinically relevant effects were observed in hematologic parameters. In the DIAMOND population, adverse events other than those related to the post-infarction and heart failure patient population were generally similar to those seen in the supraventricular arrhythmia groups.
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Peripheral Infusions A 4.25 or 5% solution of amino acids (without
additives) is slightly hypertonic. A 3.5% concentration of amino
acids (without additives) is slightly hypertonic. Local reactions
consisting of a warm sensation, erythema, phlebitis and thrombosis
at the infusion site have occurred with peripheral intravenous infusion
of amino acids particularly if other substances, such as antibiotics,
are also administered through the same site. In such cases the infusion
site should be changed promptly to another vein. Use of large peripheral
veins, inline filters, and slowing the rate of infusion may reduce
the incidence of local venous irritation. Electrolyte additives should
be spread throughout the day. Irritating additive medications may
need to be injected at another venous site. Generalized flushing, fever and nausea also have been reported during
peripheral infusions of amino acid solutions.
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Fluid and
Electrolyte Disturbances: Sodium
retention Fluid
retention Congestive
heart failure in susceptible patients Potassium
loss Hypokalemic
alkalosis Hypertension<br/>Musculoskeletal: Muscle
weakness Steroid
myopathy Loss of
muscle mass Osteoporosis Vertebral
compression fractures Aseptic
necrosis of femoral and humeral heads Pathologic
fracture of long bones Tendon
rupture<br/>Gastrointestinal: Peptic
ulcer with possible subsequent perforation and hemorrhage Perforation
of the small and large bowel, particularly in patients with
inflammatory bowel disease Pancreatitis Abdominal
distention Ulcerative
esophagitis<br/>Dermatologic: Impaired
wound healing Thin,
fragile skin Petechiae
and ecchymoses Erythema Increased
sweating May
suppress reactions to skin tests Burning or
tingling, especially in the perineal area (after IV injection) Other
cutaneous reactions, such as allergic dermatitis, urticaria,
angioneurotic edema<br/>Neurologic: Convulsions Increased
intracranial pressure with papilledema (pseudotumor cerebri)
usually after treatment Vertigo Headache Psychic
disturbances<br/>Endocrine: Menstrual
irregularities Development
of cushingoid state Suppression
of growth in children Secondary
adrenocortical and pituitary unresponsiveness, particularly in
times of stress, as in trauma, surgery or illness Decreased carbohydrate tolerance Manifestations of latent diabetes mellitus Increased
requirements for insulin or oral hypoglycemic agents in
diabetics Hirsutism<br/>Ophthalmic: Posterior
subcapsular cataracts Increased
intraocular pressure Glaucoma Exophthalmos<br/>Metabolic: Negative
nitrogen balance due to protein catabolism<br/>Cardiovascular: Myocardial
rupture following recent myocardial infarction<br/>Other: Anaphylactoid or hypersensitivity reactions Thromboembolism Weight gain Increased
appetite Nausea Malaise Hiccups The
following additional
adverse reactions are related to parenteral corticosteroid
therapy: Rare
instances of blindness associated with intralesional therapy
around the face and head Hyperpigmentation or hypopigmentation Subcutaneous and cutaneous atrophy Sterile
abscess Postinjection flare (following intra-articular use) Charcot-like arthropathy
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Reactions to Bupivacaine Hydrochloride are characteristic
of those associated with other amide-type local anesthetics. A major
cause of adverse reactions to this group of drugs is excessive plasma
levels, which may be due to overdosage, unintentional intravascular
injection, or slow metabolic degradation. The
most commonly encountered acute adverse experiences which demand immediate
counter-measures are related to the central nervous system and the
cardiovascular system. These adverse experiences are generally dose
related and due to high plasma levels which may result from overdosage,
rapid absorption from the injection site, diminished tolerance, or
from unintentional intravascular injection of the local anesthetic
solution. In addition to systemic dose-related toxicity, unintentional
subarachnoid injection of drug during the intended performance of
caudal or lumbar epidural block or nerve blocks near the vertebral
column (especially in the head and neck region) may result in underventilation
or apnea (���Total or High Spinal���). Also, hypotension
due to loss of sympathetic tone and respiratory paralysis or underventilation
due to cephalad extension of the motor level of anesthesia may occur.
This may lead to secondary cardiac arrest if untreated. Patients over
65 years, particularly those with hypertension, may be at increased
risk for experiencing the hypotensive effects of Bupivacaine Hydrochloride.
Factors influencing plasma protein binding, such as acidosis, systemic
diseases which alter protein production, or competition of other drugs
for protein binding sites, may diminish individual tolerance. Central Nervous System Reactions: These are characterized by excitation and/or depression. Restlessness,
anxiety, dizziness, tinnitus, blurred vision, or tremors may occur,
possibly proceeding to convulsions. However, excitement may be transient
or absent, with depression being the first manifestation of an adverse
reaction. This may quickly be followed by drowsiness merging into
unconsciousness and respiratory arrest. Other central nervous system
effects may be nausea, vomiting, chills, and constriction of the pupils. The incidence of convulsions associated with the use of
local anesthetics varies with the procedure used and the total dose
administered. In a survey of studies of epidural anesthesia, overt
toxicity progressing to convulsions occurred in approximately 0.1%
of local anesthetic administrations. Cardiovascular System Reactions: High doses
or unintentional intravascular injection may lead to high plasma levels
and related depression of the myocardium, decreased cardiac output,
heartblock, hypotension, bradycardia, ventricular arrhythmias, including
ventricular tachycardia and ventricular fibrillation, and cardiac
arrest. (See WARNINGS, PRECAUTIONS, and OVERDOSAGE sections.) Allergic: Allergic-type
reactions are rare and may occur as a result of sensitivity to the
local anesthetic or to other formulation ingredients, such as the
antimicrobial preservative methylparaben contained in multiple-dose
vials or sulfites in epinephrine-containing solutions. These reactions
are characterized by signs such as urticaria, pruritus, erythema,
angioneurotic edema (including laryngeal edema), tachycardia, sneezing,
nausea, vomiting, dizziness, syncope, excessive sweating, elevated
temperature, and possibly, anaphylactoid-like symptomatology (including
severe hypotension). Cross sensitivity among members of the amide-type
local anesthetic group has been reported. The usefulness of screening
for sensitivity has not been definitely established. Neurologic: The incidences of
adverse neurologic reactions associated with the use of local anesthetics
may be related to the total dose of local anesthetic administered
and are also dependent upon the particular drug used, the route of
administration, and the physical status of the patient. Many of these
effects may be related to local anesthetic techniques, with or without
a contribution from the drug. In the practice
of caudal or lumbar epidural block, occasional unintentional penetration
of the subarachnoid space by the catheter or needle may occur. Subsequent
adverse effects may depend partially on the amount of drug administered
intrathecally and the physiological and physical effects of a dural
puncture. A high spinal is characterized by paralysis of the legs,
loss of consciousness, respiratory paralysis, and bradycardia. Neurologic effects following epidural or caudal anesthesia
may include spinal block of varying magnitude (including high or total
spinal block); hypotension secondary to spinal block; urinary retention;
fecal and urinary incontinence; loss of perineal sensation and sexual
function; persistent anesthesia, paresthesia, weakness, paralysis
of the lower extremities and loss of sphincter control all of which
may have slow, incomplete, or no recovery; headache; backache; septic
meningitis; meningismus; slowing of labor; increased incidence of
forceps delivery; and cranial nerve palsies due to traction on nerves
from loss of cerebrospinal fluid. Neurologic
effects following other procedures or routes of administration may
include persistent anesthesia, paresthesia, weakness, paralysis, all
of which may have slow, incomplete, or no recovery.
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Multiple-doses of fluoxetine had been administered to 10,782 patients with various diagnoses in U.S. clinical trials as of May 8, 1995. In addition, there have been 425 patients administered fluoxetine in panic clinical trials. Adverse events were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a limited (i.e., reduced) number of standardized event categories. In the tables and tabulations that follow, COSTART Dictionary terminology has been used to classify reported adverse events. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it. The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.<br/>Incidence in Major Depressive Disorder, OCD, Bulimia and Panic Disorder Placebo-Controlled Clinical Trials (excluding data from extensions of trials): Table 2 enumerates the most common treatment-emergent adverse events associated with the use of fluoxetine (incidence of at least 5% for fluoxetine and at least twice that for placebo within at least one of the indications) for the treatment of major depressive disorder, OCD, and bulimia in U.S. controlled clinical trials and panic disorder in U.S. plus non-U.S. controlled trials. Table 3 enumerates treatment-emergent adverse events that occurred in 2% or more patients treated withfluoxetine and with incidence greater than placebo who participated in U.S. major depressive disorder, OCD, and bulimia controlled clinical trials and U.S. plus non-U.S. panic disorder controlled clinical trials. Table 3 provides combined data for the pool of studies that are provided separately by indication in Table 2.<br/>Associated with Discontinuation in Major Depressive Disorder, OCD, Bulimia and Panic Disorder Placebo-Controlled Clinical Trials (excluding data from extensions of trials): Table 4 lists the adverse events associated with discontinuation of fluoxetine treatment (incidence at least twice that for placebo and at least 1% for fluoxetine in clinical trials collecting only a primary event associated with discontinuation) in major depressive disorder, OCD, bulimia and panic disorder clinical trials, plus non-U.S. panic disorder clinical trials.<br/>Other Adverse Events in Pediatric Patients (Children and Adolescents): Treatment-emergent adverse events were collected in 322 pediatric patients (180 fluoxetine-treated, 142 placebo-treated). The overall profile of adverse events was generally similar to that seen in adult studies, as shown in Tables 2 and 3. However, the following adverse events (excluding those which appear in the body or footnotes of Tables 2 and 3 and those for which the COSTART terms were uninformative or misleading) were reported at an incidence of at least 2% for fluoxetine and greater than placebo: thirst, hyperkinesia, agitation, personality disorder, epistaxis, urinary frequency, and menorrhagia. The most common adverse event (incidence at least 1% for fluoxetine and greater than placebo) associated with discontinuation in three pediatric placebo-controlled trials (N = 418 randomized; 228 fluoxetine-treated; 190 placebo-treated) was mania/hypomania (1.8% for fluoxetine-treated, 0% for placebo-treated). In these clinical trials, only a primary event associated with discontinuation was collected.<br/>Male and Female Sexual Dysfunction with SSRIs: Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians maybe reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance, cited in product labeling, are likely to underestimate their actual incidence. In patients enrolled in U.S. major depressive disorder, OCD, and bulimia placebo-controlled clinical trials, decreased libido was the only sexual side effect reported by at least 2% of patients taking fluoxetine (4% fluoxetine,<1% placebo). There have been spontaneous reports in women taking fluoxetine of orgasmic dysfunction, including anorgasmia. There are no adequate and well controlled studies examining sexual dysfunction with fluoxetine treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.<br/>Other Events Observed in Clinical Trials: Following is a list of all treatment-emergent adverse events reported at anytime by individuals taking fluoxetine in U.S. clinical trials as of May 8, 1995 (10,782 patients) except (1) those listed in the body or footnotes of Tables 2 or 3 above or elsewhere in labeling; (2) those for which the COSTART terms were uninformative or misleading; (3) those events for which a causal relationship to fluoxetine use was considered remote; and (4) events occurring in only one patient treated with fluoxetine and which did not have a substantial probability of being acutely life-threatening. Events are classified within body system categories using the following definitions: frequent adverse events are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in less than 1/1,000 patients. Body as a Whole: Frequent: chest pain, chills; Infrequent: chills and fever, face edema, intentional overdose, malaise, pelvic pain, suicide attempt; Rare: acute abdominal syndrome, hypothermia, intentional injury, neuroleptic malignant syndrome, photosensitivity reaction Cardiovascular System: Frequent: hemorrhage, hypertension, palpitation; Infrequent: angina pectoris, arrhythmia, congestive heart failure, hypotension, migraine, myocardial infarct, postural hypotension, syncope, tachycardia, vascular headache; Rare: atrial fibrillation, bradycardia, cerebral embolism, cerebral ischemia, cerebrovascular accident, extrasystoles, heart arrest, heartblock, pallor, peripheral vascular disorder, phlebitis, shock, thrombophlebitis, thrombosis, vasospasm, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation Digestive System: Frequent: increased appetite, nausea and vomiting; Infrequent: aphthous stomatitis, cholelithiasis, colitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, glossitis, gum hemorrhage, hyperchlorhydria, increased salivation, liver function tests abnormal, melena, mouth ulceration, nausea/vomiting/diarrhea, stomach ulcer, stomatitis, thirst; Rare: biliary pain, bloody diarrhea, cholecystitis, duodenal ulcer, enteritis, esophageal ulcer, fecal incontinence, gastrointestinal hemorrhage, hematemesis, hemorrhage of colon, hepatitis, intestinal obstruction, liver fatty deposit, pancreatitis, peptic ulcer, rectal hemorrhage, salivary gland enlargement, stomach ulcer hemorrhage, tongue edema Endocrine System: Infrequent: hypothyroidism; Rare: diabetic acidosis, diabetes mellitus Hemic and Lymphatic System: Infrequent: anemia, ecchymosis; Rare: blood dyscrasia, hypochromic anemia, leukopenia, lymphedema, lymphocytosis, petechia, purpura, thrombocythemia, thrombocytopenia Metabolic and Nutritional: Frequent: weight gain; Infrequent: dehydration, generalized edema, gout, hypercholesteremia, hyperlipemia, hypokalemia, peripheral edema; Rare: alcohol intolerance, alkaline phosphatase increased, BUN increased, creatine phosphokinase increased, hyperkalemia, hyperuricemia, hypocalcemia, iron deficiency anemia, SGPT increased Musculoskeletal System: Infrequent: arthritis, bone pain, bursitis, leg cramps, tenosynovitis; Rare: arthrosis, chondrodystrophy, myasthenia, myopathy, myositis, osteomyelitis, osteoporosis, rheumatoid arthritis Nervous System: Frequent: agitation, amnesia, confusion, emotional lability, sleep disorder; Infrequent: abnormal gait, acute brain syndrome, akathisia, apathy, ataxia, buccoglossal syndrome, CNS depression, CNS stimulation, depersonalization, euphoria, hallucinations, hostility, hyperkinesia, hypertonia, hypesthesia, incoordination, libido increased, myoclonus, neuralgia, neuropathy, neurosis, paranoid reaction, personality disorder, psychosis, vertigo; Rare: abnormal electroencephalogram, antisocial reaction, circumoral paresthesia, coma, delusions, dysarthria, dystonia, extrapyramidal syndrome, foot drop, hyperesthesia, neuritis, paralysis, reflexes decreased, reflexes increased, stupor Respiratory System: Infrequent: asthma, epistaxis, hiccup, hyperventilation; Rare: apnea, atelectasis, cough decreased, emphysema, hemoptysis, hypoventilation, hypoxia, larynx edema, lung edema, pneumothorax, stridor Skin and Appendages: Infrequent: acne, alopecia, contact dermatitis, eczema, maculopapular rash, skin discoloration, skin ulcer, vesiculobullous rash; Rare: furunculosis, herpes zoster, hirsutism, petechial rash, psoriasis, purpuric rash, pustular rash, seborrhea Special Senses: Frequent: ear pain, taste perversion, tinnitus; Infrequent: conjunctivitis, dry eyes, mydriasis, photophobia; Rare: blepharitis, deafness, diplopia, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, iritis, parosmia, scleritis, strabismus, taste loss, visual field defect Urogenital System: Frequent: urinary frequency; Infrequent: abortion, albuminuria, amenorrhea, anorgasmia, breast enlargement, breast pain, cystitis, dysuria, female lactation, fibrocystic breast, hematuria, leukorrhea, menorrhagia, metrorrhagia, nocturia, polyuria, urinary incontinence, urinary retention, urinary urgency, vaginal hemorrhage; Rare: breast engorgement, glycosuria, hypomenorrhea, kidney pain, oliguria, priapism, uterine hemorrhage, uterine fibroids enlarged<br/>Postintroduction Reports: Voluntary reports of adverse events temporally associated with fluoxetine that have been received since market introduction and that may have no causal relationship with the drug include the following: aplastic anemia, atrial fibrillation, cataract, cerebral vascular accident, cholestatic jaundice, confusion, dyskinesia (including, for example, a case of buccal-lingual-masticatorysyndrome with involuntary tongue protrusion reported to develop in a 77 year old female after 5 weeks of fluoxetine therapy and which completely resolved over the next few months following drug discontinuation), eosinophilic pneumonia, epidermal necrolysis, erythema multiforme, erythema nodosum, exfoliative dermatitis, gynecomastia, heart arrest, hepatic failure/necrosis, hyperprolactinemia, hypoglycemia, immune-related hemolytic anemia, kidney failure, misuse/abuse, movement disorders developing in patients with risk factors including drugs associated with such events and worsening of preexisting movement disorders, neuroleptic malignant syndrome-like events, optic neuritis, pancreatitis, pancytopenia, priapism, pulmonary embolism, pulmonary hypertension, QT prolongation, serotonin syndrome (a range of signs and symptoms that can rarely, in its most severe form, resemble neuroleptic malignant syndrome), Stevens-Johnson Syndrome, sudden unexpected death, suicidal ideation, thrombocytopenia, thrombocytopenicpurpura, vaginal bleeding after drug withdrawal, ventricular tachycardia (including Torsades de pointes-type arrhythmias), and violent behaviors.
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| dailymed-drugs:46 |
Chemotherapy-Induced Nausea and Vomiting: Over 3700 patients have received granisetron hydrochloride tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens. In patients receiving granisetron hydrochloride tablets 1 mg bid for 1, 7 or 14 days, or 2 mg qd for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4. Other adverse events reported in clinical trials were: Gastrointestinal: In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24 hour efficacy assessment period. Hepatic: In comparative trials, elevation of AST and ALT (>2 times the upper limit of normal) following the administration of granisetron hydrochloride tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%). Cardiovascular: Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely. Central Nervous System: Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms has been reported in a patient treated with granisetron hydrochloride tablets. Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis, shortness of breath, hypotension, urticaria) have been reported. Other: Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia (9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%). Over 5000 patients have received injectable granisetron hydrochloride in clinical trials. Table 5 gives the comparative frequencies of the five commonly reported adverse events (���3%) in patients receiving granisetron hydrochloride injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24 hour period following granisetron hydrochloride injection administration. In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to granisetron hydrochloride, except for headache, which was clearly more frequent than in comparison groups.<br/>Radiation-Induced Nausea and Vomiting: In controlled clinical trials, the adverse events reported by patients receiving granisetron hydrochloride tablets and concurrent radiation were similar to those reported by patients receiving granisetron hydrochloride tablets prior to chemotherapy. The most frequently reported adverse events were diarrhea, asthenia and constipation. Headache, however, was less prevalent in this patient population.
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| dailymed-drugs:47 |
See ADVERSE REACTIONS���General.
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| dailymed-drugs:2459 |
See ADVERSE REACTIONS���General.
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| dailymed-drugs:48 |
Worldwide, controlled clinical trials of nizatidine included over 6,000 patients given nizatidine in studies of varying durations. Placebo-controlled trials in the United States and Canada included over 2,600 patients given nizatidine and over 1,700 given placebo. Among the adverse events in these placebo-controlled trials, anemia (0.2% vs 0%) and urticaria (0.5% vs 0.1%) were significantly more common in the nizatidine group. Incidence in Placebo-Controlled Clinical Trials in the United States and Canada���Table 5 lists adverse events that occurred at a frequency of 1% or more among nizatidine-treated patients who participated in placebo-controlled trials. The cited figures provide some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied. A variety of less common events were also reported; it was not possible to determine whether these were caused by nizatidine. Hepatic���Hepatocellular injury, evidenced by elevated liver enzyme tests (SGOT [AST], SGPT [ALT], or alkaline phosphatase), occurred in some patients and was possibly or probably related to nizatidine. In some cases, there was marked elevation of SGOT, SGPT enzymes (greater than 500 IU/L) and, in a single instance, SGPTwas greater than 2,000 IU/L. The overall rate of occurrences of elevated liver enzymes and elevations to 3 times the upper limit of normal, however, did not significantly differ from the rate of liver enzyme abnormalities in placebo-treated patients. All abnormalities were reversible after discontinuation of Axid. Since market introduction, hepatitis and jaundice have been reported. Rare cases of cholestatic or mixed hepatocellular and cholestatic injury with jaundice have been reported with reversal of theabnormalities after discontinuation of Axid. Cardiovascular���In clinical pharmacology studies, short episodes of asymptomatic ventricular tachycardia occurred in 2 individuals administered Axid and in 3 untreated subjects. CNS���Rare cases of reversible mental confusion have been reported. Endocrine���Clinical pharmacology studies and controlled clinical trials showed no evidence of antiandrogenic activity due to Axid. Impotence and decreased libido were reported with similar frequency by patients who received Axid and by those given placebo. Rare reports of gynecomastia occurred. Hematologic���Anemia was reported significantly more frequently in nizatidine- than in placebo-treated patients. Fatal thrombocytopenia was reported in a patient who was treated with Axid and another H-receptor antagonist. On previous occasions, this patient had experienced thrombocytopenia while taking other drugs. Rare cases of thrombocytopenic purpura have been reported. Integumental���Sweating and urticaria were reported significantly more frequently in nizatidine- than in placebo-treated patients. Rash and exfoliative dermatitis were also reported. Vasculitis has been reported rarely. Hypersensitivity���As with other H-receptor antagonists, rare cases of anaphylaxis following administration of nizatidine have been reported. Rare episodes of hypersensitivity reactions (eg, bronchospasm, laryngeal edema, rash, and eosinophilia) have been reported. Body as a Whole���Serum sickness-like reactions have occurred rarely in conjunction with nizatidine use. Genitourinary���Reports of impotence have occurred. Other���Hyperuricemia unassociated with gout or nephrolithiasis was reported. Eosinophilia, fever, and nausea related to nizatidine administration have been reported.
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| dailymed-drugs:49 |
Too rapid infusion
of a hypertonic dextrose solution may result in diuresis, hyperglycemia,
glycosuria, and hyperosmolar coma. Continual clinical monitoring of the
patient is necessary in order to identify and initiate measures for
these clinical conditions. Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation and
hypervolemia. If an adverse
reaction does occur discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the
remainder of the fluid for examination if deemed necessary.
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| dailymed-drugs:51 |
1. Salt and Water Retention (see WARNINGS: Concomitant use of Adequate Diuretic is Required) - Temporary edema developed in 7% of patients who were not edematous at the start of therapy. 2. Pericarditis, Pericardial Effusion and Tamponade . 3. Dermatologic - Hypertrichosis - Elongation, thickening, and enhanced pigmentation of fine body hair are seen in about 80% of patients taking minoxidil tablets. This develops within 3 to 6 weeks after starting therapy. It is usually first noticed on the temples, between the eyebrows, between the hairline and the eyebrows, or in the side-burn area of the upper lateral cheek, later extending to the back, arms, legs, and scalp. Upon discontinuation of minoxidil, new hair growth stops, but 1 to 6 months may be required for restoration to pretreatment appearance. No endocrine abnormalities have been found to explain the abnormal hair growth; thus, it is hypertrichosis without virilism. Hair growth is especially disturbing to children and women and such patients should be thoroughly informed about this effect before therapy with minoxidil is begun. Allergic - Rashes have been reported, including rare reports of bullous eruptions, and Stevens-Johnson Syndrome. 4. Hematologic - Thrombocytopenia and leukopenia (WBC<3000/mm) have rarely been reported. 5. Gastrointestinal - Nausea and/or vomiting has been reported. In clinical trials the incidence of nausea and vomiting associated with the underlying disease has shown a decrease from pretrial levels. 6. Miscellaneous - Breast tenderness - This developed in less than 1 % of patients. 7. Altered Laboratory Findings - (a) ECG changes - Changes in direction and magnitude of the ECG T-waves occur in approximately 60% of patients treated with minoxidil. In rare instances a large negative amplitude of the T-wave may encroach upon the S-T segment, but the S-T segment is not independently altered. These changes usually disappear with continuance of treatment and revert to the pretreatment state if minoxidil is discontinued. No symptoms have been associated with these changes, nor have there been alterations in blood cell counts or in plasma enzyme concentrations that would suggest myocardial damage. Long-term treatment of patients manifesting such changes has provided no evidence of deteriorating cardiac function. At present the changes appear to be nonspecific and without identifiable clinical significance. (b) Effects of hemodilution - hematocrit, hemoglobin and erythrocyte count usually fall about 7% initially and then recover to pretreatment levels. (c) Other - Alkaline phosphatase increased varyingly without other evidence of liver or bone abnormality. Serum creatinine increased an average of 6% and BUN slightly more, but later declined to pretreatment levels.
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| dailymed-drugs:52 |
The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or central
nervous system depression. Hypotension does occur when the drug is administered rapidly by the intravenous route. The rate of administration is very important; it should not exceed 50 mg per minute in
adults, and 1-3 mg/kg/min in neonates. At this rate, toxicity should be minimized.<br/>Cardiovascular: Severe cardiotoxic reactions and fatalities have been reported with atrial and ventricular conduction depression and
ventricular fibrillation. Severe complications are most commonly encountered in elderly or gravely ill patients.<br/>Central Nervous System: The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related.
These include nystagmus, ataxia, slurred speech, decreased coordination and mental confusion. Dizziness, insomnia, transient nervousness, motor twitchings and headaches have also
been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremorand asterixis, similar to those induced by phenothiazine and
other neuroleptic drugs. A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin
therapy.<br/>Gastrointestinal System: Nausea, vomiting and constipation.<br/>Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A
morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or
purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis .<br/>Hemopoietic System: Hemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These
have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia
have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma and Hodgkin's Disease have
been reported .<br/>Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis and Peyronie's
Disease.<br/>Injection Site: Local irritation, inflammation, tenderness, necrosis and sloughing have been reported with or without extravasation of
intravenous phenytoin.<br/>Other: Systemic lupus erythematosus, periarteritis nodosa, toxic hepatitis, liver damage, immunoglobulin abnormalities and purple
glove syndrome may occur.
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| dailymed-drugs:53 |
In patients with advanced prostate cancer treated with CASODEX in combination with an LHRH analogue, the most frequent adverse experience was hot flashes (53%). In the multicenter, double-blind, controlled clinical trial comparing CASODEX 50 mg once daily with flutamide 250 mg three times a day, each in combination with an LHRH analogue, the following adverse experiences with an incidence of 5% or greater, regardless of causality, have been reported. Other adverse experiences (greater than or equal to 2%, but less than 5%) reported in the CASODEX-LHRH analogue treatment group are listed below by body system and are in order of decreasing frequency within each body system regardless of causality. Body as a Whole: Neoplasm; Neck pain; Fever; Chills; Sepsis; Hernia; Cyst Cardiovascular: Angina pectoris; Congestive heart failure; Myocardial infarct; Heart arrest; Coronary artery disorder; Syncope Digestive: Melena; Rectal hemorrhage; Dry mouth; Dysphagia; Gastrointestinal disorder; Periodontal abscess; Gastrointestinal carcinoma Metabolic and Nutritional: Edema; Bun increased; Creatinine increased; Dehydration; Gout; Hypercholesteremia Musculoskeletal: Myalgia; Leg cramps Nervous: Hypertonia; Confusion; Somnolence; Libido decreased; Neuropathy; Nervousness Respiratory: Lung disorder; Asthma; Epistaxis; Sinusitis Skin and Appendages: Dry skin; Alopecia; Pruritus; Herpes zoster; Skin carcinoma; Skin disorder Special Senses: Cataract specified Urogenital: Dysuria; Urinary urgency; Hydronephrosis; Urinary tract disorder<br/>Abnormal Laboratory Test Values:: Laboratory abnormalities including elevated AST, ALT, bilirubin, BUN, and creatinine and decreased hemoglobin and white cell count have been reported in both CASODEX-LHRH analogue treated and flutamide-LHRH analogue treated patients.<br/>Postmarketing Experience:: Uncommon cases of hypersensitivity reactions, including angioneurotic edema and urticaria, and uncommon cases of interstitial lung disease, including interstitial pneumonitis and pulmonary fibrosis, have been reported with CASODEX.
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| dailymed-drugs:54 |
Gastrointestinal: Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea have been noted in some patients. Although Clostridium difficile has been shown in vitro to be sensitive to rifampin, pseudomembranous colitis has been reported with the use of rifampin (and other broad spectrumantibiotics). Therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Rarely, hepatitis or a shock-like syndrome with hepatic involvement and abnormal liver function tests has been reported.<br/>Hematologic: Thrombocytopenia has occurred primarily with high dose intermittent therapy, but has also been noted after resumption of interrupted treatment. It rarely occurs during well supervised daily therapy. This effect is reversible if the drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura. Rare reports of disseminated intravascular coagulation have been observed. Leukopenia, hemolytic anemia, and decreased hemoglobin have been observed. Agranulocytosis has been reported very rarely.<br/>Central Nervous System: Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, pains in extremities, and generalized numbness have been observed. Psychoses have been rarely reported.<br/>Ocular: Visual disturbances have been observed.<br/>Endocrine: Menstrual disturbances have been observed. Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.<br/>Renal: Elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted. These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted.<br/>Dermatologic: Cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions. Typically, they consist of flushing and itching with or without a rash. More serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon.<br/>Hypersensitivity Reactions: Occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme including Stevens-Johnson Syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed. Anaphylaxis has been reported rarely.<br/>Miscellaneous: Rare reports of myopathy and muscular weakness have also been observed. Edema of the face and extremities has been reported. Other reactions reported to have occurred with intermittent dosage regimens include "flu syndrome" (such as episodes of fever, chills, headache, dizziness, and bone pain), shortness of breath, wheezing, decrease in blood pressure and shock. The "flu syndrome" may also appear if rifampin is taken irregularly by the patient or if daily administration is resumed after a drug free interval.
|
| dailymed-drugs:55 |
Gastrointestinal���Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Nausea and vomiting have been reported rarely. The most frequent side effect has been diarrhea. It was very rarely severe enough to warrant cessation of therapy. Dyspepsia, gastritis, and abdominal pain have also occurred. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. Hypersensitivity���Allergic reactions in the form of rash, urticaria, angioedema, and, rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been observed. These reactions usually subsided upon discontinuation of the drug. In some of these reactions, supportive therapy may be necessary. Anaphylaxis has also been reported. Other reactions have included genital and anal pruritus, genital moniliasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible interstitial nephritis has been reported rarely. Eosinophilia, neutropenia, thrombocytopenia, and slight elevations in AST and ALT have been reported.
|
| dailymed-drugs:1338 |
Gastrointestinal���Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Nausea and vomiting have been reported rarely. The most frequent side effect has been diarrhea. It was very rarely severe enough to warrant cessation of therapy. Dyspepsia, gastritis, and abdominal pain have also occurred. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. Hypersensitivity���Allergic reactions in the form of rash, urticaria, angioedema, and, rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been observed. These reactions usually subsided upon discontinuation of the drug. In some of these reactions, supportive therapy may be necessary. Anaphylaxis has also been reported. Other reactions have included genital and anal pruritus, genital moniliasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible interstitial nephritis has been reported rarely. Eosinophilia, neutropenia, thrombocytopenia, and slight elevations in AST and ALT have been reported.
|
| dailymed-drugs:56 |
Over 1000 patients from both controlled and open trials with nifedipine extended-release tablets in hypertension and angina were included in the evaluation of adverse experiences. All side effects reported during nifedipine extended-release tablet therapy were tabulated independent of their causal relation to medication. The most common side effect reported with nifedipine extended-release was edema which was dose related and ranged in frequency from approximately 10% to about 30% at the highest dose studied (180 mg). Other common adverse experiences reported in placebo-controlled trials include: Of these, only edema and headache were more common in nifedipine extended-release patients than placebo patients. The following adverse reactions occurred with an incidence of less than 3.0%. With the exception of leg cramps, the incidence of these side effects was similar to that of placebo alone. Body as a Whole/Systemic: asthenia, flushing, painCardiovascular: palpitationsCentral Nervous System: insomnia, nervousness, paresthesia, somnolenceDermatologic: pruritus, rashGastrointestinal: abdominal pain, diarrhea, dry mouth, dyspepsia, flatulenceMusculoskeletal: arthralgia, leg crampsRespiratory: chest pain (nonspecific), dyspneaUrogenital: impotence, polyuria Other adverse reactions were reported sporadically with an incidence of 1.0% or less. These include: Body as a Whole/Systemic: face edema, fever, hot flashes, malaise, periorbital edema, rigorsCardiovascular: arrhythmia, hypotension, increased angina, tachycardia, syncopeCentral Nervous System: anxiety, ataxia, decreased libido, depression, hypertonia, hypoesthesia, migraine, paroniria, tremor, vertigoDermatologic: alopecia, increased sweating, urticaria, purpuraGastrointestinal: eructation, gastroesophageal reflux, gum hyperplasia, melena, vomiting, weight increaseMusculoskeletal: back pain, gout, myalgiasRespiratory: coughing, epistaxis, upper respiratory tract infection, respiratory disorder, sinusitisSpecial Senses: abnormal lacrimation, abnormal vision, taste perversion, tinnitusUrogenital/Reproductive: breast pain, dysuria, hematuria, nocturia Adverse experiences which occurred in less than 1 in 1000 patients cannot be distinguished from concurrent disease states or medications. The following adverse experiences, reported in less than 1% of patients, occurred under conditions (e.g., open trials, marketing experience) where a causal relationship is uncertain: gastrointestinal irritation, gastrointestinal bleeding, gynecomastia. In multiple-dose U.S. and foreign controlled studies with nifedipine capsules in which adverse reactions were reported spontaneously, adverse effects were frequent but generally not serious and rarely required discontinuation of therapy or dosage adjustment. Most were expected consequences of the vasodilator effects of nifedipine. There is also a large uncontrolled experience in over 2100 patients in the United States. Most of the patients had vasospastic or resistant angina pectoris, and about half had concomitant treatment with beta-adrenergic blocking agents. The relatively common adverse events were similar in nature to those seen with nifedipine extended-release. In addition, more serious adverse events were observed, not readily distinguishable from the natural history of the disease in these patients. It remains possible, however, that some or many of these events were drug related. Myocardial infarction occurred in about 4% of patients and congestive heart failure or pulmonary edema in about 2%. Ventricular arrhythmias or conduction disturbances each occurred in fewer than 0.5% of patients. In a subgroup of over 1000 patients receiving nifedipine immediate-release with concomitant beta blocker therapy, the pattern and incidence of adverse experiences was not different from that of the entire group of nifedipine immediate-release treated patients. In a subgroup of approximately 250 patients with a diagnosis of congestive heart failure as well as angina, dizziness or lightheadedness, peripheral edema, headache or flushing each occurred in one in eight patients. Hypotension occurred in about one in 20 patients. Syncope occurred in approximately one patient in 250. Myocardial infarction or symptoms of congestive heart failure each occurred in about one patient in 15. Atrial or ventricular dysrhythmias each occurred in about one patient in 150. In post-marketing experience, there have been rare reports of exfoliative dermatitis caused by nifedipine. There have been rare reports of exfoliative or bullous skin adverse events (such as erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis) and photosensitivity reactions.
|
| dailymed-drugs:58 |
Glipizide and Metformin Hydrochloride Tablets: In a double-blind 24 week clinical trial involving glipizide and metformin hydrochloride tablets as initial therapy, a total of 172 patients received glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, 173 received glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in Table 4. In a double-blind 18 week clinical trial involving glipizide and metformin hydrochloride tablets as second-line therapy, a total of 87 patients received glipizide and metformin hydrochloride tablets, 84 received glipizide, and 75 received metformin. The most common clinical adverse events in this clinical trial are listed in Table 5.<br/>Hypoglycemia: In a controlled initial therapy trial of glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg and 2.5 mg/500 mg the numbers of patients with hypoglycemia documented by symptoms (such as dizziness, shakiness, sweating, and hunger) and a fingerstick blood glucose measurement���50 mg/dL were 5 (2.9%) for glipizide, 0 (0%) for metformin, 13 (7.6%) for glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, and 16 (9.3%) for glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg. Among patients taking either glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg or glipizide and metformin hydrochloride tablets, 2.5 mg/500mg, nine (2.6%) patients discontinued glipizide and metformin hydrochloride tablets due to hypoglycemic symptoms and one required medical intervention due to hypoglycemia. In a controlled second-line therapy trial of glipizide and metformin hydrochloride tablets, 5 mg/500 mg, the numbers of patients with hypoglycemia documented by symptoms and a fingerstick blood glucose measurement���50 mg/dL were 0 (0%) for glipizide, 1 (1.3%) for metformin, and 11 (12.6%) for glipizide and metformin hydrochloride tablets. One (1.1%) patient discontinued glipizide and metformin hydrochloride tablet therapy due to hypoglycemic symptoms and none required medical intervention due to hypoglycemia. (See PRECAUTIONS section.)<br/>Gastrointestinal Reactions: Among the most common clinical adverse events in the initial therapy trial were diarrhea and nausea/vomiting; the incidences of these events were lower with both glipizide and metformin hydrochloride tablets dosage strengths than with metformin therapy. There were 4 (1.2%) patients in the initial therapy trial who discontinued glipizide and metformin hydrochloride tablet therapy due toGI adverse events. Gastrointestinal symptoms of diarrhea, nausea/vomiting, and abdominal pain were comparable among glipizide and metformin hydrochloride tablets, glipizide and metformin in the second-line therapy trial. There were 4 (4.6%) patients in the second-line therapy trial who discontinued glipizide and metformin hydrochloride tablet therapy due to GI adverse events.
|
| dailymed-drugs:59 |
Dimethylacetamide (DMA), the solvent used in the BUSULFEX formulation, was studied in 1962 as a potential cancer chemotherapy drug. In a Phase 1 trial, the maximum tolerated dose (MTD) was 14.8 g/m/d for four days. The daily recommended dose of BUSULFEX contains DMA equivalent to 42% of the MTD on a mg/mbasis. The dose-limiting toxicities in the Phase 1 study were hepatotoxicity as evidenced by increased liver transaminase (SGOT) levels and neurological symptoms as evidenced by hallucinations. The hallucinations had a pattern of onset at one day post completion of DMA administration and were associated with EEG changes. The lowest dose at which hallucinations were recognized was equivalent to 1.9 times that delivered in a conditioning regimen utilizing BUSULFEX 0.8 mg/kg every 6 hours x 16 doses. Other neurological toxicities included somnolence, lethargy, and confusion. The relative contribution of DMA and/or other concomitant medications to neurologic and hepatic toxicities observed with BUSULFEX is difficult to ascertain. Treatment with BUSULFEX at the recommended dose and schedule will result in profound myelosuppression in 100% of patients, including granulocytopenia, thrombocytopenia, anemia, or a combined loss of formed elements of the blood. Adverse reaction information is primarily derived from the clinical study (N=61) of BUSULFEX and the data obtained for high-dose oral busulfan conditioning in the setting of randomized, controlled trials identified through a literature review.<br/>BUSULFEX Clinical Trials: In the BUSULFEX (busulfan) Injection allogeneic stem cell transplantation clinical trial, all patients were treated with BUSULFEX 0.8 mg/kg as a two-hour infusion every six hours for 16 doses over four days, combined with cyclophosphamide 60 mg/kg x 2 days. Ninety-three percent (93%) of evaluable patients receiving this doseof BUSULFEX maintained an AUC less than 1,500��M���min for dose 9, which has generally been considered the level that minimizes the risk of HVOD. The following sections describe clinically significant events occurring in the BUSULFEX clinical trials, regardless of drug attribution. For pediatric information, see Special Populations���Pediatric section. Hematologic:At the indicated dose and schedule, BUSULFEX produced profound myelosuppression in 100% of patients. Following hematopoietic progenitor cell infusion, recovery of neutrophil counts to���500 cells/mmoccurred at median day 13 when prophylactic G-CSF was administered to the majority of participants on the study. The median number of platelet transfusions per patient on study was 6, and the median number of red blood cell transfusions on study was 4. Prolonged prothrombin time was reported in one patient (2%). Gastrointestinal:Gastrointestinal toxicities were frequent and generally considered to be related to the drug. Few were categorized as serious. Mild or moderate nausea occurred in 92% of patients in the allogeneic clinical trial, and mild or moderate vomiting occurred in 95% through BMT Day +28; nausea was severe in 7%. The incidence of vomiting during BUSULFEX administration (BMT Day���7 to���4) was 43% in the allogeneic clinical trial. Grade 3-4 stomatitis developed in 26% of the participants, and grade 3 esophagitis developed in 2%. Grade 3-4 diarrhea was reported in 5% of the allogeneic study participants, while mild or moderate diarrhea occurred in 75%. Mild or moderate constipation occurred in 38% of patients; ileus developed in 8% and was severe in 2%. Forty-four percent (44%) of patients reported mild or moderate dyspepsia. Two percent (2%) of patients experienced mild hematemesis. Pancreatitis developed in 2% of patients. Mild or moderate rectal discomfort occurred in 24% of patients. Severe anorexia occurred in 21% of patients and was mild/moderate in 64%. Hepatic:Hyperbilirubinemia occurred in 49% of patients in the allogeneic BMT trial. Grade 3/4 hyperbilirubinemia occurred in 30% of patients within 28 days of transplantation and was considered lifethreatening in 5% of these patients. Hyperbilirubinemia was associated with graft-versus-host disease in six patients and with hepatic veno-occlusive disease in 5 patients. Grade 3/4 SGPT elevations occurred in 7% of patients. Alkaline phosphatase increases were mild or moderate in 15% of patients. Mild or moderate jaundice developed in 12% of patients, and mild or moderate hepatomegaly developed in 6%. Hepatic veno-occlusive disease:Hepatic veno-occlusive disease (HVOD) is a recognized potential complication of conditioning therapy prior to transplant. Based on clinical examination and laboratory findings, hepatic veno-occlusive disease was diagnosed in 8% (5/61) of patients treated with BUSULFEX in the setting of allogeneic transplantation, was fatal in 2/5 cases (40%), and yielded an overall mortality from HVOD in the entire study population of 2/61 (3%). Three of the five patients diagnosed with HVOD were retrospectively found to meet the Jones' criteria. Graft-versus-host disease:Graft-versus-host disease developed in 18% of patients (11/61) receiving allogeneic transplants; it was severe in 3%, and mild or moderate in 15%. There were 3 deaths (5%) attributed to GVHD. Edema:Patients receiving allogeneic transplant exhibited some form of edema (79%), hypervolemia, or documented weight increase (8%); all events were reported as mild or moderate. Infection/Fever:Fifty-one percent (51%) of patients experienced one or more episodes of infection. Pneumonia was fatal in one patient (2%) and life-threatening in 3% of patients. Fever was reported in 80% of patients; it was mild or moderate in 78% and severe in 3%. Forty-six percent (46%) of patients experienced chills. Cardiovascular:Mild or moderate tachycardia was reported in 44% of patients. In 7 patients (11%) it was first reported during BUSULFEX administration. Other rhythm abnormalities, which were all mild or moderate, included arrhythmia (5%), atrial fibrillation (2%), ventricular extrasystoles (2%), and third degree heart block (2%). Mild or moderate thrombosis occurred in 33% of patients, and all episodes were associated with the central venous catheter. Hypertension was reported in 36% of patients and was Grade 3/4 in 7%. Hypotension occurred in 11% of patients and was Grade 3/4 in 3%. Mild vasodilation (flushing and hot flashes) was reported in 25% of patients. Other cardiovascular events included cardiomegaly (5%), mild ECG abnormality (2%), grade 3/4 left-sided heart failure in one patient (2%), and moderate pericardial effusion (2%). These events were reported primarily in the post-cyclophosphamide phase. Pulmonary:Mild or moderate dyspnea occurred in 25% of patients and was severe in 2%. One patient (2%) experienced severe hyperventilation; and in 2 (3%) additional patients it was mild or moderate. Mild rhinitis and mild or moderate cough were reported in 44% and 28% of patients, respectively. Mild epistaxis events were reported in 25%. Three patients (5%) on the allogeneic study developed documented alveolar hemorrhage. All required mechanical ventilatory support and all died. Non-specific interstitial fibrosis was found on wedge biopsies performed with video assisted thoracoscopy in one patient on the allogeneic study who subsequently died from respiratory failure on BMT Day +98. Other pulmonary events, reported as mild or moderate, included pharyngitis (18%), hiccup (18%), asthma (8%), atelectasis (2%), pleural effusion (3%), hypoxia (2%), hemoptysis (3%), and sinusitis (3%). Neurologic:The most commonly reported adverse events of the central nervous system were insomnia (84%), anxiety (75%), dizziness (30%), and depression (23%). Severity was mild or moderate except for one patient (1%) who experienced severe insomnia. One patient (1%) developed a life-threatening cerebral hemorrhage and a coma as a terminal event following multi-organ failure after HVOD. Other events considered severe included delirium (2%), agitation (2%), and encephalopathy (2%). The overall incidence of confusion was 11%, and 5% of patients were reported to have experienced hallucinations. The patient who developed delirium and hallucination on the allogeneic study had onset of confusion at the completion of BUSULFEX (busulfan) Injection. The overall incidence of lethargy in the allogeneic BUSULFEX clinical trial was 7%, and somnolence was reported in 2%. One patient (2%) treated in an autologous transplantation study experienced a seizure while receiving cyclophosphamide, despite prophylactic treatment with phenytoin. Renal:Creatinine was mildly or moderately elevated in 21% of patients. BUN was increased in 3% of patients and to a grade 3/4 level in 2%. Seven percent of patients experienced dysuria, 15% oliguria, and 8% hematuria. There were 4 (7%) Grade 3/4 cases of hemorrhagic cystitis in the allogeneic clinical trial. Skin:Rash (57%) and pruritus (28%) were reported; both conditions were predominantly mild. Alopecia was mild in 15% of patients and moderate in 2%. Mild vesicular rash was reported in 10% of patients and mild or moderate maculopapular rash in 8%. Vesiculo-bullous rash was reported in 10%, and exfoliative dermatitis in 5%. Erythema nodosum was reported in 2%, acne in 7%, and skin discoloration in 8%. Metabolic:Hyperglycemia was observed in 67% of patients and Grade 3/4 hyperglycemia was reported in 15%. Hypomagnesemia was mild or moderate in 77% of patients; hypokalemia was mild or moderate in 62% and severe in 2%; hypocalcemia was mild or moderate in 46% and severe in 3%; hypophosphatemia was mild or moderate in 17%; and hyponatremia was reported in 2%. Other:Other reported events included headache (mild or moderate 64%, severe 5%), abdominal pain (mild or moderate 69%, severe 3%), asthenia (mild or moderate 49%, severe 2%), unspecified pain (mild or moderate 43%, severe 2%), allergic reaction (mild or moderate 24%, severe 2%), injection site inflammation (mild or moderate 25%), injection site pain (mild or moderate 15%), chest pain (mild or moderate 26%), back pain (mild or moderate 23%), myalgia (mild or moderate 16%), arthralgia (mild or moderate 13%), and ear disorder in 3%. Deaths:There were two deaths through BMT Day +28 in the allogeneic transplant setting. There were an additional six deaths BMT Day +29 through BMT Day +100 in the allogeneic transplant setting. Oral Busulfan Literature Review.A literature review identified four randomized, controlled trials that evaluated a high-dose oral busulfan-containing conditioning regimen for allogeneic bone marrow transplantation in the setting of CML (see CLINICAL STUDIES). The safety outcomes reported in those trials are summarized in Table 4 below for a mixed population of hematological malignancies (AML, CML, and ALL).
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| dailymed-drugs:60 |
The adverse effects of parenterally administered magnesium
usually are the result of magnesium intoxication. These include flushing,
sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia,
circulatory collapse, cardiac and central nervous system depression proceeding
to respiratory paralysis. Hypocalcemia with signsof tetany secondary to magnesium
sulfate therapy for eclampsia has been reported.
|
| dailymed-drugs:61 |
Associated With Discontinuation of Treatment: Twenty percent (1,199/6,145) of patients treated with paroxetine hydrochloride in worldwide clinical trials in major depressive disorder and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), and 10.7% (79/735) of patients treated with paroxetine hydrochloride in worldwide trials in social anxiety disorder, OCD,panic disorder, and GAD, respectively, discontinued treatment due to an adverse event. The most common events (���1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for paroxetine hydrochloride compared to placebo) included the following:<br/>Commonly Observed Adverse Events:<br/>Major Depressive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 2) were: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.<br/>Obsessive Compulsive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that of placebo, derived from Table 3) were: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.<br/>Panic Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 3) were: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.<br/>Social Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 3) were: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.<br/>Generalized Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine hydrochloride at least twice that for placebo, derived from Table 4) were: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.<br/>Incidence in Controlled Clinical Trials: The prescriber should be aware that the figures in the tables following cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the populations studied.<br/>Major Depressive Disorder: Table 2 enumerates adverse events that occurred at an incidence of 1% or more among paroxetine-treated patients who participated in short-term (6 week) placebo-controlled trials in which patients were dosed in a range of 20 mg to 50 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology.<br/>Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Table 3 enumerates adverse events that occurred at a frequency of 2% or more among OCD patients on paroxetine hydrochloride who participated in placebo-controlled trials of 12 weeks duration in which patients were dosed in a range of 20 mg to 60 mg/day or among patients with panic disorder on paroxetine hydrochloride who participated in placebo-controlled trials of 10 to 12 weeks duration in which patients were dosed in a range of 10 mg to 60 mg/day or among patients with social anxiety disorder on paroxetine hydrochloride who participated in placebo-controlled trials of 12 weeks duration in which patients were dosed in a range of 20 mg to 50 mg/day.<br/>Generalized Anxiety Disorder: Table 4 enumerates adverse events that occurred at a frequency of 2% or more among GAD patients on paroxetine hydrochloride who participated in placebo-controlled trials of 8 weeks duration in which patients were dosed in a range of 10 mg/day to 50 mg/day.<br/>Dose Dependency of Adverse Events: A comparison of adverse event rates in a fixed-dose study comparing 10, 20, 30, and 40 mg/day of paroxetine hydrochloride with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of paroxetine hydrochloride, as shown in the following table: In a fixed-dose study comparing placebo and 10, 20, and 40 mg of paroxetine hydrochloride in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of paroxetine hydrochloride to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse events were observed in patients receiving 60 mg of paroxetine hydrochloride compared to any of the other treatment groups. In a fixed-dose study comparing placebo and 20, 40, and 60 mg paroxetine hydrochloride in the treatment of social anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine hydrochloride to which patients were assigned. In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine hydrochloride in the treatment of generalized anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine hydrochloride to which patients were assigned, except for the following adverse events: Asthenia, constipation, and abnormal ejaculation.<br/>Adaptation to Certain Adverse Events: Over a 4 to 6 week period, there was evidence of adaptation to some adverse events with continued therapy (e.g., nausea and dizziness), but less to other effects (e.g., dry mouth, somnolence, and asthenia).<br/>Male and Female Sexual Dysfunction With SSRIs: Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the reported incidence of sexual side effects in males and females with major depressive disorder, OCD, panic disorder, social anxiety disorder, and GAD are displayed in Table 6. There are no adequate and well-controlled studies examining sexual dysfunction with paroxetine treatment. Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.<br/>Weight and Vital Sign Changes: Significant weight loss may be an undesirable result of treatment with paroxetine hydrochloride for some patients but, on average, patients in controlled trials had minimal (about 1 pound) weight loss versus smaller changes on placebo and active control. No significant changes in vital signs (systolic and diastolic blood pressure, pulse and temperature) were observed in patients treated with paroxetine hydrochloride in controlled clinical trials.<br/>ECG Changes: In an analysis of ECGs obtained in 682 patients treated with paroxetine hydrochloride and 415 patients treated with placebo in controlled clinical trials, no clinically significant changes were seen in the ECGs of either group.<br/>Liver Function Tests: In placebo-controlled clinical trials, patients treated with paroxetine hydrochloride exhibited abnormal values on liver function tests at no greater rate than that seen in placebo-treated patients. In particular, the paroxetine hydrochloride-versus-placebo comparisons for alkaline phosphatase, SGOT, SGPT, and bilirubin revealed no differences in the percentage of patients with marked abnormalities.<br/>Hallucinations: In pooled clinical trials of immediate-release paroxetine hydrochloride, hallucinations were observed in 22 of 9089 patients receiving drug and 4 of 3187 patients receiving placebo.<br/>Other Events Observed During the Premarketing Evaluation of Paroxetine Hydrochloride: During its premarketing assessment in major depressive disorder, multiple doses of paroxetine hydrochloride were administered to 6,145 patients in phase 2 and 3 studies. The conditions and duration of exposure to paroxetine hydrochloride varied greatly and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, and fixed-dose, and titration studies. During premarketing clinical trials in OCD, panic disorder, social anxiety disorder, and generalized anxiety disorder, 542, 469,522, and 735 patients, respectively, received multiple doses of paroxetine hydrochloride. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, reported adverse events were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 9,089 patients exposed to multiple doses of paroxetine hydrochloride who experienced an event of the type cited on at least 1 occasion while receiving paroxetine hydrochloride. All reported events are included except those already listed in Tables2 to 4, those reported in terms so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that although the events reported occurred during treatment with paroxetine, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are also described in the PRECAUTIONS section. Body as a Whole: Infrequent: Allergic reaction, chills, face edema, malaise, neck pain; rare: Adrenergic syndrome, cellulitis, moniliasis, neck rigidity, pelvic pain, peritonitis, sepsis, ulcer. Cardiovascular System:Frequent: Hypertension, tachycardia; infrequent: Bradycardia, hematoma, hypotension, migraine, syncope; rare: Angina pectoris, arrhythmia nodal, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis,pulmonary embolus, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headache, ventricular extrasystoles. Digestive System: Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis, gastroenteritis, gingivitis, glossitis, increased salivation, liver function tests abnormal, rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impactions, fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries. Endocrine System: Rare: Diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis. Hemic and Lymphatic System: Infrequent: Anemia, leukopenia, lymphadenopathy, purpura; rare: Abnormal erythrocytes, basophilia, bleeding time increased, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia, thrombocytopenia. Metabolic and Nutritional: Frequent: Weight gain; infrequent: Edema, peripheral edema, SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphatase increased, bilirubinemia, BUN increased, creatinine phosphokinase increased, dehydration, gamma globulins increased, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-protein nitrogen (NPN) increased. Musculoskeletal System: Frequent: Arthralgia; infrequent: Arthritis, arthrosis; rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, tetany. Nervous System: Frequent: Emotional lability, vertigo; infrequent: Abnormal thinking, alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hallucinations, hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion, libido increased, manic reaction, neurosis, paralysis, paranoid reaction; rare: Abnormal gait, akinesia, antisocial reaction, aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, diplopia, drug dependence, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis,trismus, withdrawal syndrome. Respiratory System: Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration. Skin and Appendages: Frequent: Pruritus; infrequent: Acne, alopecia, contact dermatitis, dry skin, ecchymosis, eczema, herpes simplex, photosensitivity, urticaria; rare: Angioedema, erythema nodosum, erythema multiforme, exfoliative dermatitis, fungal dermatitis, furunculosis; herpes zoster, hirsutism, maculopapular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous rash. Special Senses: Frequent: Tinnitus; infrequent: Abnormality of accommodation, conjunctivitis, ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media; rare: Amblyopia, anisocoria, blepharitis, cataract, conjunctival edema, corneal ulcer, deafness, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness, otitis externa, parosmia, photophobia, ptosis, retinal hemorrhage, taste loss, visual field defect. Urogenital System: Infrequent: Amenorrhea, breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis.<br/>Postmarketing Reports: Voluntary reports of adverse events in patients taking paroxetine hydrochloride that have been received since market introduction and not listed above that may have no causal relationship with the drug include acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barr��syndrome, toxic epidermal necrolysis, priapism, syndrome of inappropriate ADH secretion, symptoms suggestive of prolactinemia and galactorrhea, neuroleptic malignant syndrome-like events, serotonin syndrome; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, oculogyriccrisis which has been associated with concomitant use of pimozide; tremor and trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, ventricular fibrillation, ventricular tachycardia (including torsade de pointes), thrombocytopenia, hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis) and vasculitic syndromes (such as Henoch-Sch��nlein purpura). There has been a case report of an elevated phenytoin level after 4 weeks of paroxetine hydrochloride and phenytoin coadministration. There has been a case report of severe hypotension when paroxetine hydrochloride was added to chronic metoprolol treatment.
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| dailymed-drugs:62 |
At therapeutic doses, the following have been reported; they are listed in decreasing order of severity, but not of frequency: Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache. Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus. Gastrointestinal system: toxic megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort. The following atropine sulfate effects are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes. These effects may occur, especially in children. THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.
|
| dailymed-drugs:4090 |
At therapeutic doses, the following have been reported; they are listed in decreasing order of severity, but not of frequency: Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache. Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus. Gastrointestinal system: toxic megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort. The following atropine sulfate effects are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes. These effects may occur, especially in children. THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.
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| dailymed-drugs:63 |
Associated With Discontinuation of Treatment: Twenty percent (1,199/6,145) of patients treated with paroxetine in worldwide clinical trials in major depressive disorder and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and 11.7% (79/676) of patients treated with paroxetine in worldwide trials in social anxiety disorder, OCD, panic disorder, GAD, and PTSD, respectively, discontinued treatment due to an adverse event. The most common events (���1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) included the following: Where numbers are not provided the incidence of the adverse events in patients treated with paroxetine was not>1% or was not greater than or equal to 2 times the incidence of placebo. 1. Incidence corrected for gender.<br/>Commonly Observed Adverse Events:<br/>Major Depressive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 2) were: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.<br/>Obsessive Compulsive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that of placebo, derived from Table 3) were: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.<br/>Panic Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 3) were: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.<br/>Social Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 3) were: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.<br/>Generalized Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 4) were: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.<br/>Posttraumatic Stress Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 4) were: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence.<br/>Incidence in Controlled Clinical Trials: The prescriber should be aware that the figures in the tables
following cannot be used to predict the incidence of side effects in the course
of usual medical practice where patient characteristics and other factors
differ from those that prevailed in the clinical trials. Similarly, the cited
frequencies cannot be compared with figures obtained from other clinical investigations
involving different treatments, uses, and investigators. The cited figures,
however, do provide the prescribing physician with some basis for estimating
the relative contribution of drug and nondrug factors to the side effect incidence
rate in the populations studied.<br/>Major Depressive Disorder: Table 2 enumerates adverse events that occurred at an incidence of 1% or more among paroxetine-treated patients who participated in short-term (6-week) placebo-controlled trials in which patients were dosed in a range of 20 mg to 50 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology. 1.Events reported by at least 1% of patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine: Abdominal pain, agitation, back pain, chest pain, CNS stimulation, fever, increased appetite, myoclonus, pharyngitis, postural hypotension, respiratory disorder (includes mostly���cold symptoms���or���URI���), trauma, and vomiting. 2. Includes mostly���lump in throat���and���tightness in throat.��� 3. Percentage corrected for gender. 4. Mostly���ejaculatory delay.��� 5. Includes���anorgasmia", "erectile difficulties", "delayed ejaculation/orgasm,���and���sexual dysfunction,���and���impotence.��� 6. Includes mostly���difficulty with micturition���and���urinary hesitancy.��� 7. Includes mostly���anorgasmia���and���difficulty reaching climax/orgasm.���<br/>Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Table 3 enumerates adverse events that occurred at a frequency of 2% or more among OCD patients on paroxetine who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 60 mg/day or among patients with panic disorder on paroxetine who participated in placebo-controlled trials of 10- to 12-weeks duration in which patients were dosed in a range of 10 mg to 60 mg/day or among patients with social anxiety disorder on paroxetine who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 50 mg/day. 1. Events reported by at least 2% of OCD, panic disorder, and social anxiety disorder in patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine: [OCD]: Abdominal pain, agitation, anxiety, back pain, cough increased, depression, headache, hyperkinesia, infection, paresthesia, pharyngitis, respiratory disorder, rhinitis, and sinusitis. [panic disorder]: Abnormal dreams, abnormal vision, chest pain, cough increased, depersonalization, depression, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, myalgia, nervousness, palpitation, paresthesia, pharyngitis, rash, respiratory disorder, sinusitis, taste perversion, trauma, urination impaired, and vasodilation. [social anxiety disorder]: Abdominal pain, depression, headache, infection, respiratory disorder, and sinusitis. 2.
Percentage corrected for gender.<br/>Generalized Anxiety Disorder and Posttraumatic Stress Disorder: Table 4 enumerates adverse events that occurred at a frequency of 2% or more among GAD patients on paroxetine who participated in placebo-controlled trials of 8-weeks duration in which patients were dosed in a range of 10 mg/day to 50 mg/day or among PTSD patients on paroxetine who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg/day to 50 mg/day. 1. Events reported by at least 2% of GAD and PTSD in patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine. [GAD]: Abdominal pain, back pain, trauma, dyspepsia, myalgia, and pharyngitis. [PTSD]: Back pain, headache, anxiety, depression, nervousness, respiratory disorder, pharyngitis, and sinusitis. 2. Percentage corrected for gender.<br/>Dose Dependency of Adverse Events: A comparison of adverse event rates in a fixed-dose study comparing 10, 20, 30, and 40 mg/day of paroxetine with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of paroxetine, as shown in the following table: Rule for including adverse events in table: Incidence at least 5% for 1 of paroxetine groups and���twice the placebo incidence for at least 1 paroxetine group. In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine in the treatment of OCD, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned. No new adverse events were observed in the group treated with 60 mg of paroxetine compared to any of the other treatment groups. In a fixed-dose study comparing placebo and 10, 20, and 40 mg of paroxetine in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse events were observedin patients receiving 60 mg of paroxetine compared to any of the other treatment groups. In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine in the treatment of social anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned. In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine in the treatment of generalized anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned, except for the following adverse events: Asthenia, constipation, and abnormal ejaculation. In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine in the treatment of posttraumatic stress disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned, except for impotence and abnormal ejaculation.<br/>Adaptation to Certain Adverse Events: Over a 4- to 6-week period, there was evidence of adaptation
to some adverse events with continued therapy (e.g., nausea and dizziness),
but less to other effects (e.g., dry mouth, somnolence, and asthenia).<br/>Male and Female Sexual Dysfunction With SSRIs: Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the reported incidence of sexual side effects in males and females with major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD, and PTSD are displayed in Table 6. There are no adequate and well-controlled studies examining sexual dysfunction with paroxetine treatment. Paroxetine
treatment has been associated with several cases of priapism. In those cases
with a known outcome, patients recovered without sequelae. While
it is difficult to know the precise risk of sexual dysfunction associated
with the use of SSRIs, physicians should routinely inquire about such possible
side effects.<br/>Weight and Vital Sign Changes: Significant weight loss may be an undesirable result of treatment with paroxetine for some patients but, on average, patients in controlled trials had minimal (about 1 pound) weight loss versus smaller changes on placebo and active control. No significant changes in vital signs (systolic and diastolic blood pressure, pulse and temperature) were observed in patients treated with paroxetine in controlled clinical trials.<br/>ECG Changes: In an analysis of ECGs obtained in 682 patients treated with paroxetine and 415 patients treated with placebo in controlled clinical trials, no clinically significant changes were seen in the ECGs of either group.<br/>Liver Function Tests: In placebo-controlled clinical trials, patients treated with paroxetine exhibited abnormal values on liver function tests at no greater rate than that seen in placebo-treated patients. In particular, the paroxetine-versus-placebo comparisons for alkaline phosphatase, SGOT, SGPT, and bilirubin revealed no differences in the percentage of patients with marked abnormalities.<br/>Hallucinations: In pooled clinical trials of immediate-release paroxetine
hydrochloride, hallucinations were observed in 22 of 9089 patients receiving
drug and 4 of 3187 patients receiving placebo.<br/>Other Events Observed During the Premarketing Evaluation of Paroxetine: During its premarketing assessment in major depressive disorder, multiple doses of paroxetine were administered to 6,145 patients in phase 2 and 3 studies. The conditions and duration of exposure to paroxetine varied greatly and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, and fixed-dose, and titration studies. During premarketing clinical trials in OCD, panic disorder, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder, 542, 469, 522, 735, and 676 patients, respectively, received multiple doses of paroxetine. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion ofindividuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, reported adverse events were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 9,089 patients exposed to multiple doses of paroxetine who experienced an event of the type cited on at least 1 occasion while receiving paroxetine. All reported events are included except those already listed in Tables 2 to 4, those reported in terms so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that although the events reported occurred during treatment with paroxetine, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are also described in the PRECAUTIONS section.<br/>Body as a Whole: Infrequent: Allergic reaction, chills, face edema, malaise, neck pain; rare: Adrenergic syndrome, cellulitis, moniliasis,
neck rigidity, pelvic pain, peritonitis, sepsis, ulcer.<br/>Cardiovascular System: Frequent: Hypertension,
tachycardia; infrequent: Bradycardia,
hematoma, hypotension, migraine, syncope; rare: Angina pectoris, arrhythmia nodal, atrial fibrillation, bundle
branch block, cerebral ischemia, cerebrovascular accident, congestive heart
failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia,
pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis,
thrombosis, varicose vein, vascular headache, ventricular extrasystoles.<br/>Digestive System: Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis, gastroenteritis, gingivitis, glossitis, increased salivation, liver function tests abnormal, rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impactions, fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries.<br/>Endocrine System: Rare: Diabetes mellitus,
goiter, hyperthyroidism, hypothyroidism, thyroiditis.<br/>Hemic and Lymphatic Systems: Infrequent: Anemia,
leukopenia, lymphadenopathy, purpura; rare: Abnormal
erythrocytes, basophilia, bleeding time increased, eosinophilia, hypochromic
anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes,
lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia,
thrombocytopenia.<br/>Metabolic and Nutritional: Frequent: Weight
gain; infrequent: Edema, peripheral
edema, SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphatase increased, bilirubinemia, BUN increased,
creatinine phosphokinase increased, dehydration, gamma globulins increased,
gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia,
hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, lactic dehydrogenase
increased, non-protein nitrogen (NPN) increased.<br/>Musculoskeletal System: Frequent: Arthralgia; infrequent: Arthritis, arthrosis; rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis,
tetany.<br/>Nervous System: Frequent: Emotional
lability, vertigo; infrequent: Abnormal
thinking, alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hallucinations,
hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion,
libido increased, manic reaction, neurosis, paralysis, paranoid reaction; rare: Abnormalgait, akinesia, antisocial reaction,
aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions,
diplopia, drug dependence, dysarthria, extrapyramidal syndrome, fasciculations,
grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis,
myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic
depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis,
trismus, withdrawal syndrome.<br/>Respiratory System: Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration.<br/>Skin and Appendages: Frequent: Pruritus; infrequent: Acne,
alopecia, contact dermatitis, dry skin, ecchymosis, eczema, herpes simplex,
photosensitivity, urticaria; rare: Angioedema,
erythema nodosum, erythema multiforme, exfoliative dermatitis, fungal dermatitis,
furunculosis; herpes zoster, hirsutism, maculopapular rash, seborrhea, skin
discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous
rash.<br/>Special Senses: Frequent: Tinnitus; infrequent: Abnormality of accommodation, conjunctivitis,
ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media; rare: Amblyopia, anisocoria, blepharitis, cataract,
conjunctival edema, corneal ulcer, deafness, exophthalmos, eye hemorrhage,
glaucoma, hyperacusis, night blindness, otitis externa, parosmia, photophobia,
ptosis, retinal hemorrhage, taste loss, visual field defect.<br/>Urogenital System: Infrequent: Amenorrhea,
breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polyuria,
pyuria, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement,
endometrial disorder, epididymitis, female lactation, fibrocystic breast,
kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis,
oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith,
vaginal hemorrhage, vaginal moniliasis.<br/>Postmarketing Reports: Voluntary reports of adverse events in patients taking paroxetine that have been received since market introduction and not listed above that may have no causal relationship with the drug include acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barr��syndrome, toxic epidermal necrolysis, priapism, syndrome of inappropriate ADH secretion, symptoms suggestive of prolactinemia and galactorrhea, neuroleptic malignant syndrome���like events; serotonin syndrome; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, oculogyric crisis which has been associated with concomitant use of pimozide; tremor and trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, ventricular fibrillation, ventricular tachycardia (including torsade de pointes), thrombocytopenia, hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic syndromes (such as Henoch-Sch��nlein purpura). There has been a case report of an elevated phenytoin level after 4 weeks of paroxetine and phenytoin coadministration. There has been a case report of severe hypotension when paroxetine was added to chronic metoprolol treatment.
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Hemorrhage: Hemorrhage
is the chief complication that may result from heparin therapy (see WARNINGS).
An overly prolonged clotting time or minor bleeding during therapy can usually
be controlled by withdrawing the drug (see OVERDOSAGE). It
should be appreciated that gastrointestinal or urinary tract bleeding during
anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic
complications may be difficult to detect: a. Adrenal
hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued
in patients who develop signs and symptoms of acute adrenal hemorrhage
and insufficiency. Initiation of corrective therapy should not depend
on laboratory confirmation of the diagnosis, since any delay in an acute
situation may result in the patient's death. b. Ovarian
(corpus luteum) hemorrhage developed in a number of women of reproductive
age receiving short- or long-term anticoagulant therapy. This complication
if unrecognized may be fatal. c. Retroperitoneal hemorrhage. Local Irritation: Local irritation, erythema,
mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat)
injection of heparin sodium. These complications are much more common after
intramuscular use, and such use is not recommended. Hypersensitivity: Generalized hypersensitivity
reactions have been reported with chills, fever, and urticaria as the most
usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea
and vomiting, and anaphylactoid reactions, including shock, occurring more
rarely. Itching and burning, especially on the plantar site of the feet, may
occur. Thrombocytopenia has been reported to occur in
patients receiving heparin with a reported incidence of 0 to 30%. While often
mild and of no obvious clinical significance, such thrombocytopenia can be
accompanied by severe thromboembolic complications such as skin necrosis,
gangrene of the extremities that may lead to amputation, myocardial infarction,
pulmonary embolism, stroke, and possibly death. (See WARNINGS and PRECAUTIONS.) Certain
episodes of painful, ischemic and cyanosed limbs have in the past been attributed
to allergic vasospastic reactions. Whether these are in fact identical to
the thrombocytopenia associated complications remains to be determined. Miscellaneous: Osteoporosis following long-term
administration of high doses of heparin, cutaneous necrosis after systemic
administration, suppression of aldosterone synthesis, delayed transient alopecia,
priapism and rebound hyperlipemia on discontinuation of heparin sodium have
also been reported. Significant elevations of aminotransferase
(SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high percentage
of patients (and healthy subjects) who have received heparin. Reactions
which may occur because of the solution or the technique of administration
include febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation and hypervolemia. If
an adverse reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures and save the remainder of
the fluid for examination if deemed necessary.
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Transient nausea and vomiting have been observed. Less frequent adverse reactions are body odor, nausea, and gastritis. An incidence for these reactions is difficult to estimate due to the confounding effects of the underlying pathology. Seizures have been reported to occur in patients with or without pre-existing seizure activity receiving either oral or intravenous levocarnitine. In patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported.
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See WARNINGS and SPECIAL PRECAUTIONS FOR CENTRAL VENOUS NUTRITION. Reactions
reported in clinical studies as a result of infusion of the parenteral fluid
were water weight gain, edema, increase in BUN, and dilutional hyponatremia.
Asterixis was reported to have worsened in one patient during infusion of
the amino acid solution. Reactions which may occur because
of the solution or the technique of administration include febrile response,
infection at the site of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation and hypervolemia. Symptoms
may result from an excess or deficit of one or more of the ions present in
the solution; therefore, frequent monitoring of electrolyte levels is essential. Phosphorus
deficiency may lead to impaired tissue oxygenation and acute hemolytic anemia.
Relative to calcium, excessive phosphorus intake can precipitate hypocalcemia
with cramps, tetany and muscular hyperexcitability. Ifan adverse reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures, and save the remainder
of the fluid for examination if deemed necessary.
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SPORANOX has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease nor a serious underlying medical condition. If clinical signs or symptoms develop that are consistent with liver disease, treatment should be discontinued and liver function testing performed. The risks and benefits of SPORANOX use should be reassessed.<br/>Adverse Events Reported in Trials in Patients with SPORANOX Injection: Adverse events considered at least possibly drug related are shown in Table 2 and are based on the experience of 360 patients treated with SPORANOX Injection in four pharmacokinetic, one uncontrolled and four active controlled studies where the control was amphotericin B or fluconazole. Nearly all patients were neutropenic or were otherwise immunocompromised and were treated empirically for febrile episodes, for documented systemic fungal infections, or in trials to determine pharmacokinetics. The dose of SPORANOX Injection was 200 mg twice daily for the first two days followed by a single daily dose of 200 mg for the remainder of the intravenous treatment period. The majority of patients received between 7 and 14 days of SPORANOX Injection. The following adverse events occurred in less than 2% of patients in clinical trials of SPORANOX Injection: LDH increased, edema, albuminuria, hyperglycemia, and hepatitis.<br/>Post-marketing Experience: Worldwide post-marketing experiences with the use of SPORANOX include adverse events of gastrointestinal origin, such as dyspepsia, nausea, vomiting, diarrhea, abdominal pain and constipation. Other reported adverse events include peripheral edema, congestive heart failure and pulmonary edema, headache, dizziness, peripheral neuropathy, menstrual disorders, reversible increases in hepatic enzymes, hepatitis, liver failure, hypokalemia, hypertriglyceridemia, alopecia, allergic reactions (such as pruritus, rash, urticaria, angioedema, anaphylaxis), Stevens-Johnson syndrome, anaphylactic, anaphylactoid and allergic reactions, photosensitivity and neutropenia. There is limited information on the use of SPORANOX during pregnancy. Cases of congenital abnormalities including skeletal, genitourinary tract, cardiovascular and ophthalmic malformations as well as chromosomal and multiple malformations have been reported during post-marketing experience. A causal relationship with SPORANOX has not been established.
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The following adverse reactions have been reported: Gastrointestinal: gastrointestinal upset Nervous System: tingling of extremities and tongue,
slurred speech, dizziness, vertigo and paresthesia Integumentary: generalized itching, urticaria and
rash Body as a Whole: fever Laboratory Deviations: increased blood urea nitrogen
(BUN), elevated creatinine and decreased creatinine clearance Respiratory System: respiratory distress and apnea Renal System: nephrotoxicity and decreased urine
output
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The premarketing development program for citalopram included citalopram exposures in patients and/or normal subjects from 3 different groups of studies: 429 normal subjects in clinical pharmacology/pharmacokinetic studies; 4422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1370 patient-exposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with citalopram varied greatly and included (in overlapping categories) open-label and double-blind studies, inpatient and outpatient studies, fixed-dose and dose-titration studies, and short-term and long-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.<br/>Adverse Findings Observed in Short-Term, Placebo-Controlled Trials: Adverse Events Associated with Discontinuation of Treatment Among 1063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration, 16% discontinued treatment due to an adverse event, as compared to 8% of 446 patients receiving placebo. The adverse events associated with discontinuation and considered drug-related (i.e., associated with discontinuation in at least 1% of citalopram-treated patients at a rate at least twice that of placebo) are shown in TABLE 2. It should be noted that one patient can report more than one reason for discontinuation and be counted more than once in this table. Adverse Events Occurring at an Incidence of 2% or More Among Citalopram -Treated Patients Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 1063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration. Events included are those occurring in 2% or more of patients treated with citalopram and for which the incidence in patients treated with citalopram was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The only commonly observed adverse event that occurred in citalopram patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see TABLE 3). Dose Dependency of Adverse Events The potential relationship between the dose of citalopram administered and the incidence of adverse events was examined in a fixed-dose study in depressed patients receiving placebo or citalopram 10, 20, 40, and 60 mg. Jonckheere's trend test revealed a positive dose response (p<0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning. Male and Female Sexual Dysfunction with SSRIs Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. The table below displays the incidence of sexual side effects reported by at least 2% of patients taking citalopram in a pool of placebo-controlled clinical trials in patients with depression. In female depressed patients receiving citalopram, the reported incidence of decreased libido and anorgasmia was 1.3% (n=638 females) and 1.1% (n=252 females), respectively. There are no adequately designed studies examining sexual dysfunction with citalopram treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects. Vital Sign Changes Citalopram and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with citalopram treatment. In addition, a comparison of supine and standing vital sign measures for citalopram and placebo treatments indicated that citalopram treatment is not associated with orthostatic changes. Weight Changes Patients treated with citalopram in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients. Laboratory Changes Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with citalopram treatment. ECG Changes Electrocardiograms from citalopram (N=802) and placebo (N=241) groups were compared with respect to (1) mean change from baseline in various ECG parameters, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. The only statistically significant drug-placebo difference observed was a decrease in heart rate for citalopram of 1.7 bpm compared to no change in heart rate for placebo. There were no observed differences in QT or other ECG intervals.<br/>Other Events Observed During the Premarketing Evaluation of Citalopram HBr: Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by patients treated with citalopram at multiple doses in a range of 10 to 80 mg/day during any phase of a trial within the premarketing database of 4422 patients. All reported events are included except those already listed in Table 3 or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those occurring in only one patient. It is important to emphasize that, althoughthe events reported occurred during treatment with citalopram, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Cardiovascular - Frequent: tachycardia, postural hypotension, hypotension. Infrequent: hypertension, bradycardia, edema (extremities), angina pectoris, extrasystoles, cardiac failure, flushing, myocardial infarction, cerebrovascular accident, myocardial ischemia. Rare: transient ischemic attack, phlebitis, atrial fibrillation, cardiac arrest, bundle branch block. Central and Peripheral Nervous System Disorders - Frequent: paresthesia, migraine. Infrequent: hyperkinesia, vertigo, hypertonia, extrapyramidal disorder, leg cramps, involuntary muscle contractions, hypokinesia, neuralgia, dystonia, abnormal gait, hypesthesia, ataxia. Rare: abnormal coordination, hyperesthesia, ptosis, stupor. Endocrine Disorders - Rare: hypothyroidism, goiter, gynecomastia. Gastrointestinal Disorders - Frequent: saliva increased, flatulence. Infrequent: gastritis, gastroenteritis, stomatitis, eructation, hemorrhoids, dysphagia, teeth grinding, gingivitis, esophagitis. Rare: colitis, gastric ulcer, cholecystitis, cholelithiasis, duodenal ulcer, gastroesophageal reflux, glossitis, jaundice, diverticulitis, rectal hemorrhage, hiccups. General - Infrequent: hot flushes, rigors, alcohol intolerance, syncope, influenza-like symptoms. Rare: hayfever. Hemic and Lymphatic Disorders - Infrequent: purpura, anemia, epistaxis, leukocytosis, leucopenia, lymphadenopathy. Rare: pulmonary embolism, granulocytopenia, lymphocytosis, lymphopenia, hypochromic anemia, coagulation disorder, gingival bleeding. Metabolic and Nutritional Disorders - Frequent: decreased weight, increased weight. Infrequent: increased hepatic enzymes, thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance. Rare: bilirubinemia, hypokalemia, obesity, hypoglycemia, hepatitis, dehydration. Musculoskeletal System Disorders - Infrequent: arthritis, muscle weakness, skeletal pain. Rare: bursitis, osteoporosis. Psychiatric Disorders - Frequent: impaired concentration, amnesia, apathy, depression, increased appetite, aggravated depression, suicide attempt, confusion. Infrequent: increased libido, aggressive reaction, paroniria, drug dependence, depersonalization, hallucination, euphoria, psychotic depression, delusion, paranoid reaction, emotional lability, panic reaction, psychosis. Rare: catatonic reaction, melancholia. Reproductive Disorders/Female* - Frequent: amenorrhea. Infrequent: galactorrhea, breast pain, breast enlargement, vaginal hemorrhage. *% based on female subjects only: 2955 Respiratory System Disorders - Frequent: coughing. Infrequent: bronchitis, dyspnea, pneumonia. Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased. Skin and Appendages Disorders - Frequent: rash, pruritus. Infrequent: photosensitivity reaction, urticaria, acne, skin discoloration, eczema, alopecia, dermatitis, skin dry, psoriasis. Rare: hypertrichosis, decreased sweating, melanosis, keratitis, cellulitis, pruritus ani. Special Senses - Frequent: accommodation abnormal, taste perversion. Infrequent: tinnitus, conjunctivitis, eye pain. Rare: mydriasis, photophobia, diplopia, abnormal lacrimation, cataract, taste loss. Urinary System Disorders - Frequent: polyuria. Infrequent: micturition frequency, urinary incontinence, urinary retention, dysuria. Rare: facial edema, hematuria, oliguria, pyelonephritis, renal calculus, renal pain.<br/>Other Events Observed During the Postmarketing Evaluation of Citalopram HBr: It is estimated that over 30 million patients have been treated with citalopram since market introduction. Although no causal relationship to citalopram treatment has been found, the following adverse events have been reported to be temporally associated with citalopram treatment, and have not been described elsewhere in labeling: acute renal failure, akathisia, allergic reaction, anaphylaxis, angioedema, choreoathetosis, chest pain, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema multiforme, gastrointestinal hemorrhage, grand mal convulsions, hemolytic anemia, hepatic necrosis, myoclonus, neuroleptic malignant syndrome, nystagmus, pancreatitis, priapism, prolactinemia, prothrombin decreased, QT prolonged, rhabdomyolysis, serotonin syndrome, spontaneous abortion, thrombocytopenia, thrombosis, ventricular arrhythmia, torsades de pointes, and withdrawal syndrome.
|
| dailymed-drugs:72 |
Central Nervous System: Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported. Cardiovascular - Increased or decreased blood pressure, tachycardia, bradycardia, faintness. Dermatologic - Dermatitis, photosensitivity, urticaria. Hematologic - Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis. Gastrointestinal - Dry mouth, nausea, vomiting, jaundice. Respiratory - Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). . Other - Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. .<br/>Paradoxical Reactions: Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine HCl. Consideration should be given to the discontinuation of promethazine HCl and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.
|
| dailymed-drugs:73 |
Ocular: Corneal clouding, persistent bullous keratopathy, retinal detachment and postoperative iritis following cataract extraction have been reported.<br/>Systemic: Side effects such as flushing, sweating, epigastric distress, abdominal cramps, tightness in urinary bladder, and headache have been reported with topical or systemic application of carbachol.
|
| dailymed-drugs:74 |
Serious adverse reactions are uncommon when verapamil hydrochloride therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. In clinical trials involving 285 hypertensive patients on verapamil hydrochloride extended-release for greater than 1 week the following adverse reactions were reported in greater than 1% of the patients: In clinical trials of other formulations of verapamil hydrochloride (N=4,954) the following reactions have occurred at rates greater than 1%: In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rate below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients. The following reactions, reported in 1% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and Lymphatic: ecchymosis or bruising. Nervous System: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence. Respiratory: dyspnea. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, maculae, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special Senses: blurred vision, tinnitus. Urogenital: gynecomastia, impotence, increased urination, spotty menstruation.<br/>Treatment of Acute Cardiovascular Adverse Reactions: The frequency of cardiovascular adverse reactions which require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately, e.g., intravenously administered isoproterenol hydrochloride, norepinephrine, atropine (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine, metaraminol bitartrate or methoxamine) should be used to maintain blood pressure,and isoproterenol and levarterenol should be avoided. If further support is necessary, inotropic agents (dopamine or dobutamine) may be administered. Actual treatment and dosage should depend on the severity and the clinical situation and the judgment and experience of the treating physician.
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| dailymed-drugs:75 |
Gastrointestinal: The most common side effects of
ethionamide are gastrointestinal disturbances including nausea, vomiting,
diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis,
anorexia and weight loss. Adverse gastrointestinal effects appear
to be dose related, with approximately 50% of patients unable to tolerate
1 gm as a single dose. Gastrointestinal effects may be minimized
by decreasing dosage, by changing the time of drug administration,
or by the concurrent administration of an antiemetic agent. Nervous System: Psychotic disturbances (including mental
depression), drowsiness, dizziness, restlessness, headache, and postural
hypotension have been reported with ethionamide. Rare reports of peripheral
neuritis, optic neuritis, diplopia, blurred vision, and a pellagra-like
syndrome also have been reported. Concurrent administration of pyridoxine
has been recommended to prevent or relieve neurotoxic effects. Hepatic: Transient increases in serum bilirubin, SGOT,
SGPT; Hepatitis (with or without jaundice). Other: Hypersensitivity reactions including rash, photosensitivity,
thrombocytopenia and purpura have been reported rarely. Hypoglycemia,
hypothyroidism, gynecomastia, impotence, and acne also have occurred.
The management of patients with diabetes mellitus may become more
difficult in those receiving ethionamide.
|
| dailymed-drugs:76 |
In 5 double-blind,
placebo-controlled trials, 1,124 patients were treated with ZOVIRAX Cream
and 1,161 with placebo (vehicle) cream. ZOVIRAX Cream was well tolerated;
5% of patients on ZOVIRAX Cream and 4% of patients on placebo reported local
application site reactions. The most common adverse
reactions at the site of topical application were dry lips, desquamation,
dryness of skin, cracked lips, burning skin, pruritus, flakiness of skin,
and stinging on skin; each event occurred in less than 1% of patients receiving
ZOVIRAX Cream and vehicle. Three patients on ZOVIRAX Cream and 1 patient on
placebo discontinued treatment due to an adverse event. An
additional study, enrolling 22 healthy adults, was conducted to evaluate
the dermal tolerance of ZOVIRAX Cream compared with vehicle using single
occluded and semi-occluded patch testing methodology. Both ZOVIRAX Cream and
vehicle showed a high and cumulative irritation potential. Another study,
enrolling 251 healthy adults, was conducted to evaluate the contact sensitization
potential of ZOVIRAX Cream using repeat insult patch testing methodology.
Of 202 evaluable subjects, possiblecutaneous sensitization reactions
were observed in the same 4 (2%) subjects with both ZOVIRAX Cream and
vehicle, and these reactions to both ZOVIRAX Cream and vehicle were confirmed
in 3 subjects upon rechallenge. The sensitizing ingredient(s) has not
been identified. The safety profile in patients 12
to 17 years of age was similar to that observed in adults.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials,
the following events have been identified during post-approval use of acyclovir
cream. Because they are reported voluntarily from a population of unknown
size, estimates of frequency cannot be made. These events have been chosen
for inclusion due to a combination of their seriousness, frequency of reporting,
or potential causalconnection to acyclovir cream.<br/>General: Angioedema, anaphylaxis.<br/>Skin: Contact dermatitis, eczema, application site reactions including
signs and symptoms of inflammation.
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| dailymed-drugs:77 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:255 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:594 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:697 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:912 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:1384 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:1807 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:1880 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:2897 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3060 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3072 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3169 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3396 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3535 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3746 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:3900 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:
|
| dailymed-drugs:78 |
In controlled clinical trials, the total incidence of adverse reactions associated with the use of fluticasone propionate ointment was approximately 4%. These adverse reactions were usually mild, self-limiting, and consisted primarily of pruritus, burning, hypertrichosis, increased erythema, hives, irritation, and lightheadedness. Each of these events occurred individually in less than 1% of patients. The following additional local adverse reactions have been reported infrequently with topical corticosteroids, including fluticasone propionate, and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.Also, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction or discontinuation of potent topical corticosteroid products.
|
| dailymed-drugs:79 |
The primary toxicity of ribavirin is hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1���2 weeks of oral therapy . Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients .<br/>REBETOL'/INTRON' A Combination Therapy: In clinical trials, 19% and 6% of previously untreated and relapse patients, respectively, discontinued therapy due to adverse events in the combination arms compared to 13% and 3% in the interferon arms. Selected treatment-emergent adverse events that occurred in the US studies with���5% incidence are provided in TABLE 7 by treatment group. In general, the selected treatment-emergent adverse events were reported with lower incidence in the international studies as compared to the US studies with the exception of asthenia, influenza-like symptoms, nervousness, and pruritus.<br/>Pediatric Patients: In clinical trials of 118 pediatric patients 3 to 16 years of age, 6% discontinued therapy due to adverse events. Dose modifications were required in 30% of patients, most commonly for anemia and neutropenia. In general, the adverse event profile in the pediatric population was similar to that observed in adults. Injection site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in pediatric patients compared to adult patients. Conversely, pediatric patients experienced less fatigue, dyspepsia, arthralgia, insomnia, irritability, impaired concentration, dyspnea, and pruritus compared to adult patients. Selected treatment-emergent adverse events that occurred with���5% incidence among all pediatric patients who received the recommended dose of REBETOL/INTRON A combination therapy are provided in TABLE 7. In addition, the following spontaneous adverse events have been reported during the marketing surveillance of REBETOL/INTRON A therapy: hearing disorder and vertigo.<br/>REBETOL/PegIntron Combination Therapy: Overall, in clinical trials, 14% of patients receiving REBETOL in combination with PegIntron���, discontinued therapy compared with 13% treated with REBETOL in combination with INTRON A. The most common reasons for discontinuation of therapy were related to psychiatric, systemic (e.g., fatigue, headache), or gastrointestinal adverse events. Adverse events that occurred in clinical trial at>5% incidence are provided in TABLE 8 by treatment group. Safety and effectiveness of REBETOL in combination with PegIntron has not been established in pediatric patients.<br/>Laboratory Values:<br/>REBETOL/INTRON A Combination Therapy: Changes in selected hematologic values (hemoglobin, white blood cells, neutrophils, and platelets) during therapy are described below (see TABLE 9).<br/>REBETOL/PegIntron Combination Therapy: Changes in selected hematologic values (hemoglobin, white blood cells, neutrophils, and platelets) during therapy are described below (see TABLE 10).<br/>Postmarketing Experiences: The following adverse reactions have been identified during post-approval use of REBETOL in combination with INTRON A or PegIntron therapy: hearing disorder, vertigo, aplastic anemia, pure red cell aplasia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
|
| dailymed-drugs:80 |
Most Common Adverse Events in All Clinical Studies:<br/>Adjunctive Therapy/Monotherapy in Adults Previously Treated with Other AEDs: The most commonly observed (���5%) adverse experiences seen in association with oxcarbazepine and substantially more frequent than in placebo-treated patients were: Dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, abnormal gait. Approximately 23% of these 1537 adult patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated with discontinuation were: Dizziness (6.4%), diplopia (5.9%), ataxia (5.2%), vomiting (5.1%), nausea (4.9%), somnolence (3.8%), headache (2.9%), fatigue (2.1%), abnormal vision (2.1%), tremor (1.8%), abnormal gait (1.7%), rash (1.4%), hyponatremia (1.0%).<br/>Monotherapy in Adults Not Previously Treated with Other AEDs: The most commonly observed (���5%) adverse experiences seen in association with oxcarbazepine in these patients were similar to those in previously treated patients. Approximately 9% of these 295 adult patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated with discontinuation were: Dizziness (1.7%), nausea (1.7%), rash (1.7%), headache (1.4%).<br/>Adjunctive Therapy/Monotherapy in Pediatric Patients 4 Years Old and Above Previously Treated with Other AEDs: The most commonly observed (���5%) adverse experiences seen in association with oxcarbazepine in these patients were similar to those seen in adults. Approximately 11% of these 456 pediatric patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated with discontinuation were: Somnolence (2.4%), vomiting (2.0%), ataxia (1.8%), diplopia (1.3%), dizziness (1.3%), fatigue (1.1%), nystagmus (1.1%).<br/>Monotherapy in Pediatric Patients 4 Years Old and Above Not Previously Treated with Other AEDs: The most commonly observed (���5%) adverse experiences seen in association with oxcarbazepine in these patients were similar to those in adults. Approximately 9.2% of 152 pediatric patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated (���1%) with discontinuation were rash (5.3%) and maculopapular rash (1.3%).<br/>Adjunctive Therapy/Monotherapy in Pediatric Patients 1 month to<4 Years Old Previously Treated or Not Previously Treated with Other AEDs: The most commonly observed (���5%) adverse experiences seen in association with oxcarbazepine in these patients were similar to those seen in older children and adults except for infections and infestations which were more frequently seen in these younger children. Approximately 11% of these 241 pediatric patients discontinued treatment because of an adverse experience. The adverse experiences most commonly associated with discontinuation were: Convulsions (3.7%), status epilepticus (1.2%), and ataxia (1.2%).<br/>Incidence in Controlled Clinical Studies: The prescriber should be aware that the figures in Tables 3, 4, 5 and 6 cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied.<br/>Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Adults Previously Treated with Other AEDs: Table 3 lists treatment-emergent signs and symptoms that occurred in at least 2% of adult patients with epilepsy treated with oxcarbazepine or placebo as adjunctive treatment and were numerically more common in the patients treated with any dose of oxcarbazepine. Table 4 lists treatment-emergent signs and symptoms in patients converted from other AEDs to either high dose oxcarbazepine or low dose (300 mg) oxcarbazepine. Note that in some of these monotherapy studies patients who dropped out during a preliminary tolerability phase are not included in the tables.<br/>Controlled Clinical Study of Monotherapy in Adults Not Previously Treated with Other AEDs: Table 5 lists treatment-emergent signs and symptoms in a controlled clinical study of monotherapy in adults not previously treated with other AEDs that occurred in at least 2% of adult patients with epilepsy treated with oxcarbazepine or placebo and were numerically more common in the patients treated with oxcarbazepine.<br/>Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Pediatric Patients Previously Treated with Other AEDs: Table 6 lists treatment-emergent signs and symptoms that occurred in at least 2% of pediatric patients with epilepsy treated with oxcarbazepine or placebo as adjunctive treatment and were numerically more common in the patients treated with oxcarbazepine.<br/>Other Events Observed in Association with the Administration of Oxcarbazepine: In the paragraphs that follow, the adverse events other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illnessand events likely to reflect concomitant illness are omitted particularly if minor. They are listed in order of decreasing frequency. Because the reports cite events observed in open label and uncontrolled trials, the role of oxcarbazepine in their causation cannot be reliably determined. Body as a Whole: Fever, malaise, pain chest precordial, rigors, weight decrease. Cardiovascular System: Bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia. Digestive System: Appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative. Hemic and Lymphatic System: Leukopenia, thrombocytopenia. Laboratory Abnormality: Gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased. Musculoskeletal System: Hypertonia muscle. Nervous System: Aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria, extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany. Respiratory System: Asthma, dyspnea, epistaxis, laryngismus, pleurisy. Skin and Appendages: Acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria. Special Senses: Accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia. Surgical and Medical Procedures: Procedure dental oral, procedure female reproductive, procedure musculoskeletal, procedure skin. Urogenital and Reproductive System: Dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus. Other: Systemic lupus erythematosus.<br/>Postmarketing and Other Experience: The following adverse events not seen in controlled clinical trials have been observed in named patient programs or postmarketing experience: Body as a Whole: Multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia and arthralgia (see PRECAUTIONS, Multi-Organ Hypersensitivity). Anaphylaxis (see WARNINGS, Anaphylactic Reactions and Angioedema). Digestive System: Pancreatitis and/or lipase and/or amylase increase. Skin and Appendages: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (see WARNINGS, Serious Dermatological Reactions).
|
| dailymed-drugs:81 |
Adverse reactions have been primarily bone marrow depression (leukopenia,
anemia, and occasionally thrombocytopenia), and less frequently gastrointestinal
symptoms (stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation),
and dermatological reactions such as maculopapular rash, skin ulceration,
dermatomyositis-like skin changes, peripheral and facial erythema. Hyperpigmentation,
atrophy of skin and nails, scaling, and violet papules have been observed
in some patients after several years of long-term daily maintenance therapy
with HYDREA.Skin cancer has been reported. Cutaneous vasculitic toxicities,
including vasculitic ulcerations and gangrene, have occurred in patients with
myeloproliferative disorders during therapy with hydroxyurea. These vasculitic
toxicities were reported most often in patients with a history of, or currently
receiving, interferon therapy .
Dysuria and alopecia occur very rarely. Large doses may produce moderate drowsiness.
Neurological disturbances have occurred extremely rarely and were limited
to headache, dizziness, disorientation, hallucinations, and convulsions. HYDREA
occasionally may cause temporary impairment of renal tubular function accompanied
by elevations in serum uric acid, BUN, and creatinine levels. Abnormal BSP
retention has been reported. Fever, chills, malaise, edema, asthenia, and
elevation of hepatic enzymes have also been reported. Adverse reactions observed with combined hydroxyurea and irradiation
therapy are similar to those reported with the use of hydroxyurea or radiation
treatment alone. These effects primarily include bone marrow depression (anemia
and leukopenia), gastric irritation, and mucositis. Almost all patients receiving
an adequate course of combined hydroxyurea and irradiation therapy will demonstrate
concurrent leukopenia. Platelet depression (<100,000 cells/mm)
has occurred rarely and only in the presence of marked leukopenia. HYDREA
may potentiate some adverse reactions usually seen with irradiation alone,
such as gastric distress and mucositis. The association of hydroxyurea with the development of acute pulmonary
reactions consisting of diffuse pulmonary infiltrates, fever, and dyspnea
has been reported rarely. Pulmonary fibrosis also has been reported rarely. Fatal and nonfatal pancreatitis and hepatotoxicity, and severe
peripheral neuropathy have been reported in HIV-infected patients who received
hydroxyurea in combination with antiretroviral agents, in particular, didanosine
plus stavudine. Patients treated with hydroxyurea in combination with didanosine,
stavudine, and indinavir in Study ACTG 5025 showed a median decline in CD4
cells of approximately 100/mm.
|
| dailymed-drugs:82 |
Central Nervous System: The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related. These include nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion. Dizziness, insomnia, transient nervousness, motor twitchings, and headaches have also been observed. There have also been rare reports of phenytoin-induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs. A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.<br/>Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis and liver damage.<br/>Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis .<br/>Hemopoietic System: Hemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's disease have been reported .<br/>Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis, and Peyronie's disease.<br/>Immunologic: Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, periarteritis nodosa and immunoglobulin abnormalities.
|
| dailymed-drugs:83 |
The most frequently reported adverse reaction attributed to the use of cromolyn sodium ophthalmic solution, USP 4%, on the basis of reoccurrence following readministration, is transient ocular stinging or burning upon instillation. The following adverse reactions have been reported as infrequent events. It is unclear whether they are attributable to the drug: conjunctival injection; watery eyes; itchy eyes; dryness around the eye; puffy eyes; eye irritation; and styes. Immediate hypersensitivity reactions have been reported rarely and include dyspnea, edema, and rash.
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| dailymed-drugs:85 |
The hypersensitivity reactions reported are skin eruptions (maculopapular to exfoliative dermatitis), urticaria and other serum sickness reactions, laryngeal edema and anaphylaxis. Fever and eosinophilia may frequently be the only reaction observed. Hemolytic anemia, leucopenia, thrombocytopenia, neuropathy, and nephropathy are infrequent reactions and usually associated with high doses of parenteral penicillin.
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| dailymed-drugs:87 |
Commonly Observed: The most commonly observed adverse events associated with the use of ClomiPRAMINE and not seen at an equivalent incidence among placebo-treated patients were gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus; genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes.<br/>Leading to Discontinuation of Treatment: Approximately 20% of 3616 patients who received ClomiPRAMINE in U.S. premarketing clinical trials discontinued treatment because of an adverse event. Approximately one-half of the patients who discontinued (9% of the total) had multiple complaints, none of which could be classified as primary. Where a primary reason for discontinuation could be identified, most patients discontinued because of nervous system complaints (5.4%), primarily somnolence. The second-most-frequent reason for discontinuation was digestive system complaints (1.3%), primarily vomiting and nausea. There was no apparent relationship between the adverse events and elevated plasma drug concentrations.<br/>Incidence in Controlled Clinical Trials: The following table enumerates adverse events that occurred at an incidence of 1% or greater among patients with OCD who received ClomiPRAMINE in adult or pediatric placebo-controlled clinical trials. The frequencies were obtained from pooled data of clinical trials involving either adults receiving ClomiPRAMINE (N = 322) or placebo (N = 319) or children treated with ClomiPRAMINE (N = 46) or placebo (N = 44). The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, provide the physician with a basis for estimating the relative contribution of drug and non-drug factors to the incidence of side effects in the populations studied.<br/>Other Events Observed During the Premarketing Evaluation of ClomiPRAMINE: During clinical testing in the U.S., multiple doses of ClomiPRAMINE hydrochloride capsules USP were administered to approximately 3600 subjects. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, a modified World Health Organization dictionary of terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the 3525 individuals exposed to ClomiPRAMINE who experienced an event of the type cited on at least one occasion while receiving ClomiPRAMINE. All events are included except those already listed in the previous table, those reported in terms so general as to be uninformative, and those in which an association with the drug was remote. It is important to emphasize that although the events reported occurred during treatment with ClomiPRAMINE, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events arethose occurring in less than 1/1000 patients. Body as a Whole - Infrequent - general edema, increased susceptibility to infection, malaise. Rare - dependent edema, withdrawal syndrome. Cardiovascular System - Infrequent - abnormal ECG, arrhythmia, bradycardia, cardiac arrest, extrasystoles, pallor. Rare - aneurysm, atrial flutter, bundle branch block, cardiac failure, cerebral hemorrhage, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia. Digestive System - Infrequent - abnormal hepatic function, blood in stool, colitis, duodenitis, gastric ulcer, gastritis, gastroesophageal reflux, gingivitis, glossitis, hemorrhoids, hepatitis, increased saliva, irritable bowel syndrome, peptic ulcer, rectal hemorrhage, tongue ulceration, tooth caries. Rare - cheilitis, chronic enteritis, discolored feces, gastric dilatation, gingival bleeding, hiccup, intestinal obstruction, oral/pharyngeal edema, paralytic ileus, salivary gland enlargement. Endocrine System - Infrequent - hypothyroidism. Rare - goiter, gynecomastia, hyperthyroidism. Hemic and Lymphatic System - Infrequent - lymphadenopathy. Rare - leukemoid reaction, lymphoma-like disorder, marrow depression. Metabolic and Nutritional Disorder - Infrequent - dehydration, diabetes mellitus, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypokalemia. Rare - fat intolerance, glycosuria. Musculoskeletal System - Infrequent - arthrosis. Rare - dystonia, exostosis, lupus erythematosus rash, bruising, myopathy, myositis, polyarteritis nodosa, torticollis. Nervous System - Frequent - abnormal thinking, vertigo. Infrequent - abnormal coordination, abnormal EEG, abnormal gait, apathy, ataxia, coma, convulsions, delirium, delusion, dyskinesia, dysphonia, encephalopathy, euphoria, extrapyramidal disorder, hallucinations, hostility, hyperkinesia, hypnagogic hallucinations, hypokinesia, leg cramps, manic reaction, neuralgia, paranoia, phobic disorder, psychosis, sensory disturbance, somnambulism, stimulation, suicidal ideation, suicide attempt, teeth-grinding. Rare - anticholinergic syndrome, aphasia, apraxia, catalepsy, cholinergic syndrome, choreoathetosis, generalized spasm, hemiparesis, hyperesthesia, hyperreflexia, hypoesthesia, illusion, impaired impulse control, indecisiveness, mutism, neuropathy, nystagmus, oculogyric crisis, oculomotor nerve paralysis, schizophrenic reaction, stupor, suicide. Respiratory System - Infrequent - bronchitis, hyperventilation, increased sputum, pneumonia. Rare - cyanosis, hemoptysis, hypoventilation, laryngismus. Skin and Appendages - Infrequent - alopecia, cellulitis, cyst, eczema, erythematous rash, genital pruritus, maculopapular rash, photosensitivity reaction, psoriasis, pustular rash, skin discoloration. Rare - chloasma, folliculitis, hypertrichosis, piloerection, seborrhea, skin hypertrophy, skin ulceration. Special Senses - Infrequent - abnormal accommodation, deafness, diplopia, earache, eye pain, foreign body sensation, hyperacusis, parosmia, photophobia, scleritis, taste loss. Rare - blepharitis, chromatopsia, conjunctival hemorrhage, exophthalmos, glaucoma, keratitis, labyrinth disorder, night blindness, retinal disorder, strabismus, visual field defect. Urogenital System - Infrequent - endometriosis, epididymitis, hematuria, nocturia, oliguria, ovarian cyst, perineal pain, polyuria, prostatic disorder, renal calculus, renal pain, urethral disorder, urinary incontinence, uterine hemorrhage, vaginal hemorrhage. Rare - albuminuria, anorgasmy, breast engorgement, breast fibroadenosis, cervical dysplasia, endometrial hyperplasia, premature ejaculation, pyelonephritis, pyuria, renal cyst, uterine inflammation, vulvar disorder.
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| dailymed-drugs:88 |
In a double-blind, placebo-controlled trial of 405 premature infants weighing less than or equal to 1750 g with evidence of large ductal shunting, in those neonates treated with indomethacin (n=206), there was a statistically significantly greater incidence of bleeding problems, including gross or microscopic bleeding into the gastrointestinal tract, oozing from the skin after needle stick, pulmonary hemorrhage, and disseminated intravascular coagulopathy. There was no statistically significant difference between treatment groups with reference to intracranial hemorrhage. The neonates treated with indomethacin for injection also had a significantly higher incidence of transient oliguria and elevations of serum creatinine (greater than or equal to 1.8 mg/dL) than did the neonates treated with placebo. The incidences of retrolental fibroplasia (grades III and IV) and pneumothorax in neonates treated with INDOCIN I.V. were no greater than in placebo controls and were statistically significantly lower than in surgically-treated neonates. The following additional adverse reactions in neonates have been reported from the collaborative study, anecdotal case reports, from other studies using rectal, oral, or intravenous indomethacin for treatment of patent ductus arteriosus or in marketed use. The rates are calculated from a database which contains experience of 849 indomethacin-treated neonates reported in the medical literature, regardless of the route of administration. One year follow-up is available on 175 neonates and shows no long-term sequelae which could be attributed to indomethacin. In controlled clinical studies, only electrolyte imbalance and renal dysfunction (of thereactions listed below) occurred statistically significantly more frequently after INDOCIN I.V. than after placebo. Reactions marked with a single asterisk (*) occurred in 3-9 percent of indomethacin-treated neonates; those marked with a double asterisk (**) occurred in 3-9 percent of both indomethacin- and placebo-treated neonates. Unmarked reactions occurred in less than 3 percent of neonates. Renal: renal dysfunction in 41 percent of neonates, including one or more of the following: reduced urinary output; reduced urine sodium, chloride, or potassium, urine osmolality, free water clearance, or glomerular filtration rate; elevated serum creatinine or BUN; uremia. Cardiovascular: intracranial bleeding**, pulmonary hypertension. Gastrointestinal: gastrointestinal bleeding*, vomiting, abdominal distention, transient ileus, gastric perforation, localized perforation(s) of the small and/or large intestine, necrotizing enterocolitis. Metabolic: hyponatremia*, elevated serum potassium*, reduction in blood sugar, including hypoglycemia, increased weight gain (fluid retention). Coagulation: decreased platelet aggregation . The following adverse reactions have also been reported in neonates treated with indomethacin, however, a causal relationship to therapy with INDOCIN I.V. has not been established: Cardiovascular: bradycardia. Respiratory: apnea, exacerbation of pre-existing pulmonary infection. Metabolic: acidosis/alkalosis. Hematologic: disseminated intravascular coagulation. Ophthalmic: retrolental fibroplasia.** A variety of additional adverse experiences have been reported in adults treated with oral indomethacin for moderate to severe rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute painful shoulder and acute gouty arthritis (see package insert for Capsules INDOCIN (Indomethacin) for additional information concerning adverse reactions and other cautionary statements). Their relevance to the pre-term infant receiving indomethacin for patent ductus arteriosus is unknown, however, the possibility exists that these experiences may be associated with the use of INDOCIN I.V. in pre-term infants.
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| dailymed-drugs:89 |
There have been reports of hypersensitivity reactions
and Parkinson-like symptoms. There have been instances of hypotension
reported following parenteral administration to surgical patients.
There have been reports of blood dyscrasias, blurring of vision, coma,
convulsions, depression of mood, diarrhea, disorientation, dizziness,
drowsiness, headache, jaundice, muscle cramps and opisthotonos. If
these occur, the administration of the drug should be discontinued.
Allergic-type skin reactions have been observed; therefore, the drug
should be discontinued at the���rst sign of sensitization. While
these symptoms will usually disappear spontaneously, symptomatic treatment
may be indicated in some cases.
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| dailymed-drugs:90 |
The information below is derived from a clinical trial database for SEROQUEL consisting of over 3700 patients. This database includes 698 patients exposed to SEROQUEL for the treatment of bipolar depression, 405 patients exposed to SEROQUEL for the treatment of acute bipolar mania (monotherapy and adjunct therapy) and approximately 2600 patients and/or normal subjects exposed to 1 or more doses of SEROQUEL for the treatment of schizophrenia. Of these approximately 3700 subjects, approximately 3400 (2300 in schizophrenia, 405 in acute bipolar mania, and 698 in bipolar depression) were patients who participated in multiple dose effectiveness trials, and their experience corresponded to approximately 992.6 patient-years. The conditions and duration of treatment with SEROQUEL varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. Adverse events during exposure were obtained by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard COSTART terminology has been used to classify reported adverse events for schizophrenia and bipolar mania. MedDRA terminology has been used to classify reported adverse events for bipolar depression. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.<br/>Adverse Findings Observed in Short-Term, Controlled Trials:<br/>Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Bipolar Disorder: Depression: Overall, discontinuations due to adverse events were 12.3% for SEROQUEL 300 mg vs 19.0% for SEROQUEL 600 mg and 5.2% for placebo. Mania: Overall, discontinuations due to adverse events were 5.7% for SEROQUEL vs. 5.1% for placebo in monotherapy and 3.6% for SEROQUEL vs. 5.9% for placebo in adjunct therapy. Schizophrenia: Overall, there was little difference in the incidence of discontinuation due to adverse events (4% for SEROQUEL vs. 3% for placebo) in a pool of controlled trials. However, discontinuations due to somnolence and hypotension were considered to be drug related :<br/>Adverse Events Occurring at an Incidence of 1% or More Among SEROQUEL Treated Patients in Short-Term, Placebo-Controlled Trials:: The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the population studied. Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy of schizophrenia (up to 6 weeks) and bipolar mania (up to 12 weeks) in 1% or more of patients treated with SEROQUEL (doses ranging from 75 to 800 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients. In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were somnolence (18%), dizziness (11%), dry mouth (9%), constipation (8%), SGPT increased (5%), weight gain (5%), and dyspepsia (5%). Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during therapy (up to 3-weeks) of acute mania in 5% or more of patients treated with SEROQUEL (doses ranging from 100 to 800 mg/day) used as adjunct therapy to lithium and divalproex where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients. In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were somnolence (34%), dry mouth (19%), asthenia (10%), constipation (10%), abdominal pain (7%), postural hypotension (7%), pharyngitis (6%), and weight gain (6%). Table 4 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during therapy (up to 8-weeks) of bipolar depression in 5% or more of patients treated with SEROQUEL (doses of 300 and 600 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo treated patients. In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were dry mouth (44%), sedation (30%), somnolence (28%), dizziness (18%), constipation (10%), lethargy (5%), and nasal congestion (5%). Explorations for interactions on the basis of gender, age, and race did not reveal any clinically meaningful differences in the adverse event occurrence on the basis of these demographic factors.<br/>Dose Dependency of Adverse Events in Short-Term, Placebo-Controlled Trials:<br/>Dose-related Adverse Events:: Spontaneously elicited adverse event data from a study of schizophrenia comparing five fixed doses of SEROQUEL (75 mg, 150 mg, 300 mg, 600 mg, and 750 mg/day) to placebo were explored for dose-relatedness of adverse events. Logistic regression analyses revealed a positive dose response (p<0.05) for the following adverse events: dyspepsia, abdominal pain, and weight gain. Extrapyramidal Symptoms: Data from one 6-week clinical trial of schizophrenia comparing five fixed doses of SEROQUEL (75, 150, 300, 600, 750 mg/day) provided evidence for the lack of treatment-emergent extrapyramidal symptoms (EPS) and dose-relatedness for EPS associated with SEROQUEL treatment. Three methods were used to measure EPS: (1) Simpson-Angus total score (mean change from baseline) which evaluates parkinsonism and akathisia, (2) incidence of spontaneous complaints of EPS (akathisia, akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, neck rigidity, and tremor), and (3) use of anticholinergic medications to treat emergent EPS. In six additional placebo-controlled clinical trials (3 in acute mania and 3 in schizophrenia) using variable doses of SEROQUEL, there were no differences between the SEROQUEL and placebo treatment groups in the incidence of EPS, as assessed by Simpson-Angus total scores, spontaneous complaints of EPS and the use of concomitant anticholinergic medications to treatEPS. In two placebo-controlled clinical trials for the treatment of bipolar depression using 300 mg and 600 mg of SEROQUEL, the incidence of adverse events potentially related to EPS was 12% in both dose groups and 6% in the placebo group. In these studies, the incidence of the individual adverse events (eg, akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity and muscle rigidity) were generally lowand did not exceed 4% in any treatment group. The 3 treatment groups were similar in mean change in SAS total score and BARS Global Assessment score at the end of treatment. The use of concomitant anticholinergic medications was infrequent and similar across the three treatment groups.<br/>Vital Signs and Laboratory Studies: Vital Sign Changes: SEROQUEL is associated with orthostatic hypotension . Weight Gain: In schizophrenia trials the proportions of patients meeting a weight gain criterion of���7% of body weight were compared in a pool of four 3- to 6-week placebo-controlled clinical trials, revealing a statistically significantly greater incidence of weight gain for SEROQUEL (23%) compared to placebo (6%). In mania monotherapy trials the proportions of patients meeting the same weight gain criterion were 21% compared to 7% for placebo and in mania adjunct therapy trials the proportion of patients meeting the same weight criterion were 13% compared to 4% for placebo. In bipolar depression trials, the proportions of patients meeting the same weight gain criterion were 8% compared to 2% for placebo. Laboratory Changes: An assessment of the premarketing experience for SEROQUEL suggested that it is associated with asymptomatic increases in SGPT and increases in both total cholesterol and triglycerides . In placebo controlled monotherapy clinical trials involving 3368 patients on SEROQUEL and 1515 on placebo, the incidence of at least one occurrence of neutrophil count<1.0 x 10/L among patients with a normal baseline neutrophil count and at least one available follow up laboratory measurement was 0.3% (10/2967) in patients treated with SEROQUEL, compared to 0.1% (2/1349) in patients treated with placebo. In post-marketing clinical trials, elevations in total cholesterol (predominantly LDL cholesterol) have been observed. Hyperglycemia In 2 long-term placebo-controlled clinical trials, mean exposure 213 days for SEROQUEL (646 patients) and 152 days for placebo (680 patients), the exposure-adjusted rate of any increased blood glucose level (���126 mg/dl) for patients more than 8 hours since a meal was 18.0 per 100 patient years for SEROQUEL (10.7% of patients) and 9.5 for placebo per 100 patient years (4.6% of patients). In short-term (12 weeks duration or less) placebo-controlled clinical trials (3342 patients treated with SEROQUEL and 1490 treated with placebo), the percent of patients who had a fasting blood glucose���126 mg/dl or a non fasting blood glucose���200 mg/dl was 3.5% for quetiapine and 2.1% for placebo. In a 24 week trial (active-controlled, 115 patients treated with SEROQUEL) designed to evaluate glycemic status with oral glucose tolerance testing of all patients, at week 24 the incidence of a treatment-emergent post-glucose challenge glucose level���200 mg/dl was 1.7% and the incidence of a fasting treatment-emergent post-glucose challenge glucose level���126 mg/dl was 2.6%. ECG Changes: Between group comparisons for pooled placebo-controlled trials revealed no statistically significant SEROQUEL/placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. However, the proportions of patients meeting the criteria for tachycardia were compared in four 3- to 6-week placebo-controlled clinical trials for the treatment of schizophrenia revealing a 1% (4/399) incidence for SEROQUEL compared to 0.6% (1/156) incidence for placebo. In acute (monotherapy) bipolar mania trials the proportions of patients meeting the criteria for tachycardia was 0.5% (1/192) for SEROQUEL compared to 0% (0/178) incidence for placebo. In acute bipolar mania (adjunct) trials the proportions of patients meeting the same criteria was 0.6% (1/166) for SEROQUEL compared to 0% (0/171) incidence for placebo. In bipolar depression trials, no patients had heart rate increases to>120 beats per minute. SEROQUEL use was associated with a mean increase in heart rate, assessed by ECG, of 7 beats per minute compared to a mean increase of 1 beat per minute among placebo patients. This slight tendency to tachycardia may be related to SEROQUEL's potential for inducing orthostatic changes .<br/>Other Adverse Events Observed During the Pre-Marketing Evaluation of SEROQUEL: Following is a list of COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to the ADVERSE REACTIONS section reported by patients treated with SEROQUEL at multiple doses���75 mg/day during any phase of a trial within the premarketing database of approximately 2200 patients treated for schizophrenia. All reported events are included except those already listed in Table 2 or elsewhere in labeling, those events for which a drug cause was remote, and those event terms which were so general as to be uninformative. It is important to emphasize that, although the events reported occurred during treatment with SEROQUEL, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000patients; rare events are those occurring in fewer than 1/1000 patients. Nervous System: Frequent: hypertonia, dysarthria; Infrequent: abnormal dreams, dyskinesia, thinking abnormal, tardive dyskinesia, vertigo, involuntary movements, confusion, amnesia, psychosis, hallucinations, hyperkinesia, libido increased*, urinary retention, incoordination, paranoid reaction, abnormal gait, myoclonus, delusions, manic reaction, apathy, ataxia, depersonalization, stupor, bruxism, catatonic reaction, hemiplegia; Rare: aphasia, buccoglossal syndrome, choreoathetosis, delirium, emotional lability, euphoria, libido decreased*, neuralgia, stuttering, subdural hematoma. Body as a Whole:Frequent: flu syndrome; Infrequent: neck pain, pelvic pain*, suicide attempt, malaise, photosensitivity reaction, chills, face edema, moniliasis; Rare: abdomen enlarged. Digestive System:Frequent: anorexia; Infrequent: increased salivation, increased appetite, gamma glutamyl transpeptidase increased, gingivitis, dysphagia, flatulence, gastroenteritis, gastritis, hemorrhoids, stomatitis, thirst, tooth caries, fecal incontinence, gastroesophageal reflux, gum hemorrhage, mouth ulceration, rectal hemorrhage, tongue edema; Rare: glossitis, hematemesis, intestinal obstruction, melena, pancreatitis. Cardiovascular System: Frequent: palpitation; Infrequent: vasodilatation, QT interval prolonged, migraine, bradycardia, cerebral ischemia, irregular pulse, T wave abnormality, bundle branch block, cerebrovascular accident, deep thrombophlebitis, T wave inversion; Rare: angina pectoris, atrial fibrillation, AV block first degree, congestive heart failure, ST elevated, thrombophlebitis, T wave flattening, ST abnormality, increased QRS duration. Respiratory System:Frequent: pharyngitis, rhinitis, cough increased, dyspnea; Infrequent: pneumonia, epistaxis, asthma; Rare: hiccup, hyperventilation. Metabolic and Nutritional System: Frequent: peripheral edema; Infrequent: weight loss, alkaline phosphatase increased, hyperlipemia, alcohol intolerance, dehydration, hyperglycemia, creatinine increased, hypoglycemia; Rare: glycosuria, gout, hand edema, hypokalemia, water intoxication. Skin and Appendages System: Frequent: sweating; Infrequent: pruritus, acne, eczema, contact dermatitis, maculopapular rash, seborrhea, skin ulcer; Rare: exfoliative dermatitis, psoriasis, skin discoloration. Urogenital System:Infrequent: dysmenorrhea*, vaginitis*, urinary incontinence, metrorrhagia*, impotence*, dysuria, vaginal moniliasis*, abnormal ejaculation*, cystitis, urinary frequency, amenorrhea*, female lactation*, leukorrhea*, vaginal hemorrhage*, vulvovaginitis* orchitis*; Rare: gynecomastia*, nocturia, polyuria, acute kidney failure. Special Senses:Infrequent: conjunctivitis, abnormal vision, dry eyes, tinnitus, taste perversion, blepharitis, eye pain; Rare: abnormality of accommodation, deafness, glaucoma. Musculoskeletal System: Infrequent: pathological fracture, myasthenia, twitching, arthralgia, arthritis, leg cramps, bone pain. Hemic and Lymphatic System:Frequent: leukopenia; Infrequent: leukocytosis, anemia, ecchymosis, eosinophilia, hypochromic anemia; lymphadenopathy, cyanosis; Rare: hemolysis, thrombocytopenia. Endocrine System: Infrequent: hypothyroidism, diabetes mellitus; Rare: hyperthyroidism. *adjusted for gender<br/>Post Marketing Experience:: Adverse events reported since market introduction which were temporally related to SEROQUEL therapy include: anaphylactic reaction and restless legs. Other adverse events reported since market introduction, which were temporally related to SEROQUEL therapy, but not necessarily causally related, include the following: agranulocytosis, cardiomyopathy, hyponatremia, myocarditis, rhabdomyolysis, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Stevens Johnson syndrome (SJS).
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| dailymed-drugs:91 |
Adverse reactions to betaine have been minimal. In a survey study of physicians who had treated a total of 111 homocystinuria patients with betaine, the types of adverse effects and the number of patients experiencing them were as follows: A few cases of cerebral edema have been reported secondary to severe hypermethioninemia in patients with cystathionine beta-synthase (CBS) deficiency treated with Cystadane. See PRECAUTIONS: Hypermethioninemia.
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| dailymed-drugs:92 |
The following reactions have been reported with the use of clindamycin.<br/>Gastrointestinal: Antibiotic-associated colitis , pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment . An unpleasant or metallic taste occasionally has been reported after intravenous administration of the higher doses of clindamycin phosphate.<br/>Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized
mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with
clindamycin. A few cases of anaphylactoid reactions have been reported. If a hypersensitivity reaction occurs, the
drug should be discontinued. The usual agents (epinephrine, corticosteroids, antihistamines) should be available
for emergency treatment of serious reactions.<br/>Skin and Mucous Membranes: Pruritus, vaginitis, and rare instances of exfoliative dermatitis have been reported
(see Hypersensitivity Reactions).<br/>Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.<br/>Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.<br/>Hematopoietic: Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing.<br/>Local Reactions: Pain, induration and sterile abscess have been reported after intramuscular injection and thrombophlebitis after intravenous infusion. Reactions can be minimized or avoided by giving deep intramuscular injections and avoiding prolonged use of indwelling intravenous catheters.<br/>Musculoskeletal: Rare instances of polyarthritis have been reported.<br/>Cardiovascular: Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration.
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| dailymed-drugs:93 |
Clinical: At the doses used for treatment of acute malaria infections, the symptoms possibly attributable to drug administration cannot be distinguished from those symptoms usually attributable to the disease itself. Among subjects who received mefloquine for prophylaxis of malaria, the most frequently observed adverse experience was vomiting (3%). Dizziness, syncope, extrasystoles and other complaints affecting less than 1% were also reported. Among subjects who received mefloquine for treatment, the most frequently observed adverse experiences included: dizziness, myalgia, nausea, fever, headache, vomiting, chills, diarrhea, skin rash, abdominal pain, fatigue, loss of appetite, and tinnitus. Those side effects occurring in less than 1% included bradycardia, hair loss, emotional problems, pruritus, asthenia, transient emotional disturbances and telogen effluvium (loss of resting hair). Seizures have also been reported. Two serious adverse reactions were cardiopulmonary arrest in one patient shortly after ingesting a single prophylactic dose of mefloquine while concomitantly using propranolol , and encephalopathy of unknown etiology during prophylactic mefloquine administration. The relationship of encephalopathy to drug administration could not be clearly established.<br/>Postmarketing: Postmarketing surveillance indicates that the same kind of adverse experiences are reported during prophylaxis, as well as acute treatment. The most frequently reported adverse events are nausea, vomiting, loose stools or diarrhea, abdominal pain, dizziness or vertigo, loss of balance, and neuropsychiatric events such as headache, somnolence, sleep disorders (insomnia, abnormal dreams). These are usually mild and may decrease despite continued use. Occasionally, more severe neuropsychiatric disorders have been reported such as: sensory and motor neuropathies (including paresthesia, tremor and ataxia), convulsions, agitation or restlessness, anxiety, depression, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, psychotic or paranoid reactions and encephalopathy. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug adminstration has been confirmed. Other infrequent adverse events include: Cardiovascular Disorders: circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitation, bradycardia, irregular pulse, extrasystoles, A-V block, and other transient cardiac conduction alterations. Skin Disorders: rash, exanthema, erythema, urticaria, pruritus, edema, hair loss, erythema multiforme, and Stevens-Johnson syndrome. Musculoskeletal Disorders: muscle weakness, muscle cramps, myalgia, and arthralgia. Other Symptoms: visual disturbances, vestibular disorders including tinnitus and hearing impairment, dyspnea, asthenia, malaise, fatigue, fever, sweating, chills, dyspepsia and loss of appetite.<br/>Laboratory: The most frequently observed laboratory alterations which could be possibly attributable to drug administration were decreased hematocrit, transient elevation of transaminases, leukopenia and thrombocytopenia. These alterations were observed in patients with acute malaria who received treatment doses of the drug and were attributed to the disease itself. During prophylactic administration of mefloquine to indigenous populations in malaria-endemic areas, the following occasional alterations in laboratory values were observed: transient elevation of transaminases, leukocytosis or thrombocytopenia. Because of the long half-life of mefloquine, adverse reactions to mefloquine may occur or persist up to several weeks after the last dose.
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| dailymed-drugs:94 |
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
The adverse reaction information from clinical trials does, however,
provide a basis for identifying possible adverse events and for approximating
rates. The data described below reflect
exposure in 8,877 patients randomized to ARIXTRA Injection in controlled
trials of hip fracture, hip replacement, major knee, or abdominal
surgeries, and DVT and PE treatment. Patients received ARIXTRA primarily
in 2 large peri-operative dose-response trials (n = 989),
4 active-controlled peri-operative trials with enoxaparin sodium (n = 3,616),
and an extended prophylaxis trial (n = 327), an active-controlled
trial with dalteparin sodium (n = 1,425), a dose-response trial in
DVT treatment (n = 111), an active-controlled trial with
enoxaparin sodium in DVT treatment (n = 1,091), and an active-controlled
trial with heparin in PE treatment (n = 1,092) (see CLINICAL
STUDIES).<br/>Hemorrhage: During administration of ARIXTRA, the most common
adverse reactions were bleeding complications (see WARNINGS).<br/>Hip Fracture, Hip Replacement
and Knee Replacement Surgery: The rates of major bleeding events reported during
the hip fracture, hip replacement, or knee replacement surgery clinical
trials with ARIXTRA 2.5 mg Injection are provided in Tables 8 and
9 below. A separate analysis of major bleeding across
all randomized, controlled, peri-operative, prophylaxis clinical studies
of hip fracture, hip replacement, or knee replacement surgery according
to the time of the first injection of ARIXTRA after surgical closure
was performed in patients who received ARIXTRA only post-operatively.
In this analysis, the incidences of major bleeding were as follows:<4 hours was 4.8% (5/104), 4-6 hours was 2.3% (28/1196),
6-8 hours was 1.9% (38/1965). In all studies, the majority (���75%)
of the major bleeding events occurred during the first 4 days after
surgery.<br/>Abdominal Surgery: The rates of major bleeding reported during the
abdominal surgery clinical trial with ARIXTRA 2.5 mg are provided
in Table 10 below. A separate analysis of major bleeding according
to the time of the first injection of ARIXTRA after surgical closure
was performed. In this analysis the incidences of major bleeding were
as follows:<6 hours was 3.4% (9/263) and 6-8 hours was 2.9% (32/1112).<br/>Treatment of Deep Vein Thrombosis
and Pulmonary Embolism: The rates of bleeding events reported during the
DVT and PE clinical trials with the ARIXTRA injection treatment regimen
are provided in Table 11 below.<br/>Thrombocytopenia: See WARNINGS: Thrombocytopenia.<br/>Local Reactions: Mild local irritation (injection site bleeding,
rash, and pruritus) may occur following subcutaneous injection of
ARIXTRA.<br/>Elevations of Serum Aminotransferases: In the peri-operative prophylaxis randomized clinical
trials of 7��2 days asymptomatic increases in aspartate
(AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels greater
than 3 times the upper limit of normal of the laboratory reference
range have been reported in 1.7% and 2.6% of patients, respectively,
during treatment with ARIXTRA 2.5 mg Injection versus 3.2% and
3.9%, of patients, respectively, during treatment with enoxaparin
sodium 30 mg every 12 hours or 40 mg once daily enoxaparin
sodium. Such elevations are fully reversible and are rarely associated
with increases in bilirubin. In the extended prophylaxis clinical
trial no significant differences in aspartate (AST [SGOT]) and alanine
(ALT [SGPT]) aminotransferase levels between ARIXTRA 2.5 mg Injection
and placebo treated patients were observed. In the DVT and PE treatment clinical trials asymptomatic increases
in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase
levels greater than 3 times the upper limit of normal of the laboratory
reference range have been reported in 0.7% and 1.3% of patients, respectively,
during treatment with the ARIXTRA injection treatment regimen. In
comparison, these increases have been reported in 4.8% and 12.3%,
of patients, respectively, in the DVT treatment trial during treatment
with enoxaparin sodium 1 mg/kg every 12 hours, and in 2.9%
and 8.7%, of patients, respectively, in the PE treatment trial during
treatment with aPTT adjusted heparin. Since
aminotransferase determinations are important in the differential
diagnosis of myocardial infarction, liver disease, and pulmonary emboli,
elevations that might be caused by drugs like ARIXTRA should be interpreted
with caution.<br/>Other Adverse Events: Other adverse events that occurred during treatment
with ARIXTRA, or enoxaparin sodium in clinical trials with patients
undergoing hip fracture surgery, hip replacement surgery, or knee
replacement surgery and that occurred at a rate of at least 2% in
either treatment group, are provided in Table 12 below. Other adverse
events that occurred during treatment with ARIXTRA or dalteparin sodium
in clinical trials with patients undergoing abdominal surgery and
that occurred at a rate of at least 2% in either treatment group are
provided in Table 13 below. Other adverse events that occurred during
treatment with ARIXTRA, enoxaparin sodium, or heparin in the DVT and
PE treatment clinical trials and that occurred at a rate of at least
2% in any treatment group are provided in Table 14 below.<br/>Postmarketing Experience: The following adverse reactions have been identified
during post-approval use of ARIXTRA. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to drug exposure. Rare cases of
elevated aPTT and heparin-induced thrombocytopenia have been reported.
A causal relationship of these events to fondaparinux has not been
established.
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| dailymed-drugs:95 |
The adverse reactions incidences listed below are based on observations of 1) 4,784 Ridaura treated patients in clinical trials (2,474 U.S., 2,310 foreign), of whom 2,729 were treated more than one year and 573 for more than three years; and 2) postmarketing experience. The highest incidence is during the first six months of treatment; however, reactions can occur after many months of therapy. With rare exceptions, all patients were on concomitant nonsteroidal anti-inflammatory therapy; some of them were also taking low dosages of corticosteroids.<br/>Reactions occurring in more than 1% of Ridaura-treated patients: Gastrointestinal: loose stools or diarrhea (47%); abdominal pain (14%); nausea with or without vomiting (10%); constipation; anorexia*; flatulence*; dyspepsia*; dysgeusia. Dermatological: rash (24%); pruritus (17%); hair loss; urticaria. Mucous Membrane: stomatitis (13%); conjunctivitis*; glossitis. Hematological: anemia; leukopenia; thrombocytopenia; eosinophilia. Renal: proteinuria*; hematuria. Hepatic: elevated liver enzymes. *Reactions marked with an asterisk occurred in 3-9% of the patients. The other reactions listed occurred in 1-3%.<br/>Reactions occurring in less than 1% of Ridaura-treated patients: Gastrointestinal: dysphagia; gastrointestinal bleeding���; melena���; positive stool for occult blood���; ulcerative enterocolitis. Dermatological: angioedema. Mucous Membrane: gingivitis���. Hematological: aplastic anemia; neutropenia���; agranulocytosis; pure red cell aplasia; pancytopenia. Hepatic: jaundice. Respiratory: interstitial pneumonitis. Neurological: peripheral neuropathy Ocular: gold deposits in the lens or cornea unassociated clinically with eye disorders or visual impairment. ���Reactions marked with a dagger occurred in 0.1-1% of the patients. The other reactions listed occurred in less than 0.1%.<br/>Reactions reported with injectable gold preparations, but not with Ridaura (auranofin) (based on clinical trials and on postmarketing experience): Cutaneous Reactions: generalized exfoliative dermatitis.
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| dailymed-drugs:96 |
Adverse reaction information on Ipratropium Bromide Nasal Spray 0.03% in patients with perennial rhinitis was derived from four multicenter, vehicle-controlled clinical trials involving 703 patients (356 patients on Ipratropium Bromide and 347 patients on vehicle), and a one-year, open-label, follow-up trial. In three of the trials, patients received Ipratropium Bromide Nasal Spray 0.03% three times daily, for eight weeks. In the other trial, Ipratropium Bromide Nasal Spray 0.03% was given to patients two times daily for four weeks. Of the 285 patients who entered the open-label, follow-up trial, 232 were treated for 3 months, 200 for 6 months, and 159 up to one year. The majority (>86%) of patients treated for one year were maintained on 42 mcg per nostril, two or three times daily, of Ipratropium Bromide Nasal Spray 0.03%. The following table shows adverse events, and the frequency that these adverse events led to the discontinuation of treatment, reported for patients who received Ipratropium Bromide Nasal Spray 0.03% at the recommended dose of 42 mcg per nostril, or vehicle two or three times daily for four or eight weeks. Only adverse events reported with an incidence of at least 2.0% in the Ipratropium Bromide group and higher in the Ipratropium Bromide group than in the vehicle groupare shown. Ipratropium Bromide Nasal Spray 0.03% was well tolerated by most patients. The most frequently reported nasal adverse events were transient episodes of nasal dryness or epistaxis. These adverse events were mild or moderate in nature, none was considered serious, none resulted in hospitalization and most resolved spontaneously or following a dose reduction. Treatment for nasal dryness and epistaxis was required infrequently (2% or less) and consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly or saline nasal spray). Patient discontinuation for epistaxis or nasal dryness was infrequent in both the controlled (0.3% or less) and one-year, open-label (2% or less) trials. There was no evidence of nasal rebound (i.e., a clinically significant increase in rhinorrhea, posterior nasal drip, sneezing or nasal congestion severity compared to baseline) upon discontinuation of double-blind therapy in these trials. Adverse events reported by less than 2% of the patients receiving Ipratropium Bromide Nasal Spray 0.03% during the controlled clinical trials or during the open-label follow-up trial, which are potentially related to Ipratropium Bromide's local effects or systemic anticholinergic effects include: dry mouth/throat, dizziness, ocular irritation, blurred vision, conjunctivitis, hoarseness, cough, and taste perversion. Additional anticholinergic effects noted with other Ipratropium Bromide dosage forms (Ipratropium Bromide Inhalation Solution, Ipratropium Bromide Inhalation Aerosol, and Ipratropium Bromide Nasal Spray 0.06%) include: precipitation or worsening of narrow angle glaucoma, urinary retention, prostatic disorders, tachycardia, constipation, and bowel obstruction. There were infrequent reports of skin rash in both the controlled and uncontrolled clinical studies. Allergic-type reactions such as skin rash, angioedema of the throat, tongue, lips and face, generalized urticaria, laryngospasm, and anaphylactic reactions have been reported with Ipratropium Bromide Nasal Spray 0.03% and other ipratropium bromide products.
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| dailymed-drugs:97 |
The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%), and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of bumetanide-treated patients. Less frequent clinical adverse reactions to bumetanide are impaired hearing (0.5%), pruritus (0.4%), electrocardiogram changes (0.4%), weakness (0.2%), hives (0.2%) abdominal pain (0.2%), arthritic pain (0.2%), musculoskeletal pain (0.2%), rash (0.2%) and vomiting (0.2%). One or more of these adverse reactions have been reported in approximately 2.9% of bumetanide-treated patients. Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, chest pain, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, diarrhea, premature ejaculation and difficulty maintaining an erection. Laboratory abnormalities reported have included hyperuricemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalemia (14.7%), azotemia (10.6%), hyponatremia (9.2%), increased serum creatinine (7.4%), hyperglycemia (6.6%), and variations in phosphorus (4.5%), COcontent (4.3%) bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of bumetanide, these conditions may become more pronounced by intensive therapy. Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%). There have been rare spontaneous reports of thrombocytopenia from postmarketing experience. Diuresis induced by bumetanide may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.
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| dailymed-drugs:98 |
Adverse reactions with hydralazine are usually reversible when dosage is reduced. However, in some cases it may be necessary to discontinue the drug. The following adverse reactions have been observed, but there has not been enough systematic collection of data to support an estimate of their frequency. Common: headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris. Less Frequent: Digestive: constipation, paralytic ileus. Cardiovascular: hypotension, paradoxical pressor response, edema. Respiratory: dyspnea. Neurologic: peripheral neuritis, evidenced by paresthesia, numbness, and tingling; dizziness, tremors, muscle cramps, psychotic reactions characterized by depression, disorientation or anxiety. Genitourinary: difficulty in urination. Hematologic: blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, purpura; lymphadenopathy; splenomegaly. Hypersensitive Reactions: rash, urticaria, pruritus, fever, chills, arthralgia, eosinophilia, and rarely, hepatitis. Other: nasal congestion, flushing, lacrimation, conjunctivitis.
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| dailymed-drugs:99 |
Adverse reactions include, in decreasing order of frequency, elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing. Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids. Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. The development of secondary ocular infection (bacterial, fungal and viral) has occurred. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroid. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used (SEE WARNINGS).
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| dailymed-drugs:100 |
In a U.S. double-blind clinical study of metformin in patients with type 2 diabetes, a total of 141 patients received metformin therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the metformin patients, and that were more common in metformin- than placebo-treated patients, are listed in Table 9. Diarrhea led to discontinuation of study medication in 6% of patients treated with metformin. Additionally, the following adverse reactions were reported in���1.0 -���5.0% of metformin patients and were more commonly reported with metformin than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.<br/>Pediatric Patients: In clinical trials with metformin in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.
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| dailymed-drugs:101 |
Infrequently, high dosages of intranasal DDAVP have produced transient headache and nausea. Nasal congestion, rhinitis and flushing have also been reported occasionally along with mild abdominal cramps. These symptoms disappeared with reduction in dosage. Nosebleed, sore throat, cough and upper respiratory infections have also been reported. The following table lists the percentage of patients having adverse experiences without regard to relationship to study drug from the pooled pivotal study data for nocturnal enuresis. Post Marketing: There have been rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine. See WARNINGS for the possibility of water intoxication and hyponatremia.
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| dailymed-drugs:104 |
The following reactions have been reported: Gastrointestinal: Diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia and pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment . Nausea and vomiting have been reported rarely. Allergic: Anaphylaxis, eosinophilia, itching, drug fever, skin rash, Stevens-Johnson syndrome. Hematologic: Neutropenia, leukopenia, thrombocytopenia, thrombocythemia. Hepatic: Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. As with other cephalosporins, reports of hepatitis have been received. Renal: As with other cephalosporins, reports of increased BUN and creatinine levels, as well as renal failure, have been received. Local Reactions: Rare instances of phlebitis have been reported at site of injection. Some induration has occurred. Other Reactions: Genital and anal pruritus (including vulvar pruritus, genital moniliasis and vaginitis). Cephalosporin-class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with cefazolin, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Adverse Reactions: Allergic reactions, urticaria, serum sickness-like reaction, erythema multiforme, toxic epidermal necrolysis, colitis, renal dysfunction, toxic nephropathy, abdominal pain, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and superinfection. Altered Laboratory Tests: Prolonged prothrombin time, positive direct Coombs' test, false-positive test for urinary glucose, elevated bilirubin, elevated LDH, increased creatinine, pancytopenia, and agranulocytosis. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced . If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
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| dailymed-drugs:105 |
Clinical Practice: The following events have been identified during postmarketing use of topical diclofenac sodium ophthalmic solution, 0.1% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to topical diclofenac sodium ophthalmic solution, 0.1%, or a combination of these factors, include corneal erosion, corneal infiltrates, corneal perforation, corneal thinning, corneal ulceration, epithelial breakdown, and superficial punctate keratitis, (see PRECAUTIONS, General).<br/>Ocular: Transient burning and stinging were reported in approximately 15% of patients across studies with the use of diclofenac sodium ophthalmic solution. In cataract surgery studies, keratitis was reported in up to 28% of patients receiving diclofenac sodium ophthalmic solution, although in many of these cases keratitis was initially noted prior to the initiation of treatment. Elevated intraocular pressure following cataract surgery was reported in approximately 15% of patients undergoing cataract surgery. Lacrimation complaints were reported in approximately 30% of case studies undergoing incisional refractive surgery. The following adverse reactions were reported in approximately 5% or less of the patients: abnormal vision, acute elevated IOP, blurred vision, conjunctivitis, corneal deposits, corneal edema, corneal opacity, corneal lesions, discharge, eyelid swelling, injection, iritis, irritation, itching, lacrimation disorder and ocular allergy.<br/>Systemic: The following adverse reactions were reported in 3% or less of the patients: abdominal pain, asthenia, chills, dizziness, facial edema, fever, headache, insomnia, nausea, pain, rhinitis, viral infection, and vomiting.<br/>Overdosage: Overdosage will not ordinarily cause acute problems. If diclofenac sodium ophthalmic solution is accidentally ingested, fluids should be taken to dilute the medication.
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| dailymed-drugs:106 |
The most frequently reported adverse reactions are minor ocular irritations, redness and hypersensitivity reactions.
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| dailymed-drugs:107 |
Adverse reactions to NOLVADEX are relatively mild and rarely severe enough to require discontinuation of treatment in breast cancer patients. Continued clinical studies have resulted in further information which better indicates the incidence of adverse reactions with NOLVADEX as compared to placebo.<br/>Metastatic Breast Cancer:: Increased bone and tumor pain and, also, local disease flare have occurred, which are sometimes associated with a good tumor response. Patients with increased bone pain may require additional analgesics. Patients with soft tissue disease may have sudden increases in the size of preexisting lesions, sometimes associated with marked erythema within and surrounding the lesions and/or the development of new lesions. When they occur, the bone pain or disease flare are seen shortly after starting NOLVADEX and generally subside rapidly. In patients treated with NOLVADEX for metastatic breast cancer, the most frequent adverse reaction to NOLVADEX is hot flashes. Other adverse reactions which are seen infrequently are hypercalcemia, peripheral edema, distaste for food, pruritus vulvae, depression, dizziness, light-headedness, headache, hair thinning and/or partial hair loss, and vaginal dryness.<br/>Premenopausal Women:: The following table summarizes the incidence of adverse reactions reported at a frequency of 2% or greater from clinical trials (Ingle, Pritchard, Buchanan) which compared NOLVADEX therapy to ovarian ablation in premenopausal patients with metastatic breast cancer.<br/>Male Breast Cancer:: NOLVADEX is well tolerated in males with breast cancer. Reports from the literature and case reports suggest that the safety profile of NOLVADEX in males is similar to that seen in women. Loss of libido and impotence have resulted in discontinuation of tamoxifen therapy in male patients. Also, in oligospermic males treated with tamoxifen, LH, FSH, testosterone and estrogen levels were elevated. No significant clinical changes were reported.<br/>Adjuvant Breast Cancer:: In the NSABP B-14 study, women with axillary node-negative breast cancer were randomized to 5 years of NOLVADEX 20 mg/day or placebo following primary surgery. The reported adverse effects are tabulated below (mean follow-up of approximately 6.8 years) showing adverse events more common on NOLVADEX than on placebo. The incidence of hot flashes (64% vs. 48%), vaginal discharge (30% vs. 15%), and irregular menses (25% vs. 19%) were higher with NOLVADEX compared with placebo. All other adverse effects occurred with similar frequency in the 2 treatment groups, with the exception of thrombotic events; a higher incidence was seen in NOLVADEX-treated patients (through 5 years, 1.7% vs. 0.4%). Two of the patients treated with NOLVADEX who had thrombotic events died. In the Eastern Cooperative Oncology Group (ECOG) adjuvant breast cancer trial, NOLVADEX or placebo was administered for 2 years to women following mastectomy. When compared to placebo, NOLVADEX showed a significantly higher incidence of hot flashes (19% vs. 8% for placebo). The incidence of all other adverse reactions was similar in the 2 treatment groups with the exception of thrombocytopenia where the incidence for NOLVADEX was 10% vs. 3% for placebo, an observation of borderline statistical significance. In other adjuvant studies, Toronto and NOLVADEX Adjuvant Trial Organization (NATO), women received either NOLVADEX or no therapy. In the Toronto study, hot flashes were observed in 29% of patients for NOLVADEX vs. 1% in the untreated group. In the NATO trial, hot flashes and vaginal bleeding were reported in 2.8% and 2.0% of women, respectively, for NOLVADEX vs. 0.2% for each in the untreated group.<br/>Anastrozole Adjuvant Trial���Study of Anastrozole compared to NOLVADEX for Adjuvant Treatment of Early Breast Cancer: See CLINICAL PHARMACOLOGY - Clinical Studies. At a median follow-up of 33 months, the combination of anastrozole and NOLVADEX did not demonstrate any efficacy benefit when compared to NOLVADEX therapy given alone, in all patients as well as in the hormone receptor positive subpopulation. This treatment arm was discontinued from the trial. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole 1 mg and NOLVADEX 20 mg, respectively. Adverse events occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in the following table. Certain adverse events and combinations of adverse events were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (see the following table). Patients receiving anastrozole had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving NOLVADEX. Patients receiving anastrozole had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving NOLVADEX [209 (7%)]. Patients receiving anastrozole had a decrease in hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving NOLVADEX. Patients receiving NOLVADEX had a decrease in hypercholesterolemia (108 [3.5%]) compared to patients receiving anastrozole (278 [9%]). Angina pectoris was reported in 71 [2.3%] patients in the anastrozole arm and 51 [1.6%] patients in the NOLVADEX arm; myocardial infarction was reported in 37 [1.2%] patients in the anastrozole arm and in 34 [1.1%] patients in the NOLVADEX arm. Results from the adjuvant trial bone substudy, at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving NOLVADEX had a mean increase in both lumbar spine and total hip BMD compared to baseline.<br/>Ductal Carcinoma in Situ (DCIS):: The type and frequency of adverse events in the NSABP B-24 trial were consistent with those observed in the other adjuvant trials conducted with NOLVADEX.<br/>Reduction in Breast Cancer Incidence in High Risk Women:: In the NSABP P-1 Trial, there was an increase in five serious adverse effects in the NOLVADEX group: endometrial cancer (33 cases in the NOLVADEX group vs. 14 in the placebo group); pulmonary embolism (18 cases in the NOLVADEX group vs. 6 in the placebo group); deep vein thrombosis (30 cases in the NOLVADEX group vs. 19 in the placebo group); stroke (34 cases in the NOLVADEX group vs. 24 in the placebo group); cataract formation (540 cases in the NOLVADEX group vs. 483 in the placebo group) and cataract surgery (101 cases in the NOLVADEX group vs. 63 in the placebo group) . The following table presents the adverse events observed in NSABP P-1 by treatment arm. Only adverse events more common on NOLVADEX than placebo are shown. In the NSABP P-1 trial, 15.0% and 9.7% of participants receiving NOLVADEX and placebo therapy, respectively withdrew from the trial for medical reasons. The following are the medical reasons for withdrawing from NOLVADEX and placebo therapy, respectively: Hot flashes (3.1% vs. 1.5%) and Vaginal Discharge (0.5% vs. 0.1%). In the NSABP P-1 trial, 8.7% and 9.6% of participants receiving NOLVADEX and placebo therapy, respectively withdrew for non-medical reasons. On the NSABP P-1 trial, hot flashes of any severity occurred in 68% of women on placebo and in 80% of women on NOLVADEX. Severe hot flashes occurred in 28% of women on placebo and 45% of women on NOLVADEX. Vaginal discharge occurred in 35% and 55% of women on placebo and NOLVADEX respectively; and was severe in 4.5% and 12.3% respectively. There was no difference in the incidence of vaginal bleeding between treatment arms.<br/>Pediatric Patients - McCune-Albright Syndrome:: Mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. A causal relationship has not been established; however, as an increase in the incidence of endometrial adenocarcinoma and uterine sarcoma has been noted in adults treated with NOLVADEX , continued monitoring of McCune-Albright patients treated with NOLVADEX for long-term effects is recommended. The safety and efficacy of NOLVADEX for girls aged two to 10 years with McCune-Albright Syndrome and precocious puberty have not been studied beyondone year of treatment. The long-term effects of NOLVADEX therapy in girls have not been established.<br/>Postmarketing experience:: Less frequently reported adverse reactions are vaginal bleeding, vaginal discharge, menstrual irregularities, skin rash and headaches. Usually these have not been of sufficient severity to require dosage reduction or discontinuation of treatment. Very rare reports of erythema multiforme, Stevens-Johnson syndrome, bullous pemphigoid, interstitial pneumonitis, and rare reports of hypersensitivity reactions including angioedema have been reported with NOLVADEX therapy. In some of these cases, the time to onset was more than one year. Rarely, elevation of serum triglyceride levels, in some cases with pancreatitis, may be associated with the use of NOLVADEX .
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| dailymed-drugs:108 |
Carvedilol has been evaluated for safety in patients
with heart failure (mild, moderate, and severe heart failure), in
patients with left ventricular dysfunction following myocardial infarction,
and in hypertensive patients. The observed adverse event profile was
consistent with the pharmacology of the drug and the health status
of the patients in the clinical trials. Adverse events reported for
each of these patient populations reflecting the use of either COREG CR
or immediate-release carvedilol are provided below. Excluded are adverse
events considered too general to be informative, and those not reasonably
associated with the use of the drug because they were associated with
the condition being treated or are very common in the treated population.
Rates of adverse events were generally similar across demographic
subsets (men and women, elderly and non-elderly, blacks and non-blacks).
COREG CR has been evaluated for safety in a 4-week (2 weeks of
immediate-release carvedilol and 2 weeks ofCOREG CR) clinical
study (n = 187) which included 157 patients with stable
mild, moderate, or severe chronic heart failure and 30 patients with
left ventricular dysfunction following acute myocardial infarction.The
profile of adverse events observed with COREG CR in this small,
short-term study was generally similar to that observed with immediate-release
carvedilol. Differences in safety would not be expected based on the
similarity in plasma levels for COREG CR and immediate-release
carvedilol.<br/>Heart Failure: The following information describes the safety experience
in heart failure with immediate-release carvedilol. Carvedilol has been evaluated for safety in heart failure in more
than 4,500 patients worldwide of whom more than 2,100 participated
in placebo-controlled clinical trials. Approximately 60% of the total
treated population in placebo-controlled clinical trials received
carvedilol for at least 6 months and 30% received carvedilol
for at least 12 months. In the COMET trial, 1,511 patients with
mild-to-moderate heart failure were treated with carvedilol for up
to 5.9 years (mean 4.8 years). Both in US clinical trials
in mild-to-moderate heart failure that compared carvedilol in daily
doses up to 100 mg (n = 765) to placebo (n = 437),
and in a multinational clinical trial in severe heart failure (COPERNICUS)
thatcompared carvedilol in daily doses up to 50 mg (n = 1,156)
with placebo (n = 1,133), discontinuation rates for adverse
experiences were similar in carvedilol and placebo patients. In placebo-controlled
clinical trials, the only cause of discontinuation>1%, and occurring
more often on carvedilol was dizziness (1.3% on carvedilol, 0.6% on
placebo in the COPERNICUS trial). Table 3 shows
adverse events reported in patients with mild-to-moderate heart failure
enrolled in US placebo-controlled clinical trials, and with severe
heart failure enrolled in the COPERNICUS trial. Shown are adverse
events that occurred more frequently in drug-treated patients than
placebo-treated patients with an incidence of>3% in patients treated
with carvedilol regardless of causality. Median study medication exposure
was 6.3 months for both carvedilol and placebo patients in the
trials of mild-to-moderate heart failure, and 10.4 months in
the trial of severe heart failure patients. The adverse event profile
of carvedilol observed in the long-term COMET study was generally
similar to that observed in the US Heart Failure Trials. Cardiac failure and dyspnea were also reported
in these studies, but the rates were equal or greater in patients
who received placebo. The following adverse
events were reported with a frequency of>1% but���3% and more
frequently with carvedilol in either the US placebo-controlled trials
in patients with mild-to-moderate heart failure, or in patients with
severe heart failure in the COPERNICUS trial. Incidence>1% to���3% Body as a Whole: Allergy,
malaise, hypovolemia, fever, leg edema. Cardiovascular: Fluid overload, postural
hypotension, aggravated angina pectoris, AV block, palpitation, hypertension. Central and Peripheral Nervous
System: Hypesthesia, vertigo, paresthesia. Gastrointestinal: Melena, periodontitis. Liver and Biliary System: SGPT increased, SGOT increased. Metabolic and Nutritional: Hyperuricemia,
hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria,
hypervolemia, diabetes mellitus, GGT increased, weight loss, hyperkalemia,
creatinine increased. Musculoskeletal: Muscle cramps. Platelet, Bleeding and Clotting: Prothrombin
decreased, purpura, thrombocytopenia. Psychiatric: Somnolence. Reproductive, male: Impotence. Special Senses: Blurred
vision. Urinary System: Renal insufficiency, albuminuria, hematuria.<br/>Left Ventricular Dysfunction Following
Myocardial Infarction: The following information describes the safety experience
in left ventricular dysfunction following acute myocardial infarction
with immediate-release carvedilol. Carvedilol
has been evaluated for safety in survivors of an acute myocardial
infarction with left ventricular dysfunction in the CAPRICORN trial
which involved 969 patients who received carvedilol and 980 who received
placebo. Approximately 75% of the patients received carvedilol for
at least 6 months and 53% received carvedilol for at least 12 months.
Patients were treated for an average of 12.9 months and 12.8 months
with carvedilol and placebo, respectively. The
most common adverse events reported with carvedilol in the CAPRICORN
trial were consistent with the profile of the drug in the US heart
failure trials and the COPERNICUS trial. The only additional adverse
events reported in CAPRICORN in>3% of the patients and more commonly
on carvedilol were dyspnea, anemia, and lung edema. The following
adverse events were reported with a frequency of>1% but���3%
and more frequently with carvedilol: Flu syndrome, cerebrovascular
accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal
pain, arthritis, and gout. The overall rates of discontinuations due
to adverse events were similar in both groups of patients. In this
database, the only cause of discontinuation>1%, and occurring more
often on carvedilol was hypotension (1.5% on carvedilol, 0.2% on placebo).<br/>Hypertension: COREG CR was evaluated for safety in an 8-week
double-blind trial in 337 subjects with essential hypertension. The
profile of adverse events observed with COREG CR was generally
similar to that observed with immediate-release carvedilol. The overall
rates of discontinuations due to adverse events were similar between
COREG CR and placebo. The following information describes the safety
experience in hypertension with immediate-release carvedilol. Carvedilol has been evaluated for safety in hypertension
in more than 2,193 patients in US clinical trials and in 2,976 patients
in international clinical trials. Approximately 36% of the total treated
population received carvedilol for at least 6 months. In general,
carvedilol was well tolerated at doses up to 50 mg daily. Most
adverse events reported during carvedilol therapy were of mild to
moderate severity. In US controlled clinical trials directly comparing
carvedilol monotherapy in doses up to 50 mg (n = 1,142)
to placebo (n = 462), 4.9% of carvedilol patients discontinued
for adverse events vs. 5.2% of placebo patients. Although there was
no overalldifference in discontinuation rates, discontinuations were
more common in the carvedilol group for postural hypotension (1% vs.
0). The overall incidence of adverse events in US placebo-controlled
trials was found to increase with increasing dose of carvedilol. For
individual adverse events this could only be distinguished for dizziness,
which increased in frequency from 2% to 5% as total daily dose increased
from 6.25 mg to 50 mg as single or divided doses. Table 5 shows adverse events in US placebo-controlled
clinical trials for hypertension that occurred with an incidence of���1% regardless of causality, and that were more frequent in
drug-treated patients than placebo-treated patients. Dyspnea and fatigue were also reported in these
studies, but the rates were equal or greater in patients who received
placebo. The following adverse events not
described above were reported as possibly or probably related to carvedilol
in worldwide open or controlled trials with carvedilol in patients
with hypertension or heart failure. Incidence>0.1% to���1% Cardiovascular: Peripheral
ischemia, tachycardia. Central and Peripheral Nervous System: Hypokinesia. Gastrointestinal: Bilirubinemia,
increased hepatic enzymes (0.2% of hypertension patients and 0.4%
of heart failure patients were discontinued from therapy because of
increases in hepatic enzymes; see Laboratory Abnormalities.) Psychiatric: Nervousness,
sleep disorder, aggravated depression, impaired concentration, abnormal
thinking, paroniria, emotional lability. Respiratory System: Asthma (see CONTRAINDICATIONS). Reproductive: Male:
Decreased libido. Skin and Appendages: Pruritus, rash erythematous, rash
maculopapular, rash psoriaform, photosensitivity reaction. Special Senses: Tinnitus. Urinary System: Micturition
frequency increased. Autonomic Nervous System: Dry mouth, sweating increased. Metabolic and Nutritional: Hypokalemia, hypertriglyceridemia. Hematologic: Anemia, leukopenia. The following events were reported in���0.1% of
patients and are potentially important: Complete AV block, bundle
branch block, myocardial ischemia, cerebrovascular disorder, convulsions,
migraine, neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative
dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema,
decreased hearing, respiratory alkalosis, increased BUN, decreased
HDL, pancytopenia, and atypical lymphocytes.<br/>Laboratory Abnormalities: Reversible elevations in serum transaminases (ALT
or AST) have been observed during treatment with carvedilol. Rates
of transaminase elevations (2- to 3-times the upper limit of normal)
observed during controlled clinical trials have generally been similar
between patients treated with carvedilol and those treated with placebo.
However, transaminase elevations, confirmed by rechallenge, have been
observed with carvedilol. In a long-term, placebo-controlled trial
in severe heart failure, patients treated with carvedilol had lower
values for hepatic transaminases than patients treated with placebo,
possibly because carvedilol-induced improvements in cardiac function
led to less hepatic congestion and/or improved hepatic blood flow. Carvedilol therapy has not been associated with clinically
significant changes in serum potassium, total triglycerides, total
cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
No clinically relevant changes were noted in fasting serum glucose
in hypertensive patients; fasting serum glucose was not evaluated
in the heart failure clinical trials.<br/>Postmarketing Experience: Reports of aplastic anemia and severe skin reactions
(Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema
multiforme) have been rare and received only when carvedilol was administered
concomitantly with other medications associated with such reactions.
Rare reports of hypersensitivity reactions (e.g., anaphylactic reaction,
angioedema, and urticaria) have been received for COREG' and
COREG CR, including cases occurring after the initiation of COREG
CR in patients previously treated with COREG. Urinary incontinence
in women (which resolved upon discontinuation of the medication) and
interstitial pneumonitis have been reported rarely.
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| dailymed-drugs:109 |
An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives . There is evidence of an association between the following conditions and the use of oral contraceptives: The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: The following adverse reactions have been reported in users of oral contraceptives and a causal association has been neither confirmed nor refuted: The most frequent (>1%) treatment-emergent adverse events, listed in descending order, reported with the use of YAZ in the contraception clinical trials, which may or not be drug related, included: upper respiratory infection, headache, breast pain, vaginal moniliasis, leukorrhea, diarrhea, nausea, vomiting, vaginitis, abdominal pain, flu syndrome, dysmenorrhea, moniliasis, allergic reaction, urinary tract infection, accidental injury, cystitis, tooth disorder, sore throat, infection, fever, surgery, sinusitis, back pain, emotional lability, migraine, suspicious Papanicolaou smear, dyspepsia, rhinitis, acne, gastroenteritis, bronchitis, pharyngitis, skin disorder, intermenstrual bleeding, decreased libido, weight gain, pain, depression, increased cough, dizziness, menstrual disorder, pain in extremity, pelvic pain, and asthenia. The most frequent (>1%) treatment-emergent adverse events, listed in descending order, reported with the use of YAZ in the PMDD clinical trials, which may or not be drug related, included: intermenstrual bleeding, headache, nausea, breast pain, upper respiratory infection, asthenia, abdominal pain, decreased libido, emotional lability, suspicious Papanicolaou smear, nervousness, menorrhagia, pain in extremity, depression, menstrual disorder, migraine, sinusitis, weight gain, , vaginal moniliasis, vaginitis, hyperlipidemia, back pain, diarrhea, increased appetite, enlarged abdomen, accidental injury, acne, dysmenorrhea, and urinary tract infection.
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| dailymed-drugs:110 |
Approximately 760 subjects have been treated with telbivudine in clinical studies at a dose of 600 mg once daily. Assessment of adverse reactions is primarily based on the pivotal 007 GLOBE study in which 1,367 patients with chronic hepatitis B received double-blind treatment with telbivudine 600 mg/day (n=680 patients) or lamivudine (n=687 patients) for up to 104 weeks. Medianduration of treatment in the 007 GLOBE study was 60 weeks for telbivudine- and lamivudine-treated patients. The safety profiles of telbivudine and lamivudine were generally comparable in this study.<br/>Clinical Adverse Events: In clinical studies telbivudine was generally well tolerated, with most adverse experiences classified as mild or moderate in severity and not attributed to telbivudine. In the 007 GLOBE study patient discontinuations for adverse events, clinical disease progression or lack of efficacy were 0.6% for telbivudine and 2.0% for lamivudine. Frequently occurring adverse events regardless of attributability to telbivudine were upper respiratory tract infection (14%), fatigue and malaise (12%), abdominal pain (12%), nasopharyngitis (11%), headache (11%), blood CPK increased (9%), cough (7%), nausea and vomiting (7%), influenza and influenza-like symptoms (7%), post-procedural pain (7%), diarrhea and loose stools (7%), pharyngolaryngeal pain (5%), pyrexia (4%), arthralgia (4%), rash (4%), back pain (4%), dizziness (4%), myalgia (3%), insomnia (3%), and dyspepsia (3%). Frequently occurring adverse events regardless of attributability to lamivudine were headache (14%), upper respiratory tract infection (13%), abdominal pain (13%), fatigue and malaise (11%), nasopharyngitis (10%), influenza and influenza-like symptoms (8%), blood CPK increased (7%), cough (6%), post-procedural pain (6%), nausea and vomiting (6%), dyspepsia (5%), diarrhea and loose stools (5%), dizziness (5%), pharyngolaryngeal pain (4%), rash (4%), hepatic/RUQ pain (4%), arthralgia (4%), back pain (4%), pyrexia (3%), rhinorrhea (3%), ALT increased (3%), and pruritus (3%). Selected, treatment-emergent, clinical adverse events of moderate to severe intensity, without consideration of study drug causality, during the pivotal 007 GLOBE study clinical trial are presented in Table 4. Frequencies of selected treatment-emergent laboratory abnormalities in the 007 GLOBE study are listed in Table 5. Creatine kinase (CK) elevations were more frequent among subjects on telbivudine treatment, as shown above in Table 5. CK elevations occurred in both treatment arms; however median CK levels were higher in telbivudine-treated patients by Week 52. Grade 1-4 CK elevations occurred in 72% of telbivudine-treated patients and 42% of lamivudine-treated patients, whereas Grade 3/4 CK elevations occurred in 9% of telbivudine-treated patients and 3% of lamivudine-treated patients. Most CK elevations were asymptomatic but the mean recovery time was longer for subjects on telbivudine than subjects on lamivudine. While there was not a uniform pattern with regard to the type of adverse event and timing with respectto the CK elevation, 8% of telbivudine-treated patients with Grade 1-4 CK elevations experienced a CK-related adverse event(within a 30-day window) compared to 6% of lamivudine-treated patients. In this subgroup of patients with CK-related adverse events, 9% of telbivudine-treated patients subsequently interrupted or discontinued study drug. These patients recovered after study drug discontinuation or interruption. Less than 1 % of telbivudine-subjects overall (n=3/680) were diagnosed with myopathy with muscular weakness; these patients also recovered after study drug discontinuation . As shown in Table 5, on-treatment ALT elevations were more frequent on lamivudine treatment. Additionally, the overall incidence of on-treatment ALT flares, using AASLD criteria (ALT>10 x ULN and>2.0 x baseline), was slightly higher in the lamivudine arm (5.1%) than the telbivudine arm (3.2%). The incidence of ALT flares was similar in the two treatment arms in the first six months. ALT flares occurred less frequently in both arms after Week 24, with a lower incidence in the telbivudine arm (0.4%) compared to the lamivudine arm (2.2%). For both lamivudine and telbivudine subjects, the occurrence of ALT flares was more common in HBeAg positive subjects than in HBeAg negative subjects. Periodic monitoring of hepatic function is recommended during treatment.<br/>Exacerbations of Hepatitis After Discontinuation of Treatment (See WARNINGS): There are insufficient data on post-treatment exacerbations of hepatitis after discontinuation of telbivudine treatment.
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Cevimeline was administered to 1777 patients during clinical trials worldwide, including Sj��gren's patients and patients with other conditions. In placebo-controlled Sj��gren's studies in the U.S., 320 patients received cevimeline doses ranging from 15 mg tid to 60 mg tid, of whom 93% were women and 7% were men. Demographic distribution was 90% Caucasian, 5% Hispanic, 3% Black and 2% of other origin. In these studies, 14.6% of patients discontinued treatment with cevimeline due to adverse events. The following adverse events associated with muscarinic agonism were observed in the clinical trials of cevimeline in Sj��gren's syndrome patients: In addition, the following adverse events (���3% incidence) were reported in the Sj��gren's clinical trials: The following events were reported in Sj��gren's patients at incidences of<3% and���1%: constipation, tremor, abnormal vision, hypertonia, peripheral edema, chest pain, myalgia, fever, anorexia, eye pain, earache, dry mouth, vertigo, salivary gland pain, pruritus, influenza-like symptoms, eye infection, post-operative pain, vaginitis, skin disorder, depression, hiccup, hyporeflexia, infection, fungal infection, sialoadenitis, otitis media, erythematous rash, pneumonia, edema, salivary gland enlargement, allergy, gastroesophageal reflux, eye abnormality, migraine, tooth disorder, epistaxis, flatulence, toothache, ulcerative stomatitis, anemia, hypoesthesia, cystitis, leg cramps, abscess, eructation, moniliasis, palpitation, increased amylase, xerophthalmia, allergic reaction. The following events were reported rarely in treated Sj��gren's patients (<1%): Causal relation is unknown: Body as a Whole Disorders: aggravated allergy, precordial chest pain, abnormal crying, hematoma, leg pain, edema, periorbital edema, activated pain trauma, pallor, changed sensation temperature, weight decrease, weight increase, choking, mouth edema, syncope, malaise, face edema, substernal chest pain Cardiovascular Disorders: abnormal ECG, heart disorder, heart murmur, aggravated hypertension, hypotension, arrhythmia, extrasystoles, t wave inversion, tachycardia, supraventricular tachycardia, angina pectoris, myocardial infarction, pericarditis, pulmonary embolism, peripheral ischemia, superficial phlebitis, purpura, deep thrombophlebitis, vascular disorder, vasculitis, hypertension Digestive Disorders: appendicitis, increased appetite, ulcerative colitis, diverticulitis, duodenitis, dysphagia, enterocolitis, gastric ulcer, gastritis, gastroenteritis, gastrointestinal hemorrhage, gingivitis, glossitis, rectum hemorrhage, hemorrhoids, ileus, irritable bowel syndrome, melena, mucositis, esophageal stricture, esophagitis, oral hemorrhage, peptic ulcer, periodontal destruction, rectal disorder, stomatitis, tenesmus, tongue discoloration, tongue disorder, geographic tongue, tongue ulceration, dental caries Endocrine Disorders: increased glucocorticoids, goiter, hypothyroidism Hematologic Disorders: thrombocytopenic purpura, thrombocythemia, thrombocytopenia, hypochromic anemia, eosinophilia, granulocytopenia, leucopenia, leukocytosis, cervical lymphadenopathy, lymphadenopathy Liver and Biliary System Disorders: cholelithiasis, increased gamma-glutamyl transferase, increased hepatic enzymes, abnormal hepatic function, viral hepatitis, increased serum glutamate oxaloacetic transaminase (SGOT) (also called AST-aspartate aminotransferase), increased serum glutamate pyruvate transaminase (SGPT) (also called ALT-alanine aminotransferase) Metabolic and Nutritional Disorders: dehydration, diabetes mellitus, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, thirst Musculoskeletal Disorders: arthritis, aggravated arthritis, arthropathy, femoral head avascular necrosis, bone disorder, bursitis, costochondritis, plantar fasciitis, muscle weakness, osteomyelitis, osteoporosis, synovitis, tendinitis, tenosynovitis Neoplasms: basal cell carcinoma, squamous carcinoma Nervous Disorders: carpal tunnel syndrome, coma, abnormal coordination, dysesthesia, dyskinesia, dysphonia, aggravated multiple sclerosis, involuntary muscle contractions, neuralgia, neuropathy, paresthesia, speech disorder, agitation, confusion, depersonalization, aggravated depression, abnormal dreaming, emotional lability, manic reaction, paroniria, somnolence, abnormal thinking, hyperkinesia, hallucination Miscellaneous Disorders: fall, food poisoning, heat stroke, joint dislocation, post-operative hemorrhage Resistance Mechanism Disorders: cellulitis, herpes simplex, herpes zoster, bacterial infection, viral infection, genital moniliasis, sepsis Respiratory Disorders: asthma, bronchospasm, chronic obstructive airway disease, dyspnea, hemoptysis, laryngitis, nasal ulcer, pleural effusion, pleurisy, pulmonary congestion, pulmonary fibrosis, respiratory disorder Rheumatologic Disorders: aggravated rheumatoid arthritis, lupus erythematosus rash, lupus erythematosus syndrome Skin and Appendages Disorders: acne, alopecia, burn, dermatitis, contact dermatitis, lichenoid dermatitis, eczema, furunculosis, hyperkeratosis, lichen planus, nail discoloration, nail disorder, onychia, onychomycosis, paronychia, photosensitivity reaction, rosacea, scleroderma, seborrhea, skin discoloration, dry skin, skin exfoliation, skin hypertrophy,skin ulceration, urticaria, verruca, bullous eruption, cold clammy skin Special Senses Disorders: deafness, decreased hearing, motion sickness, parosmia, taste perversion, blepharitis, cataract, corneal opacity, corneal ulceration, diplopia, glaucoma, anterior chamber eye hemorrhage, keratitis, keratoconjunctivitis, mydriasis, myopia, photopsia, retinal deposits, retinal disorder, scleritis, vitreous detachment, tinnitus Urogenital Disorders: epididymitis, prostatic disorder, abnormal sexual function, amenorrhea, female breast neoplasm, malignant female breast neoplasm, female breast pain, positive cervical smear test, dysmenorrhea, endometrial disorder, intermenstrual bleeding, leukorrhea, menorrhagia, menstrual disorder, ovarian cyst, ovarian disorder, genital pruritus, uterine hemorrhage, vaginal hemorrhage, atrophic vaginitis, albuminuria, bladder discomfort, increased blood urea nitrogen, dysuria, hematuria, micturition disorder, nephrosis, nocturia, increasednonprotein nitrogen, pyelonephritis, renal calculus, abnormal renal function, renal pain, strangury, urethral disorder, abnormal urine, urinary incontinence, decreased urine flow, pyuria In one subject with lupus erythematosus receiving concomitant multiple drug therapy, a highly elevated ALT level was noted after the fourth week of cevimeline therapy. In two other subjects receiving cevimeline in the clinical trials, very high AST levels were noted. The significance of these findings is unknown. Additional adverse events (relationship unknown) which occurred in other clinical studies (patient population different from Sj��gren's patients) are as follows: cholinergic syndrome, blood pressure fluctuation, cardiomegaly, postural hypotension, aphasia, convulsions, abnormal gait, hyperesthesia, paralysis, abnormal sexual function, enlarged abdomen, change in bowel habits, gum hyperplasia, intestinal obstruction, bundle branch block, increased creatine phosphokinase, electrolyte abnormality, glycosuria, gout, hyperkalemia, hyperproteinemia, increased lactic dehydrogenase (LDH), increased alkaline phosphatase, failure to thrive, abnormal platelets, aggressive reaction, amnesia, apathy, delirium, delusion, dementia, illusion, impotence, neurosis, paranoid reaction, personality disorder, hyperhemoglobinemia, apnea, atelectasis, yawning, oliguria, urinary retention, distended vein, lymphocytosis The following adverse reaction has been identified during post-approval use of EVOXAC'. Because post-marketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.<br/>Post-marketing Adverse Events: Liver and Biliary System Disorders: cholecystitis
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| dailymed-drugs:112 |
The most frequently reported adverse events in the overall study population were headache and a taste disturbance following instillation. These events occurred in approximately 8-10% of patients. Adverse events occurring in approximately 1-2% of patients included decreased/blurred vision, diarrhea, dyspepsia, fever, infection, instillation site irritation/discomfort, ocular infection, nausea, ocular pain/discomfort, and throat irritation. Other reported ocular reactions occurring in less than 1% of patients included chemosis, corneal erosion, corneal ulcer, diplopia, floaters, hyperemia, lid edema, and lid erythema.
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| dailymed-drugs:113 |
Adults::<br/>Osteoarthritis and Rheumatoid Arthritis:: The Meloxicam Phase 2/3 clinical trial database includes 10,122 OA patients and 1012RA patients treated with meloxicam 7.5 mg/day, 3,505 OA patients and 1351 RA patients treated with meloxicam 15 mg/day. Meloxicam at these doses was administered to 661 patients for at least 6 months and to 312 patients for at least one year. Approximately 10,500 of these patients were treated in ten placebo and/or active-controlled osteoarthritis trials and 2363 of these patients were treated in ten placebo and/or active-controlled rheumatoid arthritis trials. Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across meloxicam trials. A 12-week multicenter, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of meloxicam with placebo and with an active control. Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of meloxicam with placebo. Table 2a depicts adverse events that occurred in (2% of the( meloxicam treatment groups in a 12-week placebo and active-controlled osteoarthritis trial. Table 2b depicts adverse events that occurred in���2% of the meloxicam treatment groups in two 12-week placebo controlled rheumatoid arthritis trials. The adverse events that occurred with meloxicam in (2% of patients treated short-term (4-6 weeks) and long-term (6 months) in active-controlled osteoarthritis trials are presented in Table 3. Higher doses of meloxicam (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore the daily dose of meloxicam should not exceed 15 mg. The following is a list of adverse drug reactions occurring in<2% of patients receiving meloxicam in clinical trials involving approximately 16,200 patients. Adverse reactions reported only in worldwide post-marketing experience or the literature are shown in italics.
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| dailymed-drugs:114 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence beginning with column 1:
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| dailymed-drugs:115 |
Serious cardiac events, including some that have been fatal, have occurred following use of dihydroergotamine mesylate injection but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. Fibrotic complications have been reported in association with long term use of injectabledihydroergotamine mesylate<br/>Post-introduction Reports: The following events derived from postmarketing experience have been occasionally reported in patients receiving dihydroergotamine mesylate injection: vasospasm, paraesthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine. Extremely rare cases of myocardial infarction and stroke have been reported. A causal relationship has not been established. Dihydroergotamine mesylate injection is not recommended for prolonged daily use.
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| dailymed-drugs:116 |
Adverse effects reported in patients taking cimetidine are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.<br/>Gastrointestinal: Diarrhea (usually mild) has been reported in approximately 1 in 100 patients.<br/>CNS: Headaches, ranging from mild to severe, have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day. Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of cimetidine therapy and have cleared within 3 to 4 days of discontinuation of the drug.<br/>Endocrine: Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing cimetidine treatment. Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving cimetidine, particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.<br/>Hematologic: Decreased white blood cell counts in cimetidine-treated patients (approximately 1 per 100,000 patients), including agranulocytosis (approximately 3 per million patients), have been reported, including a few reports of recurrence on rechallenge. Most of these reports were in patients who had serious concomitant illnesses and received drugs and/or treatment known to produce neutropenia. Thrombocytopenia (approximately 3 per million patients) and, very rarely, cases of pancytopenia or aplastic anemia have also been reported. As with some other H-receptor antagonists, there have been extremely rare reports of immune hemolytic anemia.<br/>Hepatobiliary: Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of therapy. There have been rare reports of cholestatic or mixed cholestatic-hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in the occasional liver injury with other H-receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported. There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving cimetidine. Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.<br/>Hypersensitivity: Rare cases of fever and allergic reactions including anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the drug, have been reported.<br/>Renal: Small, possibly dose-related increases in plasma creatinine, presumably due to competition for renal tubular secretion, are not uncommon and do not signify deteriorating renal function. Rare cases of interstitial nephritis and urinary retention, which cleared on withdrawal of the drug, have been reported.<br/>Cardiovascular: Rare cases of bradycardia, tachycardia and A-V heart block have been reported with H-receptor antagonists.<br/>Musculoskeletal: There have been rare reports of reversible arthralgia and myalgia; exacerbation of joint symptoms in patients with preexisting arthritis has also been reported. Such symptoms have usually been alleviated by a reduction in cimetidine dosage. Rare cases of polymyositis have been reported, but no causal relationship has been established.<br/>Integumental: Mild rash and, very rarely, cases of severe generalized skin reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have been reported with H-receptor antagonists. Reversible alopecia has been reported very rarely.<br/>Immune Function: There have been extremely rare reports of strongyloidiasis hyperinfection in immunocompromised patients.
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| dailymed-drugs:117 |
The adverse reactions listed below have been reported during domestic and international clinical trials in approximately 2500 patients. In those controlled clinical trials in which famotidine tablets were compared to placebo, the incidence of adverse experiences in the group which received famotidine tablets, 40 mg at bedtime, was similar to that in the placebo group. The following adverse reactions have been reported to occur in more than 1% of patients on therapy with famotidine in controlled clinical trials, and may be causally related to the drug: headache (4.7%), dizziness (1.3%), constipation (1.2%) and diarrhea (1.7%). The following other adverse reactions have been reported infrequently in clinical trials or since the drug was marketed. The relationship to therapy with famotidine has been unclear in many cases. Within each category the adverse reactions are listed in order of decreasing severity: Body As A Whole: fever, asthenia, fatigue Cardiovascular: arrhythmia, AV block, palpitation Gastrointestinal: cholestatic jaundice, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth Hematologic: rare cases of agranulocytosis, pancytopenia, leukopenia, thrombocytopenia Hypersensitivity: anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection Musculoskeletal: musculoskeletal pain including muscle cramps, arthralgia Nervous System/Psychiatric: grand mal seizure; psychic disturbances, which were reversible in cases for which follow-up was obtained, including hallucinations, confusion, agitation, depression, anxiety, decreased libido; paresthesia; insomnia; somnolence Respiratory: bronchospasm Skin: toxic epidermal necrolysis (very rare), alopecia, acne, pruritus, dry skin, flushing Special Senses: tinnitus, taste disorder Other: rare cases of impotence and rare cases of gynecomastia have been reported; however, in controlled clinical trials, the incidences were not greater than those seen with placebo. The adverse reactions reported for famotidine tablets may also occur with famotidine for Oral Suspension.<br/>Pediatric Patients: In a clinical study in 35 pediatric patients<1 year of age with GERD symptoms [e.g., vomiting (spitting up), irritability (fussing)], agitation was observed in 5 patients on famotidine that resolved when the medication was discontinued.
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The adverse reactions for Capsules INDOCIN listed in the following
table have been arranged into two groups: (1) incidence greater than
1%; and (2) incidence less than 1%. The incidence for group (1) was
obtained from 33 double-blind controlled clinical trials reported
in the literature (1,092 patients). The incidence for group (2) was
based on reports in clinical trials, in the literature, and on voluntary
reports since marketing. The probability of acausal relationship
exists between INDOCIN and these adverse reactions, some of which
have been reported only rarely. The adverse reactions reported with Capsules INDOCIN may
also occur with use of the suspension. Causal relationship unknown: Other reactions have been reported but occurred under circumstances
where a causal relationship could not be established. However, in
these rarely reported events, the possibility cannot be excluded.
Therefore, these observations are being listed to serve as alerting
information to physicians: Cardiovascular: Thrombophlebitis Hematologic: Although
there have been several reports of leukemia, the supporting information
is weak Genitourinary: Urinary frequency A rare occurrence of fulminant
necrotizing fasciitis, particularly in association with Group A��hemolytic streptococcus, has been described in persons treated with
non-steroidal anti-inflammatory agents, including indomethacin, sometimes
with fatal outcome .
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CLAFORAN is generally well tolerated. The most common adverse reactions have been local reactions following IM or IV injection. Other adverse reactions have been encountered infrequently. The most frequent adverse reactions (greater than 1%) are: Local (4.3%) - Injection site inflammation with IV administration. Pain, induration, and tenderness after IM injection. Hypersensitivity (2.4%) - Rash, pruritus, fever, eosinophilia and less frequently urticaria and anaphylaxis (e.g., angioedema, bronchospasm, malaise possibly culminating in shock). Gastrointestinal (1.4%) - Colitis, diarrhea, nausea, and vomiting. Symptoms of pseudomembranous colitis can appear during or after antibiotic treatment. Nausea and vomiting have been reported rarely. Less frequent adverse reactions (less than 1%) are: Cardiovascular System - Potentially life-threatening arrhythmias following rapid (less than 60 seconds) bolus administration via central venous catheter have been observed. Hematologic System - Neutropenia, transient leukopenia, eosinophilia, thrombocytopenia and agranulocytosis have been reported. Some individuals have developed positive direct Coombs Tests during treatment with CLAFORAN and other cephalosporin antibiotics. Rare cases of hemolytic anemia have been reported. Genitourinary System - Moniliasis, vaginitis. Central Nervous System - Administration of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal insufficiency may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions). Headache. Liver - Transient elevations in SGOT, SGPT, serum LDH, gamma GT, bilirubin, and serum alkaline phosphatase levels have been reported. These laboratory abnormalities, which may also be explained by the infection, may rarely exceed twice the upper limit of the normal range and elicit a pattern of liver injury, usually cholestatic and most often asymptomatic. Hepatitis, sometimes with jaundice, has been reported. Kidney - As with some other cephalosporins, interstitial nephritis and transient elevations of BUN and creatinine have been occasionally observed with CLAFORAN. Cutaneous - As with other cephalosporins, isolated cases of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.<br/>Cephalosporin Class Labeling: In addition to the adverse reactions listed above which have been observed in patients treated with cefotaxime sodium, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics: allergic reactions, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and false-positive test for urinary glucose. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. See DOSAGE AND ADMINISTRATION and OVERDOSAGE. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
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The pattern of adverse reactions is similar whether Vinorelbine is used as a single agent or in combination. Adverse reactions from studies with single-agent and combination use of Vinorelbine are summarized in Tables 2-4.<br/>Single-Agent Vinorelbine: Data in the following table are based on the experience of 365 patients (143 patients with NSCLC; 222 patients with advanced breast cancer) treated with IV Vinorelbine as a single agent in 3 clinical studies. The dosing schedule in each study was 30 mg/mVinorelbine on a weekly basis.<br/>Hematologic: Granulocytopenia is the major dose-limiting toxicity with Vinorelbine. Dose adjustments are required for hematologic toxicity and hepatic insufficiency (see DOSAGE AND ADMINISTRATION). Granulocytopenia was generally reversible and not cumulative over time.
Granulocyte nadirs occurred 7 to 10 days after the dose, with granulocyte recovery usually within the following 7 to 14 days. Granulocytopenia resulted in hospitalizations for fever and/or sepsis in 8% of patients. Septic deaths occurred in approximately 1% of patients. Prophylactic hematologic growth factors have not been routinely used with Vinorelbine. If medically necessary, growth factors may be administered at recommended doses no earlier than 24 hours after the administration of cytotoxic chemotherapy. Growth factors should not be administered in the period 24 hours before the administration of chemotherapy. Whole blood and/or packed red blood cells were administered to 18% of patients who received Vinorelbine.<br/>Neurologic: Loss of deep tendon reflexes occurred in less than 5% of patients. The development of severe peripheral neuropathy was infrequent (1%) and generally reversible.<br/>Skin: Like other anticancer vinca alkaloids, Vinorelbine is a moderate vesicant. Injection site reactions, including erythema, pain at injection site, and vein discoloration, occurred in approximately one third of patients; 5% were severe. Chemical phlebitis along the vein proximal to the site of injection was reported in 10% of patients.<br/>Gastrointestinal: Prophylactic administration of antiemetics was not routine in patients treated with single-agent Vinorelbine. Due to the low incidence of severe nausea and vomiting with single-agent Vinorelbine, the use of serotonin antagonists is generally not required.<br/>Hepatic: Transient elevations of liver enzymes were reported without clinical symptoms.<br/>Cardiovascular: Chest pain was reported in 5% of patients. Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest. There have been rare reports of myocardial infarction.<br/>Pulmonary: Shortness of breath was reported in 3% of patients; it was severe in 2% (see WARNINGS). Interstitial pulmonary changes were documented.<br/>Other: Fatigue occurred in 27% of patients. It was usually mild or moderate but tended to increase with cumulative dosing. Other toxicities that have been reported in less than 5% of patients include jaw pain, myalgia, arthralgia, and rash. Hemorrhagic cystitis and the syndrome of inappropriate ADH secretion were each reported in<1% of patients.<br/>Combination Use: Adverse events for combination use are summarized in Tables 3 and 4. Vinorelbine in Combination with Cisplatin: Vinorelbine plus Cisplatin versus Single-Agent Cisplatin (Table 3): Myelosuppression was the predominant toxicity in patients receiving combination therapy, Grade 3 and 4 granulocytopenia of 82% compared to 5% in the single-agent cisplatin arm. Fever and/or sepsis related to granulocytopenia occurred in 11% of patients on Vinorelbine and cisplatin compared to 0% on the cisplatin arm. Four patients on the combination died of granulocytopenia-related sepsis. During this study, the use of granulocyte colony-stimulating factor ([G-CSF] filgrastim) was permitted, but not mandated, after the first course of treatment for patients who experienced Grade 3 or 4 granulocytopenia (���1,000 cells/mm) or in those who developed neutropenic fever between cycles of chemotherapy. Beginning 24 hours after completion of chemotherapy, G-CSF was started at a dose of 5 mcg/kg per day and continued until the total granulocyte count was>1,000 cells/mmon 2 successive determinations. G-CSF was not administered on the day of treatment. Grade 3 and 4 anemia occurred more frequently in the combination arm compared to control, 24% vs. 8%, respectively. Thrombocytopenia occurred in 6% of patients treated with Vinorelbine plus cisplatin compared to 2% of patients treated with cisplatin. The incidence of severe non-hematologic toxicity was similar among the patients in both treatment groups. Patients receiving Vinorelbine plus cisplatin compared to single-agent cisplatin experienced more Grade 3 and/or 4 peripheral numbness (2% vs.<1%), phlebitis/thrombosis/embolism (3% vs.<1%), and infection (6% vs.<1%). Grade 3-4 constipation and/or ileus occurred in 3% of patients treated with combination therapy and in 1% of patients treated with cisplatin. Seven deaths were reported on the combination arm; 2 were related to cardiac ischemia, 1 massive cerebrovascular accident, 1 multisystem failure due to an overdose of Vinorelbine, and 3 from febrile neutropenia. One death, secondary to respiratory infection unrelated to granulocytopenia, occurred with single-agent cisplatin. Vinorelbine plus Cisplatin versus Vindesine plus Cisplatin versus Single-Agent Vinorelbine (Table 4): Myelosuppression, specifically Grade 3 and 4
granulocytopenia, was significantly greater with the combination of Vinorelbine plus cisplatin
(79%) than with either single-agent Vinorelbine (53%) or vindesine plus cisplatin (48%),P<0.0001. Hospitalization due to documented sepsis occurred in 4.4% of patients treated with Vinorelbine plus cisplatin; 2% of patients treated with vindesine and cisplatin, and 4% of patients treated with single-agent Vinorelbine. Grade 3 and 4 thrombocytopenia was infrequent in patients receiving combination chemotherapy and no events were reported with single-agent Vinorelbine. The incidence of Grade 3 and/or 4 nausea and vomiting, alopecia, and renal toxicity were reported more frequently in the cisplatin-containing combinations compared to single-agent Vinorelbine. Severe local reactions occurred in 2% of patients treated with combinations containing Vinorelbine; none were observed in the vindesine plus cisplatin arm. Grade 3 and 4
neurotoxicity was significantly more frequent in patients receiving vindesine plus cisplatin (17%) compared to Vinorelbine plus cisplatin (7%) and single-agent Vinorelbine (9%) (P<0.005).
Cisplatin did not appear to increase the incidence of neurotoxicity observed with single-agent Vinorelbine.<br/>Observed During Clinical Practice: In addition to the adverse events reported from clinical trials, the following events have been identified during post-approval use of Vinorelbine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Vinorelbine. Body as a Whole: Systemic allergic reactions reported as anaphylaxis, pruritus, urticaria, and angioedema; flushing; and radiation recall events such as dermatitis and esophagitis (see
PRECAUTIONS) have been reported. Hematologic:Thromboembolic events, including pulmonary embolus and deep venous thrombosis, have been reported primarily in seriously ill and debilitated patients with known predisposing risk factors for these events. Neurologic: Peripheral neurotoxicities such as, but not limited to, muscle weakness and disturbance of gait, have been observed in patients with and without prior symptoms. There may be increased potential for neurotoxicity in patients with pre-existing neuropathy, regardless of etiology, who receive Vinorelbine. Vestibular and auditory deficits have been observed with Vinorelbine, usually when used in combination with cisplatin. Skin: Injection site reactions, including localized rash and urticaria, blister formation, and skin sloughing have been observed in clinical practice. Some of these reactions may be delayed in appearance. Gastrointestinal: Dysphagia, mucositis, and pancreatitis have been reported. Cardiovascular: Hypertension, hypotension, vasodilation, tachycardia, and pulmonary edema have been reported. Pulmonary:Pneumonia has been reported. Musculoskeletal:Headache has been reported, with and without other musculoskeletal aches and pains. Other: Pain in tumor-containing tissue, back pain, and abdominal pain have been reported.
Electrolyte abnormalities, including hyponatremia with or without the syndrome of inappropriate
ADH secretion, have been reported in seriously ill and debilitated patients. Combination Use:Patients with prior exposure to paclitaxel and who have demonstrated neuropathy should be monitored closely for new or worsening neuropathy. Patients who have experienced neuropathy with previous drug regimens should be monitored for symptoms of neuropathy while receiving Vinorelbine. Vinorelbine may result in radiosensitizing effects with prior or concomitant radiation therapy (see PRECAUTIONS).
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During two randomized, double-blind placebo-controlled 12 week trials to evaluate the efficacy of naltrexone as an adjunctive treatment of alcohol dependence, most patients tolerated naltrexone well. In these studies, a total of 93 patients received naltrexone hydrochloride at a dose of 50 mg once daily. Five of these patients discontinued naltrexone because of nausea. No serious adverse events were reported during these two trials. While extensive clinical studies evaluating the use of naltrexone in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone use, placebo-controlled studies employing up to five-fold higher doses of naltrexone hydrochloride (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that naltrexone causes hepatocellular injury in a substantial proportion of patients exposed at higher doses . Aside from this finding, and the risk of precipitated opioid withdrawal, available evidence does not incriminate naltrexone, used at any dose, as a cause of any other serious adverse reaction for the patient who is���opioid free.���It is critical to recognize that naltrexone can precipitate or exacerbate abstinence signs and symptoms in any individual who is not completely free of exogenous opioids. Patients with addictive disorders, especially opioid addiction, are at risk for multiple numerous adverse events and abnormal laboratory findings, including liver function abnormalities. Data from both controlled and observational studies suggest that these abnormalities, other than the dose-related hepatotoxicity described above, are not related to the use of naltrexone. Among opioid free individuals, naltrexone administration at the recommended dose has not been associated with a predictable profile of serious adverse or untoward events. However, as mentioned above, among individuals using opioids, naltrexone may cause serious withdrawal reactions .<br/>Reported Adverse Events:: Naltrexone has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be free of opioids for more than 7 to 10 days. Studies in alcoholic populations and in volunteers in clinical pharmacology studies have suggested that a small fraction of patients may experience an opioid withdrawal-like symptom complex consisting of tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, myalgia, and nasal symptoms. This may represent the unmasking of occult opioid use, or it may represent symptoms attributable to naltrexone. A number of alternative dosing patterns have been recommended to try to reduce the frequency of these complaints (see Individualization of Dosage).<br/>Alcoholism:: In an open label safety study with approximately 570 individuals with alcoholism receiving naltrexone, the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%). Depression, suicidal ideation, and suicidal attempts have been reported in all groups when comparing naltrexone, placebo, or controls undergoing treatment for alcoholism. Although no causal relationship with naltrexone is suspected, physicians should be aware that treatment with naltrexone does not reduce the risk of suicide in these patients .<br/>Opioid Addiction:: The following adverse reactions have been reported both at baseline and during the naltrexone clinical trials in opioid addiction at an incidence rate of more than 10%: Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache. The incidence was less than 10% for: Loss of appetite, diarrhea, constipation, increased thirst, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased potency, and chills. The following events occurred in less than 1% of subjects: Respiratory: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath. Cardiovascular: nose bleeds, phlebitis, edema, increased blood pressure, non-specific ECG changes, palpitations, tachycardia. Gastrointestinal: excessive gas, hemorrhoids, diarrhea, ulcer. Musculoskeletal: painful shoulders, legs or knees; tremors, twitching. Genitourinary: increased frequency of, or discomfort during, urination; increased or decreased sexual interest. Dermatologic: oily skin, pruritus, acne, athlete's foot, cold sores, alopecia. Psychiatric: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams. Special senses: eyes-blurred, burning, light sensitive, swollen, aching, strained; ears-���clogged���, aching, tinnitus. General: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head���pounding���, inguinal pain, swollen glands,���side���pains, cold feet,���hot spells.��� Post-marketing Experience: Data collected from post-marketing use of naltrexone show that most events usually occur early in the course of drug therapy and are transient. It is not always possible to distinguish these occurrences from those signs and symptoms that may result from a withdrawal syndrome. Events that have been reported include anorexia, asthenia, chest pain, fatigue, headache, hot flashes, malaise, changes in blood pressure, agitation, dizziness, hyperkinesia, nausea, vomiting, tremor, abdominal pain, diarrhea, elevations in liver enzymes or bilirubin, hepatic function abnormalities or hepatitis, palpitations, myalgia, anxiety, confusion, euphoria, hallucinations, insomnia, nervousness, somnolence, abnormal thinking, dyspnea, rash, increased sweating, and vision abnormalities. Depression, suicide, attempted suicide and suicidal ideation have been reported in the post-marketing experience with naltrexone used in the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. In some individuals the use of opioid antagonists has been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones. The clinical significance of such changes is not fully understood. Adverse events, including withdrawal symptoms and death, have been reported with the use of naltrexone in ultra rapid opiate detoxification programs. The cause of death in these cases is not known . Laboratory Tests: With the exception of liver test abnormalities , results of laboratory tests, like adverse reaction reports, have not shown consistent patterns of abnormalities that can be attributed to treatment with naltrexone. Idiopathic thrombocytopenic purpura was reported in one patient who may have been sensitized to naltrexone in a previous course of treatment with naltrexone. The condition cleared without sequelae after discontinuation of naltrexone and corticosteroid treatment.
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| dailymed-drugs:123 |
Overview: Dexrazoxane has been studied previously as a cytotoxic agent. Adverse reactions of nausea/vomiting, diarrhea, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), altered liver function (increased AST/ALT), and infusion site burning have been observed. These adverse reactions have been reversible.<br/>Discussion of Adverse Reaction Information: Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice. In the two clinical studies, Totect���was administered to patients also receiving chemotherapeutic agents for cancer, and the adverse reaction profile reflects the combination of Totect���, underlying disease, and chemotherapy. The adverse reaction data reflect exposure to Totect���in 80 patients who received the first dose, 72 patients who received two doses, and 69 patients who received all three doses. Table 1 summarizes adverse reaction occurring with���5% frequency. Neutropenia and febrile neutropenia each occurred in 2.5% of patients. Table 2 summarizes laboratory adverse reactions from studies 1 and 2 combined.
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Cefuroxime is generally well tolerated. The most common adverse effects have been local reactions following IV administration. Other adverse reactions have been encountered only rarely.<br/>Local Reactions: Thrombophlebitis has occurred with IV administration in 1 in 60 patients.<br/>Gastrointestinal: Gastrointestinal symptoms occurred in 1 in 150 patients and included diarrhea (1 in 220 patients) and nausea (1 in 440 patients). The onset of pseudomembranous colitis may occur during or after antibacterial treatment .<br/>Hypersensitivity Reactions: Hypersensitivity reactions have been reported in fewer than 1% of the patients treated with cefuroxime and include rash (1 in 125). Pruritus, urticaria, and positive Coombs' test each occurred in fewer than 1 in 250 patients, and, as with other cephalosporins, rare cases of anaphylaxis, drug fever, erythema multiforme, interstitial nephritis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have occurred.<br/>Blood: A decrease in hemoglobin and hematocrit has been observed in 1 in 10 patients and transient eosinophilia in 1 in 14 patients. Less common reactions seen were transient neutropenia (fewer than 1 in 100 patients) and leukopenia (1 in 750 patients). A similar pattern and incidence were seen with other cephalosporins used in controlled studies. As with other cephalosporins, there have been rare reports of thrombocytopenia.<br/>Hepatic: Transient rise in SGOT and SGPT (1 in 25 patients), alkaline phosphatase (1 in 50 patients), LDH (1 in 75 patients), and bilirubin (1 in 500 patients) levels has been noted.<br/>Kidney: Elevations in serum creatinine and/or blood urea nitrogen and a decreased creatinine clearance have been observed, but their relationship to cefuroxime is unknown.<br/>Postmarketing Experience with Cefuroxime: In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with cefuroxime and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation.<br/>Cephalosporin-class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with cefuroxime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:<br/>Adverse Reactions: Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, and hemorrhage. Several cephalosporins, including cefuroxime, have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced . If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.<br/>Altered Laboratory Tests: Prolonged prothrombin time, pancytopenia, agranulocytosis.
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The following adverse effects, listed by organ system in decreasing frequency have been associated with the use of DUO-MEDIHALER and are similar to those produced by other sympathomimetic agents:
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Most adverse reactions to benzodiazepines, including CNS effects and respiratory depression, are dose dependent, with more severe effects occurring with high doses. In a sample of about 3500 patients treated for anxiety, the most frequent adverse reaction to Ativan (lorazepam) was sedation (15.9%), followed by dizziness (6.9%),
weakness (4.2%), and unsteadiness (3.4%). The incidence of sedation and unsteadiness
increased with age. Other adverse reactions to benzodiazepines, including lorazepam are fatigue, drowsiness, amnesia, memory impairment, confusion, disorientation, depression, unmasking of depression, disinhibition, euphoria, suicidal ideation/attempt, ataxia, asthenia, extrapyramidal symptoms, convulsions/seizures tremor, vertigo, eye-function/visual disturbance (including diplopia and blurred vision), dysarthria/slurred speech, change in libido, impotence, decreased orgasm; headache, coma; respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease; gastrointestinal symptoms including nausea, change in appetite, constipation, jaundice, increase in bilirubin, increase inliver transaminases, increase in alkaline phosphatase; hypersensitivity reactions, anaphylactic/oid reactions; dermatological symptoms, allergic skin reactions, alopecia; SIADH, hyponatremia; thrombocytopenia, agranulocytosis, pancytopenia; hypothermia; and autonomic manifestations. Paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. Small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by Ativan (lorazepam).
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During clinical trials 45 (5%) of 905 patients treated with ketoconazole cream, 2% and 5 (2.4%) of 208 patients treated with placebo reported side effects consisting mainly of severe irritation, pruritus and stinging. One of the patients treated with ketoconazole cream developed a painful allergic reaction. In worldwide postmarketing experience, rare reports of contact dermatitis have been associated with ketoconazole cream or one of its excipients, namely sodium sulfite or propylene glycol.
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Most adverse reactions have been mild. The incidences listed in the following table are derived from 12-week comparative double-blind, parallel design trials in hypertensive patients given Visken (pindolol) as monotherapy, given various active control drugs as monotherapy, or given placebo. Data for Visken (pindolol) and the positive controls were pooled from several trials because no striking differences were seen in the individual studies, with 1 exception. When considering all adverse reactions reported, the frequency of edema was noticeably higher in positive control trials [16% Visken (pindolol) vs. 9% positive control] than in placebo controlled trials[6%Visken (pindolol) vs. 3% placebo]. The table includes adverse reactions either volunteered or elicited, and at least possibly drug related, which were reported in greater than 2% of Visken (pindolol) patients and other selected important reactions. Active Controls: Patients received either propranolol,��-methyldopa or a diuretic (hydrochlorothiazide or chlorthalidone). The following selected (potentially important) adverse reactions were seen in 2% or fewer patients and their relationship to Visken (pindolol) is uncertain. CENTRAL NERVOUS SYSTEM: anxiety, lethargy; AUTONOMIC NERVOUS SYSTEM: visual disturbances, hyperhidrosis; CARDIOVASCULAR: bradycardia, claudication, cold extremities, heart block, hypotension, syncope, tachycardia, weight gain; GASTROINTESTINAL: diarrhea, vomiting; RESPIRATORY: wheezing; UROGENITAL: impotence, pollakiuria; MISCELLANEOUS: eye discomfort or burning eyes.
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The following have been reported as events in
clinical trials or in the routine management of patients treated with
ZANTAC. The relationship to therapy with ZANTAC has been unclear in
many cases. Headache, sometimes severe, seems to be related to administration
of ZANTAC.<br/>Central Nervous System: Rarely, malaise, dizziness, somnolence, insomnia,
and vertigo. Rare cases of reversible mental confusion, agitation,
depression, and hallucinations have been reported, predominantly in
severely ill elderly patients. Rare cases of reversible blurred vision
suggestive of a change in accommodation have been reported. Rare reports
of reversible involuntary motor disturbances have been received.<br/>Cardiovascular: As with other H-blockers, rare reports
of arrhythmias such as tachycardia, bradycardia, atrioventricular
block, and premature ventricular beats.<br/>Gastrointestinal: Constipation, diarrhea, nausea/vomiting, abdominal
discomfort/pain, and rare reports of pancreatitis.<br/>Hepatic: There have been occasional reports of hepatocellular,
cholestatic, or mixed hepatitis, with or without jaundice. In such
circumstances, ranitidine should be immediately discontinued. These
events are usually reversible, but in rare circumstances death has
occurred. Rare cases of hepatic failure have also been reported. In
normal volunteers, SGPT values were increased to at least twice the
pretreatment levels in 6 of 12 subjects receiving 100 mg
q.i.d. intravenously for 7 days, and in 4 of 24 subjects
receiving 50 mg q.i.d. intravenously for 5 days.<br/>Musculoskeletal: Rare reports of arthralgias and myalgias.<br/>Hematologic: Blood count changes (leukopenia, granulocytopenia,
and thrombocytopenia) have occurred in a few patients. These were
usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes
with marrow hypoplasia, and aplastic anemia and exceedingly rare cases
of acquired immune hemolytic anemia have been reported.<br/>Endocrine: Controlled studies in animals and man have shown
no stimulation of any pituitary hormone by ZANTAC and no antiandrogenic
activity, and cimetidine-induced gynecomastia and impotence in hypersecretory
patients have resolved when ZANTAC has been substituted. However,
occasional cases of gynecomastia, impotence, and loss of libido have
been reported in male patients receiving ZANTAC, but the incidence
did not differ from that in the general population.<br/>Integumentary: Rash, including rare cases of erythema multiforme.
Rare cases of alopecia and vasculitis.<br/>Respiratory: A large epidemiological study suggested an increased
risk of developing pneumonia in current users of histamine-2���receptor
antagonists (HRAs) compared to patients who had stopped
HRA treatment, with an observed adjusted relative risk
of 1.63 (95% CI, 1.07���2.48). However, a causal relationship
between use of HRAs and pneumonia has not been established.<br/>Other: Rare cases of hypersensitivity reactions (e.g.,
bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic
edema, acute interstitial nephritis, and small increases in serum
creatinine.
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Worldwide, more than 11,100
patients have been treated with pantoprazole in clinical trials involving
various dosages and duration of treatment. In general, pantoprazole
has been well tolerated in both short-term and long-term trials. The adverse reaction profile for PROTONIX (pantoprazole sodium) For Delayed-Release Oral Suspension is similar
to the established safety profile of PROTONIX (pantoprazole
sodium) Delayed-Release Tablets. In two U.S. controlled clinical trials involving PROTONIX 10-, 20-, or
40-mg doses for up to 8 weeks, there were no dose-related effects
on the incidence of adverse events. The following adverse events considered
by investigators to be possibly, probably, or definitely related to
drug occurred in 1% or more in the individual studies of GERD patients
on therapy with PROTONIX. Note: Only adverse events
with an incidence greater than or equal to the comparators are shown. In international short-term,
double-blind or open-label clinical trials involving 20 mg to 80 mg
per day, the following adverse events were reported to occur
in 1% or more of 2805 GERD patients receiving pantoprazole for
up to 8 weeks. In two U.S. controlled clinical trials involving
PROTONIX 10-, 20-, or 40-mg doses for up to 12 months,
the following adverse events considered by investigators to be possibly,
probably, or definitely related to drug occurred in 1% or more of
GERD patients on long-term therapy. In addition, in these short- and long-term domestic
and international trials, the following treatment-emergent events,
regardless of causality, occurred at a rate of���1% in pantoprazole-treated
patients: anxiety, arthralgia, asthenia, back pain, bronchitis, chest
pain, constipation, cough increased, dizziness, dyspepsia, dyspnea,
flu syndrome, gastroenteritis, gastrointestinal disorder, hyperlipemia,
hypertonia, infection, liver function tests abnormal, migraine, nausea,
neck pain, pain, pharyngitis, rectal disorder, rhinitis, SGPT increased,
sinusitis, upper respiratory tract infection, urinary frequency, urinary
tract infection, and vomiting. Additional treatment-emergent adverse experiences occurring in<1% of pantoprazole-treated patients from these trials are listed below
by body system. In most instances the relationship to pantoprazole
was unclear. BODY
AS A WHOLE: abscess, allergic reaction, chills, cyst, face edema,
fever, generalized edema, heat stroke, hernia, laboratory test abnormal,
malaise, moniliasis, neoplasm, non-specified drug reaction, photosensitivity
reaction. CARDIOVASCULAR
SYSTEM: abnormal electrocardiogram, angina pectoris, arrhythmia, atrial
fibrillation/flutter, cardiovascular disorder, chest pain substernal,
congestive heart failure, hemorrhage, hypertension, hypotension, myocardial
infarction, myocardial ischemia, palpitation, retinal vascular disorder,
syncope, tachycardia, thrombophlebitis, thrombosis, vasodilatation. DIGESTIVE SYSTEM: anorexia, aphthous
stomatitis, cardiospasm, colitis, dry mouth, duodenitis, dysphagia,
enteritis, esophageal hemorrhage, esophagitis, gastrointestinal carcinoma,
gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis,
glossitis, halitosis, hematemesis, increased appetite, melena, mouth
ulceration, oral moniliasis, periodontal abscess, periodontitis, rectal
hemorrhage, stomach ulcer, stomatitis, stools abnormal, tongue discoloration,
ulcerative colitis. ENDOCRINE SYSTEM: diabetes mellitus, glycosuria, goiter. HEPATO-BILIARY SYSTEM: biliary
pain, hyperbilirubinemia, cholecystitis, cholelithiasis, cholestatic
jaundice, hepatitis, alkaline phosphatase increased, gamma glutamyl
transpeptidase increased, SGOT increased. HEMIC AND LYMPHATIC SYSTEM: anemia, ecchymosis, eosinophilia, hypochromic
anemia, iron deficiency anemia, leukocytosis, leukopenia, thrombocytopenia. METABOLIC AND NUTRITIONAL: dehydration,
edema, gout, peripheral edema, thirst, weight gain, weight loss. MUSCULOSKELETAL SYSTEM: arthritis,
arthrosis, bone disorder, bone pain, bursitis, joint disorder, leg
cramps, neck rigidity, myalgia, tenosynovitis. NERVOUS SYSTEM: abnormal dreams, confusion, convulsion, depression,
dry mouth, dysarthria, emotional lability, hallucinations, hyperkinesia,
hypesthesia, libido decreased, nervousness, neuralgia, neuritis, neuropathy,
paresthesia, reflexes decreased, sleep disorder, somnolence, thinking
abnormal, tremor, vertigo. RESPIRATORY SYSTEM: asthma, epistaxis, hiccup, laryngitis, lung disorder,
pneumonia, voice alteration. SKIN AND APPENDAGES: acne, alopecia, contact dermatitis, dry skin,
eczema, fungal dermatitis, hemorrhage, herpes simplex, herpes zoster,
lichenoid dermatitis, maculopapular rash, pruritus, skin disorder,
skin ulcer, sweating, urticaria. SPECIAL SENSES: abnormal vision, amblyopia, cataract specified, deafness,
diplopia, ear pain, extraocular palsy, glaucoma, otitis externa, taste
perversion, tinnitus. UROGENITAL SYSTEM: albuminuria, balanitis, breast pain, cystitis,
dysmenorrhea, dysuria, epididymitis, hematuria, impotence, kidney
calculus, kidney pain, nocturia, prostatic disorder, pyelonephritis,
scrotal edema, urethral pain, urethritis, urinary tract disorder,
urination impaired, vaginitis. In an open-label US clinical trial conducted in 35 patients with
pathological hypersecretory conditions treated with PROTONIX for up
to 27 months, the adverse events reported were consistent with the
safety profile of the drug in other populations.<br/>Postmarketing Reports: There have been
spontaneous reports of adverse events with the postmarketing use of
pantoprazole. These reports include the following: BODY AS A WHOLE: anaphylaxis (including anaphylactic shock), angioedema
(Quincke's edema). DIGESTIVE SYSTEM: increased salivation, nausea, pancreatitis. HEMIC AND LYMPHATIC SYSTEM:
pancytopenia. HEPATO-BILIARY SYSTEM: hepatocellular damage leading to jaundice
and hepatic failure. MUSCULOSKELETAL SYSTEM: elevated CPK (creatine phosphokinase), rhabdomyolysis. NERVOUS SYSTEM: confusion,
hypokinesia, speech disorder, vertigo. SKIN AND APPENDAGES: severe dermatologic reactions, including erythema
multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis
(TEN, some fatal). SPECIAL SENSES: anterior ischemic optic neuropathy, blurred vision,
tinnitus. UROGENITAL SYSTEM: interstitial nephritis.<br/>Laboratory Values: In two U.S. controlled,
short-term trials in patients with erosive esophagitis associated
with GERD, 0.4% of the patients on PROTONIX 40 mg experienced
SGPT elevations of greater than three times the upper limit of normal
at the final treatment visit. In two U.S. controlled, long-term trials
in patients with erosive esophagitis associated with GERD, none of
178 patients (0%) on PROTONIX 40 mg and two of 181 patients (1.1%)
on PROTONIX 20 mg experienced significant transaminase elevations
at 12 months (or earlier if a patient discontinued prematurely). Significant
elevations of SGOT or SGPT were defined as values at least three times
the upper limit of normal that were non-sporadic and had no clear
alternative explanation. The following changes in laboratory parameters
were reported as adverse events: creatinine increased, hypercholesterolemia,
and hyperuricemia.
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The information included in the subsection on Adverse Events Observed in Short-Term, Placebo-Controlled Trials with alprazolam extended-release tablets is based on pooled data of five 6- and 8-week placebo-controlled clinical studies in panic disorder. Adverse event reports were elicited either by general inquiry or by checklist, and were recorded by clinical investigators using terminology of their own choosing. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened during therapy following baseline evaluation. In the tables and tabulations that follow, standard MedDRA terminology (version 4.0) was used to classify reported adverse events.<br/>Adverse Events Observed in Short-Term, Placebo-Controlled Trials of Alprazolam Extended-Release Tablets:<br/>Adverse Events Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials: Approximately 17% of the 531 patients who received alprazolam extended-release tablets in placebo-controlled clinical trials for panic disorder had at least one adverse event that led to discontinuation compared to 8% of 349 placebo-treated patients. The most common events leading to discontinuation and considered to be drug-related (i.e., leading to discontinuation in at least 1% of the patients treated with alprazolam extended-release tablets at a rate at leasttwice that of placebo) are shown in the following table.<br/>Adverse Events Occurring at an Incidence of 1% or More among Patients Treated with Alprazolam Extended-Release Tablets: The prescriber should be aware that adverse event incidence cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with event incidence obtained from other clinical investigations involving different treatments, uses, and investigators. The cited values, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The following table shows the incidence of treatment-emergent adverse events that occurred during 6- to 8-week placebo-controlled trials in 1% or more of patients treated with alprazolam extended-release tablets where the incidence in patients treated with alprazolam extended-release tablets was greater than the incidence in placebo-treated patients. The most commonly observed adverse events in panic disorder patients treated with alprazolam extended-release tablets (incidence of 5% or greater and at least twice the incidence in placebo patients) were: sedation, somnolence, memory impairment, dysarthria, coordination abnormal, ataxia, libido decreased (see table).<br/>Other Adverse Events Observed during the Pre-marketing Evaluation of Alprazolam Extended-Release Tablets: Following is a list of MedDRA terms that reflect treatment-emergent adverse events reported by 531 patients with panic disorder treated with alprazolam extended-release tablets. All potentially important reported events are included except those already listed in the above table or elsewhere in labeling, those events for which a drug cause was remote, those event terms that were so general as to be uninformative, and those events that occurred at rates similar to background rates in the general population. It is important to emphasize that, although the events reported occurred during treatment with alprazolam extended-release tablets, they were not necessarily caused by the drug. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least l/l00 patients; infrequent adverse events are those occurring in less than l/100 patients but at least l/1000 patients; rare events are those occurring in fewer than l/1000 patients.<br/>Cardiac disorders: Frequent: palpitation; Infrequent: sinus tachycardia<br/>Ear and Labyrinth disorders: Frequent: Vertigo; Infrequent: tinnitus, ear pain<br/>Eye disorders: Frequent: blurred vision; Infrequent: mydriasis, photophobia<br/>Gastrointestinal disorders: Frequent: diarrhea, vomiting, dyspepsia, abdominal pain; Infrequent: dysphagia, salivary hypersecretion<br/>General disorders and administration site conditions: Frequent: malaise, weakness, chest pains; Infrequent: fall, pyrexia, thirst, feeling hot and cold, edema, feeling jittery, sluggishness, asthenia, feeling drunk, chest tightness, increased energy, feeling of relaxation, hangover, loss of control of legs, rigors<br/>Musculoskeletal and connective tissue disorders: Frequent: back pain, muscle cramps, muscle twitching<br/>Nervous system disorders: Frequent: headache, dizziness, tremor; Infrequent: amnesia, clumsiness, syncope, hypotonia, seizures, depressed level of consciousness, sleep apnea syndrome, sleep talking, stupor<br/>Psychiatric system disorders: Frequent: irritability, insomnia, nervousness, derealization, libido increased, restlessness, agitation, depersonalization, nightmare; Infrequent: abnormal dreams, apathy, aggression, anger, bradyphrenia, euphoric mood, logorrhea, mood swings, dysphonia, hallucination, homicidal ideation, mania, hypomania, impulse control, psychomotor retardation, suicidal ideation<br/>Renal and urinary disorders: Frequent: difficulty in micturition; Infrequent: urinary frequency, urinary incontinence<br/>Respiratory, thoracic, and mediastinal disorders: Frequent: nasal congestion, hyperventilation; Infrequent: choking sensation, epistaxis, rhinorrhea<br/>Skin and subcutaneous tissue disorders: Frequent: sweating increased; Infrequent: clamminess, rash, urticaria<br/>Vascular disorders: Infrequent: hypotension The categories of adverse events reported in the clinical development program for alprazolam tablets in the treatment of panic disorder differ somewhat from those reported for alprazolam extended-release tablets because the clinical trials with alprazolam tablets and alprazolam extended-release tablets used different standard medical nomenclature for reporting the adverse events. Nevertheless, the types of adverse events reported in the clinical trials with alprazolam tablets were generally the same as those reported in the clinical trials with alprazolam extended-release tablets.<br/>Discontinuation-Emergent Adverse Events Occurring at an Incidence of 5% or More among Patients Treated with Alprazolam Extended-Release Tablets: The following table shows the incidence of discontinuation-emergent adverse events that occurred during short-term, placebo-controlled trials in 5% or more of patients treated with alprazolam extended-release tablets where the incidence in patients treated with alprazolam extended-release tablets was two times greater than the incidence in placebo-treated patients. There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam . To discontinue treatment in patients taking alprazolam extended-release tablets, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam extended-release tablets be decreased by no more than 0.5 mg every three days . Some patients may benefit from an even slower dosage reduction. In a controlled post-marketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. As with all benzodiazepines, paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations, and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with posttraumatic stress disorder.<br/>Post Introduction Reports: Various adverse drug reactions have been reported in association with the use of alprazolam tablets since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of alprazolam tablets cannot be readily determined. Reported events include: liver enzyme elevations, hepatitis, hepatic failure, Stevens-Johnson syndrome, hyperprolactinemia, gynecomastia, and galactorrhea.
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Associated With Discontinuation of Treatment: Twenty percent (1,199/6,145) of patients treated with paroxetine in worldwide clinical trials in major depressive disorder and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), and 10.7% (79/735) of patients treated with paroxetine in worldwide trials in social anxiety disorder, OCD, panic disorder, and GAD respectively, discontinued treatment due to an adverse event. The most common events (���1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) included the following: Where numbers are not provided the
incidence of the adverse events in patients treated with paroxetine was not>1%
or was not greater than or equal to 2 times the incidence of placebo. 1. Incidence corrected for gender.<br/>Commonly Observed Adverse Events:<br/>Major Depressive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 2) were: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.<br/>Obsessive Compulsive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that of placebo, derived from Table 3) were: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.<br/>Panic Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 3) were: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.<br/>Social Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 3) were: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.<br/>Generalized Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for paroxetine at least twice that for placebo, derived from Table 4) were: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.<br/>Incidence in Controlled Clinical Trials: The prescriber should be aware that the figures in the tables
following cannot be used to predict the incidence of side effects in the course
of usual medical practice where patient characteristics and other factors
differ from those that prevailed in the clinical trials. Similarly, the cited
frequencies cannot be compared with figures obtained from other clinical investigations
involving different treatments, uses, and investigators. The cited figures,
however, do provide the prescribing physician with some basis for estimating
the relative contribution of drug and nondrug factors to the side effect incidence
rate in the populations studied.<br/>Major Depressive Disorder: Table 2 enumerates adverse events that occurred at an incidence of 1% or more among paroxetine-treated patients who participated in short-term (6-week) placebo-controlled trials in which patients were dosed in a range of 20 mg to 50 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology. 1. Events reported by at least 1% of patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine: Abdominal pain, agitation, back pain, chest pain, CNS stimulation, fever, increased appetite, myoclonus, pharyngitis, postural hypotension, respiratory disorder (includes mostly���cold symptoms���or���URI���), trauma, and vomiting. 2. Includes
mostly���lump in throat���and���tightness in throat.��� 3. Percentage corrected for gender. 4. Mostly���ejaculatory delay.��� 5. Includes���anorgasmia,������erectile difficulties,������delayed ejaculation/orgasm,���and���sexual dysfunction,���and���impotence.��� 6. Includes mostly���difficulty with micturition���and���urinary hesitancy.��� 7. Includes mostly���anorgasmia���and���difficulty reaching climax/orgasm.���<br/>Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Table 3 enumerates adverse events that occurred at a frequency of 2% or more among OCD patients on paroxetine who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 60 mg/day or among patients with panic disorder on paroxetine who participated in placebo-controlled trials of 10- to 12-weeks duration in which patients were dosed in a range of 10 mg to 60 mg/day or among patients with social anxiety disorder on paroxetine who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 50 mg/day. 1. Events reported by at least 2% of OCD, panic disorder, and social anxiety disorder in patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine: [OCD]: Abdominal pain, agitation, anxiety, back pain, cough increased, depression, headache, hyperkinesia, infection, paresthesia, pharyngitis, respiratory disorder, rhinitis, and sinusitis. [panic disorder]: Abnormal dreams, abnormal vision, chest pain, cough increased, depersonalization, depression, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, myalgia, nervousness, palpitation, paresthesia, pharyngitis, rash, respiratory disorder, sinusitis, taste perversion, trauma, urination impaired, and vasodilation. [social anxiety disorder]: Abdominal pain, depression, headache, infection, respiratory disorder, and sinusitis. 2.
Percentage corrected for gender.<br/>Generalized Anxiety Disorder: Table 4 enumerates adverse events that occurred at a frequency of 2% or more among GAD patients on paroxetine who participated in placebo-controlled trials of 8-weeks duration in which patients were dosed in a range of 10 mg/day to 50 mg/day. 1. Events reported by at least 2% of GAD in patients treated with paroxetine are included, except the following events which had an incidence on placebo���paroxetine [GAD]: Abdominal pain, back pain, trauma, dyspepsia, myalgia, and pharyngitis. 2. Percentage corrected
for gender.<br/>Dose Dependency of Adverse Events: A comparison of adverse event rates in a fixed-dose study comparing 10, 20, 30, and 40 mg/day of paroxetine with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of paroxetine, as shown in the following table: Rule for including adverse
events in table: Incidence at least 5% for 1 of paroxetine groups and���twice the placebo incidence for at least 1 paroxetine group. In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine in the treatment of OCD, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned. No new adverse events were observed in the group treated with 60 mg paroxetine compared to any of the other treatment groups. In a fixed-dose study comparing placebo and 10, 20, and 40 mg of paroxetine in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse events were observed in patients receiving 60 mg of paroxetine compared to any of the other treatment groups. In a fixed-dose study comparing placebo and 20, 40, and 60 mg of paroxetine in the treatment of social anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned. In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine in the treatment of generalized anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of paroxetine to which patients were assigned, except for the following adverse events: Asthenia, constipation, and abnormal ejaculation.<br/>Adaptation to Certain Adverse Events: Over a 4- to 6-week period, there was evidence of adaptation
to some adverse events with continued therapy (e.g., nausea and dizziness),
but less to other effects (e.g., dry mouth, somnolence, and asthenia).<br/>Male and Female Sexual Dysfunction With SSRIs: Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. In placebo-controlled clinical trials involving more than 3,200 patients, the ranges for the reported incidence of sexual side effects in males and females with major depressive disorder, OCD, panic disorder, social anxiety disorder, and GAD are displayed in Table 6. There are no adequate and well-controlled studies examining
sexual dysfunction with paroxetine treatment. Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. While
it is difficult to know the precise risk of sexual dysfunction associated
with the use of SSRIs, physicians should routinely inquire about such possible
side effects.<br/>Weight and Vital Sign Changes: Significant weight loss may be an undesirable result of
treatment with paroxetine for some patients but, on average, patients in controlled
trials had minimal (about 1 pound) weight loss versus smaller changes on placebo
and active control. No significant changes in vital signs (systolic and diastolic
blood pressure, pulse and temperature) were observed in patients treated with
paroxetine in controlled clinical trials.<br/>ECG Changes: In an analysis of ECGs obtained in 682 patients treated
with paroxetine and 415 patients treated with placebo in controlled clinical trials,
no clinically significant changes were seen in the ECGs of either group.<br/>Liver Function Tests: In placebo-controlled clinical trials, patients treated
with paroxetine exhibited abnormal values on liver function tests at no greater
rate than that seen in placebo-treated patients. In particular, the paroxetine-versus-placebo
comparisons for alkaline phosphatase, SGOT, SGPT, and bilirubin revealed no
differences in the percentage of patients with marked abnormalities.<br/>Hallucinations: In pooled clinical trials of immediate-release paroxetine
hydrochloride, hallucinations were observed in 22 of 9089 patients receiving
drug and 4 of 3187 patients receiving placebo.<br/>Other Events Observed During the Premarketing Evaluation of Paroxetine: During its premarketing assessment in major depressive disorder, multiple doses of paroxetine were administered to 6,145 patients in phase 2 and 3 studies. The conditions and duration of exposure to paroxetine varied greatly and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, and fixed-dose, and titration studies. During premarketing clinical trials in OCD, panic disorder, social anxiety disorder, and generalized anxiety disorder, 542, 469, 522, and 735 patients, respectively, received multiple doses of paroxetine. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, reported adverse events were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 9,089 patients exposed to multiple doses of paroxetine who experienced an event of the type cited on at least 1 occasion while receiving paroxetine. All reported events are included except those already listed in Tables 2 to 4, those reported in terms so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that although the events reported occurred during treatment with paroxetine, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are also described in the PRECAUTIONS section.<br/>Body as a Whole: Infrequent: Allergic reaction, chills, face edema, malaise, neck pain; rare: Adrenergic syndrome, cellulitis, moniliasis,
neck rigidity, pelvic pain, peritonitis, sepsis, ulcer.<br/>Cardiovascular System: Frequent: Hypertension,
tachycardia; infrequent: Bradycardia,
hematoma, hypotension, migraine, syncope; rare: Angina pectoris, arrhythmia nodal, atrial fibrillation, bundle
branch block, cerebral ischemia, cerebrovascular accident, congestive heart
failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia,
pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis,
thrombosis, varicose vein, vascular headache, ventricular extrasystoles.<br/>Digestive System: Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis, gastroenteritis, gingivitis, glossitis, increased salivation, liver function tests abnormal, rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis,esophagitis, fecal impactions, fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries.<br/>Endocrine System: Rare: Diabetes mellitus,
goiter, hyperthyroidism, hypothyroidism, thyroiditis.<br/>Hemic and Lymphatic Systems: Infrequent: Anemia,
leukopenia, lymphadenopathy, purpura; rare: Abnormal
erythrocytes, basophilia, bleeding time increased, eosinophilia, hypochromic
anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes,
lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia,
thrombocytopenia.<br/>Metabolic and Nutritional: Frequent: Weight
gain; infrequent: Edema, peripheral
edema, SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphatase increased, bilirubinemia, BUN increased,
creatinine phosphokinase increased, dehydration, gamma globulins increased,
gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia,
hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, lactic dehydrogenase
increased, non-protein nitrogen (NPN) increased.<br/>Musculoskeletal System: Frequent: Arthralgia; infrequent: Arthritis, arthrosis; rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis,
tetany.<br/>Nervous System: Frequent: Emotional
lability, vertigo; infrequent: Abnormal
thinking, alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hallucinations,
hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion,
libido increased, manic reaction, neurosis, paralysis, paranoid reaction; rare: Abnormal gait, akinesia, antisocial reaction,
aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions,
diplopia, drug dependence, dysarthria, extrapyramidal syndrome, fasciculations,
grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis,
myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic
depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis,
trismus, withdrawal syndrome.<br/>Respiratory System: Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration.<br/>Skin and Appendages: Frequent: Pruritus; infrequent: Acne,
alopecia, contact dermatitis, dry skin, ecchymosis, eczema, herpes simplex,
photosensitivity, urticaria; rare: Angioedema,
erythema nodosum, erythema multiforme, exfoliative dermatitis, fungal dermatitis,
furunculosis; herpes zoster, hirsutism, maculopapular rash, seborrhea, skin
discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous
rash.<br/>Special Senses: Frequent: Tinnitus; infrequent: Abnormality of accommodation, conjunctivitis,
ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media; rare: Amblyopia, anisocoria, blepharitis, cataract,
conjunctival edema, corneal ulcer, deafness, exophthalmos, eye hemorrhage,
glaucoma, hyperacusis, night blindness, otitis externa, parosmia, photophobia,
ptosis, retinal hemorrhage, taste loss, visual field defect.<br/>Urogenital System: Infrequent: Amenorrhea,
breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polyuria,
pyuria, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement,
endometrial disorder, epididymitis, female lactation, fibrocystic breast,
kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis,
oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith,
vaginal hemorrhage, vaginal moniliasis.<br/>Postmarketing Reports: Voluntary reports of adverse events in patients taking paroxetine
that have been received since market introduction and not listed above that
may have no causal relationship with the drug include acute pancreatitis,
elevated liver function tests (the most severe cases were deaths due to liver
necrosis, and grossly elevated transaminases associated with severe liverdysfunction), Guillain-Barr��syndrome, toxic epidermal necrolysis, priapism,
syndrome of inappropriate ADH secretion, symptoms suggestive of prolactinemia
and galactorrhea, neuroleptic malignant syndrome���like events, serotonin
syndrome; extrapyramidal symptoms which have included akathisia, bradykinesia,
cogwheel rigidity, dystonia, hypertonia, oculogyric crisis which has been
associated with concomitant use of pimozide; tremor and trismus; status epilepticus,
acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis,
eclampsia, laryngismus, optic neuritis, porphyria, ventricular fibrillation,
ventricular tachycardia (including torsade de pointes), thrombocytopenia,
hemolytic anemia, events related to impaired hematopoiesis (including aplastic
anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic
syndromes (such as Henoch-Sch��nlein purpura). There has been a case report
of an elevated phenytoin level after 4 weeks of paroxetine and phenytoin coadministration.
There has been a case report of severe hypotension when paroxetine was added to
chronic metoprolol treatment.
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See WARNING box.<br/>Nephrotoxic reactions:: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage.<br/>Neurotoxic reactions:: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias (circumoral and stocking glove), apnea due to concurrent use of curariform muscle relaxants, other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal administration, e.g., fever, headache, stiff neck and increased cell count and protein cerebrospinal fluid.<br/>Other reactions occasionally reported:: Drug fever, urticarial rash, pain (severe) at intramuscular injection sites, and thrombophlebitis at intravenous injection sites.
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Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See
DOSAGE AND ADMINISTRATION
.) The physician should also be alert to the possibility of adverse reactions to drug additives. Prescribing information for drug additives to be administered in this manner should be consulted. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
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Central Nervous System: The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants. Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as Benztropine Mesylate or Intravenous Caffeine and Sodium Benzoate Injection, and by subsequent reduction in dosage.<br/>Tardive Dyskinesia: See WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely. The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.<br/>Other CNS Effects: Occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS, Neuroleptic Malignant Syndrome); leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS. Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered. Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.<br/>Autonomic Nervous System: Hypertension and fluctuation in blood pressure have been reported with fluphenazine hydrochloride. Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Levarterenol Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure. Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage. In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.<br/>Metabolic and Endocrine: Weight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results of pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.<br/>Allergic Reactions: Skin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.<br/>Hematologic: Routine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.<br/>Hepatic: Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, have been reported in patients receiving fluphenazine hydrochloride who havehad no clinical evidence of liver damage.<br/>Others: Sudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions. Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur. The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use - skin pigmentation, and lenticular and corneal opacities.
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Clinical Trials: There were 3272 patients treated with multiple doses of cefaclor extended-release tablets in controlled clinical trials and an additional 211 subjects in pharmacology studies. There were no deaths in these trials thought to be related to toxicity from cefaclor extended-release tablets. Treatment was discontinued in 1.7% of patients due to adverse events thought to be possibly or probably drug-related. The following adverse clinical and laboratory events were reported during the cefaclor extended-release tablets clinical trials conducted in North America at doses of 375 mg or 500 mg BID; however, relatedness of the adverse events to the drug was not assigned by clinical investigators during the trials (see Tables 2 and 3). Adverse reactions occurring during the clinical trials with cefaclor extended-release tablets with an incidence of less than 1% but greater than 0.1% included the following (listed alphabetically): Accidental injury, anorexia, anxiety, arthralgia, asthma, bronchitis, chest pain, chills, congestive heart failure, conjunctivitis, constipation, dizziness, dysmenorrhea, dyspepsia, dysuria, ear pain, edema, fever, flatulence, flu syndrome, gastritis, infection, insomnia, leukorrhea, lung disorder, maculopapular rash, malaise, menstrual disorder, myalgia, nausea and vomiting, neck pain, nervousness, nocturia, otitis media, pain, palpitation, peripheral edema, rash, respiratory disorder, sinusitis, somnolence, surgical procedure, sweating, tremor, urticaria, vomiting. NOTE: One case of serum-sickness-like reaction was reported among the 3272 adult patients treated with cefaclor extended-release tablets during the controlled clinical trials. These reactions have also been reported with the use of cefaclor in other oral formulations and are seen more frequently in pediatric patients than in adults. These reactions are characterized by findings of erythema multiforme, rash, and other skin manifestations accompanied by arthritis/arthralgia, with or without fever, and differ from classic serum sickness in that there is infrequently associated lymphadenopathy and proteinuria, no circulating immune complexes and no evidence to date of sequelae of the reaction. While further investigation is ongoing, serum-sickness-like reactions appear tobe due to hypersensitivity and more often occur during or following a second (or subsequent) course of therapy with cefaclor. Such reactions have been reported with overall occurrence ranging from 1 in 200 (0.5%) in one focused trial; to 2 in 8346 (0.024%) in overall clinical trials (with an incidence in pediatric patients in clinical trials of 0.055%); to 1 in 38,000 (0.003%) in spontaneous event reports. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy. Occasionally these reactions have resulted in hospitalization, usually of short duration (median hospitalization = 2 to 3 days, based on postmarketing surveillance studies). In those patients requiring hospitalization, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in pediatric patients.<br/>In Postmarketing Experience: In addition to the events reported during clinical trials with cefaclor extended-release tablets, the following adverse experiences are among those that have been reported during worldwide postmarketing surveillance: allergic reaction, anaphylactoid reaction, angioedema, face edema, hypotension, Stevens-Johnson syndrome, syncope, paresthesia, vasodilatation and vertigo.<br/>Other Adverse Reactions Associated With Other Formulations of Cefaclor: In addition to the above, the following other adverse reactions and altered laboratory tests have been associated with cefaclor in other oral formulations: Clinical���Severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis, have been reported rarely. Anaphylactoid events may be manifested by solitary symptoms, including angioedema, edema (including face and limbs), paresthesias, syncope, or vasodilatation. Anaphylaxis may be more common in patients with a history of penicillin allergy. Rarely, hypersensitivity symptoms may persist for several months. Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. (See WARNINGS.) Laboratory���Abnormal urinalysis, eosinophilia, leukopenia, neutropenia, transient elevations in AST, and transient thrombocytopenia have been reported. Cephalosporin-Class Reactions���In addition to the adverse reactions listed above, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Clinical���Confusion, erythema multiforme, genital pruritus, hepatic dysfunction including cholestasis, hemolytic anemia, reversible hyperactivity, hypertonia, and reversible interstitial nephritis. Laboratory���Positive direct Coombs' test.
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Peginterferon alfa-2a in combination with ribavirin tablets causes a broad variety of serious adverse reactions . The most common life-threatening or fatal events induced or aggravated by peginterferon alfa-2a and ribavirin tablets were depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurred at a frequency of<1%. Hepatic decompensation occurred in 2% (10/574) of CHC/HIV patients . In all studies, one or more serious adverse reactions occurred in 10% of CHC monoinfected patients and in 19% of CHC/HIV receiving peginterferon alfa-2a alone or in combination with ribavirin tablets. The most common serious adverse event (3% in CHC and 5% in CHC/HIV) was bacterial infection (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia). Other SAEs occurred at a frequency of<1% and included: suicide, suicidal ideation, psychosis, aggression, anxiety, drug abuse and drug overdose, angina, hepatic dysfunction, fatty liver, cholangitis, arrhythmia, diabetes mellitus, autoimmune phenomena (e.g., hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), peripheral neuropathy, aplastic anemia, peptic ulcer, gastrointestinal bleeding, pancreatitis, colitis, corneal ulcer, pulmonary embolism, coma, myositis, cerebral hemorrhage, thrombotic thrombocytopenic purpura, psychotic disorder, and hallucination. Nearly all patients in clinical trials experienced one or more adverse events. The most commonly reported adverse reactions were psychiatric reactions, including depression, insomnia, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache and rigors. Other common reactions were anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. Ten percent of CHC monoinfected patients receiving 48 weeks of therapy with peginterferon alfa-2a in combination with ribavirin tablets discontinued therapy; 16% of CHC/HIV coinfected patients discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (e.g., lethargy, fatigue, headache), dermatologic and gastrointestinal disordersand laboratory abnormalities (thrombocytopenia, neutropenia, and anemia). Overall 39% of patients with CHC or CHC/HIV required modification of peginterferon alfa-2a and/or ribavirin tablets therapy. The most common reason for dose modification of peginterferon alfa-2a in CHC and CHC/HIV patients was for laboratory abnormalities; neutropenia (20% and 27%, respectively) and thrombocytopenia (4% and 6%, respectively). The most common reason for dose modification of ribavirin tablets in CHC and CHC/HIV patients was anemia (22% and 16%, respectively). Peginterferon alfa-2a dose was reduced in 12% of patients receiving 1000 mg to 1200 mg ribavirin tablets for 48 weeks and in 7% of patients receiving 800 mg ribavirin tablets for 24 weeks. Ribavirin tablet dose was reduced in 21% of patients receiving 1000 mg to 1200 mg ribavirin tablets for 48 weeks and in 12% of patients receiving 800 mg ribavirin tablets for 24 weeks. Chronic hepatitis C monoinfected patients treated for 24 weeks with peginterferon alfa-2a and 800 mg ribavirin tablets were observed to have lower incidence of serious adverse events (3% vs. 10%), hemoglobin<10 g/dL (3% vs. 15%), dose modification of peginterferon alfa-2a (30% vs. 36%) and ribavirin tablets (19% vs. 38%), and of withdrawal from treatment (5% vs. 15%) compared to patients treated for 48 weeks with peginterferon alfa-2a and 1000 mg or 1200 mg ribavirin tablets. On the other hand, the overall incidence of adverse events appeared to be similar in the two treatment groups. Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug. Also, the adverse event rates listed here may not predict the rates observed in a broader patient population in clinical practice.<br/>Common Adverse Reactions in CHC With HIV Coinfection: The adverse event profile of coinfected patients treated with peginterferon alfa-2a and ribavirin tablets in Study NR15961 was generally similar to that shown for monoinfected patients in Study NV15801 (Table 4). Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%), and mood alteration (9%).<br/>Laboratory Test Values: Anemia due to hemolysis is the most significant toxicity of ribavirin therapy. Anemia (hemoglobin<10 g/dL) was observed in 13% of all ribavirin tablets and peginterferon alfa-2a combination-treated patients in clinical trials. The maximum drop in hemoglobin occurred during the first 8 weeks of initiation of ribavirin therapy .<br/>Postmarketing Experience:: The reactions have been identified and reported during post-approval use of peginterferon alfa-2a following adverse therapy: dehydration, hearing impairment, hearing loss, and serious skin reactions .
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Reactions which may occur because of the solution
or the technique of administration include febrile response, infection
at the site of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the
infusion, evaluate the patient, institute appropriate therapeutic
countermeasures and save the remainder of the fluid for examination
if deemed necessary.
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| dailymed-drugs:238 |
Reactions which may occur because of the solution
or the technique of administration include febrile response, infection
at the site of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the
infusion, evaluate the patient, institute appropriate therapeutic
countermeasures and save the remainder of the fluid for examination
if deemed necessary.
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| dailymed-drugs:2053 |
Reactions which may occur because of the solution
or the technique of administration include febrile response, infection
at the site of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the
infusion, evaluate the patient, institute appropriate therapeutic
countermeasures and save the remainder of the fluid for examination
if deemed necessary.
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Mania: The incidence of treatment-emergent events has been
ascertained based on combined data from two placebo-controlled clinical trials
of DEPAKOTE in the treatment of manic episodes associated with bipolar disorder.
The adverse events were usually mild or moderate in intensity, but sometimes
were serious enough to interrupt treatment. In clinical trials, the rates
of premature termination due to intolerance were not statistically different
between placebo, DEPAKOTE, and lithium carbonate. A total of 4%, 8% and 11%
of patients discontinued therapy due to intolerance in the placebo, DEPAKOTE,
and lithium carbonate groups, respectively. Table 1
summarizes those adverse events reported for patients in these trials where
the incidence rate in the DEPAKOTE-treated group was greater than 5% and greater
than the placebo incidence, or where the incidence in the DEPAKOTE-treated
group was statistically significantly greater than the placebo group. Vomiting
was the only event that was reported by significantly (p���0.05)
more patients receiving DEPAKOTE compared to placebo. The following additional adverse events were reported
by greater than 1% but not more than 5% of the 89 divalproex sodium-treated
patients in controlled clinical trials:<br/>Body as a Whole: Chest pain, chills, chills and fever, fever, neck pain, neck
rigidity.<br/>Cardiovascular System: Hypertension, hypotension, palpitations, postural hypotension,
tachycardia, vasodilation.<br/>Digestive System: Anorexia, fecal incontinence, flatulence, gastroenteritis,
glossitis, periodontal abscess.<br/>Hemic and Lymphatic System: Ecchymosis.<br/>Metabolic and Nutritional Disorders: Edema, peripheral edema.<br/>Musculoskeletal System: Arthralgia, arthrosis, leg cramps, twitching.<br/>Nervous System: Abnormal dreams, abnormal gait, agitation, ataxia, catatonic
reaction, confusion, depression, diplopia, dysarthria, hallucinations, hypertonia,
hypokinesia, insomnia, paresthesia, reflexes increased, tardive dyskinesia,
thinking abnormalities, vertigo.<br/>Respiratory System: Dyspnea, rhinitis.<br/>Skin and Appendages: Alopecia, discoid lupus erythematosis, dry skin, furunculosis,
maculopapular rash, seborrhea.<br/>Special Senses: Amblyopia, conjunctivitis, deafness, dry eyes, ear pain,
eye pain, tinnitus.<br/>Urogenital System: Dysmenorrhea, dysuria, urinary incontinence.<br/>Migraine: Based on two placebo-controlled clinical trials
and their long term extension, DEPAKOTE was generally well tolerated with
most adverse events rated as mild to moderate in severity. Of the 202 patients
exposed to DEPAKOTE in the placebo-controlled trials, 17% discontinued for
intolerance. This is compared to a rate of 5% for the 81 placebo patients.
Including the long term extension study, the adverse events reported as the
primaryreason for discontinuation by���1% of 248 DEPAKOTE-treated
patients were alopecia (6%), nausea and/or vomiting (5%), weight gain (2%),
tremor (2%), somnolence (1%), elevated SGOT and/or SGPT (1%), and depression
(1%). Table 2 includes those adverse events
reported for patients in the placebo-controlled trials where the incidence
rate in the DEPAKOTE-treated group was greater than 5% and was greater than
that for placebo patients. The following additional adverse events were reported
by greater than 1% but not more than 5% of the 202 divalproex sodium-treated
patients in the controlled clinical trials:<br/>Body as a Whole: Chest pain, chills, face edema, fever and malaise.<br/>Cardiovascular System: Vasodilatation.<br/>Digestive System: Anorexia, constipation, dry mouth, flatulence, gastrointestinal
disorder (unspecified), and stomatitis.<br/>Hemic and Lymphatic System: Ecchymosis.<br/>Metabolic and Nutritional Disorders: Peripheral edema, SGOT increase, and SGPT increase.<br/>Musculoskeletal System: Leg cramps and myalgia.<br/>Nervous System: Abnormal dreams, amnesia, confusion, depression, emotional
lability, insomnia, nervousness, paresthesia, speech disorder, thinking abnormalities,
and vertigo.<br/>Respiratory System: Cough increased, dyspnea, rhinitis, and sinusitis.<br/>Skin and Appendages: Pruritus and rash.<br/>Special Senses: Conjunctivitis, ear disorder, taste perversion, and tinnitus.<br/>Urogenital System: Cystitis, metrorrhagia, and vaginal hemorrhage.<br/>Epilepsy: Based on a placebo-controlled trial of adjunctive
therapy for treatment of complex partial seizures, DEPAKOTE was generally
well tolerated with most adverse events rated as mild to moderate in severity.
Intolerance was the primary reason for discontinuation in the DEPAKOTE-treated
patients (6%), compared to 1% of placebo-treated patients. Table 3 lists treatment-emergent adverse events which
were reported by���5% of DEPAKOTE-treated patients and for which the
incidence was greater than in the placebo group, in the placebo-controlled
trial of adjunctive therapy for treatment of complex partial seizures. Since
patients were also treated with other antiepilepsy drugs, it is not possible,
in most cases, to determine whether the following adverse events can be ascribed
to DEPAKOTE alone, or the combination of DEPAKOTE and other antiepilepsy drugs. Table 4 lists treatment-emergent adverse
events which were reported by���5% of patients in the high dose
DEPAKOTE group, and for which the incidence was greater than in the low dose
group, in a controlled trial of DEPAKOTE monotherapy treatment of complex
partial seizures. Since patients were being titrated off another antiepilepsy
drug during the first portion of the trial, it is not possible, in many cases,
to determine whether the following adverse events can be ascribed to DEPAKOTE
alone, or the combination of DEPAKOTE and other antiepilepsy drugs. The following additional adverse events were reported
by greater than 1% but less than 5% of the 358 patients treated with DEPAKOTE
in the controlled trials of complex partial seizures:<br/>Body as a Whole: Back pain, chest pain, malaise.<br/>Cardiovascular System: Tachycardia, hypertension, palpitation.<br/>Digestive System: Increased appetite, flatulence, hematemesis, eructation,
pancreatitis, periodontal abscess.<br/>Hemic and Lymphatic System: Petechia.<br/>Metabolic and Nutritional Disorders: SGOT increased, SGPT increased.<br/>Musculoskeletal System: Myalgia, twitching, arthralgia, leg cramps, myasthenia.<br/>Nervous System: Anxiety, confusion, abnormal gait, paresthesia, hypertonia,
incoordination, abnormal dreams, personality disorder.<br/>Respiratory System: Sinusitis, cough increased, pneumonia, epistaxis.<br/>Skin and Appendages: Rash, pruritus, dry skin.<br/>Special Senses: Taste perversion, abnormal vision, deafness, otitis media.<br/>Urogenital System: Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea,
urinary frequency.<br/>Other Patient Populations: Adverse events that have been reported with all
dosage forms of valproate from epilepsy trials, spontaneous reports, and other
sources are listed below by body system.<br/>Gastrointestinal: The most commonly reported side effects at the
initiation of therapy are nausea, vomiting, and indigestion. These effects
are usually transient and rarely require discontinuation of therapy. Diarrhea,
abdominal cramps, and constipation have been reported. Both anorexia with
some weight loss and increased appetite with weight gain have also been reported.
The administration of delayed-release divalproex sodium may result in reduction
of gastrointestinal side effects in some patients.<br/>CNS Effects: Sedative effects have occurred in patients receiving
valproate alone but occur most often in patients receiving combination therapy.
Sedation usually abates upon reduction of other antiepileptic medication.
Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus,
diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion,
hypesthesia, vertigo, incoordination, and parkinsonism have been reported
with the use of valproate. Rare cases of coma have occurred in patients receiving
valproate alone or in conjunction with phenobarbital. In rare instances encephalopathy
with or without fever has developed shortly after the introduction of valproate
monotherapy without evidence of hepatic dysfunction or inappropriately high
plasma valproate levels. Although recovery has been described following drug
withdrawal, there have been fatalities in patients with hyperammonemic encephalopathy,
particularly in patients with underlying urea cycle disorders (see WARNINGS���Urea Cycle Disorders and PRECAUTIONS). Several
reports have noted reversible cerebral atrophy and dementia in association
with valproate therapy.<br/>Dermatologic: Transient hair loss, skin rash, photosensitivity,
generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome.
Rare cases of toxic epidermal necrolysis have been reported including a fatal
case in a 6 month old infant taking valproate and several other concomitant
medications. An additional case of toxic epidermal necrosis resulting in
death was reported in a 35 year old patient with AIDS taking several concomitant
medications and with a history of multiple cutaneous drug reactions. Serious
skin reactions have been reported with concomitant administration of lamotrigine
and valproate (see PRECAUTIONS - Drug Interactions).<br/>Psychiatric: Emotional upset, depression, psychosis, aggression,
hyperactivity, hostility, and behavioral deterioration.<br/>Musculoskeletal: Weakness.<br/>Hematologic: Thrombocytopenia and inhibition of the secondary
phase of platelet aggregation may be reflected in altered bleeding time, petechiae,
bruising, hematoma formation, epistaxis, and frank hemorrhage (see PRECAUTIONS - General and Drug
Interactions). Relative lymphocytosis, macrocytosis, hypofibrinogenemia,
leukopenia, eosinophilia, anemia including macrocytic with or without folate
deficiency, bone marrow suppression, pancytopenia, aplastic anemia, agranulocytosis,
and acute intermittent porphyria.<br/>Hepatic: Minor elevations of transaminases (eg, SGOT and
SGPT) and LDH are frequent and appear to be dose-related. Occasionally, laboratory
test results include increases in serum bilirubin and abnormal changes in
other liver function tests. These results may reflect potentially serious
hepatotoxicity (see WARNINGS).<br/>Endocrine: Irregular menses, secondary amenorrhea, breast
enlargement, galactorrhea, and parotid gland swelling. Abnormal thyroid function
tests (see PRECAUTIONS). There have been rare spontaneous reports of polycystic
ovary disease. A cause and effect relationship has not been established.<br/>Pancreatic: Acute pancreatitis including fatalities (see WARNINGS).<br/>Metabolic: Hyperammonemia (see PRECAUTIONS), hyponatremia, and inappropriate ADH secretion. There have been rare reports of Fanconi's syndrome
occurring chiefly in children. Decreased
carnitine concentrations have been reported although the clinical relevance
is undetermined. Hyperglycinemia has occurred
and was associated with a fatal outcome in a patient with preexistent nonketotic
hyperglycinemia.<br/>Genitourinary: Enuresis and urinary tract infection.<br/>Special Senses: Hearing loss, either reversible or irreversible, has been
reported; however, a cause and effect relationship has not been established.
Ear pain has also been reported.<br/>Other: Allergic reaction, anaphylaxis, edema of the extremities,
lupus erythematosus, bone pain, cough increased, pneumonia, otitis media,
bradycardia, cutaneous vasculitis, fever, and hypothermia.
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The premarketing development program for citalopram included citalopram exposures in patients and/or normal subjects from 3 different groups of studies: 429 normal subjects in clinical pharmacology/pharmacokinetic studies; 4,422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1,370 patient-exposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with citalopram varied greatly and included (in overlapping categories) open-label and double-blind studies, inpatient and outpatient studies, fixed-dose and dose-titration studies, and short-term and long-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.<br/>Adverse Findings Observed in Short-Term, Placebo-Controlled Trials:<br/>Adverse Events Associated with Discontinuation of Treatment: Among 1,063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration, 16% discontinued treatment due to an adverse event, as compared to 8% of 446 patients receiving placebo. The adverse events associated with discontinuation and considered drug-related (i.e., associated with discontinuation in atleast 1% of citalopram-treated patients at a rate at least twice that of placebo) are shown in TABLE 2. It should be noted that one patient can report more than one reason for discontinuation and be counted more than once in this table.<br/>Adverse Events Occurring at an Incidence of 2% or More Among Citalopram - Treated Patients: TABLE 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 1,063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration. Events included are those occurring in 2% or more of patients treated with citalopram and for which the incidence in patients treated with citalopram was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The only commonly observed adverse event that occurred in citalopram patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see TABLE 3). *Events reported by at least 2% of patients treated with citalopram are reported, except for the following events which had an incidence on placebo���citalopram: headache, asthenia, dizziness, constipation, palpitation, vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain. Denominator used was for females only (N=638 citalopram; N=252 placebo). Primarily ejaculatory delay. Denominator used was for males only (N=425 citalopram; N=194 placebo).<br/>Dose Dependency of Adverse Events: The potential relationship between the dose of citalopram administered and the incidence of adverse events was examined in a fixed-dose study in depressed patients receiving placebo or citalopram 10, 20, 40, and 60 mg. Jonckheere's trend test revealed a positive dose response (p<0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning.<br/>Male and Female Sexual Dysfunction with SSRIs: Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in the product labeling, are likely to underestimate their actual incidence. The table below displays the incidence of sexual side effects reported by at least 2% of patients taking citalopram in a pool of placebo-controlled clinical trials in patients with depression. In female depressed patients receiving citalopram, the reported incidence of decreased libido and anorgasmia was 1.3% (n=638 females) and 1.1% (n=252 females), respectively. There are no adequately designed studies examining sexual dysfunction with citalopram treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.<br/>Vital Sign Changes: Citalopram and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with citalopram treatment. In addition, a comparison of supine and standing vital sign measures for citalopram and placebo treatments indicated that citalopram treatment is not associated with orthostatic changes.<br/>Weight Changes: Patients treated with citalopram in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients.<br/>Laboratory Changes: Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with citalopram treatment.<br/>ECG Changes: Electrocardiograms from citalopram (N=802) and placebo (N=241) groups were compared with respect to (1) mean change from baseline in various ECG parameters, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. The only statistically significant drug-placebo difference observed was a decrease in heart rate for citalopram of 1.7 bpm compared to no change in heart rate for placebo. There were no observed differences in QT or other ECG intervals.<br/>Other Events Observed During the Premarketing Evaluation of Citalopram: Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by patients treated with citalopram at multiple doses in a range of 10 to 80 mg/day during any phase of a trial within the premarketing database of 4,422 patients. All reported events are included except those already listed in TABLE 3 or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those occurring in only one patient. It is important to emphasize that, although the events reported occurred during treatment with citalopram, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Cardiovascular - Frequent: tachycardia, postural hypotension, hypotension. Infrequent: hypertension, bradycardia, edema (extremities), angina pectoris, extrasystoles, cardiac failure, flushing, myocardial infarction, cerebrovascular accident, myocardial ischemia. Rare: transient ischemic attack, phlebitis, atrial fibrillation, cardiac arrest, bundle branch block. Central and Peripheral Nervous System Disorders - Frequent: paresthesia, migraine. Infrequent: hyperkinesia, vertigo, hypertonia, extrapyramidal disorder, leg cramps, involuntary muscle contractions, hypokinesia, neuralgia, dystonia, abnormal gait, hypesthesia, ataxia. Rare: abnormal coordination, hyperesthesia, ptosis, stupor. Endocrine Disorders - Rare: hypothyroidism, goiter, gynecomastia. Gastrointestinal Disorders - Frequent: saliva increased, flatulence. Infrequent: gastritis, gastroenteritis, stomatitis, eructation, hemorrhoids, dysphagia, teeth grinding, gingivitis, esophagitis. Rare: colitis, gastric ulcer, cholecystitis, cholelithiasis, duodenal ulcer, gastroesophageal reflux, glossitis, jaundice, diverticulitis, rectal hemorrhage, hiccups. General - Infrequent: hot flushes, rigors, alcohol intolerance, syncope, influenza-like symptoms. Rare: hayfever. Hemic and Lymphatic Disorders - Infrequent: purpura, anemia, epistaxis, leukocytosis, leucopenia, lymphadenopathy. Rare: pulmonary embolism, granulocytopenia, lymphocytosis, lymphopenia, hypochromic anemia, coagulation disorder, gingival bleeding. Metabolic and Nutritional Disorders - Frequent: decreased weight, increased weight. Infrequent: increased hepatic enzymes, thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance. Rare: bilirubinemia, hypokalemia, obesity, hypoglycemia, hepatitis, dehydration. Musculoskeletal System Disorders - Infrequent: arthritis, muscle weakness, skeletal pain. Rare: bursitis, osteoporosis. Psychiatric Disorders - Frequent: impaired concentration, amnesia, apathy, depression, increased appetite, aggravated depression, suicide attempt, confusion. Infrequent: increased libido, aggressive reaction, paroniria, drug dependence, depersonalization, hallucination, euphoria, psychotic depression, delusion, paranoid reaction, emotional lability, panic reaction, psychosis. Rare: catatonic reaction, melancholia. Reproductive Disorders/Female* - Frequent: amenorrhea. Infrequent: galactorrhea, breast pain, breast enlargement, vaginal hemorrhage. *% based on female subjects only: 2,955 Respiratory System Disorders - Frequent: coughing. Infrequent: bronchitis, dyspnea, pneumonia. Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased. Skin and Appendages Disorders - Frequent: rash, pruritus. Infrequent: photosensitivity reaction, urticaria, acne, skin discoloration, eczema, alopecia, dermatitis, skin dry, psoriasis. Rare: hypertrichosis, decreased sweating, melanosis, keratitis, cellulitis, pruritus ani. Special Senses - Frequent: accommodation abnormal, taste perversion. Infrequent: tinnitus, conjunctivitis, eye pain. Rare: mydriasis, photophobia, diplopia, abnormal lacrimation, cataract, taste loss. Urinary System Disorders - Frequent: polyuria. Infrequent: micturition frequency, urinary incontinence, urinary retention, dysuria. Rare: facial edema, hematuria, oliguria, pyelonephritis, renal calculus, renal pain.<br/>Other Events Observed During the Postmarketing Evaluation of Citalopram: It is estimated that over 30 million patients have been treated with citalopram since market introduction. Although no causal relationship to citalopram treatment has been found, the following adverse events have been reported to be temporally associated with citalopram treatment, and have not been described elsewhere in the labeling: acute renal failure, akathisia, allergic reaction, anaphylaxis, angioedema, choreoathetosis, chest pain, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema multiforme, gastrointestinal hemorrhage, grand mal convulsions, hemolytic anemia, hepatic necrosis, myoclonus, neuroleptic malignant syndrome, nystagmus, pancreatitis, priapism, prolactinemia, prothrombin decreased, QT prolonged, rhabdomyolysis, serotonin syndrome, spontaneous abortion, thrombocytopenia, thrombosis, ventricular arrhythmia, torsades de pointes, and withdrawal syndrome.
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Adverse Reactions in Adult Patients: During clinical investigations with oral and parenteral ciprofloxacin, 49,038 patients received courses of the drug. Most of the adverse events reported were described as only mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Ciprofloxacin was discontinued because of an adverse event in 1.0% of orally treated patients. The most frequently reported drug related events, from clinical trials of all formulation, all dosages, all drug-therapy durations, and for all indications of ciprofloxacin therapy were nausea (2.5%), diarrhea (1.6%), liver function tests abnormal (1.3%), vomiting (1.0%), and rash (1.0%). Additional medically important events that occurred in less than 1% of ciprofloxacin patients are listed below. In several instances nausea, vomiting, tremor, irritability, or palpitation were judged by investigators to be related to elevated serum levels of theophylline possibly as a result of drug interaction with ciprofloxacin. In randomized, double-blind controlled clinical trials comparing ciprofloxacin tablets (500 mg BID) to cefuroxime axetil (250 mg - 500 mg BID) and to clarithromycin (500 mg BID) in patients with respiratory tract infections, ciprofloxacin demonstrated a CNS adverse event profile comparable to the control drugs.<br/>Adverse Reactions in Pediatric Patients: Adverse Reactions in Pediatric Patients: Ciprofloxacin, administered I.V. and /or orally, was compared to a cephalosporin for treatment of complicated urinary tract infections (cUTI) or pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6��4 years). The trial was conducted in the US, Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). The primary objective of the study was to assess musculoskeletal and neurological safety within 6 weeks of therapy and through one year of follow-up in the 335 ciprofloxacin- and 349 comparator-treated patients enrolled. An Independent Pediatric Safety Committee (IPSC) reviewed all cases of musculoskeletal adverse events as well as all patients with an abnormal gait or abnormal joint exam (baseline or treatment-emergent). These events were evaluated in a comprehensive fashion and included such conditions as arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint. The affectedjoints included: knee, elbow, ankle, hip, wrist, and shoulder. Within 6 weeks of treatment initiation, the rates of these events were 9.3% (31/335) in the ciprofloxacin-treated group versus 6.0 % (21/349) in comparator-treated patients. The majority of these events were mild or moderate in intensity. All musculoskeletal events occurring by 6 weeks resolved (clinical resolution of signs and symptoms), usually within 30 days of end of treatment. Radiological evaluations were not routinely used to confirm resolution of the events. The events occurred more frequently in ciprofloxacin-treated patients than control patients, regardless of whether they received I.V. or oral therapy. Ciprofloxacin-treated patients were more likely to report more than one event and on more than one occasion compared to control patients. These events occurred in all age groups and the rates were consistently higher in the ciprofloxacin group compared to the control group. At the end of 1 year, the rate of these events reported at anytime during that period was 13.7% (46/335) in the ciprofloxacin-treated group versus 9.5% (33/349) comparator-treated patients. An adolescent female discontinued ciprofloxacin for wrist pain that developed during treatment. An MRI performed 4 weeks later showed a tear in the right ulnar fibrocartilage. A diagnosis of overuse syndrome secondary to sports activity was made, but a contribution from ciprofloxacin cannot be excluded. The patient recovered by 4 months without surgical intervention. The incidence rates of neurological events within 6 weeks of treatment initiation were 3% (9/335) in the ciprofloxacin group versus 2% (7/349) in the comparator group and included dizziness, nervousness, insomnia, and somnolence. In this trial, the overall incidence rates of adverse events regardless of relationship to study drug and within 6 weeks of treatment initiation were 41% (138/335) in the ciprofloxacin group versus 31% (109/349) in the comparator group. The most frequent events were gastrointestinal: 15% (50/335) of ciprofloxacin patients compared to 9% (31/349) of comparator patients. Serious adverse events were seen in 7.5% (25/335) of ciprofloxacin-treated patients compared to 5.7% (20/349) of control patients. Discontinuation of drug due to an adverse event was observed in 3% (10/335) of ciprofloxacin-treated patients versus 1.4% (5/349) of comparator patients. Other adverse events that occurred in at least 1% of ciprofloxacin patients were diarrhea 4.8%, vomiting 4.8%, abdominal pain 3.3%, accidental injury 3.0%, rhinitis 3.0%, dyspepsia 2.7%, nausea 2.7%, fever 2.1%, asthma 1.8% and rash 1.8%. In addition to the events reported in pediatric patients in clinical trials, it should be expected that events reported in adults during clinical trials or post-marketing experience may also occur in pediatric patients.<br/>Post-Marketing Adverse Events: The following adverse events have been reported from worldwide marketing experience with quinolones, including ciprofloxacin. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, or (3) strength of causal connection to the drug. Agitation, agranulocytosis, albuminuria, anaphylactic reactions (including life-threatening anaphylactic shock), anosmia, candiduria, cholesterol elevation (serum), confusion, constipation, delirium, dyspepsia, dysphagia, erythema multiforme, exfoliative dermatitis, fixed eruption, flatulence, glucose elevation (blood), hemolytic anemia, hepatic failure (including fatal cases), hepatic necrosis, hyperesthesia, hypertonia, hypesthesia, hypotension (postural), jaundice, marrow depression (life threatening), methemoglobinemia, moniliasis (oral, gastrointestinal, vaginal), myalgia, myasthenia, myasthenia gravis (possible exacerbation), myoclonus, nystagmus, pancreatitis, pancytopenia (life threatening or fatal outcome), peripheral neuropathy, phenytoin alteration (serum), photosensitivity/phototoxicity reaction, potassium elevation (serum), prothrombin time prolongation or decrease, pseudomembranous colitis (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.), psychosis (toxic), renal calculi, serum sickness like reaction, Stevens-Johnson syndrome, taste loss, tendinitis, tendon rupture, torsade de pointes, toxic epidermal necrolysis (Lyell's Syndrome), triglyceride elevation (serum), twitching, vaginal candidiasis, and vasculitis Adverse events were also reported by persons who received ciprofloxacin for anthrax post-exposure prophylaxis following the anthrax bioterror attacks of October 2001.<br/>Adverse Laboratory Changes: Changes in laboratory parameters listed as adverse events without regard to drug relationship are listed below: Other changes occurring in less than 0.1% of courses were: elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, leukocytosis.
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The following adverse reactions have been observed,
but there are not enough data to support an estimate of their frequency. Cardiovascular System ventricular arrhythmia (at very high doses) ectopic beats tachycardia anginal pain palpitation cardiac conduction abnormalities widened QRS complex bradycardia hypotension hypertension vasoconstriction Respiratory System dyspnea Gastrointestinal
System nausea vomiting Metabolic/Nutritional
System azotemia Central Nervous System headache anxiety Dermatological System piloerection Other Gangrene of the extremities
has occurred when high doses were administered for prolonged periods
or in patients with occlusive vascular disease receiving low doses
of dopamine HCl.
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In rare cases, anaphylaxis
has been reported after the first dose. Several cases of hypersensitivity
reactions including urticaria have also been reported. However, the most frequent
adverse reactions were nausea and/or vomiting in approximately 3%, abdominal
pain in 1.2%, pruritus in 1.5%, and the following in less than 1% of the patients:
headache, dizziness, somnolence, fever and chills, photophobia, diarrhea,
gynecomastia, impotence, thrombocytopenia, leukopenia, hemolytic anemia, and
bulging fontanelles. Oligospermia has been reported in investigational studies
with the drug at dosages above those currently approved. Oligospermia has
not been reported at dosages up to 400 mg daily, however sperm counts have
been obtained infrequently in patients treated with these dosages. Most of
these reactions were mild and transient and rarely required discontinuation
of NIZORAL (ketoconazole) Tablets. In contrast, the rare
occurrences of hepatic dysfunction require special attention . In
worldwide postmarketing experience with NIZORAL Tablets there
have been rare reports of alopecia, paresthesia, and signs of increased intracranial
pressure including bulging fontanelles and papilledema. Hypertriglyceridemia
has also been reported but a causal association with NIZORAL Tablets
is uncertain. Neuropsychiatric disturbances,
including suicidal tendencies and severe depression, have occurred rarely
in patients using NIZORAL Tablets. Ventricular
dysrhythmias (prolonged QT intervals) have occurred with the concomitant use
of terfenadine with ketoconazole tablets. (See BOX
WARNING, CONTRAINDICATIONS,
and WARNINGS sections.) Data suggest
that coadministration of ketoconazole tablets and cisapride can result in
prolongation of the QT interval and has rarely been associated with ventricular
arrhythmias.
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The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity. Body as a Whole: Weakness. Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs). Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia. Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura. Metabolic: Electrolyte imbalance , hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal: Muscle spasm. Nervous System/Psychiatric: Vertigo, paresthesias, dizziness, headache, restlessness. Renal: Renal failure, renal dysfunction, interstitial nephritis . Skin: Erythema multiforme including Stevens-Johnson Syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia. Special Senses: Transient blurred vision, xanthopsia. Urogenital: Impotence. Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
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Potassium
intoxication with mild or severe hyperkalemia has been reported. The
signs and symptoms of intoxication include, paresthesia of the
extremities, areflexia, muscular or respiratory paralysis, mental
confusion, weakness, hypotension, cardiac arrhythmia, heart block,
electrographic abnormalities and cardiac arrest. EKG abnormalities serve
as a clinical reflection of the seriousness of changes in serum
potassium concentrations; peaked T waves and prolonged P-R intervals
usually occur with modest elevations above the upper limit of normal
potassium concentrations; P waves disappear, the QRS complex widens, and
eventual asystole usually occurs with higher elevations. Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation and
hypervolemia. Infusion of highly
concentrated potassium chloride solutions may cause local pain and vein irritation. . Reactions reported
with the use of potassium-containing solutions include nausea, vomiting,
and abdominal pain and diarrhea. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder
of the fluid for examination if deemed necessary.
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Peripheral Infusions A 3.5% to 5% solution of amino acids (without
additives) is slightly hypertonic. Use of large peripheral veins,
inline filters, and slowing the rate of infusion may reduce the incidence
of local venous irritation. Electrolyte additives should be spread
throughout the day. Irritating additive medications may need to be
infused at another venous site. Generalized
flushing, fever and nausea also have been reported during peripheral
infusions of amino acid solutions.
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Postherpetic Neuralgia: The most commonly observed adverse events associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema. In the 2 controlled studies in postherpetic neuralgia, 16% of the 336 patients who received gabapentin and 9% of the 227 patients who received placebo discontinued treatment because of an adverse event. The adverse events that most frequently led to withdrawal in gabapentin-treated patients were dizziness, somnolence, and nausea.<br/>Incidence in Controlled Clinical Trials: Table 2 lists treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the gabapentin group than in the placebo group. Adverse events were usually mild to moderate in intensity. Table 2. Treatment-Emergent Adverse Event Incidence in Controlled Trials in Postherpetic Neuralgia (Events in at least 1% of Gabapentin-Treated Patients and Numerically More Frequent Than in the Placebo Group) Reported as blurred vision Other events in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome. There were no clinically important differences between men and women in the types and incidence of adverse events. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse events by race.<br/>Epilepsy: The most commonly observed adverse events associated with the use of gabapentin in combination with other antiepileptic drugs in patients>12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most commonly observed adverse events reported with the use of gabapentin in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility (see WARNINGS, Neuropsychiatric Adverse Events). Approximately 7% of the 2074 patients>12 years of age and approximately 7% of the 449 pediatric patients 3 to 12 years of age who received gabapentin in premarketing clinical trials discontinued treatment because of an adverse event. The adverse events most commonly associated with withdrawal in patients>12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or vomiting (0.6%), and dizziness (0.6%). The adverse events most commonly associated with withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%).<br/>Incidence in Controlled Clinical Trials: Table 3 lists treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-treated patients>12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the gabapentin group. In these studies, either gabapentin or placebo was added to the patient's current antiepileptic drug therapy. Adverse events were usually mild to moderate in intensity. The prescriber should be aware that these figures, obtained when gabapentin was added to concurrent antiepileptic drug therapy, cannot be used to predict the frequency of adverse events in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, doesprovide the prescribing physician with one basis to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied. Plus background antiepileptic drug therapy Amblyopia was often described as blurred vision. Other events in more than 1% of patients>12 years of age but equally or more frequent in the placebo group included: headache, viral infection, fever, nausea and/or vomiting, abdominal pain, diarrhea, convulsions, confusion, insomnia, emotional lability, rash, acne. Among the treatment-emergent adverse events occurring at an incidence of at least 10% of gabapentin-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship. The overall incidence of adverse events and the types of adverse events seen were similar among men and women treated with gabapentin. The incidence of adverse events increased slightly with increasing age in patients treated with either gabapentin or placebo. Because only 3% of patients (28/921) in placebo-controlled studies were identified as nonwhite (black or other), there are insufficient data to support a statement regarding the distribution of adverse events by race. Table 4 lists treatment-emergent signs and symptoms that occurred in at least 2% of gabapentin-treated patients age 3 to 12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the gabapentin group. Adverse events were usually mild to moderate in intensity. Plus background antiepileptic drug therapy Other events in more than 2% of pediatric patients 3 to 12 years of age but equally or more frequent in the placebo group included: pharyngitis, upper respiratory infection, headache, rhinitis, convulsions, diarrhea, anorexia, coughing, and otitis media.<br/>Other Adverse Events Observed During All Clinical Trials:<br/>Clinical Trials in Adults and Adolescents (Except Clinical Trials in Neuropathic Pain): Gabapentin has been administered to 4717 patients>12 years of age during all adjunctive therapy clinical trials (except clinical trials in patients with neuropathic pain), only some of which were placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. The frequencies presented represent the proportion of the 4717 patients>12 years of age exposed to gabapentin who experienced an event of the type cited on at least one occasion while receiving gabapentin. All reported events are included except those already listed in Table 3, those too general to be informative, and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Body As A Whole: Frequent: asthenia, malaise, face edema; Infrequent: allergy, generalized edema, weight decrease, chill; Rare: strange feelings, lassitude, alcohol intolerance, hangover effect. Cardiovascular System: Frequent: hypertension; Infrequent: hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, migraine, murmur; Rare: atrial fibrillation, heart failure, thrombophlebitis, deep thrombophlebitis, myocardial infarction, cerebrovascular accident, pulmonary thrombosis, ventricular extrasystoles, bradycardia, premature atrial contraction, pericardial rub, heart block, pulmonary embolus, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis. Digestive System: Frequent: anorexia, flatulence, gingivitis; Infrequent: glossitis, gum hemorrhage, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly; Rare: dysphagia, eructation, pancreatitis, peptic ulcer, colitis, blisters in mouth, tooth discolor, perl��che, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm. Endocrine System: Rare: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicle, cushingoid appearance. Hematologic and Lymphatic System: Frequent: purpura most often described as bruises resulting from physical trauma; Infrequent: anemia, thrombocytopenia, lymphadenopathy; Rare: WBC count increased, lymphocytosis, non-Hodgkin's lymphoma, bleeding time increased. Musculoskeletal System: Frequent: arthralgia; Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test; Rare: costochondritis, osteoporosis, bursitis, contracture. Nervous System: Frequent: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased reflexes, anxiety, hostility; Infrequent: CNS tumors, syncope, dreaming abnormal, aphasia, hypesthesia, intracranial hemorrhage, hypotonia, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor, cerebellar dysfunction, positive Babinski sign, decreased position sense, subdural hematoma, apathy, hallucination, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, feeling high, doped-up sensation, suicide attempt, psychosis; Rare: choreoathetosis, orofacial dyskinesia, encephalopathy, nerve palsy, personality disorder, increased libido, subdued temperament, apraxia, fine motor control disorder, meningismus, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria, antisocial reaction, suicide. Respiratory System: Frequent: pneumonia; Infrequent: epistaxis, dyspnea, apnea; Rare: mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema. Dermatological: Infrequent: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst, herpes simplex; Rare: herpes zoster, skin discolor, skin papules, photosensitive reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous nodule, melanosis, skin necrosis, local swelling. Urogenital System: Infrequent: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vaginal hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejaculation abnormal; Rare: kidney pain, leukorrhea, pruritis genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain, testicle pain. Special Senses: Frequent: abnormal vision; Infrequent: cataract, conjunctivitis, eyes dry, eye pain, visual field defect, photophobia, bilateral or unilateral ptosis, eye hemorrhage, hordeolum, hearing loss, earache, tinnitus, inner ear infection, otitis, taste loss, unusual taste, eye twitching, ear fullness; Rare: eye itching, abnormal accommodation, perforated ear drum, sensitivity to noise, eye focusing problem, watery eyes, retinopathy, glaucoma, iritis, corneal disorders, lacrimal dysfunction, degenerative eye changes, blindness, retinal degeneration, miosis, chorioretinitis, strabismus, eustachian tube dysfunction, labyrinthitis, otitis externa, odd smell.<br/>Clinical Trials in Pediatric Patients With Epilepsy: Adverse events occurring during epilepsy clinical trials in 449 pediatric patients 3 to 12 years of age treated with gabapentin that were not reported in adjunctive trials in adults are: Body as a Whole: dehydration, infectious mononucleosis Digestive System: hepatitis Hemic and Lymphatic System: coagulation defect Nervous System: aura disappeared, occipital neuralgia Psychobiologic Function: sleepwalking Respiratory System: pseudocroup, hoarseness<br/>Clinical Trials in Adults With Neuropathic Pain of Various Etiologies: Safety information was obtained in 1173 patients during double-blind and open-label clinical trials including neuropathic pain conditions for which efficacy has not been demonstrated. Adverse events reported by investigators were grouped into standardized categories using modified COSTART IV terminology. Listed below are all reported events except those already listed in Table 2 and those not reasonably associated with the use of the drug. Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Body as a Whole: Infrequent: chest pain, cellulitis, malaise, neck pain, face edema, allergic reaction, abscess, chills, chills and fever, mucous membrane disorder; Rare: body odor, cyst, fever, hernia, abnormal BUN value, lump in neck, pelvic pain, sepsis, viral infection. Cardiovascular System: Infrequent: hypertension, syncope, palpitation, migraine, hypotension, peripheral vascular disorder, cardiovascular disorder, cerebrovascular accident, congestive heart failure, myocardial infarction, vasodilatation; Rare: angina pectoris, heart failure, increased capillary fragility, phlebitis, thrombophlebitis,varicose vein. Digestive System: Infrequent: gastroenteritis, increased appetite, gastrointestinal disorder, oral moniliasis, gastritis, tongue disorder, thirst, tooth disorder, abnormal stools, anorexia, liver function tests abnormal, periodontal abscess; Rare: cholecystitis, cholelithiasis, duodenal ulcer, fecal incontinence, gamma glutamyl transpeptidase increased, gingivitis, intestinal obstruction, intestinal ulcer, melena, mouth ulceration, rectal disorder, rectal hemorrhage, stomatitis. Endocrine System: Infrequent: diabetes mellitus. Hemic and Lymphatic System: Infrequent: ecchymosis, anemia; Rare: lymphadenopathy, lymphoma-like reaction, prothrombin decreased. Metabolic and Nutritional: Infrequent: edema, gout, hypoglycemia, weight loss; Rare: alkaline phosphatase increased, diabetic ketoacidosis, lactic dehydrogenase increased. Musculoskeletal: Infrequent: arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia; Rare: shin bone pain, joint disorder, tendon disorder. Nervous System: Frequent: confusion, depression; Infrequent: vertigo, nervousness, paresthesia, insomnia, neuropathy, libido decreased, anxiety, depersonalization, reflexes decreased, speech disorder, abnormal dreams, dysarthria, emotional lability, nystagmus, stupor, circumoral paresthesia, euphoria, hyperesthesia, hypokinesia, suicide attempt; Rare: agitation, hypertonia, libido increased, movement disorder, myoclonus, vestibular disorder. Respiratory System: Infrequent: cough increased, bronchitis, rhinitis, sinusitis, pneumonia, asthma, lung disorder, epistaxis; Rare: hemoptysis, voice alteration. Skin and Appendages: Infrequent: pruritus, skin ulcer, dry skin, herpes zoster, skin disorder, fungal dermatitis, furunculosis, herpes simplex, psoriasis, sweating, urticaria, vesiculobullous rash; Rare: acne, hair disorder, maculopapular rash, nail disorder, skin carcinoma, skin discoloration, skin hypertrophy. Special Senses: Infrequent: abnormal vision, ear pain, eye disorder, taste perversion, deafness; Rare: conjunctival hyperemia, diabetic retinopathy, eye pain, fundi with microhemorrhage, retinal vein thrombosis, taste loss. Urogenital System: Infrequent: urinary tract infection, dysuria, impotence, urinary incontinence, vaginal moniliasis, breast pain, menstrual disorder, polyuria, urinary retention; Rare: cystitis, ejaculation abnormal, swollen penis, gynecomastia, nocturia, pyelonephritis, swollen scrotum, urinary frequency, urinary urgency, urine abnormality.<br/>Postmarketing and Other Experience: In addition to the adverse experiences reported during clinical testing of gabapentin, the following adverse experiences have been reported in patients receiving marketed gabapentin. These adverse experiences have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. The listing is alphabetized: angioedema, blood glucose fluctuation, erythema multiforme, elevated liver function tests, fever, hyponatremia, jaundice, movement disorder,Stevens-Johnson syndrome. Adverse events following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.
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Central Nervous System: The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related. These include nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion. Dizziness, insomnia, transient nervousness, motor twitchings, and headaches have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by pheno-thiazine and other neuroleptic drugs. A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.<br/>Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis and liver damage.<br/>Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis .<br/>Hemopoietic System: Hemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's disease have been reported .<br/>Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis, and Peyronie's disease.<br/>Immunologic: Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, periarteritis nodosa and immunoglobulin abnormalities.
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Labetalol HCl injection is usually well tolerated. Most adverse effects have been mild and transient and, in controlled trials involving 92 patients, did not require labetalol withdrawal. Symptomatic postural hypotension (incidence, 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol HCl. Moderate hypotension occurred in 1 of 100 patients while supine. Increased sweating was noted in 4 of 100 patients, and flushing occurred in 1 of 100 patients. The following also were reported with labetalol HCl with the incidence per 100 patients as noted: Cardiovascular System:Ventricular arrhythmia in 1. Central and Peripheral Nervous Systems: Dizziness in 9, tingling of the scalp/skin in 7, hypoesthesia (numbness) and vertigo in 1 each. Gastrointestinal System: Nausea in 13, vomiting in 4, dyspepsia and taste distortion in 1 each. Metabolic Disorders: Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8 of 100 patients; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency. Psychiatric Disorders: Somnolence/yawning in 3. Respiratory System: Wheezing in 1. Skin: Pruritus in 1. The incidence of adverse reactions depends upon the dose of labetalol HCl. The largest experience is with oral labetalol HCl (see Labetalol HCl Tablet Product Information for details). Certain of the side effects increased with increasing oral dose, as shown in the following table that depicts the entire US therapeutic trials data base for adverse reactions thatare clearly or possibly dose related. In addition, a number of other less common adverse events have been reported: Cardiovascular: Hypotension, and rarely, syncope, bradycardia, heart block. Liver and Biliary System: Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests. Hypersensitivity: Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol HCl during investigational use and extensive foreign marketing experience.<br/>Clinical Laboratory Tests: Among patients dosed with labetalol, there have been reversible increases of serum transaminases in 4% of patients tested and, more rarely, reversible increases in blood urea.
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A. Benign Prostatic Hyperplasia: The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented below (TABLE 3) are based on combined data from seven placebo-controlled trials involving once daily administration of doxazosin mesylate in doses of 1 to 16 mg in hypertensives and 0.5 to 8 mg in normotensives. The adverse events when the incidence in the doxazosin mesylate group was at least 1% are summarized in TABLE 3. No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema, and dyspnea. Dizziness and dyspnea appeared to be dose-related. In these placebo-controlled studies of 665 doxazosin mesylate patients, treated for a mean of 85 days, additional adverse reactions have been reported. These are less than 1% and not distinguishable from those that occurred in the placebo group. Adverse reactions with an incidence of less than 1% but of clinical interest are (doxazosin mesylate vs. placebo): Cardiovascular System: angina pectoris (0.6% vs. 0.7%), postural hypotension (0.3% vs. 0.3%), syncope (0.5% vs. 0.0%), tachycardia (0.9% vs. 0.0%); Urogenital System: dysuria (0.5% vs. 1.3%), and Psychiatric Disorders: libido decreased (0.8% vs. 0.3%). The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies. The majority of adverse experiences with doxazosin mesylate were mild.<br/>B. Hypertension: Doxazosin mesylate has been administered to approximately 4000 hypertensive patients, of whom 1679 were included in the hypertension clinical development program. In that program, minor adverse effects were frequent, but led to discontinuation of treatment in only 7% of patients. In placebo-controlled studies adverse effects occurred in 49% and 40% of patients in the doxazosin and placebo groups, respectively, and led to discontinuation in 2% of patients in each group. The major reasons for discontinuation were postural effects (2%), edema, malaise/fatigue, and some heart rate disturbance, each about 0.7%. In controlled hypertension clinical trials directly comparing doxazosin mesylate to placebo there was no significant difference in the incidence of side effects, except for dizziness (including postural), weight gain, somnolence, and fatigue/malaise. Postural effects and edema appeared to be dose related. The prevalence rates presented below are based on combined data from placebo-controlled studies involving once daily administration of doxazosin at doses ranging from 1 to 16 mg. TABLE 4 summarizes those adverse experiences (possibly/probably related) reported for patients in these hypertension studies where the prevalence rate in the doxazosin group was at least 0.5% or where the reaction is of particular interest. Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin. The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight. The following additional adverse reactions were reported by<0.5% of 3960 patients who received doxazosin in controlled or open, short- or long-term clinical studies, including international studies. Cardiovascular System: angina pectoris, myocardial infarction, cerebrovascular accident; Autonomic Nervous System: pallor; Metabolic: thirst, gout, hypokalemia; Hematopoietic: lymphadenopathy, purpura; Reproductive System: breast pain; Skin Disorders: alopecia, dry skin, eczema; Central Nervous System: paresis, tremor, twitching, confusion, migraine, impaired concentration; Psychiatric: paroniria, amnesia, emotional lability, abnormal thinking, depersonalization; Special Senses: parosmia, earache, taste perversion, photophobia, abnormal lacrimation; Gastrointestinal System: increased appetite, anorexia, fecal incontinence, gastroenteritis; Respiratory System: bronchospasm, sinusitis, coughing, pharyngitis; Urinary System: renal calculus; General Body System: hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms. Doxazosin mesylate has not been associated with any clinically significant changes in routine biochemical tests. No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine, or liver function tests. Doxazosin mesylate has been associated with decreases in white blood cell counts (see PRECAUTIONS). In postmarketing experience the following additional adverse reactions have been reported: Autonomic Nervous System: priapism; Central Nervous System: hypoesthesia; Endocrine System: gynecomastia; Gastrointestinal System: vomiting; General Body System: allergic reaction; Heart Rate/Rhythm: bradycardia; Hematopoietic: leukopenia, thrombocytopenia; Liver/Biliary System: hepatitis, hepatitis cholestatic; Respiratory System: bronchospasm aggravated; Skin Disorders: urticaria; Special Senses:Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery); Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.
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The premarketing development program for citalopram hydrobromide included citalopram exposures in patients and/or normal subjects from 3 different groups of studies: 429 normal subjects in clinical pharmacology/pharmacokinetic studies; 4422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1370 patient exposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with citalopram hydrobromide varied greatly and included (in overlapping categories) open-label and double-blind studies, inpatient and outpatient studies, fixed-dose and dose-titration studies, and short-term and long-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.<br/>Adverse Findings Observed in Short-Term, Placebo-Controlled Trials:<br/>Adverse Events Associated with Discontinuation of Treatment: Among 1063 depressed patients who received citalopram hydrobromide at doses ranging from 10 mg/day to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration, 16% discontinued treatment due to an adverse event, as compared to 8% of 446 patients receiving placebo. The adverse events associated with discontinuation and considered drug-related (i.e., associated with discontinuation in at least 1% of citalopram hydrobromide-treated patients at a rate at least twice that of placebo) are shown in TABLE 2. It should be noted that one patient can report more than one reason for discontinuation and be counted more than once in this table.<br/>Adverse Events Occurring at an Incidence of 2% or More Among Citalopram Hydrobromide-Treated Patients: Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 1063 depressed patients who received citalopram hydrobromide at doses ranging from 10 mg/day to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration. Events included are those occurring in 2% or more of patients treated with citalopram hydrobromide and for which the incidence in patients treated with citalopram hydrobromide was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The only commonly observed adverse event that occurred in citalopram hydrobromide patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see TABLE 3).<br/>Other Events Observed During the Premarketing Evaluation of Citalopram Hydrobromide: Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by patients treated with citalopram hydrobromide at multiple doses in a range of 10 to 80 mg/day during any phase of a trial within the premarketing database of 4422 patients. All reported events are included except those already listedin Table 3 or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those occurring in only one patient. It is important to emphasize that, although the events reported occurred during treatment with citalopram hydrobromide, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Cardiovascular:Frequent: tachycardia, postural hypotension, hypotension. Infrequent: hypertension, bradycardia, edema (extremities), angina pectoris, extrasystoles, cardiac failure, flushing, myocardial infarction, cerebrovascular accident, myocardial ischemia. Rare: transient ischemic attack, phlebitis, atrial fibrillation, cardiac arrest, bundle branch block. Central and Peripheral Nervous System Disorders:Frequent: paresthesia, migraine. Infrequent: hyperkinesia, vertigo, hypertonia, extrapyramidal disorder, leg cramps, involuntary muscle contractions, hypokinesia, neuralgia, dystonia, abnormal gait, hypesthesia, ataxia. Rare: abnormal coordination, hyperesthesia, ptosis, stupor. Endocrine Disorders:Rare: hypothyroidism, goiter, gynecomastia. Gastrointestinal Disorders:Frequent: saliva increased, flatulence. Infrequent: gastritis, gastroenteritis, stomatitis, eructation, hemorrhoids, dysphagia, teeth grinding, gingivitis, esophagitis. Rare: colitis, gastric ulcer, cholecystitis, cholelithiasis, duodenal ulcer, gastroesophageal reflux, glossitis, jaundice, diverticulitis, rectal hemorrhage, hiccups. General:Infrequent: hot flushes, rigors, alcohol intolerance, syncope, influenza-like symptoms. Rare: hayfever. Hemic and Lymphatic Disorders:Infrequent: purpura, anemia, epistaxis, leukocytosis, leucopenia, lymphadenopathy. Rare: pulmonary embolism, granulocytopenia, lymphocytosis, lymphopenia, hypochromic anemia, coagulation disorder, gingival bleeding. Metabolic and Nutritional Disorders:Frequent: decreased weight, increased weight. Infrequent: increased hepatic enzymes, thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance. Rare: bilirubinemia, hypokalemia, obesity, hypoglycemia, hepatitis, dehydration. Musculoskeletal System Disorders:Infrequent: arthritis, muscle weakness, skeletal pain. Rare: bursitis, osteoporosis. Psychiatric Disorders:Frequent: impaired concentration, amnesia, apathy, depression, increased appetite, aggravated depression, suicide attempt, confusion. Infrequent: increased libido, aggressive reaction, paroniria, drug dependence, depersonalization, hallucination, euphoria, psychotic depression, delusion, paranoid reaction, emotional lability, panic reaction, psychosis. Rare: catatonic reaction, melancholia. Reproductive Disorders/Female*:Frequent: amenorrhea. Infrequent: galactorrhea, breast pain, breast enlargement, vaginal hemorrhage. * % based on female subjects only: 2955 Respiratory System Disorders:Frequent: coughing. Infrequent: bronchitis, dyspnea, pneumonia. Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased. Skin and Appendages Disorders:Frequent: rash, pruritus. Infrequent: photosensitivity reaction, urticaria, acne, skin discoloration, eczema, alopecia, dermatitis, skin dry, psoriasis. Rare: hypertrichosis, decreased sweating, melanosis, keratitis, cellulitis, pruritus ani. Special Senses:Frequent: accommodation abnormal, taste perversion. Infrequent: tinnitus, conjunctivitis, eye pain. Rare: mydriasis, photophobia, diplopia, abnormal lacrimation, cataract, taste loss. Urinary System Disorders:Frequent: polyuria. Infrequent: micturition frequency, urinary incontinence, urinary retention, dysuria. Rare: facial edema, hematuria, oliguria, pyelonephritis, renal calculus, renal pain.<br/>Other Events Observed During the Postmarketing Evaluation of Citalopram Hydrobromide: It is estimated that over 30 million patients have been treated with citalopram hydrobromide since market introduction. Although no causal relationship to citalopram hydrobromide treatment has been found, the following adverse events have been reported to be temporally associated with citalopram hydrobromide treatment, and have not been described elsewhere in labeling: acute renal failure, akathisia, allergic reaction, anaphylaxis, angioedema, choreoathetosis, chest pain, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema multiforme, gastrointestinal hemorrhage, glaucoma, grand mal convulsions, hemolytic anemia, hepatic necrosis, myoclonus, neuroleptic malignant syndrome, nystagmus, pancreatitis, priapism, prolactinemia, prothrombin decreased, QT prolonged, rhabdomyolysis, serotonin syndrome, spontaneous abortion, thrombocytopenia, thrombosis, ventricular arrhythmia, torsades de pointes, and withdrawal syndrome.
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Neomycin occasionally causes skin sensitization. Ototoxicity
and nephrotoxicity have also been reported.
Adverse reactions have occurred with topical use of antibiotic combinations
including neomycin, bacitracin, and polymyxin B. Exact incidence figures are
not available since no denominator of treated patients is available. The reaction
occurring most often is allergic sensitization. In one clinical study, using
a 20% neomycin patch, neomycin-induced allergic skin reactions occurred in
two of 2,175 (0.09%) individuals in the general population.In
another study, the incidence was found to be approximately 1%. The
following local adverse reactions have been reported with topical corticosteroids,
especially under occlusive dressings: burning, itching, irritation, dryness,
folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral
dermatitis, allergic contact dermatitis, maceration of the skin, secondary
infection, skin atrophy, striae, and miliaria. When
steroid preparations are used for long periods of time in intertriginous areas
or over extensive body areas, with or without occlusive non-permeable dressings,
striae may occur; also there exists the possibility of systemic side effects
when steroid preparations are used over large areas or for a long period of
time.
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A single case (approximately one percent of patients studied) of acneform eruption occurred with use of combined nystatin and triamcinolone acetonide in clinical studies. Nystatin is virtually nontoxic and nonsensitizing and is well tolerated by all age groups, even during prolonged use. Rarely, irritation may occur. The following local adverse reactions are reported infrequently with topical corticosteroids (reactions are listed in an approximate decreasing order of occurrence): burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.
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The most frequently reported adverse events in the overall study population were transient decreased vision, fever, foreign body sensation, headache, transient ocular burning, ocular pain or discomfort, pharyngitis and photophobia. These events occurred in approximately 1-3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness, and ocular itching.
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Endocrine and urogenital: Female: the most common side effects of androgen therapy are amenorrhea and other menstrual irregularities; inhibition of gonadotropin secretion; and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman, androgens can cause virilizationof external genitalia of the female fetus. Male: Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosage.<br/>Skin and appendages: Hirsutism, male pattern of baldness, seborrhea, and acne.<br/>Fluid and electrolyte disturbances: Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.<br/>Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis .<br/>Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.<br/>Nervous system: Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.<br/>Allergic: Hypersensitivity, including skin manifestations and anaphylactoid reactions.
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Side effects most commonly reported were drowsiness,
fatigue, and ataxia; venous thrombosis and phlebitis at the site of
injection. Other adverse reactions less frequently reported include: Central Nervous System: Confusion, depression, dysarthria, headache, hypoactivity, slurred
speech, syncope, tremor, vertigo. Gastrointestinal: Constipation, nausea. Genitourinary: Incontinence,
changes in libido, urinary retention. Cardiovascular: Bradycardia, cardiovascular
collapse, hypotension. EENT: Blurred vision, diplopia, nystagmus. Skin: Urticaria, skin rash. Other: Hiccups,
changes in salivation, neutropenia, jaundice. Paradoxical reactions
such as acute hyperexcited states, anxiety, hallucinations, increased
muscle spasticity, insomnia, rage, sleep disturbances and stimulation
have been reported; should these occur, use of the drug should be
discontinued. Minor changes in EEG patterns, usually low-voltage fast
activity, have been observed in patients during and after diazepam
therapy and are of no known significance. In
peroral endoscopic procedures, coughing, depressed respiration, dyspnea,
hyperventilation, laryngospasm, and pain in throat or chest have been
reported. Because of isolated reports of neutropenia
and jaundice, periodic blood counts and liver function tests are advisable
during long-term therapy.
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Side effects most commonly reported were drowsiness,
fatigue, and ataxia; venous thrombosis and phlebitis at the site of
injection. Other adverse reactions less frequently reported include: Central Nervous System: Confusion, depression, dysarthria, headache, hypoactivity, slurred
speech, syncope, tremor, vertigo. Gastrointestinal: Constipation, nausea. Genitourinary: Incontinence,
changes in libido, urinary retention. Cardiovascular: Bradycardia, cardiovascular
collapse, hypotension. EENT: Blurred vision, diplopia, nystagmus. Skin: Urticaria, skin rash. Other: Hiccups,
changes in salivation, neutropenia, jaundice. Paradoxical reactions
such as acute hyperexcited states, anxiety, hallucinations, increased
muscle spasticity, insomnia, rage, sleep disturbances and stimulation
have been reported; should these occur, use of the drug should be
discontinued. Minor changes in EEG patterns, usually low-voltage fast
activity, have been observed in patients during and after diazepam
therapy and are of no known significance. In
peroral endoscopic procedures, coughing, depressed respiration, dyspnea,
hyperventilation, laryngospasm, and pain in throat or chest have been
reported. Because of isolated reports of neutropenia
and jaundice, periodic blood counts and liver function tests are advisable
during long-term therapy.
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Benazepril has been evaluated for safety in over 6000 patients with hypertension; over 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was comparable in benazepril and placebo patients. The reported side effects were generally mild and transient, and there was no relation between side effects and age, duration of therapy, or total dosage within the range of 2 to 80 mg. Discontinuation of therapy because of a side effect was required in approximately 5% of U.S. patients treated with benazepril and in 3% of patients treated with placebo. The most common reasons for discontinuation were headache (0.6%) and cough (0.5%) . The side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with benazepril are shown below.<br/>Cardiovascular: Symptomatic hypotension was seen in 0.3% of patients, postural hypotension in 0.4%, and syncope in 0.1%; these reactions led to discontinuation of therapy in 4 patients who had received benazepril monotherapy and in 9 patients who had received benazepril with hydrochlorothiazide . Other reports included angina pectoris, palpitations, and peripheral edema.<br/>Renal: Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving benazepril, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine.<br/>Fetal/Neonatal Morbidity and Mortality: See WARNINGS, Fetal/Neonatal Morbidity and Mortality.<br/>Angioedema: Angioedema has been reported in patients receiving ACE inhibitors. During clinical trials in hypertensive patients with benazepril, 0.5% of patients experienced edema of the lips or face without other manifestations of angioedema. Angioedema associated with laryngeal edema and/or shock may be fatal. If angioedema of the face, extremities, lips, tongue, or glottis and/or larynx occurs, treatment with benazepril should be discontinued and appropriate therapy instituted immediately .<br/>Dermatologic: Stevens-Johnson syndrome, pemphigus, apparent hypersensitivity reactions (manifested by dermatitis, pruritus, or rash), photosensitivity, and flushing.<br/>Gastrointestinal: Pancreatitis, constipation, gastritis, vomiting, and melena.<br/>Hematologic: Thrombocytopenia and hemolytic anemia.<br/>Neurologic and Psychiatric: Anxiety, decreased libido, hypertonia, insomnia, nervousness, and paresthesia.<br/>Other: Asthma, bronchitis, dyspnea, sinusitis, urinary tract infection, frequent urination, infection, arthritis, impotence, alopecia, arthralgia, myalgia, asthenia, and sweating. Another potentially important adverse experience, eosinophilic pneumonitis, has been attributed to other ACE inhibitors. The following adverse events of unknown frequency have been reported during post-marketing use of benazepril: small bowel angioedema, anaphylactoid reactions, hyperkalemia, agranulocytosis, and neutropenia.<br/>Pediatric Patients: The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients. Infants below the age of 1 year should not be given ACE inhibitors due to concerns over possible effects on kidney development. The long-term effects of benazepril on growth and development have not been studied.<br/>Clinical Laboratory Test Findings:<br/>Creatinine and Blood Urea Nitrogen: Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving benazepril, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine. None of these increases required discontinuation of treatment. Increases in these laboratory values are more likely to occur in patients with renal insufficiency or those pretreated with a diuretic and, based on experience with other ACE inhibitors, would be expected to be especially likely in patients with renal artery stenosis .<br/>Potassium: Since benazepril decreases aldosterone secretion, elevation of serum potassium can occur. Potassium supplements and potassium-sparing diuretics should be given with caution, and the patient's serum potassium should be monitored frequently .<br/>Hemoglobin: Decreases in hemoglobin (a low value and a decrease of 5 g/dL) were rare, occurring in only 1 of 2,014 patients receiving benazepril alone and in 1 of 1,357 patients receiving benazepril plus a diuretic. No U.S. patients discontinued treatment because of decreases in hemoglobin.<br/>Other (causal relationships unknown): Clinically important changes in standard laboratory tests were rarely associated with benazepril administration. Elevations of uric acid, blood glucose, serum bilirubin, and liver enzymes have been reported, as have scattered incidents of hyponatremia, electrocardiographic changes, leukopenia, eosinophilia, and proteinuria. In U.S. trials, less than 0.5% of patients discontinued treatment because of laboratory abnormalities.
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| dailymed-drugs:168 |
Nervousness and insomnia are the most common adverse reactions but are usually controlled by reducing dosage and omitting the drug in the afternoon or evening. Other reactions include hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; blood pressure and pulse changes, both up and down; tachycardia; angina; cardiac arrhythmia; abdominal pain; weight loss during prolonged therapy. There have been rare reports of Tourette's syndrome. Toxic psychosis has been reported. Although a definite causal relationship has not been established, the following have been reported in patients taking this drug: instances of abdominal liverfunction, ranging from transaminase elevation to hepatic coma; isolated cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood; a few instances of scalp hair loss. Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a ten year old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed above may also occur.
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| dailymed-drugs:170 |
Hypoglycemia: See Precautions and Overdosage Sections.<br/>Gastrointestinal Reactions: Cholestatic jaundice and hepatitis may occur rarely; MICRONASE Tablets should be discontinued if this occurs. Liver function abnormalities, including isolated transaminase elevations, have been reported. Gastrointestinal disturbances, eg, nausea, epigastric fullness, and heartburn are the most common reactions, having occurred in 1.8% of treated patients during clinical trials. They tend to be dose related and may disappear when dosage is reduced.<br/>Dermatologic Reactions: Allergic skin reactions, eg, pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions occurred in 1.5% of treated patients during clinical trials. These may be transient and may disappear despite continued use of MICRONASE; if skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.<br/>Hematologic Reactions: Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas.<br/>Metabolic Reactions: Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas; however, hepatic porphyria has not been reported with MICRONASE and disulfiram-like reactions have been reported very rarely. Cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.<br/>Other Reactions: Changes in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. These are thought to be related to fluctuation in glucose levels. In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.
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| dailymed-drugs:171 |
Approximately 550 patients with AML have received idarubicin in combination with cytarabine in controlled clinical trials worldwide. In addition, over 550 patients with acute leukemia have been treated in uncontrolled trials utilizing idarubicin as a single agent or in combination. The table below lists the adverse experiences reported in U.S. Study 2 and is representative of the experiences in other studies. These adverse experiences constitute all reported or observed experiences, including those not considered to be drug related. Patients undergoing induction therapy for AML are seriously ill due to their disease, are receiving multiple transfusions, and concomitant medications including potentially toxic antibiotics and antifungal agents. The contribution of the study drug to the adverse experience profile is difficult to establish. The duration of aplasia and incidence of mucositis were greater on the IDR arm than the DNR arm, especially during consolidation in some U.S. controlled trials . The following information reflects experience based on U.S. controlled clinical trials.<br/>Myelosuppression: Severe myelosuppression is the major toxicity associated with idarubicin therapy, but this effect of the drug is required in order to eradicate the leukemic clone. During the period of myelosuppression, patients are at risk of developing infection and bleeding which may be life-threatening or fatal.<br/>Gastrointestinal: Nausea and/or vomiting, mucositis, abdominal pain and diarrhea were reported frequently, but were severe (equivalent to WHO Grade 4) in less than 5% of patients. Severe enterocolitis with perforation has been reported rarely. The risk of perforation may be increased by instrumental intervention. The possibility of perforation should be considered in patients who develop severe abdominal pain and appropriate steps for diagnosis and management should be taken.<br/>Dermatologic: Alopecia was reported frequently and dermatologic reactions including generalized rash, urticaria and a bullous erythrodermatous rash of the palms and soles have occurred. The dermatologic reactions were usually attributed to concomitant antibiotic therapy. Local reactions including hives at the injection site have been reported. Recall of skin reaction due to prior radiotherapy has occurred with idarubicin administration.<br/>Hepatic and Renal: Changes in hepatic and renal function tests have been observed. These changes were usually transient and occurred in the setting of sepsis and while patients were receiving potentially hepatotoxic and nephrotoxic antibiotics and antifungal agents. Severe changes in renal function (equivalent to WHO Grade 4) occurred in no more than 1% of patients, while severe changes in hepatic function (equivalentto WHO Grade 4) occurred in less than 5% of patients.<br/>Cardiac: Congestive heart failure (frequently attributed to fluid overload), serious arrhythmias including atrial fibrillation, chest pain, myocardial infarction and asymptomatic declines in LVEF have been reported in patients undergoing induction therapy for AML. Myocardial insufficiency and arrhythmias were usually reversible and occurred in the setting of sepsis, anemia and aggressive intravenous fluid administration. The events were reported more frequently in patients over age 60 years and in those with pre-existing cardiac disease.
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| dailymed-drugs:172 |
An increased risk of the
following serious adverse reactions (see WARNINGS section for additional
information) has been associated with the use of oral contraceptives: Thromboembolic and thrombotic
disorders and other vascular problems (including thrombophlebitis
and venous thrombosis with or without pulmonary embolism, mesenteric
thrombosis, arterial thromboembolism, myocardial infarction, cerebral
hemorrhage, cerebral thrombosis, transient ischemic attack), carcinoma
of the reproductive organs and breasts, hepatic neoplasia/liver disease
(including hepatic adenomas or benign liver tumors), ocular lesions
(including retinal vascular thrombosis), gallbladder disease, carbohydrate
and lipid effects, elevated blood pressure, and headache including
migraine. The following
adverse reactions have been reported in patients receiving oral contraceptives
and are believed to be drug related (alphabetically listed): AcneAmenorrheaAnaphylactic/anaphylactoid
reactions, including urticaria, angioedema, and severe reactions with
respiratory and circulatory symptomsBreast changes: tenderness,
pain, enlargement, secretionBudd-Chiari syndromeCervical
erosion and secretion, change inCholestatic jaundiceChorea,
exacerbation ofColitisContact lenses, intolerance toCorneal curvature (steepening), change inDizzinessEdema/fluid
retentionErythema multiformeErythema nodosumFocal nodular
hyperplasiaGastrointestinal symptoms (such as abdominal pain,
cramps, and bloating)HirsutismInfertility after discontinuation
of treatment, temporaryLactation, diminution in, when given immediately
postpartumLibido, change inMelasma/chloasma which may persistMenstrual flow, change inMood changes, including depressionNauseaNervousnessPancreatitisPorphyria, exacerbation
ofRash (allergic)Scalp hair, loss ofSerum folate levels,
decrease inSpottingSystemic lupus erythematosus, exacerbation
ofUnscheduled bleedingVaginitis, including candidiasisVaricose veins, aggravation ofVomitingWeight or appetite
(increase or decrease), change in The following adverse reactions have been reported in users of oral
contraceptives:CataractsCystitis-like syndromeDysmenorrheaHemolytic uremic syndromeHemorrhagic eruptionOptic neuritis,
which may lead to partial or complete loss of visionPremenstrual
syndromeRenal function, impaired
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| dailymed-drugs:173 |
Side effects following this relatively high dose urography are usually mild and transitory and do not appear to occur more frequently or severely than those induced by "standard dose" urography. Nausea, facial flushing, and emesis are not uncommon reactions.
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| dailymed-drugs:174 |
Because clinical trials
are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared
to rates in the clinical trials of another drug and may not reflect
the rates observed in practice. The adverse reaction information from
clinical trials does, however, provide a basis for identifying the
adverse events that appear to be related to drug use and for approximating
rates. The data described
below reflect exposure to ELITEK in 703 patients [63% male, 37% female;
median age 10 years (range 10 days to 88 years); 73% Caucasian, 9%
African, 4% Asian, 14% other/unknown]. ELITEK was studied for adverse
reactions, regardless of severity, in 347 patients (265 pediatric
and 82 adults) enrolled in one active-controlled trial (Study 1),
two uncontrolled trials (Studies 2 and 3), and one uncontrolled safety
trial (n=82). Additionally, an expanded access experience enrolled
356 patients, for whom reliably collected data were limited to serious
adverse reactions. Among the 703 patients for whom serious adverse reactions were assessed,
the most serious adverse reactions caused by ELITEK were allergic
reactions including anaphylaxis (<1%), rash (1%), hemolysis (<1%),
and methemoglobinemia (<1%) . The commonly observed serious adverse reactions were fever (5%),
neutropenia with fever (4%), respiratory distress (3%), sepsis (3%),
neutropenia (2%), and mucositis (2%). The following additional serious
adverse reactions were observed in���1% of patients regardless
of causality: acute renal failure, arrhythmia, cardiac failure, cardiac
arrest, cellulitis, cerebrovascular disorder, chest pain, convulsions,
cyanosis, diarrhea, dehydration, hot flushes, ileus, infection, intestinal
obstruction, hemorrhage, myocardial infarction, paresthesia, pancytopenia,
pneumonia, pulmonary edema, pulmonary hypertension, retinal hemorrhage,
rigors, thrombosis, and thrombophlebitis. Among the 347 patients for whom all adverse reactions regardless
of severity were assessed, the most frequently observed adverse reactions
(incidence���10%) were vomiting (50%), fever (46%), nausea (27%),
headache (26%), abdominal pain (20%), constipation (20%), diarrhea
(20%), mucositis (15%), and rash (13%). In Study 1, an active control
study, the following adverse events occurred more frequently in ELITEK-treated
subjects than allopurinol-treated subjects: vomiting, fever, nausea,
diarrhea, and headache. Although the incidence of rash was similar
in the two arms, severe rash (NCI CTC, Grade 3 or 4) was
reported only in one ELITEK-treated patient.<br/>Immunogenicity: ELITEK is immunogenic
in healthy volunteers, and can elicit antibodies that inhibit the
activity of rasburicase in vitro . In a study
of 28 healthy volunteers, the incidence of antibody responses to either
a single dose or to 5 daily doses was assessed. Binding antibodies
to rasburicase were detected by ELISA in 17/28 (61%) volunteers and
neutralizing antibodies were detected in 18/28 (64%) volunteers. Time
to detection of antibodies ranged from 1 to 6 weeks after ELITEK exposure.
In two subjects with extended follow-up, antibodies persisted for
333 and 494 days. The incidence of antibody responses in patients with hematologic
malignancy has not been adequately assessed. In clinical trials of
patients with hematologic malignancies, 24 of the 218 patients tested
(11%) developed antibodies by day 28 following ELITEK administration.
However, this is not a reliable estimate of the true incidence of
antibody responses in patients with hematologic malignancies, because
the data from the healthy volunteer study indicate that antibody may
not be detectable until some time point beyond day 28. The incidence of antibody
responses detected is highly dependent on the sensitivity and specificity
of the assay, which have not been fully evaluated. Additionally, the
observed incidence of antibody positivity in an assay may be influenced
by several factors, including serum sampling, timing and methodology,
concomitant medications, and underlying disease. For these reasons,
comparison of the incidence of antibodies to ELITEK with the incidence
of antibodies to other products may be misleading.
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| dailymed-drugs:175 |
The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity. Body as a WholeWeakness CardiovascularHypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates,
narcotics or antihypertensive drugs) DigestivePancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis,
cramping, constipation, gastric irritation, nausea, anorexia HematologicAplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia HypersensitivityAnaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory
distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria,
rash, purpura MetabolicElectrolyte imbalance , hyperglycemia, glycosuria, hyperuricemia MusculoskeletalMuscle spasm Nervous System/PsychiatricVertigo, paresthesias, dizziness, headache, restlessness. RenalRenal failure, renal dysfunction, interstitial nephritis SkinErythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including
toxic epidermal necrolysis, alopecia Special SensesTransient blurred vision, xanthopsia UrogenitalImpotence Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
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| dailymed-drugs:176 |
In two multicenter clinical trials, a total of 270 patients received 750 mg Flagyl ER tablets orally once daily for 7 days, and 287 were treated with a comparator agent administered intravaginally once daily for 7 days. Most adverse events were described as being of mild or moderate severity. Among patients taking Flagyl ER who reported headaches, 10% considered them severe, and less than 2% of reported episodes of nausea were considered severe. Metallic taste was reported by 9% of patients taking Flagyl ER. Adverse events reported at���2% incidence for either treatment group, irrespective of treatment causality, are summarized in the table below. Vulvovaginal candidiasis is a recognized consequence of treatment with many anti-infective agents. In these multicenter clinical trials, there were no statistically significant differences in the incidence rates of yeast vaginitis for groups of patients treated with Flagyl ER or the vaginal comparator. The following reactions have also been reported during treatment with metronidazole: Central Nervous System: Two serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur. In addition, patients have reported dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia. Gastrointestinal: The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea reported by about 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting, diarrhea, epigastric distress, and abdominal cramping. Constipation has also been reported. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy. Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported. Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia. Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings. Hypersensitivity: Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever. Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance. Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling "serum sickness." If patients receiving metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache. A modification of the taste of alcoholic beverages has also been reported. Patients with Crohn's disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn's disease is not an approved indication for Flagyl ER 750 mg tablets.
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| dailymed-drugs:177 |
CLINICAL TRIALS: VIAGRA was administered to over 3700 patients (aged 19���87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year. In placebo-controlled clinical studies, the discontinuation rate due to adverse events for VIAGRA (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature. In trials of all designs, adverse events reported by patients receiving VIAGRA were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies. When VIAGRA was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported: Other adverse reactions occurred at a rate of>2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia. In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently. The following events occurred in<2% of patients in controlled clinical trials; a causal relationship to VIAGRA is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful: Body as a whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury. Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy. Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis. Hemic and Lymphatic: anemia and leukopenia. Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia. Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis. Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia. Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis. Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes. Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.<br/>POST-MARKETING EXPERIENCE:<br/>Cardiovascular and cerebrovascular: Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had preexisting cardiovascular riskfactors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors (see WARNINGS forfurther important cardiovascular information).<br/>Special senses: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors .<br/>Other events: Other events reported post-marketing to have been observed in temporal association with VIAGRA and not listed in the clinical trial adverse reactions section above include: Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia. Urogenital: prolonged erection, priapism , and hematuria. Special Senses: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/traction, paramacular edema and epistaxis. Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors .
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| dailymed-drugs:178 |
The most frequently reported adverse events were arrhythmia (6% of patients) and tachycardia (3%). Cardiopulmonary arrest, hypotension and myocardial infarction occurred in approximately 2% of patients. The following events occurred in approximately 1% or fewer of patients: angina, congestive heart failure, fever, hypertension, phlebitis and twitching. In
rare instances, allergic skin reactions have been reported with liothyronine sodium tablets.
|
| dailymed-drugs:179 |
Carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses. The only adverse reactions that have been observed have been with concomitant use of carbidopa with other drugs such as levodopa, and with carbidopa-levodopa combination products. When LODOSYN is administered concomitantly with levodopa or carbidopa-levodopa combination products, the most common adverse reactions have included dyskinesias such as choreiform, dystonic, and other involuntary movements, and nausea. Other adverse reactions reported with LODOSYN when administered concomitantly with levodopa alone or carbidopa-levodopa combination products were psychotic episodes including delusions, hallucinations, and paranoid ideation, depression with or without development of suicidal tendencies, and dementia. Convulsions also have occurred; however, a causal relationship with concomitant use of LODOSYN and levodopa has not been established. The following other adverse reactions have been reported with levodopa and carbidopa-levodopa combination products. These same adverse reactions may also occur when LODOSYN is administered with these products. Body as a Whole: abdominal pain and distress, asthenia, chest pain, fatigue. Cardiovascular: cardiac irregularities, hypertension, myocardial infarction, hypotension including orthostatic hypotension, palpitation, phlebitis, syncope. Gastrointestinal: anorexia, bruxism, burning sensation of the tongue, constipation, dark saliva, development of duodenal ulcer, diarrhea, dry mouth, dyspepsia, dysphagia, flatulence, gastrointestinal bleeding, gastrointestinal pain, heartburn, hiccups, sialorrhea, taste alterations, vomiting. Hematologic: hemolytic and non-hemolytic anemia, leukopenia, thrombocytopenia, agranulocytosis. Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schonlein purpura, bullous lesions (including pemphigus-like reactions). Metabolic: edema, weight gain, weight loss. Musculoskeletal: back pain, leg pain, muscle cramps, shoulder pain. Nervous System/Psychiatric: agitation, anxiety, ataxia, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), bradykinetic episodes ("on-off" phenomenon), confusion, decreased mental acuity, disorientation, euphoria, dizziness, dream abnormalities including nightmares, extrapyramidal disorder, falling, gait abnormalities, headache, increased tremor, insomnia, memory impairment, muscle twitching, nervousness, numbness, paresthesia, peripheral neuropathy, somnolence, trismus, activation of latent Horner's syndrome, increased libido. Respiratory: upper respiratory infection, dyspnea, pharyngeal pain, cough. Skin: flushing, increased sweating, malignant melanoma , rash, alopecia, dark sweat. Special Senses: oculogyric crises, diplopia, blurred vision, dilated pupils. Urogenital: dark urine, priapism, urinary frequency, urinary incontinence, urinary retention, urinary tract infection. Laboratory Tests: abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, bilirubin, blood urea nitrogen (BUN), Coombs test; elevated serum glucose; decreased hemoglobin and hematocrit; decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; white blood cells, bacteria and blood in the urine; protein and glucose in the urine. Miscellaneous: bizarre breathing patterns, faintness, hoarseness, hot flashes, malaise, neuroleptic malignant syndrome, sense of stimulation.
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| dailymed-drugs:180 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:743 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:874 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:2125 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:2232 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:2648 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:3109 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:3237 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:3246 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
|
| dailymed-drugs:3994 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
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| dailymed-drugs:4066 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
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| dailymed-drugs:1333 |
The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.
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| dailymed-drugs:182 |
Bacterial and fungal corneal ulcers have developed during treatment with gentamicin ophthalmic preparations. The most frequently reported adverse reactions are ocular burning and irritation upon drug instillation, non-specific conjunctivitis, conjunctival epithelial defects and conjunctival hyperemia. Other reactions which have occurred rarely are allergic reactions, thrombocytopenic purpura and hallucinations.
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| dailymed-drugs:184 |
Hypertension and Angina: Most adverse effects have been mild and transient. Central Nervous System: Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported. Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 to 100 patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported very rarely. Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients . Rhinitis has also been reported. Gastrointestinal: Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. Post-marketing experience reveals very rare reports of hepatitis, jaundice and non-specific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also beenreported. Hypersensitive Reactions: Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis has been reported. Miscellaneous: Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported. There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to metoprolol tartrate has not been definitely established). The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with metoprolol tartrate.<br/>Myocardial Infarction: Central Nervous System: Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear. Cardiovascular: In the randomized comparison of metoprolol tartrate and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported: Respiratory: Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients. Gastrointestinal: Nausea and abdominal pain have been reported in fewer than 1 of 100 patients. Dermatologic: Rash and worsened psoriasis have been reported, but a drug relationship is not clear. Miscellaneous: Unstable diabetes and claudication have been reported, but a drug relationship is not clear.<br/>Potential Adverse Reactions: A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol tartrate. Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular: Intensification of AV block . Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura. Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress.
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| dailymed-drugs:186 |
In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received amiodarone I.V. for at least 1 week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days. The most important treatment-emergent adverse effects were hypotension, asystole/cardiac arrest/electromechanical issociation (EMD), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse effects. The most common adverse effects leading to discontinuation of amiodarone I.V. therapy were hypotension (1.6%), asystole/cardiac arrest/EMD (1.2%), VT (1.1%), and cardiogenic shock (1%). The following table lists the most common (incidence���2%) treatment-emergent adverse events during amiodarone I.V. therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse events appeared to be dose-related. Other treatment-emergent possibly drug-related adverse events reported in less than 2% of patients receiving amiodarone I.V. in Wyeth-Ayerst controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.<br/>Postmarketing Reports: In postmarketing surveillance, hypotension (sometimes fatal), sinus arrest, anaphylactic/anaphylactoid reaction (including shock), angioedema, hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, renal impairment, renal insufficiency, acute renal failure, bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pleuritis, pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimesreversible with discontinuation of therapy), syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma, myopathy, muscle weakness, rhabdomyolysis, hallucination, confusional state, disorientation, delirium, epididymitis, and impotence also have been reported with amiodarone therapy. Also, in patients receiving recommended dosages of amiodarone I.V., there have been postmarketing reports of the following injection site reactions: pain, erythema, edema, pigment changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing .
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| dailymed-drugs:187 |
Gastrointestinal: Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea have been noted in some patients. Although Clostridium difficile has been shown in vitro to be sensitive to rifampin, pseudomembranous colitis has been reported with the use of rifampin (and other broad spectrum antibiotics). Therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Rarely, hepatitis or a shock-like syndrome with hepatic involvement and abnormal liver function tests has been reported.<br/>Hematologic: Thrombocytopenia has occurred primarily with high dose intermittent therapy, but has also been noted after resumption of interrupted treatment. It rarely occurs during well supervised daily therapy. This effect is reversible if the drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampin administration has been continued or resumed after the appearance of purpura. Rare reports of disseminated intravascular coagulation have been observed. Transient leukopenia, hemolytic anemia, and decreased hemoglobin have been observed.<br/>Central Nervous System: Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, pains in extremities, and generalized numbness have been observed. Psychosis has been rarely reported.<br/>Ocular: Visual disturbances have been observed.<br/>Endocrine: Menstrual disturbances have been observed. Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.<br/>Renal: Elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been noted. These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted.<br/>Dermatologic: Cutaneous reactions are mild and self-limiting and do not appear to be hypersensitivity reactions. Typically, they consist of flushing and itching with or without a rash. More serious cutaneous reactions which may be due to hypersensitivity occur but are uncommon.<br/>Hypersensitivity Reactions: Occasionally, pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme including Stevens-Johnson Syndrome, toxic epidermal necrolysis, vasculitis, eosinophilia, sore mouth, sore tongue, and conjunctivitis have been observed. Anaphylaxis has been reported rarely.<br/>Miscellaneous: Rare reports of myopathy and muscular weakness have also been observed. Edema of the face and extremities has been reported. Other reactions reported to have occurred with intermittent dosage regimens include���flu syndrome���(such as episodes of fever, chills, headache, dizziness, and bone pain), shortness of breath, wheezing, decrease in blood pressure and shock. The���flu syndrome���may also appear if rifampin is taken irregularly by the patient or if daily administration is resumed after a drug free interval.
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| dailymed-drugs:188 |
The table below shows the frequencies of the adverse events that occurred in>5% of the subjects in three placebo-controlled North American studies in which patients in the active treatment arm received 30 mg, 60 mg, 120 mg, or 240 mg of isosorbide mononitrate as Isosorbide Mononitrate Tablets once daily. In parentheses, the same table shows the frequencies with which these adverse events were associated with the discontinuation of treatment. Overall, 8% of the patients who received 30 mg, 60 mg, 120 mg, or 240 mg of isosorbide mononitrate in the three placebo-controlled North American studies discontinued treatment because of adverse events. Most of these discontinued because of headache. Dizziness was rarely associated with withdrawal from these studies. Since headache appears to be a dose-related adverse effect and tends to disappear with continued treatment, it is recommended that isosorbide mononitrate treatment be initiated at low doses for several days before being increasedto desired levels. In addition, the three North American trials were pooled with 11 controlled trials conducted in Europe. Among the 14 controlled trials, a total of 711 patients were randomized to Isosorbide Mononitrate Tablets. When the pooled data were reviewed, headache and dizziness were the only adverse events that were reported by>5% of patients. Other adverse events, each reported by���5% of exposed patients, and in many cases of uncertain relation to drug treatment, were: Autonomic Nervous System Disorders: Dry mouth, hot flushes. Body as a Whole: Asthenia, back pain, chest pain, edema, fatigue, fever, flu-like symptoms, malaise, rigors. Cardiovascular Disorders, General: Cardiac failure, hypertension, hypotension. Central and Peripheral Nervous System Disorders: Dizziness, headache, hypoesthesia, migraine, neuritis, paresis, paresthesia, ptosis, tremor, vertigo. Gastrointestinal System Disorders: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gastric ulcer, gastritis, glossitis, hemorrhagic gastric ulcer, hemorrhoids, loose stools, melena, nausea, vomiting. Hearing and Vestibular Disorders: Earache, tinnitus, tympanic membrane perforation. Heart Rate and Rhythm Disorders: Arrhythmia, arrhythmia atrial, atrial fibrillation, bradycardia, bundle branch block, extrasystole, palpitation, tachycardia, ventricular tachycardia. Liver and Biliary System Disorders: SGOT increase, SGPT increase. Metabolic and Nutritional Disorders: Hyperuricemia, hypokalemia. Musculoskeletal System Disorders: Arthralgia, frozen shoulder, muscle weakness, musculoskeletal pain, myalgia, myositis, tendon disorder, torticollis. Myo-, Endo-, Pericardial, and Valve Disorders: Angina pectoris aggravated, heart murmur, heart sound abnormal, myocardial infarction, Q wave abnormality. Platelet, Bleeding, and Clotting Disorders: Purpura, thrombocytopenia. Psychiatric Disorders: Anxiety, concentration impaired, confusion, decreased libido, depression, impotence, insomnia, nervousness, paroniria, somnolence. Red Blood Cell Disorder: Hypochromic anemia. Reproductive Disorders, Female: Atrophic vaginitis, breast pain. Resistance Mechanism Disorders: Bacterial infection, moniliasis, viral infection. Respiratory System Disorders: Bronchitis, bronchospasm, coughing, dyspnea, increased sputum, nasal congestion, pharyngitis, pneumonia, pulmonary infiltration, rales, rhinitis, sinusitis. Skin and Appendages Disorders: Acne, hair texture abnormal, increased sweating, pruritus, rash, skin nodule. Urinary System Disorders: Polyuria, renal calculus, urinary tract infection. Vascular (Extracardiac) Disorders: Flushing, intermittent claudication, leg ulcer, varicose vein. Vision Disorders: Conjunctivitis, photophobia, vision abnormal. In addition, the following spontaneous adverse event has been reported during the marketing of isosorbide mononitrate: syncope.
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| dailymed-drugs:189 |
���(See WARNINGS for possible adverse effects on the fetus)���breakthrough bleeding���spotting���change in menstrual flow���amenorrhea���headache���nervousness���dizziness���edema���change in weight (increase or decrease)���changes in cervical erosion and cervical secretions���cholestatic jaundice, including neonatal jaundice���breast tenderness and galactorrhea���skin sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash���acne, alopecia and hirsutism���rash (allergic) with and without pruritis���anaphylactoid reactions and anaphylaxis���mental depression���pyrexia���fatigue���insomnia���nausea���somnolence In a few instances there have been undesirable sequelae at the site of injection, such as residual lump, change in color of skin, or sterile abscess. A statistically significant association has been demonstrated between use of estrogen-progestin combination drugs and pulmonary embolism and cerebral thrombosis and embolism. For this reason patients on progestin therapy should be carefully observed. There is also evidence suggestive of an association with neuro-ocular lesions, e.g. retinal thrombosis and optic neuritis. The following adverse reactions have been observed in patients receiving estrogen-progestin combination drugs: ���rise in blood pressure in susceptible individuals���premenstrual syndrome���changes in libido���changes in appetite���cystitis-like syndrome���headache���nervousness���fatigue���backache���hirsutism���loss of scalp hair���erythema multiforma���erythema nodosum���hemorrhagic eruption���itching���dizziness The following laboratory results may be altered by the use of estrogen-progestin combination drugs: ���increased sulfobromophthalein retention and other hepatic function tests���coagulation tests: increase in prothrombin factors VII, VIII, IX, and X���metyrapone test���pregnanediol determinations���thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in Tuptake values
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| dailymed-drugs:190 |
In 1 of 3 placebo���controlled, continuous���dosing trials and 1 placebo���controlled, intermittent���dosing trial of fluoxetine in PMDD, treatment���emergent adverse events reporting rates were assessed. The information from Table 2 included under ADVERSE REACTIONS is based on data from the continuous���dosing trial at the recommended dose of SARAFEM (SARAFEM 20 mg, N=104; placebo, N=108) and data from the intermittent���dosing trial of fluoxetine in PMDD (SARAFEM 20 mg, N=86; placebo, N=88). In addition, a broader set of information on treatment���emergent adverse events in the population of female patients, 18 to 45 years of age from the US placebo���controlled depression, OCD, and bulimia clinical trials, is presented for comparison (see Table 3). Adverse events were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a limited (i.e., reduced) number of standardized event categories. In the tables and tabulations that follow, COSTART Dictionary terminology has been used to classify reported adverse events. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment���emergent adverse event of the type listed. An event was considered treatment���emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it. The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribingphysician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied. Incidence in placebo���controlled PMDD clinical trials���Table 2 enumerates the most common treatment���emergent adverse events associated with the use of SARAFEM 20 mg (incidence of at least 5% for SARAFEM 20 mg and greater than placebo) for the treatment of PMDD. Incidence in US depression, OCD, and bulimia placebo���controlled clinical trials (excluding data from extensions of trials)���Table 3 enumerates the most common treatment���emergent adverse events associated with the use of fluoxetine up to 80 mg (incidence of at least 2% for fluoxetine and greater than placebo) in female patients ages 18 to 45 years from US placebo���controlled clinical trials in the treatment of depression, OCD, and bulimia. Associated with discontinuation in two placebo���controlled PMDD clinical trials���In a continuous���dosing PMDD placebo���controlled trial, the most common adverse event (incidence at least 2% for SARAFEM 20 mg and greater than placebo) associated with discontinuation was nausea (3% for SARAFEM 20 mg, N=104 and 1% for placebo, N=108). In an intermittent���dosing placebo���controlled trial, no events associated with discontinuation reached an incidence of 2% for SARAFEM 20 mg. In these clinical trials, more than one event may have been recorded as the cause of discontinuation. Associated with discontinuation in US depression, OCD, and bulimia placebo���controlled clinical trials (excluding data from extensions of trials)���In female patients age 18 to 45 years in US depression, OCD, and bulimia placebo���controlled clinical trials combined, which collected a single primary event associated with discontinuation (incidence at least 1% for fluoxetine and at least twice that for placebo), insomnia (1%, N=561) was the only event reported. Female sexual dysfunction with SSRIs���Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a mood���related disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance, cited in product labeling, are likely to underestimate their actual incidence. For example, in women (age 18 to 45) receiving fluoxetine for indications other than PMDD, decreased libido was seen at an incidence of 4% for fluoxetine compared with 1% for placebo. There have been spontaneous reportsin women (age 18 to 45) taking fluoxetine for indications other than PMDD of orgasmic dysfunction, including anorgasmia. There are no adequate and well���controlled studies examining sexual dysfunction with fluoxetine treatment. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects. Other Events Observed in US Clinical Trials Following is a list of all treatment���emergent adverse events reported at anytime by females and males taking fluoxetine in all US clinical trials for conditions other than PMDD as of May 8, 1995 (10,782 patients) except (1) those listed in the body or footnotes of Tables 2 or 3 above or elsewhere in labeling; (2) those for which the COSTART terms were uninformative or misleading; (3) those events for which a causal relationship to fluoxetine use was considered remote; (4) events occurring in only 1 patient treated with fluoxetine and which did not have a substantial probability of being acutely life���threatening; and (5) events that could only occur in males. Events are classified within body system categories using the following definitions: frequent adverse events are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients. Body as a Whole���Frequent: chest pain and chills; Infrequent: chills and fever, face edema, intentional overdose, malaise, pelvic pain, suicide attempt; Rare: acute abdominal syndrome, hypothermia, intentional injury, neuroleptic malignant syndrome, photosensitivity reaction. Cardiovascular System���Frequent: hemorrhage, hypertension; Infrequent: angina pectoris, arrhythmia, congestive heart failure, hypotension, migraine, myocardial infarct, postural hypotension, syncope, tachycardia, vascular headache; Rare: atrial fibrillation, bradycardia, cerebral embolism, cerebral ischemia, cerebrovascular accident, extrasystoles, heart arrest, heart block, pallor, peripheral vascular disorder, phlebitis, shock, thrombophlebitis, thrombosis, vasospasm, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation. Digestive System���Frequent: increased appetite, nausea and vomiting; Infrequent: aphthous stomatitis, cholelithiasis, colitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, glossitis, gum hemorrhage, hyperchlorhydria, increased salivation, liver function tests abnormal, melena, mouth ulceration, nausea/vomiting/diarrhea, stomach ulcer, stomatitis, thirst; Rare: biliary pain, bloody diarrhea, cholecystitis, duodenal ulcer, enteritis, esophageal ulcer, fecal incontinence, gastrointestinal hemorrhage, hematemesis, hemorrhage of colon, hepatitis, intestinal obstruction, liver fatty deposit, pancreatitis, peptic ulcer, rectal hemorrhage, salivary gland enlargement, stomach ulcer hemorrhage, tongue edema. Endocrine System���Infrequent: hypothyroidism; Rare: diabetic acidosis, diabetes mellitus. Hemic and Lymphatic System���Infrequent: anemia, ecchymosis; Rare: blood dyscrasia, hypochromic anemia, leukopenia, lymphedema, lymphocytosis, petechia, purpura, thrombocythemia, thrombocytopenia. Metabolic and Nutritional���Frequent: weight gain; Infrequent: dehydration, generalized edema, gout, hypercholesteremia, hyperlipemia, hypokalemia, peripheral edema; Rare: alcohol intolerance, alkaline phosphatase increased, BUN increased, creatine phosphokinase increased, hyperkalemia, hyperuricemia, hypocalcemia, iron deficiency anemia, SGPT increased. Musculoskeletal System���Infrequent: arthritis, bone pain, bursitis, leg cramps, tenosynovitis; Rare: arthrosis, chondrodystrophy, myasthenia, myopathy, myositis, osteomyelitis, osteoporosis, rheumatoid arthritis. Nervous System���Frequent: agitation, amnesia, confusion, emotional lability, paresthesia, and sleep disorder; Infrequent: abnormal gait, acute brain syndrome, akathisia, apathy, ataxia, buccoglossal syndrome, CNS depression, CNS stimulation, depersonalization, euphoria, hallucinations, hostility, hyperkinesia, hypertonia, hypesthesia, incoordination, libido increased, myoclonus, neuralgia, neuropathy, neurosis, paranoid reaction, personality disorder, psychosis, vertigo; Rare: abnormal electroencephalogram, antisocial reaction, circumoral paresthesia, coma, delusions, dysarthria, dystonia, extrapyramidal syndrome, foot drop, hyperesthesia, neuritis, paralysis, reflexes decreased, reflexes increased, stupor. Respiratory System���Infrequent: asthma, epistaxis, hiccup, hyperventilation; Rare: apnea, atelectasis, cough decreased, emphysema, hemoptysis, hypoventilation, hypoxia, larynx edema, lung edema, pneumothorax, stridor. Skin and Appendages���Infrequent: acne, alopecia, contact dermatitis, eczema, maculopapular rash, skin discoloration, skin ulcer, vesiculobullous rash; Rare: furunculosis, herpes zoster, hirsutism, petechial rash, psoriasis, purpuric rash, pustular rash, seborrhea. Special Senses���Frequent: ear pain, taste perversion, tinnitus; Infrequent: conjunctivitis, dry eyes, mydriasis, photophobia; Rare: blepharitis, deafness, diplopia, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, iritis, parosmia, scleritis, strabismus, taste loss, visual field defect. Urogenital System���Infrequent: abortion, albuminuria, amenorrhea, anorgasmia, breast enlargement, breast pain, cystitis, dysuria, female lactation, fibrocystic breast, hematuria, leukorrhea, menorrhagia, metrorrhagia, nocturia, polyuria, urinary incontinence, urinary retention, urinary urgency, vaginal hemorrhage; Rare: breast engorgement, glycosuria, hypomenorrhea, kidney pain, oliguria, uterine hemorrhage, uterine fibroids enlarged. Postintroduction Reports Voluntary reports of adverse events temporally associated with fluoxetine that have been received since market introduction of fluoxetine and that may have no causal relationship with the drug include the following: aplastic anemia, atrial fibrillation, cataract, cerebral vascular accident, cholestatic jaundice, confusion, dyskinesia (including, for example, a case of buccal���lingual���masticatory syndrome with involuntary tongue protrusion reported to develop in a 77���year���old female after 5 weeks of fluoxetine therapy and which completely resolved over the next few months following drug discontinuation), eosinophilic pneumonia, epidermal necrolysis, erythema multiforme, erythema nodosum, exfoliative dermatitis, gynecomastia, heart arrest, hepatic failure/necrosis, hyperprolactinemia, hypoglycemia, immune���related hemolytic anemia, kidney failure, misuse/abuse, movement disorders developing in patients with risk factors including drugs associated with such events and worsening of preexisting movement disorders, neuroleptic malignant syndrome���like events, optic neuritis, pancreatitis, pancytopenia, priapism, pulmonary embolism, pulmonary hypertension, QT prolongation, Stevens���Johnson syndrome, sudden unexpected death, suicidal ideation, thrombocytopenia, thrombocytopenic purpura, vaginal bleeding after drug withdrawal, ventricular tachycardia (including torsades de pointes���type arrhythmias), and violent behaviors.
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| dailymed-drugs:191 |
See WARNINGS, and Special Precautions
for Central Venous Nutrition. Reactions reported
in clinical studies as a result of infusion of the parenteral fluid were
water weight gain, edema, increase in BUN, and dilutional hyponatremia. Asterixis was reported to have worsened in one patient during infusion
of this amino acid formulation. Reactions which may
occur because of the solution or the technique of administration include
febrile response, infection at the site of injection, venous thrombosis
or phlebitis extending from the site of injection, extravasation and
hypervolemia. Symptoms may result
from an excess or deficit of one or more of the ions present in the
solution; therefore, frequent monitoring of electrolyte levels is
essential. Phosphorus
deficiency may lead to impaired tissue oxygenation and acute hemolytic
anemia. Relative to calcium, excessive phosphorus intake can precipitate
hypocalcemia with cramps, tetany and muscular hyperexcitability. If an adverse
reaction does occur, discontinue the infusion, evaluate the patient,
institute appropriate therapeutic countermeasures and save the remainder
of the fluid for examination if deemed necessary.
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| dailymed-drugs:192 |
Hypertension and Angina: Most adverse effects have been mild and transient.<br/>Central Nervous System: Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported.<br/>Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported very rarely.<br/>Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients . Rhinitis has also been reported.<br/>Gastrointestinal: Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. Post-marketing experience reveals very rare reports of hepatitis, jaundice and non-specific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported.<br/>Hypersensitive Reactions: Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis has been reported.<br/>Miscellaneous: Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported. There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to metoprolol tartrate has not been definitely established). The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with metoprolol tartrate.<br/>Myocardial Infarction:<br/>Central Nervous System: Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear.<br/>Cardiovascular: In the randomized comparison of metoprolol tartrate and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported:<br/>Respiratory: Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.<br/>Gastrointestinal: Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.<br/>Dermatologic: Rash and worsened psoriasis have been reported, but a drug relationship is not clear.<br/>Miscellaneous: Unstable diabetes and claudication have been reported, but a drug relationship is not clear.<br/>Potential Adverse Reactions: A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol tartrate.<br/>Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.<br/>Cardiovascular: Intensification of AV block .<br/>Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.<br/>Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress.<br/>Postmarketing Experience: The following adverse reactions have been reported during postapproval use of metoprolol tartrate: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.
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| dailymed-drugs:193 |
Hypervitaminosis D is characterized by effects on the following organ system: Renal:Impairment of renal function with polyuria, nocturia, polydipsia, hypercalciuria, reversible azotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or irreversible renal insufficiency which may result in death. CNS:Mental retardation. Soft Tissues:Widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs. Skeletal:Bone demineralization (osteoporosis) in adults occurs concomitantly. Decline in the average rate of linear growth and increased mineralization of bones in infants and children (dwarfism) vague aches, stiffness, and weakness. Gastrointestinal:Nausea, anorexia, constipation. Metabolic:Mild acidosis, anemia, weight loss.
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| dailymed-drugs:194 |
Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported: General: Edema, headache, malaise. Hypersensitivity Reactions: Allergic and anaphylactoid reactions, anaphylaxis. Local Reactions: Injection site reactions, pain and necrosis. Cardiovascular: Bradycardia, hypotension, peripheral ischemia, thrombosis. Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting. Hematologic: Agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia. Musculoskeletal: CPK increased, muscle weakness, myalgia, myopathy , myositis, rhabdomyolysis. Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope. Respiratory: Dyspnea, nasal congestion, pulmonary embolism. Skin: Pruritis, rash. Special Senses: Tinnitus, vision decreased, watery eyes. Urogenital: BUN increased, renal failure. There have been some reports of dry ejaculation during the period of aminocaproic acid treatment. These have been reported to date only in hemophilia patients who received the drug after undergoing dental surgical procedures. However, this symptom resolved in all patients within 24 to 48 hours of completion of therapy.<br/>OVERDOSAGE: A few cases of acute overdosage with aminocaproic acid administered intravenously have been reported. The effects ranged from no reaction to transient hypotension to severe acute renal failure leading to death. One patient with a history of brain tumor and seizures experienced seizures after receiving an 8 gram bolus injection of aminocaproic acid. The single dose of aminocaproic acid causing symptoms of overdosage or considered to be life-threatening is unknown. Patients have tolerated doses as high as 100 grams while acute renal failure has been reported following a dose of 12 grams. The intravenous and oral LDof aminocaproic acid were 3 and 12 g/kg respectively in the mouse and 3.2 and 16.4 g/kg respectively in the rat. An intravenous infusion dose of 2.3 g/kg was lethal in the dog. On intravenous administration, tonic-clonic convulsions were observed in dogs and mice. No treatment for overdosage is known, although evidence exists that aminocaproic acid is removed by hemodialysis and may be removed by peritoneal dialysis. Pharmacokinetic studies have shown that total body clearance of aminocaproic acid is markedly decreased in patients with severe renal failure.
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Possible adverse effects arising from the irrigation of body cavities, tissues, or indwelling catheters and tubes should be avoidable when proper procedures are followed. Displaced catheters or drainage tubes can lead to irrigation or infiltration of unintended structures or cavities. Excessive volume or pressure during irrigation of closed cavities may cause undue distension or disruption of tissues. Accidental contamination from careless technique may transmit infection. If an adverse reaction does occur, discontinue administration of the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
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The most serious adverse reactions observed in
the clinical trials were severe and prolonged cytopenias and the sequelae
of cytopenias which included infections (sepsis) and hemorrhage in
thrombocytopenic patients, allergic reactions (bronchospasm and angioedema),
secondary leukemia and myelodysplasia (see BOXED WARNINGS and WARNINGS). The most common adverse reactions occurring
in the clinical trials included neutropenia, thromobocytopenia, and
anemia that are both prolonged and severe. Less common but severe
adverse reactions included pneumonia, pleural effusion and dehydration. Data regarding adverse events were primarily obtained
in 230 patients with non-Hodgkin's lymphoma enrolled in five
clinical trials using the recommended dose and schedule. Patients
had a median follow-up of 39 months and 79% of the patients were followed
at least 12 months for survival and selected adverse events. Patients
had a median of 3 prior chemotherapy regimens, a median age of 55
years, 60% male, 27% had transformation to a highergrade histology,
29% were intermediate grade and 2% high grade histology (IWF) and
68% had Ann Arbor stage IV disease. Patients enrolled in these studies
were not permitted to have prior hematopoietic stem cell transplantation
or irradiation to more than 25% of the red marrow. In the expanded
access program, which included 765 patients, data regarding clinical
serious adverse events and HAMA and TSH levels were used to supplement
the characterization of delayed adverse events (see ADVERSE REACTIONS, Hypothyroidism, Secondary Leukemia
and Myelodysplastic Syndrome, Immunogenicity). Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
The adverse reaction information from clinical trials does, however,
provide a basis for identifying the adverse events that appear to
be related todrug use and for approximating rates.<br/>Hematologic Events: Hematologic toxicity was the most frequently observed
adverse event in clinical trials with the BEXXAR therapeutic regimen
(Table 6). Sixty-three (27%) of 230 patients received one or more
hematologic supportive care measures following the therapeutic dose:
12% received G-CSF; 7% received Epoetin alfa; 15% received platelet
transfusions; and 16% received packed red blood cell transfusions.
Twenty-eight (12%) patients experienced hemorrhagic events; the majority
were mild to moderate.<br/>Infectious Events: One hundred and four of the 230 (45%) patients experienced
one or more adverse events possibly related to infection. The majority
were viral (e.g., rhinitis, pharyngitis, flu symptoms, or herpes)
or other minor infections. Twenty of 230 (9%) patients experienced
infections that were considered serious because the patient was hospitalized
to manage the infection. Documented infections included pneumonia,
bacteremia, septicemia, bronchitis, and skin infections.<br/>Hypersensitivity Reactions: Fourteen patients
(6%) experienced one or more of the following adverse events: allergic
reaction, face edema, injection site hypersensitivity, anaphylactic
reaction, laryngismus, and serum sickness. In the post-marketing setting,
severe hypersensitivity reactions, including fatal anaphylaxis have
been reported.<br/>Gastrointestinal Toxicity: Eighty-seven patients (38%) experienced one or more
gastrointestinal adverse events, including nausea, emesis, abdominal
pain, and diarrhea. These events were temporally related to the infusion
of the antibody. Nausea, vomiting, and abdominal pain were often reported
within days of infusion, whereas diarrhea was generally reported days
to weeks after infusion.<br/>Infusional Toxicity: A constellation of symptoms, including fever, rigors
or chills, sweating, hypotension, dyspnea, bronchospasm, and nausea,
have been reported during or within 48 hours of infusion. Sixty-seven
patients (29%) reported fever, rigors/chills, or sweating within 14
days following the dosimetric dose. Although all patients in the clinical
studies received pretreatment with acetaminophen and an antihistamine,
the value of premedication in preventing infusion-related toxicity
was not evaluated in any of the clinical studies. Infusional toxicities
were managed by slowing and/or temporarily interrupting the infusion.
Symptomatic management was required in more severe cases. Adjustment
of the rate of infusion to control adverse reactions occurred in 16
patients (7%); seven patients required adjustments for only the dosimetric
infusion, two required adjustments for only the therapeutic infusion,
and seven required adjustments for both the dosimetric and the therapeutic
infusions. Adjustments included reduction in the rate of infusion
by 50%, temporary interruption of the infusion, and in 2 patients,
infusion was permanently discontinued. Table
5 lists clinical adverse events that occurred in���5% of patients.
Table 6 provides a detailed description of the hematologic toxicity. Excludes laboratory
derived hematologic adverse events (see Table 6). The COSTART term for infection
includes a subset of infections (e.g., upper respiratory infection).
Other terms are mapped to preferred terms (e.g., pneumonia and sepsis).
For a more inclusive summary see ADVERSE REACTIONS, Infectious Events. Grade 3/4
toxicity was assumed if patient was missing 2 or more weeks of hematology
data between Week 5 and Week 9. Duration of Grade 3/4 of 1,000+
days (censored) was assumed for those patients with undocumented Grade
3/4 and no hematologic data on or after Week 9. Grade 4 toxicity was assumed
if patient had documented Grade 3 toxicity and was missing 2 or more
weeks of hematology data between Week 5 and Week 9.<br/>Delayed Adverse Reactions: Delayed adverse reactions,
including hypothyroidism, HAMA, and myelodysplasia/leukemia, were
assessed in 230 patients included in clinical studies and 765 patients
included in expanded access programs. The entry characteristics of
patients included from the expanded access programs were similar to
the characteristics of patients enrolled in the clinical studies,
except that the median number of prior chemotherapy regimens was fewer
(2 vs. 3) and the proportion with low-grade histology was higher (77%
vs. 70%) in patients from the expanded access programs.<br/>Secondary Leukemia and Myelodysplastic
Syndrome (MDS): There were 44 cases of MDS/secondary leukemia reported
among 995 (4.0%) patients included in clinical studies and expanded
access programs, with a median follow-up of 29 months. The overall
incidence of MDS/secondary leukemia among the 230 patients included
in the clinical studies was 10% (24/230), with a median follow-up
of 39 months and a median time to development of MDS of 34 months.
The cumulative incidence of MDS/secondary leukemiain this patient
population was 4.7% at 2 years and 15% at 5 years. The incidence of
MDS/secondary leukemia among the 765 patients in the expanded access
programs was 3% (20/765), with a median follow-up of 27 months
and a median time to development of MDS of 31 months. The cumulative
incidence of MDS/secondary leukemia in this patient population was
1.6% at 2 years and 6% at 5 years.<br/>Secondary Malignancies: Of the 995 patients in clinical studies and the
expanded access programs, there were 65 reports of second malignancies
in 54 patients, excluding secondary leukemias. The most common included
non-melanomatous skin cancers (26), colorectal cancer (7), head and
neck cancer (6), breast cancer (5), lung cancer (4), bladder cancer
(4), melanoma (3), and gastric cancer (2). Someof these events included
recurrence of an earlier diagnosis of cancer.<br/>Hypothyroidism: Of the 230 patients in the clinical studies, 203
patients did not have elevated TSH upon study entry. Of these, 137
patients had at least one post-treatment TSH value available and were
not taking thyroid hormonal treatment upon study entry. With a median
follow up period of 46 months, the incidence of hypothyroidism based
on elevated TSH or initiation of thyroid replacement therapy in these
patients was 18% with a median time to development of hypothyroidism
of 16 months. The cumulative incidences of hypothyroidism at 2 and
5 years in these 137 patients were 11% and 19% respectively. New events
have been observed up to 90 months post-treatment. Of the 765 patients in the expanded access programs, 670 patients
did not have elevated TSH upon study entry. Of these, 455 patients
had at least one post-treatment TSH value available and were not taking
thyroid hormonal treatment upon study entry. With a median follow
up period of 33 months, the incidence of hypothyroidism based on elevated
TSH or initiation of thyroid replacement therapy in these 455 patients
was 13% with a median time to development of hypothyroidism of 15
months. The cumulative incidences of hypothyroidismat 2 and 5 years
in these patients were 9% and 17%, respectively.<br/>Immunogenicity: One percent (11/989) of the chemotherapy-relapsed
or refractory patients included in the clinical studies or the expanded
access program had a positive serology for HAMA prior to treatment
and six patients had no baseline assessment for HAMA. Of the 230 patients
in the clinical studies, 220 patients were seronegative for HAMA prior
to treatment, and 219 had at least one post-treatment HAMA value obtained.
With a median observation period of 6 months, a total of 23 patients
(11%) became seropositive for HAMA post-treatment. The median time
of HAMA development was 6 months. The cumulative incidences of HAMA
seropositivity at 6 months, 12 months, and 18 months were 6%, 17%
and 21% respectively. Of the 765 patients
in the expanded access programs, 758 patients were seronegative for
HAMA prior to treatment, and 569 patients had at least one post-treatment
HAMA value obtained. With a median observation period of 7 months,
a total of 57 patients (10%) became seropositive for HAMA post-treatment.
The median time of HAMA development was 5 months. The cumulative incidences
of HAMA seropositivity at 6 months, 12 months, and 18 months were
7%, 12% and 13%, respectively. In a study
of 76 previously untreated patients with low-grade non-Hodgkin's
lymphoma who received the BEXXAR therapeutic regimen, the incidence
of conversion to HAMA seropositivity was 70%, with a median time to
development of HAMA of 27 days. The data
reflect the percentage of patients whose test results were consideredpositive for HAMA in an ELISA assay that detects antibodies to the
Fc portion of IgGmurine immunoglobulin and are highly
dependent on the sensitivity and specificity of the assay. Additionally,
the observed incidence of antibody positivity in an assay may be influenced
by several factors including sample handling, concomitant medications,
and underlying disease. For these reasons, comparison of the incidence
of HAMA in patients treated with the BEXXAR therapeutic regimen with
the incidence of HAMA in patients treated with other products may
be misleading.
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| dailymed-drugs:197 |
Extensive use of mannitol over the last several decades has produced recorded adverse events, in a variety of clinical settings,
that are isolated or idiosyncratic in nature. None of these adverse reactions have occurred with any great frequency nor with any security in attributing them to mannitol. The inability to clearly exclude the drug related nature of such events in these isolated reports prompts the necessity to list the
reactions that have been observed in patients during or following mannitol infusion. In this fashion, patients have exhibited nausea, vomiting, rhinitis, local pain, skin necrosis and
thrombophlebitis at the site of injection, chills, dizziness, urticaria, hypotension, hypertension, tachycardia, fever and angina-like chest pains. Of far greater clinical significance is a variety of events that are related to inappropriate recognition and monitoring of fluid
shifts. These are not intrinsic adverse reactions to the drug but the consequence of manipulating osmolarity by any agency in a therapeutically inappropriate manner. Failure to recognize
severe impairment of renal function with the high likelihood of nondiuretic response can lead to aggravated dehydration of tissues and increased vascular fluid load. Induced diuresis in
the presence of preexisting hemoconcentration and preexisting deficiency of water and electrolytes can lead to serious imbalances. Expansion of the extracellular space can aggravate
cardiac decompensation or induce it in the presence of latent heart failure. Pulmonary congestion or edema can be seriously aggravated with the expansion of the extracellular and
therefore intravascular fluid load. Hemodilution and dilution of the extracellular fluid space by osmotic shift of water can induce or aggravate preexisting hyponatremia. If unrecognized, such fluid and/or electrolyte shift can produce the reported adverse reactions of pulmonary congestion, acidosis,
electrolyte loss, dryness of mouth, thirst, edema, headache, blurred vision, convulsions and congestive cardiac failure. These are not truly adverse reactions to the drug and can be appropriately prevented by evaluation of degree of renal failure with
a test dose response to mannitol when indicated; evaluation of hypervolemia and hypovolemia; sodium and potassium levels; hemodilution or hemoconcentration; and evaluation of renal,
cardiac and pulmonary function at the onset of therapy.
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| dailymed-drugs:198 |
In controlled US studies, more than 3,300 patients with seasonal allergic, perennial allergic, or perennial nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical studies have been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by patients treated with thevehicle itself. The complaints did not usually interfere with treatment. Less than 2% of patients in clinical trials discontinued because of adverse events; this rate was similar for vehicle placebo and active comparators. Systemic corticosteroid side effects were not reported during controlled clinical studies up to 6 months' duration with Fluticasone Propionate Nasal Spray. If recommended doses are exceeded, however, or if individuals are particularly sensitive or taking Fluticasone Propionate Nasal Spray in conjunction with administration of other corticosteroids, symptoms of hypercorticism, e.g., Cushing syndrome, could occur. The following incidence of common adverse reactions (>3%, where incidence in fluticasone propionate-treated subjects exceeded placebo) is based upon seven controlled clinical trials in which 536 patients (57 girls and 108 boys aged 4 to 11 years, 137 female and 234 male adolescents and adults) were treated with Fluticasone Propionate Nasal Spray 200 mcg once daily over 2 to 4 weeks and two controlled clinical trials in which 246 patients (119 female and 127 male adolescents and adults) were treated with Fluticasone Propionate Nasal Spray 200 mcg once daily over 6 months. Also included in the table are adverse events from two studies in which 167 children (45 girls and 122 boys aged 4 to 11 years) were treated with Fluticasone Propionate Nasal Spray 100 mcg once daily for 2 to 4 weeks. Other adverse events that occurred in���3% but���1% of patients and that were more common with fluticasone propionate (with uncertain relationship to treatment) included: blood in nasal mucus, runny nose, abdominal pain, diarrhea, fever, flu-like symptoms, aches and pains, dizziness, bronchitis.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of intranasal fluticasone propionate in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency ofreporting, or causal connection to fluticasone propionate or a combination of these factors.<br/>General: Hypersensitivity reactions, including angioedema, skin rash, edema of the face and tongue, pruritus, urticaria, bronchospasm, wheezing, dyspnea, and anaphylaxis/anaphylactoid reactions, which in rare instances were severe.<br/>Ear, Nose, and Throat: Alteration or loss of sense of taste and/or smell and, rarely, nasal septal perforation, nasal ulcer, sore throat, throat irritation and dryness, cough, hoarseness, and voice changes.<br/>Eye: Dryness and irritation, conjunctivitis, blurred vision, glaucoma, increased intraocular pressure, and cataracts. Cases of growth suppression have been reported for intranasal corticosteroids, including Fluticasone Propionate Nasal Spray .
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| dailymed-drugs:200 |
Diovan has been evaluated for safety in more than 4000 patients, including over 400 treated for over 6 months, and more than 160 for over 1 year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse experiences with Diovan was similar to placebo. The overall frequency of adverse experiences was neither dose-related nor related to gender, age, race, or regimen. Discontinuation of therapy due to side effects was required in 2.3% of valsartan patients and 2.0% of placebo patients. The most common reasons for discontinuation of therapy with Diovan were headache and dizziness. The adverse experiences that occurred in placebo-controlled clinical trials in at least 1% of patients treated with Diovan and at a higher incidence in valsartan (n=2316) than placebo (n=888) patients included viral infection (3% vs. 2%), fatigue (2% vs. 1%), and abdominal pain (2% vs. 1%). Headache, dizziness, upper respiratory infection, cough, diarrhea, rhinitis, sinusitis, nausea, pharyngitis, edema, and arthralgia occurred at a more than 1% rate but at about the same incidence in placebo and valsartan patients. In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of dry cough was significantly greater in the ACE-inhibitor group (7.9%) than in the groups who received valsartan (2.6%) or placebo (1.5%). In a 129-patient trial limited to patients who had had dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p<0.001). Dose-related orthostatic effects were seen in less than 1% of patients. An increase in the incidence of dizziness was observed in patients treated with Diovan 320 mg (8%) compared to 10 to 160 mg (2% to 4%). Diovan has been used concomitantly with hydrochlorothiazide without evidence of clinically important adverse interactions. Other adverse experiences that occurred in controlled clinical trials of patients treated with Diovan (>0.2% of valsartan patients) are listed below. It cannot be determined whether these events were causally related to Diovan. Body as a Whole: Allergic reaction and asthenia Cardiovascular: Palpitations Dermatologic: Pruritus and rash Digestive: Constipation, dry mouth, dyspepsia, and flatulence Musculoskeletal: Back pain, muscle cramps, and myalgia Neurologic and Psychiatric: Anxiety, insomnia, paresthesia, and somnolence Respiratory: Dyspnea Special Senses: Vertigo Urogenital: Impotence Other reported events seen less frequently in clinical trials included chest pain, syncope, anorexia, vomiting, and angioedema.<br/>Post-Marketing Experience: The following additional adverse reactions have been reported in post-marketing experience: Hypersensitivity: There are rare reports of angioedema. Digestive: Elevated liver enzymes and very rare reports of hepatitis. Renal: Impaired renal function. Clinical Laboratory tests: Hyperkalemia Dermatologic: Alopecia<br/>Clinical Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Diovan. Creatinine: Minor elevations in creatinine occurred in 0.8% of patients taking Diovan and 0.6% given placebo in controlled clinical trials. Hemoglobin and Hematocrit: Greater than 20% decreases in hemoglobin and hematocrit were observed in 0.4% and 0.8%, respectively, of Diovan patients, compared with 0.1% and 0.1% in placebo-treated patients. One valsartan patient discontinued treatment for microcytic anemia. Liver function tests: Occasional elevations (greater than 150%) of liver chemistries occurred in Diovan-treated patients. Three patients (<0.1%) treated with valsartan discontinued treatment for elevated liver chemistries. Neutropenia: Neutropenia was observed in 1.9% of patients treated with Diovan and 0.8% of patients treated with placebo. Serum Potassium: Greater than 20% increases in serum potassium were observed in 4.4% of Diovan-treated patients compared to 2.9% of placebo-treated patients.
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| dailymed-drugs:201 |
Body As A Whole: Allergic reaction. Gastrointestinal System: Gastrointestinal symptoms occur frequently and include anorexia, vague gastric upset, nausea and vomiting, cramps, epigastric and abdominal pain, weight loss, and diarrhea. There have been reports of gum hypertrophy and swelling of the tongue. Hemopoietic System: Hemopoietic complications associated with the administration of ethosuximide have included leukopenia, agranulocytosis, pancytopenia, with or without bone marrow suppression, and eosinophilia. Nervous System: Neurologic and sensory reactions reported during therapy with ethosuximide have included drowsiness, headache, dizziness, euphoria, hiccups, irritability, hyperactivity, lethargy, fatigue, and ataxia. Psychiatric or psychological aberrations associated with ethosuximide administration have included disturbances of sleep, night terrors, inability to concentrate, and aggressiveness. These effects may be noted particularly in patients who have previously exhibited psychological abnormalities. There have been rare reports of paranoid psychosis, increased libido, and increased state of depression with overt suicidal intentions. Integumentary System: Dermatologic manifestations which have occurred with the administration of ethosuximide have included urticaria, Stevens-Johnson syndrome, systemic lupus erythematosus, pruritic erythematous rashes, and hirsutism. Special Senses: Myopia. Genitourinary System: Vaginal bleeding, microscopic hematuria.
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| dailymed-drugs:1916 |
Body As A Whole: Allergic reaction. Gastrointestinal System: Gastrointestinal symptoms occur frequently and include anorexia, vague gastric upset, nausea and vomiting, cramps, epigastric and abdominal pain, weight loss, and diarrhea. There have been reports of gum hypertrophy and swelling of the tongue. Hemopoietic System: Hemopoietic complications associated with the administration of ethosuximide have included leukopenia, agranulocytosis, pancytopenia, with or without bone marrow suppression, and eosinophilia. Nervous System: Neurologic and sensory reactions reported during therapy with ethosuximide have included drowsiness, headache, dizziness, euphoria, hiccups, irritability, hyperactivity, lethargy, fatigue, and ataxia. Psychiatric or psychological aberrations associated with ethosuximide administration have included disturbances of sleep, night terrors, inability to concentrate, and aggressiveness. These effects may be noted particularly in patients who have previously exhibited psychological abnormalities. There have been rare reports of paranoid psychosis, increased libido, and increased state of depression with overt suicidal intentions. Integumentary System: Dermatologic manifestations which have occurred with the administration of ethosuximide have included urticaria, Stevens-Johnson syndrome, systemic lupus erythematosus, pruritic erythematous rashes, and hirsutism. Special Senses: Myopia. Genitourinary System: Vaginal bleeding, microscopic hematuria.
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| dailymed-drugs:202 |
Lovastatin is generally well tolerated; adverse reactions usually have been mild and transient.<br/>Phase III Clinical Studies: In Phase III controlled clinical studies involving 613 patients treated with lovastatin, the adverse experience profile was similar to that shown below for the 8,245 patient EXCEL study (see Expanded Clinical Evaluation of Lovastatin [EXCEL] Study). Persistent increases of serum transaminases have been noted (see WARNINGS, LiverDysfunction). About 11% of patients had elevations of CK levels of at least twice the normal value on one or more occasions. The corresponding values for the control agent cholestyramine were 9 percent. This was attributable to the noncardiac fraction of CK. Large increases in CK have sometimes been reported (see WARNINGS, Myopathy/Rhabdomyolysis).<br/>Expanded Clinical Evaluation of Lovastatin (EXCEL) Study: Lovastatin was compared to placebo in 8,245 patients with hypercholesterolemia (total-C 240 to 300 mg/dL [6.2 to 7.8 mmol/L]) in the randomized, double-blind, parallel, 48 week EXCEL study. Clinical adverse experiences reported as possibly, probably or definitely drug-related in���1% in any treatment group are shown in the table below. For no event was the incidence on drug and placebo statistically different. Other clinical adverse experiences reported as possibly, probably or definitely drug-related in 0.5 to 1.0 percent of patients in any drug-treated group are listed below. In all these cases the incidence on drug and placebo was not statistically different. Body as a Whole: chest pain; Gastrointestinal: acid regurgitation, dry mouth, vomiting; Musculoskeletal: leg pain, shoulder pain, arthralgia; Nervous System/Psychiatric: insomnia, paresthesia; Skin: alopecia, pruritus; Special Senses: eye irritation. In the EXCEL study (see CLINICAL PHARMACOLOGY, Clinical Studies in Adults), 4.6% of the patients treated up to 48 weeks were discontinued due to clinical or laboratory adverse experiences which were rated by the investigator as possibly, probably or definitely related to therapy with lovastatin. The value for the placebo group was 2.5%.<br/>Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): In AFCAPS/TexCAPS (see CLINICAL PHARMACOLOGY, Clinical Studies in Adults) involving 6,605 participants treated with 20 to 40 mg/day of lovastatin (n = 3,304) or placebo (n = 3,301), the safety and tolerability profile of the group treated with lovastatin was comparable to that of the group treated with placebo during a median of 5.1 years of follow-up. The adverse experiences reported in AFCAPS/TexCAPS were similar tothose reported in EXCEL (see ADVERSE REACTIONS, Expanded Clinical Evaluation of Lovastatin (EXCEL) Study).<br/>Concomitant Therapy: In controlled clinical studies in which lovastatin was administered concomitantly with cholestyramine, no adverse reactions peculiar to this concomitant treatment were observed. The adverse reactions that occurred were limited to those reported previously with lovastatin or cholestyramine. Other lipid-lowering agents were not administered concomitantly with lovastatin during controlled clinical studies. Preliminary data suggests that the addition of gemfibrozil to therapy with lovastatin is not associated with greater reduction in LDL-C than that achieved with lovastatin alone. In uncontrolled clinical studies, most of the patients who have developed myopathy were receiving concomitant therapy with cyclosporine, gemfibrozil or niacin (nicotinic acid). The combined use of lovastatin at doses exceeding 20 mg/day with cyclosporine, gemfibrozil, other fibrates or lipid-lowering doses (��1 g/day) of niacin should be avoided (see WARNINGS, Myopathy/Rhabdomyolysis). The following effects have been reported with drugs in this class. Not all the effects listed below have necessarily been associated with lovastatin therapy. Skeletal: muscle cramps, myalgia, myopathy, rhabdomyolysis, arthralgias. Neurological: dysfunction of certain cranial nerves (including alteration of taste, impairment of extra-ocular movement, facial paresis), tremor, dizziness, vertigo, memory loss, paresthesia, peripheral neuropathy, peripheral nerve palsy, psychic disturbances, anxiety, insomnia, depression. Hypersensitivity Reactions: An apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome. Gastrointestinal: pancreatitis, hepatitis, including chronic active hepatitis, cholestatic jaundice, fatty change in liver; and rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma; anorexia, vomiting. Skin: alopecia, pruritus. A variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails) have been reported. Reproductive: gynecomastia, loss of libido, erectile dysfunction. Eye: progression of cataracts (lens opacities), ophthalmoplegia. Laboratory Abnormalities: elevated transaminases, alkaline phosphatase, g-glutamyl transpeptidase, and bilirubin; thyroid function abnormalities.<br/>Adolescent Patients (ages 10 to 17 years): In a 48 week controlled study in adolescent boys with heFH (n = 132) and a 24 week controlled study in girls who were at least 1 year post-menarche with heFH (n = 54), the safety and tolerability profile of the groups treated with lovastatin (10 to 40 mg daily) was generally similar to that of the groups treatedwith placebo (see CLINICAL PHARMACOLOGY, Clinical Studies in Adolescent Patients and PRECAUTIONS, Pediatric Use).
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| dailymed-drugs:203 |
In controlled clinical trials of twice daily administration, the total incidence of adverse reactions associated with the use of Fluticasone Propionate Cream, 0.05% was approximately 4%. These adverse reactions were usually mild, self-limiting, and consisted primarily of pruritus, dryness, numbness of fingers, and burning. These events occurred in 2.9%, 1.2%, 1.0%, and 0.6% of patients, respectively. Two clinical studies compared once to twice-daily administration of Fluticasone Propionate Cream, 0.05% for the treatment of moderate to severe eczema. The local drug-related adverse events for the 491 patients enrolled in both studies are shown in Table 1. In the study enrolling both adult and pediatric patients, the incidence of local adverse events in the 119 pediatric patients ages 1to 12 years was comparable to the 140 patients ages 13 to 62 years. Fifty-one pediatric patients ages 3 months to 5 years, with moderate to severe eczema, were enrolled in an open-label HPA axis safety study. Fluticasone Propionate Cream, 0.05% was applied twice daily for 3 to 4 weeks over and arithmetic mean body surface area of 64% (range 35-95%). The mean morning cortisol levels with standard deviations before treatment (pre-stimulation mean value = 13.766.94 mcg/dL, post-stimulation mean value = 30.537.23 mcg/dL) and at end treatment (pre-stimulation mean value = 12.326.92 mcg/dL, poststimulation mean value = 28.847.16 mcg/dL) showed little change. In 2 of 43 (4.7%) patients with end-treatment results, peak cortisol levels following cosyntropin stimulation testing were���18 ug/dL indicating adrenal suppression. Follow-up testing after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis. Local drug-related adverse events were: transient burning, resolving the same day it was reported; transient urticaria, resolving the same day it was reported; erythematous rash; dusky erythema, resolving within one month after cessation of Fluticasone Propionate Cream, 0.05%; and telangiectasia resolving within 3 months after stopping Fluticasone Propionate Cream, 0.05%. The following local adverse reactions have been reported infrequently with topical corticosteroids and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria. Also, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction or discontinuation of potent topical corticosteroid products.
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| dailymed-drugs:204 |
Adverse reactions have occurred with corticosteroid/antibacterial combination drugs which can be attributed to the corticosteroid component, the antibacterial component, or the combination. Exact incidence figures are not available since no denominator of treated patients is available. Reactions occurring most often from the presence of the antibacterial ingredient are allergic sensitizations. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias . Sulfacetamide sodium may cause local irritation. The reactions due to the corticosteroid component in decreasing order of frequency are: elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing. Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical corticosteroids. Corticosteroid-containing preparations can also cause acute anterior uveitis or perforation of the globe. Mydriasis, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids. Secondary Infection: The development of secondary infection has occurred after use of combinations containing corticosteroids and antibacterials. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of corticosteroid. The possibility of fungal invasion must be considered in any persistent corneal ulceration where corticosteroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs.
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| dailymed-drugs:205 |
Hypertension:<br/>Heart Failure:<br/>Acute Myocardial Infarction:<br/>Clinical Laboratory Findings:
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| dailymed-drugs:206 |
The most frequently reported ocular adverse events were conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, and tearing. These events occurred in approximately 1-6% of patients. Nonocular adverse events reported at a rate of 1-4% were fever, increased cough, infection, otitis media, pharyngitis, rash, and rhinitis.
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| dailymed-drugs:207 |
Adverse reactions have been very common in virtually all series of patients treated with amiodarone for ventricular arrhythmias with relatively large doses of drug (400 mg/day and above), occurring in about three-fourths of all patients and causing discontinuation in 7 to 18%. The most serious reactions are pulmonary toxicity, exacerbation of arrhythmia, and rare serious liver injury (see WARNINGS), but other adverse effects constitute important problems. They are often reversible with dose reduction or cessation of amiodarone treatment. Most of the adverse effects appear to become more frequent with continued treatment beyond six months, although rates appear to remain relatively constant beyond one year. The time and dose relationships of adverse effects are under continued study. Neurologic problems are extremely common, occurring in 20 to 40% of patients and including malaise and fatigue, tremor and involuntary movements, poor coordination and gait, and peripheral neuropathy; they are rarely a reason to stop therapy and may respond to dose reductions or discontinuation (see PRECAUTIONS). Gastrointestinal complaints, most commonly nausea, vomiting, constipation, and anorexia, occur in about 25% of patients but rarely require discontinuation of drug. These commonly occur during high-dose administration (i.e., loading dose) and usually respond to dose reduction or divided doses. Ophthalmic abnormalities including optic neuropathy and/or optic neuritis, in some cases progressing to permanent blindness, papilledema, corneal degeneration, photosensitivity, eye discomfort, scotoma, lens opacities, and macular degeneration have been reported. (See WARNINGS.) Asymptomatic corneal microdeposits are present in virtually all adult patients who have been on drug for more than 6 months. Some patients develop eye symptoms of halos, photophobia, and dry eyes. Vision is rarely affected and drug discontinuation is rarely needed. Dermatological adverse reactions occur in about 15% of patients, with photosensitivity being most common (about 10%). Sunscreen and protection from sun exposure may be helpful, and drug discontinuation is not usually necessary. Prolonged exposure to amiodarone occasionally results in a blue-gray pigmentation. This is slowly and occasionally incompletely reversible on discontinuation of drug but is of cosmetic importance only. Cardiovascular adverse reactions, other than exacerbation of the arrhythmias, include the uncommon occurrence of congestive heart failure (3%) and bradycardia. Bradycardia usually responds to dosage reduction but may require a pacemaker for control. CHF rarely requires drug discontinuation. Cardiac conduction abnormalities occur infrequently and are reversible on discontinuation of drug. The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days). The Following Side Effects Were Each Reported in 10 to 33% of Patients Gastrointestinal: Nausea and vomiting. The Following Side Effects Were Each Reported in 4 to 9% of Patients Dermatologic: Solar dermatitis/photosensitivity. Neurologic: Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias. Gastrointestinal: Constipation, anorexia. Ophthalmologic: Visual disturbances. Hepatic: Abnormal liver-function tests. Respiratory: Pulmonary inflammation or fibrosis. The Following Side Effects Were Each Reported in 1 to 3% of Patients Thyroid: Hypothyroidism, hyperthyroidism. Neurologic: Decreased libido, insomnia, headache, sleep disturbances. Cardiovascular: Congestive heart failure, cardiac arrhythmias, SA node dysfunction. Gastrointestinal: Abdominal pain. Hepatic: Nonspecific hepatic disorders. Other: Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities. The Following Side Effects Were Each Reported in Less Than 1% of Patients Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension, and cardiac conduction abnormalities. In surveys of almost 5,000 patients treated in open U.S. studies and in published reports of treatment with amiodarone, the adverse reactions most frequently requiring discontinuation of amiodarone included pulmonary infiltrates or fibrosis, paroxysmal ventricular tachycardia, congestive heart failure,and elevation of liver enzymes. Other symptoms causing discontinuations less often included visual disturbances, solar dermatitis, blue skin discoloration, hyperthyroidism, and hypothyroidism.<br/>Postmarketing Reports: In postmarketing surveillance, hypotension (sometimes fatal), sinus arrest, anaphylactic/anaphylactoid reaction (including shock), angioedema, hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, renal impairment, renal insufficiency, acute renal failure, bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pulmonary alveolar hemorrhage, pleuritis, pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy), syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, toxic epidermal necrolysis (sometime+es fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma, myopathy, muscle weakness, rhabdomyolysis, hallucination, confusional state, disorientation, delirium, epididymitis, and impotence, also have been reported with amiodarone therapy.
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| dailymed-drugs:209 |
The following table shows the adverse reactions that were reported in patients previously receiving bronchodilators and/or orally inhaled corticosteroids in two double-blind, placebo-controlled US clinical studies, in which 519 adult and pediatric patients age 4-78 years (279 males and 240 females) were treated with the AEROSPAN Inhalation Aerosol (80 mcg to 320 mcg twice daily for 12 weeks) or placebo. The mean duration of exposure was 76.7, 78.2, 80.5, and 69.4 days for AEROSPAN Inhalation Aerosol 80 mcg, 160 mcg, 320 mcg, and placebo, all dosed twice daily, respectively. The table includes all events (whether considered drug-related ornon-drug-related by the investigators) that occurred at a rate of>3% in any AEROSPAN Inhalation Aerosol group and were more common than in the placebo group. In considering these data, the increased average duration of exposure for AEROSPAN Inhalation Aerosol patients should be taken into account, compared with placebo-treated patients. The following other adverse events occurred in patients in these clinical studies using AEROSPAN Inhalation Aerosol with an incidence of 1 to 3% and were more common in AEROSPAN Inhalation Aerosol than in the placebo group. Cases of growth suppression have been reported for orally inhaled corticosteroids
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| dailymed-drugs:210 |
Clinical trials were conducted using either extended-release pentoxifylline tablets for up to 60 weeks or immediate-release pentoxifylline capsules for up to 24 weeks. Dosage ranges in the tablet studies were 400 mg bid to tid and in the capsule studies, 200 to 400 mg tid. The table summarizes the incidence (in percent) of adverse reactions considered drug related, as well as the numbers of patients who received extended-release pentoxifylline tablets, immediate-release pentoxifylline capsules, or the corresponding placebos. The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies. Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S. The table indicates that in the tablet studies few patients discontinued because of adverse effects. Pentoxifylline has been marketed in Europe and elsewhere since 1972. In addition to the above symptoms, the following have been reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain: Cardiovascular: dyspnea, edema, hypotension. Digestive: anorexia, cholecystitis, constipation, dry mouth/thirst. Nervous: anxiety, confusion, depression, seizures, aseptic meningitis. Respiratory: epistaxis, flu-like symptoms, laryngitis, nasal congestion. Skin and Appendages: brittle fingernails, pruritus, rash, urticaria, angioedema. Special Senses: blurred vision, conjunctivitis, earache, scotoma. Miscellaneous: bad taste, excessive salivation, leukopenia, malaise, sore throat/swollen neck glands, weight change. A few rare events have been reported spontaneously worldwide since marketing in 1972. Although they occurred under circumstances in which a causal relationship with pentoxifylline could not be established, they are listed to serve as information for physicians: Cardiovascular���angina, arrhythmia, tachycardia, anaphylactoid reaction; Digestive���hepatitis, jaundice, increased liver enzymes; and Hemic and Lymphatic���decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, thrombocytopenia.
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| dailymed-drugs:211 |
TENORETIC is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient. The adverse effects observed for TENORETIC are essentially the same as those seen with the individual components.<br/>Atenolol: The frequency estimates in the following table were derived from controlled studies in which adverse reactions were either volunteered by the patient (US studies) or elicited, eg, by checklist (foreign studies). The reported frequency of elicited adverse effects was higher for both atenolol and placebo-treated patients than when these reactions were volunteered. Where frequency of adverse effects for atenolol and placebo is similar, causal relationship to atenolol is uncertain. During postmarketing experience, the following have been reported in temporal relationship to the use of the drug: elevated liver enzymes and/or bilirubin, hallucinations, headache, impotence, Peyronie's disease, postural hypotension which may be associated with syncope, psoriasiform rash or exacerbation of psoriasis,psychoses, purpura, reversible alopecia, thrombocytopenia, visual disturbance, sick sinus syndrome, and dry mouth. TENORETIC, like other beta blockers, has been associated with the development of antinuclear antibodies (ANA), lupus syndrome, and Raynaud's phenomenon.<br/>Chlorthalidone: Cardiovascular: orthostatic hypotension; Gastrointestinal: anorexia, gastric irritation, vomiting, cramping, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis; CNS: vertigo, paresthesia, xanthopsia; Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia; Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell's syndrome (toxic epidermal necrolysis); Miscellaneous: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness. Clinical trials of TENORETIC conducted in the United States (89 patients treated with TENORETIC) revealed no new or unexpected adverse effects.<br/>POTENTIAL ADVERSE EFFECTS: In addition, a variety of adverse effects not observed in clinical trials with atenolol but reported with other beta-adrenergic blocking agents should be considered potential adverse effects of atenolol. Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time andplace, short-term memory loss, emotional lability, slightly clouded sensorium, decreased performance on neuropsychometrics; Cardiovascular: Intensification of AV block ; Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis; Hematologic: Agranulocytosis; Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm and respiratory distress.<br/>Miscellaneous: There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small, and, in most cases, the symptoms have cleared when treatment was withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy. The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with atenolol (TENORMIN). Furthermore, a number of patients who had previously demonstrated established practolol reactions were transferred to atenolol (TENORMIN) therapy with subsequent resolution or quiescence of the reaction.<br/>Clinical Laboratory Test Findings: Clinically important changes in standard laboratory parameters were rarely associated with the administration of TENORETIC. The changes in laboratory parameters were not progressive and usually were not associated with clinical manifestations. The most common changes were increases in uric acid and decreases in serum potassium.
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| dailymed-drugs:212 |
The most frequent adverse reactions are underlined: Body as a Whole: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose and throat. Cardiovascular: Hypotension, headache, palpitations, tachycardia, extrasystoles. Hematologic: Hemolytic anemia, thrombocytopenia, agranulocytosis. Central Nervous System:Sedation, sleepiness, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions. Gastrointestinal:Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation. Urogenital: Urinary frequency, difficult urination, urinary retention, early menses. Respiratory:Thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.
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| dailymed-drugs:213 |
In Phases II and III clinical trials, a total of 937 patients were treated with CIPRODEX' Otic. This included 400 patients with acute otitis media with tympanostomy tubes and 537 patients with acute otitis externa. The reported treatment-related adverse events are listed below: Acute Otitis Media in pediatric patients with
tympanostomy tubesThe following treatment-related adverse events occurred in 0.5% or more of the patients with non-intact tympanic membranes. The following treatment-related adverse events were each reported in a single patient: tympanostomy tube blockage; ear pruritus; tinnitus; oral moniliasis; crying; dizziness; and erythema. Acute Otitis ExternaThe following treatment-related adverse events occurred in 0.4% or more of the patients with intact tympanic membranes. The following treatment-related adverse events occurred in 0.4% or more of the patients with intact tympanic membranes. The following treatment-related adverse events were each reported in a single patient: ear discomfort; decreased hearing; and ear disorder (tingling).
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| dailymed-drugs:214 |
Clinical experience with SYPRINE has been limited. The following adverse reactions have been reported in a clinical study in patients with Wilson's disease who were on therapy with trientine hydrochloride: iron deficiency, systemic lupus erythematosus . In addition, the following adverse reactions have been reported in marketed use: dystonia, muscular spasm, myasthenia gravis. SYPRINE is not indicated for treatment of biliary cirrhosis, but in one study of 4 patients treated with trientine hydrochloride for primary biliary cirrhosis, the following adverse reactions were reported: heartburn; epigastric pain and tenderness; thickening, fissuring and flaking of the skin; hypochromic microcytic anemia; acute gastritis; aphthoid ulcers; abdominal pain; melena; anorexia; malaise; cramps; muscle pain; weakness; rhabdomyolysis. A causal relationship of these reactions to drug therapy could not be rejected or established.
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| dailymed-drugs:216 |
Precise frequency data are not available. Initial dosing may produce flatulence and intestinal cramps, which are usually transient. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia. Nausea and vomiting have been reported.
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| dailymed-drugs:1672 |
Precise frequency data are not available. Initial dosing may produce flatulence and intestinal cramps, which are usually transient. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia. Nausea and vomiting have been reported.
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| dailymed-drugs:2835 |
Precise frequency data are not available. Initial dosing may produce flatulence and intestinal cramps, which are usually transient. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia. Nausea and vomiting have been reported.
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| dailymed-drugs:3256 |
Precise frequency data are not available. Initial dosing may produce flatulence and intestinal cramps, which are usually transient. Excessive dosage can lead to diarrhea with potential complications such as loss of fluids, hypokalemia, and hypernatremia. Nausea and vomiting have been reported.
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| dailymed-drugs:217 |
Ocular: Mydriasis, increased redness, irritation, discomfort, blurring, punctate keratitis, lacrimation, increased intraocular pressure.<br/>Systemic: Dizziness, headache, nausea, sweating, nervousness drowsiness, weakness, hypertension, cardiac irregularities, and hyperglycemia.
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| dailymed-drugs:219 |
Peginterferon alfa-2a in combination with ribavirin causes a broad variety of serious adverse reactions . The most common life-threatening or fatal events induced or aggravated by peginterferon alfa-2a and ribavirin were depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurring at a frequency of<1%. In all studies, one or more serious adverse reactions occurred in 10% of CHC monoinfected patients receiving peginterferon alfa-2a alone or in combination with ribavirin. The most common serious adverse event (3% in CHC) was bacterial infection (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia). Other SAEsoccurred at a frequency of<1% and included: suicide, suicidal ideation, psychosis, aggression, anxiety, drug abuse and drug overdose, angina, hepatic dysfunction, fatty liver, cholangitis, arrhythmia, diabetes mellitus, autoimmune phenomena (e.g., hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), peripheral neuropathy, aplastic anemia, peptic ulcer, gastrointestinal bleeding, pancreatitis, colitis, corneal ulcer, pulmonary embolism, coma, myositis, cerebral hemorrhage, and thrombotic thrombocytopenic purpura. Nearly all patients in clinical trials experienced one or more adverse events. The most commonly reported adverse reactions were psychiatric reactions, including depression, insomnia, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors. Other common reactions were anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. Ten percent of CHC monoinfected patients receiving 48 weeks of therapy with peginterferon alfa-2a in combination with ribavirin discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (e.g., lethargy, fatigue, headache), dermatologic and gastrointestinal disorders and laboratory abnormalities (thrombocytopenia, neutropenia, and anemia). Overall 39% of patients with CHC required modification of peginterferon alfa-2a and/or ribavirin therapy. The most common reason for dose modification of peginterferon alfa-2a in CHC patients was for laboratory abnormalities; neutropenia (20%) and thrombocytopenia (4%). The most common reason for dose modification of ribavirin in CHC patients was anemia (22%). Peginterferon alfa-2a dose was reduced in 12% of patients receiving 1000 mg to 1200 mg ribavirin for 48 weeks and in 7% of patients receiving 800 mg ribavirin for 24 weeks. Ribavirin dose was reduced in 21% of patients receiving 1000 mg to1200 mg ribavirin for 48 weeks and in 12% of patients receiving 800 mg ribavirin for 24 weeks. Chronic hepatitis C monoinfected patients treated for 24 weeks with peginterferon alfa-2a and 800 mg ribavirin were observed to have lower incidence of serious adverse events (3% vs. 10%), hemoglobin<10 g/dL (3% vs. 15%), dose modifications of peginterferon alfa-2a (30% vs. 36%) and ribavirin (19% vs. 38%), and of withdrawal from treatment (5% vs. 15%) compared to patients treated for 48 weeks with peginterferon alfa-2a and 1000 mg or 1200 mg ribavirin. On the other hand, the overall incidence of adverse events appeared to be similar in the two treatment groups. Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug. Also, the adverse event rates listed here may not predict the rates observed in a broader patient population in clinical practice.<br/>Laboratory Test Values: Anemia due to hemolysis is the most significant toxicity of ribavirin therapy. Anemia (hemoglobin<10 g/dL) was observed in 13% of all ribavirin and peginterferon alfa-2a combination-treated patients in clinical trials. The maximum drop in hemoglobin occurred during the first 8 weeks of initiation of ribavirin therapy .
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| dailymed-drugs:220 |
Adverse reaction data were derived from patients who received oxaprozin in multidose, controlled, and open-label clinical trials, and from worldwide marketing experience. Rates for events occurring in more than 1% of patients, and for most of the less common events, are based on 2253 patients who took 1200 to 1800 mg oxaprozin per day in clinical trials. Of these, 1721 were treated for at least 1 month, 971 for at least 3 months, and 366 for more than 1 year. Rates for the rarer events and for events reported from worldwide marketing experience are difficult to estimate accurately and are only listed as less than 1%.<br/>Incidence greater than 1%: In clinical trials of oxaprozin or in patients taking other NSAIDs, the following adverse reactions occurred at an incidence greater than 1%. CARDIOVASCULAR SYSTEM: edema. DIGESTIVE SYSTEM: abdominal pain/distress, anorexia, constipation, diarrhea, dyspepsia, flatulence, gastrointestinal ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, liver enzyme elevations, nausea, vomiting. HEMATOLOGIC SYSTEM: anemia, increased bleeding time. NERVOUS SYSTEM: CNS inhibition (depression, sedation, somnolence, or confusion), disturbance of sleep, dizziness, headache. SKIN AND APPENDAGES: pruritus, rash. SPECIAL SENSES: tinnitus. UROGENITAL SYSTEM: abnormal renal function, dysuria or frequency. Incidence less than 1% The following adverse reactions were reported in clinical trials, from worldwide marketing experience (in italics) or in patients taking other NSAIDs. BODY AS A WHOLE: appetite changes, death, drug hypersensitivity reactions including anaphylaxis, fever, infection, sepsis, serum sickness. CARDIOVASCULAR SYSTEM: arrhythmia, blood pressure changes, congestive heart failure, hypertension, hypotension, myocardial infarction, palpitations, tachycardia, syncope, vasculitis. DIGESTIVE SYSTEM: alteration in taste, dry mouth, eructation, esophagitis, gastritis, glossitis, hematemesis, jaundice, liver function abnormalities including hepatitis, liver failure, stomatitis, hemorrhoidal or rectal bleeding, pancreatitis. HEMATOLOGIC SYSTEM: agranulocytosis, aplastic anemia, ecchymoses, eosinophilia, hemolytic anemia, lymphadenopathy, melena, pancytopenia, purpura, thrombocytopenia, leukopenia. METABOLIC SYSTEM: hyperglycemia, weight changes. NERVOUS SYSTEM: anxiety, asthenia, coma, convulsions, dream abnormalities, drowsiness, hallucinations, insomnia, malaise, meningitis, nervousness, paresthesia, tremors, vertigo, weakness. RESPIRATORY SYSTEM: asthma, dyspnea, pulmonary infections, pneumonia, sinusitis, symptoms of upper respiratory tract infection, respiratory depression. SKIN: alopecia, angioedema, urticaria, photosensitivity, pseudoporphyria, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, sweat, toxic epidermal necrolysis (Lyell's syndrome). SPECIAL SENSES: blurred vision, conjuctivitis, hearing decrease. UROGENITAL: acute interstitial nephritis, cystitis, hematuria, increase in menstrual flow, nephrotic syndrome, oliguria/polyuria, proteinuria, renal insufficiency, acute renal failure, decreased menstrual flow.
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| dailymed-drugs:221 |
See BOXED WARNINGS, WARNINGS and PRECAUTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Adverse events reported with Activella 1.0 mg/0.5 mg by investigators in the Phase 3 studies regardless of causality assessment are shown in Table 6. Adverse events reported with Activella 0.5 mg/0.1 mg by investigators during the Phase 3 study regardless of causality assessment are shown in Table 7. The following adverse reactions have been reported with estrogen and/or progestin therapy:<br/>1. Genitourinary system: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.<br/>2. Breasts: Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.<br/>3. Cardiovascular: Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure.<br/>4. Gastrointestinal: Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas.<br/>5. Skin: Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.<br/>6. Eyes: Retinal vascular thrombosis, intolerance to contact lenses.<br/>7. Central nervous system: Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; probable dementia.<br/>8. Miscellaneous: Increase or decrease in weight; aggravation of porphyria; edema; leg cramps; changes in libido; fatigue; reduced carbohydrate tolerance; anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides; back pain; arthralgia; myalgia.
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| dailymed-drugs:222 |
Occasional temporary stinging, burning and conjunctival redness may occur with the use of proparacaine. A rare, severe, immediate-type, apparently hyperallergic corneal reaction, characterized by acute, intense and diffuse epithelial keratitis, a gray, ground glass appearance, sloughing of large areas of necrotic epithelium, corneal filaments and, sometimes, iritis with descemetitis has been reported. Allergic contact dermatitis from proparacaine with drying and fissuring of the fingertips has also been reported.
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| dailymed-drugs:223 |
Adverse reactions to sucralfate tablets in clinical trials were minor and only rarely led to discontinuation of the drug. In studies involving over 2700 patients treated with sucralfate, adverse effects were reported in 129 (4.7%). Constipation was the most frequent complaint (2%). Other adverse effects reported in less than 0.5% of the patients are listed below by body system: Gastrointestinal: diarrhea, dry mouth, flatulence, gastric discomfort, indigestion, nausea, vomiting Dermatological: pruritus, rash Nervous System: dizziness, insomnia, sleepiness, vertigo Other: back pain, headache Postmarketing reports of hypersensitivity reactions, including urticaria (hives), angioedema, respiratory difficulty, rhinitis, laryngospasm, and facial swelling have been reported in patients receiving sucralfate tablets. Similar events were reported with sucralfate suspension. However, a causal relationship has not been established. Bezoars have been reported in patients treated with sucralfate. The majority of patients had underlying medical conditions that may predispose to bezoar formation (such as delayed gastric emptying) or were receiving concomitant enteral tube feedings. Inadvertent injection of insoluble sucralfate and its insoluble excipients has led to fatal complications, including pulmonary and cerebral emboli. Sucralfate is not intended for intravenous administration.
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| dailymed-drugs:225 |
Hypertension: ALTACE has been evaluated for safety in over 4,000 patients with hypertension; of these, 1,230 patients were studied in US controlled trials, and 1,107 were studied in foreign controlled trials. Almost 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was similar in ALTACE and placebo patients. The most frequent clinical side effects (possibly or probably related to study drug) reported by patients receiving ALTACE in US placebo-controlled trials were: headache (5.4%),���dizziness���(2.2%) and fatigue or asthenia (2.0%), but only the last was more common in ALTACE patients than in patients given placebo. Generally, the side effects were mild and transient, and there was no relation to total dosage within the range of 1.25 to 20 mg. Discontinuation of therapy because of a side effect was required inapproximately 3% of US patients treated with ALTACE. The most common reasons for discontinuation were: cough (1.0%),���dizziness���(0.5%), and impotence (0.4%). Of observed side effects considered possibly or probably related to study drug that occurred in US placebo-controlled trials in more than 1% of patients treated with ALTACE, only asthenia (fatigue) was more common on Altace than placebo (2% vs. 1%). In placebo-controlled trials, there was also an excess of upper respiratory infection and flu syndrome in the ramipril group, not attributed at that time to ramipril. As these studies were carried out before the relationship of cough to ACE inhibitors was recognized, some of these events may represent ramipril-induced cough. In a later 1-year study, increased cough was seen in almost 12% of ramipril patients, with about 4% of patients requiring discontinuation of treatment.<br/>Heart Failure Post Myocardial Infarction: Adverse reactions (except laboratory abnormalities) considered possibly/probably related to study drug that occurred in more than one percent of patients and more frequently on ramipril are shown below. The incidences represent the experiences from the AIRE study. The follow-up time was between 6 and 46 months for this study. Percentage of Patients with Adverse Events Possibly/ Probably Related to Study Drug Placebo-Controlled (AIRE) Mortality Study HOPE Study: Safety data in the HOPE trial were collected as reasons for discontinuation or temporary interruption of treatment. The incidence of cough was similar to that seen in the AIRE trial. The rate of angioedema was the same as in previous clinical trials . Other adverse experiences reported in controlled clinical trials (in less than 1% of ramipril patients), or rarer events seen in postmarketing experience, include the following (in some, a causal relationship to drug use is uncertain): Body As a Whole: Anaphylactoid reactions. Cardiovascular: Symptomatic hypotension (reported in 0.5% of patients in US trials) , syncope and palpitations. Hematologic: Pancytopenia, hemolytic anemia and thrombocytopenia. Renal: Some hypertensive patients with no apparent pre-existing renal disease have developed minor, usually transient, increases in blood urea nitrogen and serum creatinine when taking ALTACE, particularly when ALTACE was given concomitantly with a diuretic. Acute renal failure. Angioneurotic Edema: Angioneurotic edema has been reported in 0.3% of patients in US clinical trials. Gastrointestinal: Hepatic failure, hepatitis, jaundice, pancreatitis, abdominal pain (sometimes with enzyme changes suggesting pancreatitis), anorexia, constipation, diarrhea, dry mouth, dyspepsia, dysphagia, gastroenteritis, increased salivation and taste disturbance. Dermatologic: Apparent hypersensitivity reactions (manifested by urticaria, pruritus, or rash, with or without fever), photosensitivity, purpura, onycholysis, pemphigus, pemphigoid, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome. Neurologic and Psychiatric: Anxiety, amnesia, convulsions, depression, hearing loss, insomnia, nervousness, neuralgia, neuropathy, paresthesia, somnolence, tinnitus, tremor, vertigo, and vision disturbances. Miscellaneous: As with other ACE inhibitors, a symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, photosensitivity, rash and other dermatologic manifestations. Additionally, as with other ACE inhibitors, eosinophilic pneumonitis has been reported. Fetal/Neonatal Morbidity and Mortality. See WARNINGS : Fetal/Neonatal Morbidity and Mortality . Other: arthralgia, arthritis, dyspnea, edema, epistaxis, impotence, increased sweating, malaise, myalgia, and weight gain. Post-Marketing Experience: In addition to adverse events reported from clinical trials, there have been rare reports of hypoglycemia reported during ALTACE therapy when given to patients concomitantly taking oral hypoglycemic agents or insulin. The causal relationship is unknown.<br/>Clinical Laboratory Test Findings:: Creatinine and Blood Urea Nitrogen: Increases in creatinine levels occurred in 1.2% of patients receiving ALTACE alone, and in 1.5% of patients receiving ALTACE and a diuretic. Increases in blood urea nitrogen levels occurred in 0.5% of patients receiving ALTACE alone and in 3% of patients receiving ALTACE with a diuretic. None of these increases required discontinuation of treatment. Increases in these laboratory values are more likely to occur in patients with renal insufficiency or those pretreated with a diuretic and, based on experience with other ACE inhibitors, would be expected to be especially likely in patients with renal artery stenosis. Since ramipril decreases aldosterone secretion, elevation of serum potassium can occur. Potassium supplements and potassium-sparing diuretics should be given with caution, and the patient's serum potassium should be monitored frequently. Hemoglobin and Hematocrit: Decreases in hemoglobin or hematocrit (a low value and a decrease of 5 g/dl or 5% respectively) were rare, occurring in 0.4% of patients receiving ALTACE alone and in 1.5% of patients receiving ALTACE plus a diuretic. No US patients discontinued treatment because of decreases in hemoglobin or hematocrit. Other (causal relationships unknown): Clinically important changes in standard laboratory tests were rarely associated with ALTACE administration. Elevations of liver enzymes, serum bilirubin, uric acid, and blood glucose have been reported, as have cases of hyponatremia and scattered incidents of leukopenia, eosinophilia, and proteinuria. In US trials, less than 0.2% of patients discontinued treatment for laboratory abnormalities; all of these were cases of proteinuria or abnormal liver-function tests.
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| dailymed-drugs:226 |
The following adverse reactions have been reported and, within each category (body system), are listed in order of decreasing severity. Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Endocrine: Gynecomastia (see Precautions), inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding. Carcinoma of the breast has been reported in patients taking spironolactone but a cause and effect relationship has not been established. Hematologic: Agranulocytosis. Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis. Nervous system /psychiatric: Mental confusion, ataxia, headache, drowsiness, lethargy. Liver / biliary: A very few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with spironolactone administration. Renal: Renal dysfunction (including renal failure).
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| dailymed-drugs:749 |
The following adverse reactions have been reported and, within each category (body system), are listed in order of decreasing severity. Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Endocrine: Gynecomastia (see Precautions), inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding. Carcinoma of the breast has been reported in patients taking spironolactone but a cause and effect relationship has not been established. Hematologic: Agranulocytosis. Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis. Nervous system /psychiatric: Mental confusion, ataxia, headache, drowsiness, lethargy. Liver / biliary: A very few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with spironolactone administration. Renal: Renal dysfunction (including renal failure).
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| dailymed-drugs:227 |
Adult Patients: Ampicillin
and Sulbactam for Injection is generally well tolerated. The
following adverse reactions have been reported.<br/>Local
Adverse Reactions: Pain at IM injection site���16% Pain at IV injection site���3% Thrombophlebitis���3%<br/>Systemic
Adverse Reactions: The
most frequently reported adverse reactions were diarrhea
in 3% of the patients and rash in less than 2% of the
patients. Additional systemic reactions reported in less than 1%
of the patients were: itching, nausea, vomiting,
candidiasis, fatigue, malaise, headache, chest pain,
flatulence, abdominal distension, glossitis, urine
retention, dysuria, edema, facial swelling, erythema,
chills, tightness in throat, substernal pain, epistaxis
and mucosal bleeding.<br/>Pediatric Patients: Available
safety data for pediatric patients treated with Ampicillin and
Sulbactam for Injection demonstrate a similar adverse events
profile to those observed in adult patients. Additionally,
atypical lymphocytosis has been observed in one pediatric
patient receiving Ampicillin and Sulbactam for
Injection.<br/>Adverse Laboratory Changes: Adverse
laboratory changes without regard to drug relationship that were
reported during clinical trials were:<br/>Hepatic: Increased AST (SGOT), ALT (SGPT), alkaline phosphatase,
and LDH.<br/>Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC,
neutrophils, lymphocytes, platelets and increased
lymphocytes, monocytes, basophils, eosinophils, and
platelets.<br/>Blood
Chemistry: Decreased serum albumin and total proteins.<br/>Renal: Increased BUN and creatinine.<br/>Urinalysis: Presence of RBCs and hyaline casts in urine. The
following adverse reactions have been reported with
ampicillin-class antibiotics and can also occur with
Ampicillin and Sulbactam for Injection.<br/>Gastrointestinal: Gastritis,
stomatitis, black "hairy" tongue and enterocolitis. Onset of
pseudomembranous colitis symptoms may occur during or after
antibiotic treatment.<br/>Hypersensitivity
Reactions: Urticaria,
erythema multiforme, and an occasional case of exfoliative
dermatitis have been reported. These reactions may be controlled
with antihistamines and, if necessary, systemic corticosteroids.
Whenever such reactions occur, the drug should be discontinued,
unless the opinion of the physician dictates otherwise. Serious
and occasional fatal hypersensitivity (anaphylactic) reactions
can occur with a penicillin.<br/>Hematologic: In addition
to the adverse laboratory changes listed above for Ampicillin
and Sulbactam for Injection, agranulocytosis has been reported
during therapy with penicillins. All of these reactions are
usually reversible on discontinuation of therapy and are
believed to be hypersensitivity phenomena. Some individuals have
developed positive direct Coombs Tests during treatment with
Ampicillin and Sulbactam for Injection, as with other
beta-lactam antibiotics.
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| dailymed-drugs:228 |
Serious adverse reactions that may be associated with oxycodone and acetaminophen tablet use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock . The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus. Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions. Hematologic reactions may include: Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis has likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur. Other adverse reactions obtained from postmarketing experiences with oxycodone and acetaminophen tablets are listed by organ system and in decreasing order of severity and/or frequency as follows: Body as a Whole Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose Cardiovascular Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias Central and Peripheral Nervous System Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness Fluid and Electrolyte Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis Gastrointestinal Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus Hepatic Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder Hearing and Vestibular Hearing loss, tinnitus Hematologic Thrombocytopenia Hypersensitivity Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction Metabolic and Nutritional Hypoglycemia, hyperglycemia, acidosis, alkalosis Musculoskeletal Myalgia, rhabdomyolysis Ocular Miosis, visual disturbances, red eye Psychiatric Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide Respiratory System Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema Skin and Appendages Erythema, urticaria, rash, flushing Urogenital Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention
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| dailymed-drugs:229 |
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a well-placed small bore needle is recommended. Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential. Hypernatremia may be associated with edema and exacerbation of congestive heart failure due to the retention of water, resulting in an expanded extracellular fluid volume. Reactions reported with the use of potassium-containing solutions include nausea, vomiting, abdominal pain and diarrhea. The signs and symptoms of potassium intoxication include paresthesias of the extremities, areflexia, muscular or respiratory paralysis, mental confusion, weakness, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities and cardiac arrest. Potassium deficits result in disruption of neuromuscular function, and intestinal ileus and dilatation. If infused in large amounts, chloride ions may cause a loss of bicarbonate ions, resulting in an acidifying effect. Abnormally high plasma levels of calcium can result in depression, amnesia, headaches, drowsiness, disorientation, syncope, hallucinations, hypotonia of both skeletal and smooth muscles, dysphagia, arrhythmias and coma. Calcium deficits can result in neuromuscular hyperexcitability, including cramps and convulsions. Dextrose may be administered at a rate of 0.5 g/kg/hour without producing glycosuria. Hyperglycemia and glycosuria may be a function of rate of administration or metabolic insufficiency. If undetected and untreated this can lead to osmotic dehydration, hyperosmolar coma and death. Appropriate therapy may include slowing of the infusion rate and administration of insulin. The physician should also be alert to the possibility of adverse reactions to drug additives. Prescribing information for drug additives to be administered in this manner should be consulted. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:230 |
Blood Dyscrasias: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia, purpura, hypoprothrombinemia, and methemoglobinemia.<br/>Allergic Reactions: Erythema multiforme (Stevens-Johnson syndrome), generalized skin eruptions, epidermal necrolysis, urticaria, serum sickness, pruritus, exfoliative dermatitis, anaphylactoid reactions, periorbital edema, conjunctival and scleral injection, photosensitization, arthralgia, allergic myocarditis, drug fever, and chills.<br/>Gastrointestinal Reactions: Nausea, emesis, abdominal pains, hepatitis, diarrhea, anorexia, pancreatitis, and stomatitis.<br/>C.N.S. Reactions: Headache, peripheral neuritis, mental depression, convulsions, ataxia, hallucinations, tinnitus, vertigo, and insomnia.<br/>Renal: Crystalluria, stone formation, toxic nephrosis with oliguria and anuria; periarteritis nodosa and lupus erythematosus phenomenon have been noted.<br/>Miscellaneous Reactions: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist with these agents.
|
| dailymed-drugs:232 |
Reactions which may occur because of the technique
of administration include febrile response, infection at the site
of injection, venous thrombosis or phlebitis extending from the site
of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the infusion,
evaluate the patient, institute appropriate therapeutic countermeasures
and save the remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:1940 |
Reactions which may occur because of the technique
of administration include febrile response, infection at the site
of injection, venous thrombosis or phlebitis extending from the site
of injection, extravasation and hypervolemia. If an adverse reaction does occur, discontinue the infusion,
evaluate the patient, institute appropriate therapeutic countermeasures
and save the remainder of the fluid for examination if deemed necessary.
|
| dailymed-drugs:233 |
Gastrointestinal: Transient symptoms of abdominal pain and diarrhea in cases of massive infection and expulsion of worms.<br/>Hypersensitivity: Rash, urticaria and angioedema have been observed on rare occasions.<br/>Central Nervous System: Very rare cases of convulsions have been reported.<br/>Liver: There have been liver function test elevations [AST (SGOT), ALT (SGPT), and GGT] and rare reports of hepatitis when mebendazole was taken for prolonged periods and at dosages substantially above those recommended.<br/>Hematologic: Neutropenia and agranulocytosis. (See WARNINGS).
|
| dailymed-drugs:234 |
Adverse reactions have been very common in virtually all series of patients treated with amiodarone hydrochloride for ventricular arrhythmias with relatively large doses of drug (400 mg/day and above), occurring in about three-fourths of all patients and causing discontinuation in 7% to 18%. The most serious reactions are pulmonary toxicity, exacerbation of arrhythmia, and rare serious liver injury , but other adverse effects constitute important problems. They are often reversible with dose reduction or cessation of amiodarone treatment. Most of the adverse effects appear to become more frequent with continued treatment beyond six months, although rates appear to remain relatively constant beyond one year. The time and dose relationships of adverse effects are under continued study. Neurologic problems are extremely common, occurring in 20% to 40% of patients and including malaise and fatigue, tremor and involuntary movements, poor coordination and gait, and peripheral neuropathy; they are rarely a reason to stop therapy and may respond to dose reductions or discontinuation . Gastrointestinal complaints, most commonly nausea, vomiting, constipation and anorexia, occur in about 25% of patients but rarely require discontinuation of drug. These commonly occur during high-dose administration (i.e., loading dose) and usually respond to dose reduction or divided doses. Ophthalmic abnormalities including optic neuropathy and/or optic neuritis, in some cases progressing to permanent blindness, papilledema, corneal degeneration, photosensitivity, eye discomfort, scotoma, lens opacities and macular degeneration have been reported . Asymptomatic corneal microdeposits are present in virtually all adult patients who have been on drug for more than 6 months. Some patients develop eye symptoms of halos, photophobia and dry eyes. Vision is rarely affected and drug discontinuation is rarely needed. Dermatological adverse reactions occur in about 15% of patients, with photosensitivity being most common (about 10%). Sunscreen and protection from sun exposure may be helpful, and drug discontinuation is not usually necessary. Prolonged exposure to amiodarone occasionally results in a blue-gray pigmentation. This is slowly and occasionally incompletely reversible on discontinuation of drug but is of cosmetic importance only. Cardiovascular adverse reactions, other than exacerbation of the arrhythmias, include the uncommon occurrence of congestive heart failure (3%) and bradycardia. Bradycardia usually responds to dosage reduction but may require a pacemaker for control. CHF rarely requires drug discontinuation. Cardiac conduction abnormalities occur infrequently and are reversible on discontinuation of drug. The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days). The following side effects were each reported in 10% to 33% of patients: Gastrointestinal: Nausea and vomiting. The following side effects were each reported in 4% to 9% of patients: Dermatologic: Solar dermatitis/photosensitivity. Neurologic: Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias. Gastrointestinal: Constipation, anorexia. Ophthalmologic: Visual disturbances. Hepatic: Abnormal liver-function tests. Respiratory: Pulmonary inflammation or fibrosis. The following side effects were each reported in 1% to 3% of patients: Thyroid: Hypothyroidism, hyperthyroidism. Neurologic: Decreased libido, insomnia, headache, sleep disturbances. Cardiovascular: Congestive heart failure, cardiac arrhythmias, SA node dysfunction. Gastrointestinal: Abdominal pain. Hepatic: Nonspecific hepatic disorders. Other: Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities. The following side effects were each reported in less than 1% of patients: Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension and cardiac conduction abnormalities. In surveys of almost 5,000 patients treated in open U.S. studies and in published reports of treatment with amiodarone hydrochloride, the adverse reactions most frequently requiring discontinuation of amiodarone included pulmonary infiltrates or fibrosis, paroxysmal ventricular tachycardia, congestive heart failure and elevation of liver enzymes. Other symptoms causing discontinuations less often included visual disturbances, solar dermatitis, blue skin discoloration, hyperthyroidism and hypothyroidism.<br/>Postmarketing Reports: In postmarketing surveillance, hypotension (sometimes fatal), sinus arrest, anaphylactic/anaphylactoid reaction (including shock), angioedema, hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, renal impairment, renal insufficiency, acute renal failure, bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pulmonary alveolar hemorrhage, pleuritis, pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy), syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma, myopathy, muscle weakness, rhabdomyolysis, hallucination, confusional state, disorientation, delirium, epididymitis and impotence, also have been reported with amiodarone therapy.
|
| dailymed-drugs:235 |
The most common adverse event following the use of RESTASIS was ocular burning (17%). Other events reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring).
|
| dailymed-drugs:237 |
The following additional adverse reactions have been reported with estrogen therapy (see WARNINGS regarding induction of neoplasia, adverse effects on the fetus, increased incidence of gallbladder disease, cardiovascular disease, elevated blood pressure, and hypercalcemia). 1. Genitourinary System. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting. Increase in size of uterine leiomyomata. Vaginal candiasis. Change in amount of cervical secretion. 2. Breast. Tenderness, enlargement. 3. Gastrointestinal. Nausea, vomiting. Abdominal cramps, bloating. Cholestatic jaundice. Increased incidence of gallbladder disease. 4. Skin. Chloasma or melasma which may persist when drug is discontinued. Erythema multiforme. Erythema nodosum. Hemorrhagic eruption. Loss of scalp hair. Hirsutism. 5. Eyes. Steepening of corneal curvature. Intolerance to contact lenses. 6. Central Nervous System. Headache, migraine, dizziness. Mental depression. Chorea. 7. Miscellaneous. Increase or decrease in weight. Reduced carbohydrate tolerance. Aggravation of porphyria. Edema. Changes in libido.
|
| dailymed-drugs:239 |
Fluid and Electrolyte Disturbances Musculoskeletal Gastrointestinal Dermatologic Metabolic Neurological Endocrine Ophthalmic Additional Reactions
|
| dailymed-drugs:240 |
Most adverse effects are mild, transient and occur early in the course of treatment. In controlled clinical trials of 3 to 4 months duration, discontinuation of labetalol HCl tablets due to one or more adverse effects was required in 7% of all patients. In these same trials, beta-blocker control agents led to discontinuation in 8% to 10% of patients, and a centrally acting alpha-agonist in 30% of patients. The incidence rates of adverse reactions listed in the following table were derived from multicenter controlled clinical trials, comparing labetalol, placebo, metoprolol, and propranolol, over treatment periods of 3 and 4 months. Where the frequency of adverse effects for labetalol and placebo is similar, causal relationship is uncertain. The rates are based on adverse reactions considered probably drug related by the investigator. If all reports are considered, the rates are somewhat higher (e.g., dizziness 20%, nausea 14%, fatigue 11%), but the overall conclusions are unchanged. The adverse effects were reported spontaneously and are representative of the incidence of adverse effects that may be observed in a properly selected hypertensive patient population, i.e., a group excluding patients with bronchospastic disease, overt congestive heart failure, or other contraindications to beta-blocker therapy. Clinical trials also included studies utilizing doses up to 2400 mg in more severely hypertensive patients. Certain of the side effects increased with increasing dose as shown in the table below which depicts the entire U.S. therapeutic trials data base for adverse reactions that are clearly or possibly drug related. In addition a number of other less common adverse events have been reported: Body as a Whole: Fever. Cardiovascular: Hypotension, and rarely, syncope, bradycardia, heart block. Central and Peripheral Nervous Systems: Paresthesias, most frequently described as scalp tingling. In most cases, it was mild, transient and usually occurred at the beginning of treatment. Collagen Disorders: Systemic lupus erythematosus; positive antinuclear factor (ANF). Eyes: Dry eyes. Immunological System: Antimitochondrial antibodies. Liver and Biliary System: Hepatic necrosis; hepatitis; cholestatic jaundice; elevated liver function tests. Musculoskeletal System: Muscle cramps; toxic myopathy. Respiratory System: Bronchospasm. Skin and Appendages: Rashes of various types, such as generalized maculopapular; lichenoid; urticarial; bullous lichen planus; psoriaform; facial erythema; Peyronie's disease, reversible alopecia. Urinary System: Difficulty in micturition, including acute urinary bladder retention. Hypersensitivity: Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions. Following approval for marketing in the United Kingdom, a monitored release survey involving approximately 6,800 patients was conducted for further safety and efficacy evaluation of this product. Results of this survey indicate that the type, severity, and incidence of adverse effects were comparable to those cited above.<br/>Potential Adverse Effects: In addition, other adverse effects not listed above have been reported with other beta-adrenergic blocking agents. Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular: Intensification of AV block . Allergic: Fever combined with aching and sore throat; laryngospasm; respiratory distress. Hematologic: Agranulocytosis; thrombocytopenic or nonthrombocytopenic purpura. Gastrointestinal: Mesenteric artery thrombosis; ischemic colitis. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with labetalol.<br/>Clinical Laboratory Tests: There have been reversible increases of serum transaminases in 4% of patients treated with labetalol and tested, and more rarely, reversible increases in blood urea.
|
| dailymed-drugs:241 |
Serious cardiac events, including some that have been fatal, have occurred following use of Dihydroergotamine Mesylate Injection, USP, but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. . Fibrotic complications have been reported in association with long term use of injectable dihydroergotamine mesylate .<br/>Post-Introduction Reports: The following events derived from postmarketing experience have been occasionally reported in patients receiving Dihydroergotamine Mesylate Injection, USP: vasospasm, paraesthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine. Extremely rare cases of myocardial infarction and stroke have been reported. A causal relationship has not been established. Dihydroergotamine Mesylate Injection, USP is not recommended for prolonged daily use.
|
| dailymed-drugs:242 |
Causal Relationship Unknown:
|
| dailymed-drugs:243 |
Adjuvant Therapy: Adverse reaction data for adjuvant therapy are based on the adjuvant trial (see CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant Treatment of Breast Cancer in Postmenopausal Women). At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving ARIMIDEX 1 mg and tamoxifen 20 mg, respectively. Adverse events occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 8. Certain adverse events and combinations of adverse events were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (See table 9). Patients receiving ARIMIDEX had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving ARIMIDEX had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)]. Patients receiving ARIMIDEX had a decrease in hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen. Patients receiving ARIMIDEX had an increase in hypercholesterolemia (278 [9%]) compared to patients receiving tamoxifen (108 [3.5%]). Angina pectoris was reported in 71 [2.3%] patients in the ARIMIDEX arm and 51 [1.6%] patients in the tamoxifen arm; myocardial infarction was reported in 37 [1.2%] patients in the ARIMIDEX arm and in 34 [1.1%] patients in the tamoxifen arm. Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving ARIMIDEX had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.<br/>First Line Therapy: ARIMIDEX was generally well tolerated in two well-controlled clinical trials (ie, Trials 0030 and 0027). Adverse events occurring with an incidence of at least 5% in either treatment group of trials 0030 and 0027 during or within 2 weeks of the end of treatment are shown in Table 10. Less frequent adverse experiences reported in patients receiving ARIMIDEX l mg in either Trial 0030 or Trial 0027 were similar to those reported for second-line therapy. Based on results from second-line therapy and the established safety profile of tamoxifen, the incidences of 9 prespecified adverse event categories potentially causally related to one or both of the therapies because of their pharmacology were statistically analyzed. No significant differences were seen between treatment groups. Despite the lack of estrogenic activity for ARIMIDEX, there was no increase in myocardial infarction or fracture when compared with tamoxifen.<br/>Second Line Therapy: ARIMIDEX was generally well tolerated in two well-controlled clinical trials (ie, Trials 0004 and 0005), with less than 3.3% of the ARIMIDEX-treated patients and 4.0% of the megestrol acetate-treated patients withdrawing due to an adverse event. The principal adverse event more common with ARIMIDEX than megestrol acetate was diarrhea. Adverse events reported in greater than 5% of the patients in any of the treatment groups in these two well-controlled clinical trials, regardless of causality, are presented below: Other less frequent (2% to 5%) adverse experiences reported in patients receiving ARIMIDEX l mg in either Trial 0004 or Trial 0005 are listed below. These adverse experiences are listed by body system and are in order of decreasing frequency within each body system regardless of assessed causality. Body as a Whole: Flu syndrome; fever; neck pain; malaise; accidental injury; infection Cardiovascular: Hypertension; thrombophlebitis Hepatic: Gamma GT increased; SGOT increased; SGPT increased Hematologic: Anemia; leukopenia Metabolic and Nutritional: Alkaline phosphatase increased; weight loss Mean serum total cholesterol levels increased by 0.5 mmol/L among patients receiving ARIMIDEX. Increases in LDL cholesterol have been shown to contribute to these changes. Musculoskeletal: Myalgia; arthralgia; pathological fracture Nervous: Somnolence; confusion; insomnia; anxiety; nervousness Respiratory: Sinusitis; bronchitis; rhinitis Skin and Appendages: Hair thinning; pruritus Urogenital: Urinary tract infection; breast pain The incidences of the following adverse event groups potentially causally related to one or both of the therapies because of their pharmacology, were statistically analyzed: weight gain, edema, thromboembolic disease, gastrointestinal disturbance, hot flushes, and vaginal dryness. These six groups, and the adverse events captured in the groups, were prospectively defined. The results are shown in the table below. More patients treated with megestrol acetate reported weight gain as an adverse event compared to patients treated with ARIMIDEX 1 mg (p<0.0001). Other differences were not statistically significant. An examination of the magnitude of change in weight in all patients was also conducted. Thirty-four percent (87/253) of the patients treated with megestrol acetate experienced weight gain of 5% or more and 11% (27/253) of the patients treated with megestrol acetate experienced weight gain of 10% or more. Among patients treated with ARIMIDEX 1 mg, 13% [33/262] experienced weight gain of 5% or more and 3% [6/262] experienced weight gain of 10% or more. On average, this 5 to 10% weight gain represented between 6 and 12 pounds. No patients receiving ARIMIDEX or megestrol acetate discontinued treatment due to drug-related weight gain.<br/>Post-Marketing Experience: Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase have been reported commonly (>1% and<10%) and gamma-GT, bilirubin and hepatitis have been reported uncommonly (>0.1% and<1%) in patients receiving ARIMIDEX. Vaginal bleeding has been reported infrequently, mainly in patients during the first few weeks after changing from existing hormonal therapy to treatment with ARIMIDEX. If bleeding persists, further evaluation should be considered. During clinical trials and postmarketing experience joint pain/stiffness has been reported in association with the use of ARIMIDEX. Carpal tunnel syndrome was reported more frequently in patients receiving ARIMIDEX than in those receiving tamoxifen in clinical trials; carpal tunnel has also been reported during post-marketing experience with ARIMIDEX. The majority of these reports occurred in patients with identifiable risk factors for the condition. ARIMIDEX may also be associated with rash including very rare cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome. Very rare cases of allergic reactions including angioedema, urticaria and anaphylaxis have been reported in patients receiving ARIMIDEX.
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| dailymed-drugs:245 |
Adverse effects include metabolic, fluid, electrolyte and
acid-base imbalances unless appropriate monitoring and corrective management
are accomplished during Aminosyn-RF 5.2%, Sulfite-Free, (an amino acid injection���renal formula) therapy.
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| dailymed-drugs:246 |
Side effects reported with the administration of hydroxyzine hydrochloride are usually mild and transitory in nature. Anticholinergic: Dry mouth. Central Nervous System: Drowsiness is usually transitory and may disappear in a few days of continued therapy or upon reduction of the dose. Involuntary motor activity including rare instances of tremor and convulsions have been reported, usually with doses considerably higher than those recommended. Clinically significant respiratory depression has not been reported at recommended doses.
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| dailymed-drugs:2438 |
Side effects reported with the administration of hydroxyzine hydrochloride are usually mild and transitory in nature. Anticholinergic: Dry mouth. Central Nervous System: Drowsiness is usually transitory and may disappear in a few days of continued therapy or upon reduction of the dose. Involuntary motor activity including rare instances of tremor and convulsions have been reported, usually with doses considerably higher than those recommended. Clinically significant respiratory depression has not been reported at recommended doses.
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| dailymed-drugs:248 |
Serious Adverse Reactions: Deaths have occurred in patients who received flumazenil in a variety of clinical settings. The majority of deaths occurred in patients with serious underlying disease or in patients who had ingested large amounts of non-benzodiazepine drugs (usually cyclic antidepressants), as part of an overdose. Serious adverse events have occurred in all clinical settings, and convulsions are the most common serious adverse events reported. Flumazenil administration has been associated with the onset of convulsions in patients with severe hepatic impairment and in patients who are relying on benzodiazepine effects to control seizures, are physically dependent on benzodiazepines, or who have ingested large doses of other drugs (mixed-drug overdose) . Two of the 446 patients who received flumazenil in controlled clinical trials for the management of a benzodiazepine overdose had cardiac dysrhythmias (1 ventricular tachycardia, 1 junctional tachycardia).<br/>Adverse Events in Clinical Studies: The following adverse reactions were considered to be related to flumazenil administration (both alone and for the reversal of benzodiazepine effects) and were reported in studies involving 1875 individuals who received flumazenil in controlled trials. Adverse events most frequently associated with flumazenil alone were limited to dizziness, injection site pain, increased sweating, headache, and abnormal or blurred vision (3% to 9%).<br/>Body as a Whole:: fatigue (asthenia, malaise), headache, injection site pain*, injection site reaction (thrombophlebitis, skin abnormality, rash)<br/>Cardiovascular System:: cutaneous vasodilation (sweating, flushing, hot flushes)<br/>Digestive System:: nausea, vomiting (11%)<br/>Nervous System:: agitation (anxiety, nervousness, dry mouth, tremor, palpitations, insomnia, dyspnea, hyperventilation)*, dizziness (vertigo, ataxia) (10%), emotional lability (crying abnormal, depersonalization, euphoria, increased tears, depression, dysphoria, paranoia)<br/>Special Senses:: abnormal vision (visual field defect, diplopia), paresthesia (sensation abnormal, hypoesthesia) All adverse reactions occurred in 1% to 3% of cases unless otherwise marked. *indicates reaction in 3% to 9% of cases. Observed percentage reported if greater than 9%. The following adverse events were observed infrequently (less than 1%) in the clinical studies, but were judged as probably related to flumazenil administration and/or reversal of benzodiazepine effects:<br/>Nervous System:: confusion (difficulty concentrating, delirium), convulsions , somnolence (stupor)<br/>Special Senses:: abnormal hearing (transient hearing impairment, hyperacusis, tinnitus) The following adverse events occurred with frequencies less than 1% in the clinical trials. Their relationship to flumazenil administration is unknown, but they are included as alerting information for the physician.<br/>Body as a Whole:: rigors, shivering<br/>Cardiovascular System:: arrhythmia (atrial, nodal, ventricular extrasystoles), bradycardia, tachycardia, hypertension, chest pain.<br/>Digestive System:: hiccup<br/>Nervous System:: speech disorder (dysphonia, thick tongue) Not included in this list is operative site pain that occurred with the same frequency in patients receiving placebo as in patients receiving flumazenil for reversal of sedation following a surgical procedure.<br/>Additional Adverse Reactions Reported During Postmarketing Experience: The following events have been reported during post-approval use of flumazenil.<br/>Nervous System:: Fear, panic attacks in patients with a history of panic disorders. Withdrawal symptoms may occur following rapid injection of flumazenil in patients with long-term exposure to benzodiazepines.
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| dailymed-drugs:249 |
(listed alphabetically under each subsection) Cardiovascular: Hypertrophic cardiomyopathy in premature infants. Dermatologic: Facial erythema; increased sweating; impaired wound healing; may suppress reactions to skin tests; petechiae and ecchymoses; thin fragile skin; urticaria; edema. Endocrine: Decreased carbohydrate tolerance; development of cushingoid state; hirsutism; increased requirements for insulin or oral hypoglycemic agents in diabetic patients; manifestations of latent diabetes mellitus; menstrual irregularities; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness; suppression of growth in children. Fluid and Electrolyte Disturbances: Congestive heart failure in susceptible patients; fluid retention; hypertension; hypokalemic alkalosis; potassium loss; sodium retention. Gastrointestinal: Abdominal distention; elevation in serum liver enzyme levels (usually reversible upon discontinuation); pancreatitis; peptic ulcer with possible perforation and hemorrhage; ulcerative esophagitis. Metabolic: Negative nitrogen balance due to protein catabolism. Musculoskeletal: Aseptic necrosis of femoral and humeral heads; loss of muscle mass; muscle weakness; osteoporosis; pathologic fracture of long bones; steroid myopathy; tendon rupture; vertebral compression fractures. Neurological: Convulsions; headache; increased intracranial pressure with papilledema (pseudotumor cerebri), usually following discontinuation of treatment; psychic disorders; vertigo. Ophthalmic: Exophthalmos; glaucoma; increased intraocular pressure; posterior subcapsular cataracts. Other: Increased appetite; malaise; nausea; weight gain.
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| dailymed-drugs:250 |
The adverse reactions which were reported in Disopyramide Phosphate clinical trials encompass observations in 1,500 patients, including 90 patients studied for at least 4 years. The most serious adverse reactions are hypotension and congestive heart failure. The most common adverse reactions, which are dose dependent, are associated with the anticholinergic properties of the drug. These may be transitory, but may be persistent or can be severe. Urinary retention is the most serious anticholinergic effect. The following reactions were reported in 10% to 40% of patients: Anticholinergic: dry mouth (32%), urinary hesitancy (14%), constipation (11%) The following reactions were reported in 3% to 9% of patients: Anticholinergic: blurred vision, dry nose/eyes/throat Genitourinary: urinary retention, urinary frequency and urgency Gastrointestinal: nausea, pain/bloating/gas General: dizziness, general fatigue/muscle weakness, headache, malaise, aches/pains The following reactions were reported in 1% to 3% of patients: Genitourinary: impotence Cardiovascular: hypotension with or without congestive heart failure, increased congestive heart failure (see WARNINGS), cardiac conduction disturbances (see WARNINGS), edema/weight gain, shortness of breath, syncope, chest pain Gastrointestinal: anorexia, diarrhea, vomiting Dermatologic: generalized rash/dermatoses, itching Central nervous system: nervousness Other: hypokalemia, elevated cholesterol/triglycerides The following reactions were reported in less than 1%: Depression, insomnia, dysuria, numbness/tingling, elevated liver enzymes, AV block, elevated BUN, elevated creatinine, decreased hemoglobin/hematocrit Hypoglycemia has been reported in association with Disopyramide Phosphate administration (see WARNINGS). Infrequent occurrences of reversible cholestatic jaundice, fever, and respiratory difficulty have been reported in association with disopyramide therapy, as have rare instances of thrombocytopenia, reversible agranulocytosis, and gynecomastia. Some cases of LE (lupus erythematosus) symptoms have been reported; most cases occurred in patients who had been switched to disopyramide from procainamide following the development of LE symptoms. Rarely, acute psychosis has been reported following Disopyramide Phosphate therapy, with prompt return to normal mental status whentherapy was stopped. The physician should be aware of these possible reactions and should discontinue Disopyramide Phosphate therapy promptly if they occur.
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| dailymed-drugs:251 |
Ocular: Transient burning and stinging was reported in 15% of patients with the use of topical diclofenac sodium ophthalmic solution, 0.1%. In cataract studies, keratitis occurred in 28% of patients receiving diclofenac sodium ophthalmic solution, 0.1%; however, most of the cases of keratitis occurred prior to drug therapy. Elevated intraocular pressure was reported in 15% of patients receiving diclofenac sodium ophthalmic solution, 0.1%. The following adverse reactions were reported in approximately 5% or less of the patients: abnormal vision, anterior chamber reaction, blurred vision, conjunctivitis, corneal deposits, corneal edema, corneal lesions, corneal opacity, discharge, injection, iritis, irritation, itching and ocular allergy.<br/>Systemic: The following adverse reactions were reported in 3% or less of the patients: abdominal pain, asthenia, chills, dizziness, facial edema, fever, headache, insomnia, nausea, pain, rhinitis, viral infection, and vomiting.
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| dailymed-drugs:252 |
Quinidine preparations have been used for many years, but there are only sparse data
from which to estimate the incidence of various adverse reactions. The adverse
reactions most frequently reported have consistently been gastrointestinal,
including diarrhea, nausea, vomiting, and heart���burn/esophagitis. In
one study of 245 adult outpatients who received quinidine to
suppress premature ventricular contractions, the incidences of reported adverse
experiences were as shown in the table below. The most serious quinidine���associated
adverse reactions are described above under Warnings. Intramuscular injections of quinidine gluconate are
typically followed by moderate to severe local pain. Some patients will develop
tender nodules at the site of injection that persist for several weeks. Vomiting and diarrhea can occur as isolated
reactions to therapeutic levels of quinidine,
but they may also be the first signs of cinchonism, a syndrome that may also include
tinnitus, reversible high���frequency hearing loss, deafness, vertigo,
blurred vision, diplopia, photophobia, headache, confusion, and delirium.
Cinchonism is most often a sign of chronic quinidine toxicity,
but it may appear in sensitive patients after a single moderate dose. A few cases of hepatotoxicity, including granulomatous hepatitis,
have been reported in patients receiving quinidine.
All of these have appeared during the first few weeks of therapy, and most
(not all) have remitted once quinidine was withdrawn. Autoimmune
and inflammatory syndromes associated with quinidine therapy
have included fever, urticaria, flushing, exfoliative rash, bronchospasm,
pneumonitis, psoriasiform rash, pruritus and lymphadenopathy, hemolytic anemia,
vasculitis, thrombocytopenic purpura, uveitis, angioedema, agranulocytosis,
the sicca syndrome, arthralgia, myalgia, elevation in serum levels of skeletal���muscle
enzymes, and a disorder resembling systemic lupus erythematosus. Convulsions, apprehension, and ataxia have been
reported, but it was not clear that these were not simply the results of hypotension
and consequent cerebral hypoperfusion. There are many reports of syncope.
Acute psychotic reactions have been reported to follow the first dose of quinidine,
but these reactions appear to be extremely rare. Other adverse reactions occasionally reported
include depression, mydriasis, disturbed color perception, night blindness,
scotomata, optic neuritis, visual field loss, photo���sensitivity, and
abnormalities of pigmentation.
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| dailymed-drugs:253 |
Acute and prolonged hypotensive episodes, tachycardia, and cardiac arrhythmias have been reported. In addition, weakness, dizziness, flushing, orthostatic hypotension, nasal stuffiness, nausea, vomiting, and diarrhea may occur.
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| dailymed-drugs:254 |
Transient burning and stinging upon instillation and other minor symptoms of ocular irritation have been reported with the use of flurbiprofen sodium ophthalmic solution. Other adverse reactions reported with the use of flurbiprofen sodium ophthalmic solution include: fibrosis, miosis, and mydriasis. Increased bleeding tendency of ocular tissues in conjunction with ocular surgery has also been reported.
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| dailymed-drugs:256 |
The following adverse reactions have been observed and within each category are listed in order of decreasing severity. Central Nervous System: headache, dizziness. Metabolic: precipitation of acute gouty arthritis. Gastrointestinal: hepatic necrosis, vomiting, nausea, anorexia, sore gums. Genitourinary: nephrotic syndrome, uric acid stones with or without hematuria, renal colic, costovertebral pain, urinary frequency. Hypersensitivity: anaphylaxis, fever, urticaria, pruritus. Hematologic: aplastic anemia, leukopenia, hemolytic anemia which in some patients could be related to genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells, anemia. Integumentary: dermatitis, alopecia, flushing.
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| dailymed-drugs:2969 |
The following adverse reactions have been observed and within each category are listed in order of decreasing severity. Central Nervous System: headache, dizziness. Metabolic: precipitation of acute gouty arthritis. Gastrointestinal: hepatic necrosis, vomiting, nausea, anorexia, sore gums. Genitourinary: nephrotic syndrome, uric acid stones with or without hematuria, renal colic, costovertebral pain, urinary frequency. Hypersensitivity: anaphylaxis, fever, urticaria, pruritus. Hematologic: aplastic anemia, leukopenia, hemolytic anemia which in some patients could be related to genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells, anemia. Integumentary: dermatitis, alopecia, flushing.
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| dailymed-drugs:257 |
Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are the result of isosorbide dinitrate's activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred . Data are not available to allow estimation of the frequency of adverse reactions during treatment with Isosorbide Dinitrate Extended-release Tablets.
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| dailymed-drugs:258 |
During its premarketing assessment, multiple doses of sertraline hydrochloride tablets were administered to over 4000 adult subjects as of February 18, 2000. The conditions and duration of exposure to sertraline hydrochloride tablets varied greatly, and included (in overlapping categories) clinical pharmacology studies, open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies, and studies for multiple indications, including major depressive disorder. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories. In the tabulations that follow, a World Health Organization dictionary of terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the over 4000 adult individuals exposed to multiple doses of sertraline hydrochloride tablets who experienced a treatment-emergent adverse event of the type cited on at least one occasion while receiving sertraline hydrochloride tablets. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it. The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.<br/>Incidence in Placebo-Controlled Trials-: Table 2 enumerates the most common treatment-emergent adverse events associated with the use of sertraline hydrochloride tablets (incidence of at least 5% for sertraline hydrochloride tablets and at least twice that for placebo within at least one of the indications) for the treatment of adult patients with major depressive disorder/otherin placebo-controlled clinical trials. Most patients in major depressive disorder/otherstudies received doses of 50 to 200 mg/day.<br/>Associated with Discontinuation in Placebo-Controlled Clinical Trials: Table 3 lists the adverse events associated with discontinuation of sertraline hydrochloride treatment (incidence at least twice that for placebo and at least 1% for sertraline hydrochloride tablets in clinical trials) in major depressive disorder/other.<br/>Male and Female Sexual Dysfunction with SSRIs: Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. Table 4 below displays the incidence of sexual side effects reported by at least 2% of patients taking sertraline hydrochloride tablets in placebo-controlled trials. There are no adequate and well-controlled studies examining sexual dysfunction with sertraline treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.<br/>Other Adverse Events in Pediatric Patients-: In over 600 pediatric patients treated with sertraline hydrochloride tablets, the overall profile of adverse events was generally similar to that seen in adult studies. However, the following adverse events, from controlled trials, not appearing in Table 2, were reported at an incidence of at least 2% and occurred at a rate of at least twice the placebo rate (N=281 patients treated with sertraline hydrochloride tablets): fever, hyperkinesia, urinary incontinence, aggressive reaction, sinusitis, epistaxis, and purpura.<br/>Other Events Observed During the Premarketing Evaluation of Sertraline Hydrochloride Tablets���: Following is a list of treatment-emergent adverse events reported during premarketing assessment of sertraline hydrochloride tablets in clinical trials (over 4000 adult subjects) except those already listed in the previous tables or elsewhere in labeling. In the tabulations that follow, a World Health Organization dictionary of terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the over 4000 adult individuals exposed to multiple doses of sertraline hydrochloride tablets who experienced an event of the type cited on at least one occasion while receiving sertraline hydrochloride tablets. All events are included except those already listed in the previous tables or elsewhere in labeling and those reported in terms so general as to be uninformative and those for which a causal relationship to sertraline hydrochloride tablets treatment seemed remote. It is important to emphasize that although the events reported occurred during treatment with sertraline hydrochloride tablets, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Events of major clinical importance are also described in the PRECAUTIONS section.<br/>Autonomic Nervous System Disorders-: Frequent: impotence; Infrequent: flushing, increased saliva, cold clammy skin, mydriasis; Rare: pallor, glaucoma, priapism, vasodilation.<br/>Body as a Whole-General Disorders-: Rare: allergic reaction, allergy.<br/>Cardiovascular-: Frequent: palpitations, chest pain; Infrequent: hypertension, tachycardia, postural dizziness, postural hypotension, periorbital edema, peripheral edema, hypotension, peripheral ischemia, syncope, edema, dependent edema; Rare: precordial chest pain, substernal chest pain, aggravated hypertension, myocardial infarction, cerebrovascular disorder.<br/>Central and Peripheral Nervous System Disorders-: Frequent: hypertonia, hypoesthesia; Infrequent: twitching, confusion, hyperkinesia, vertigo, ataxia, migraine, abnormal coordination, hyperesthesia, leg cramps, abnormal gait, nystagmus, hypokinesia; Rare: dysphonia, coma, dyskinesia, hypotonia, ptosis, choreoathetosis, hyporeflexia.<br/>Disorders of Skin and Appendages-: Infrequent: pruritus, acne, urticaria, alopecia, dry skin, erythematous rash, photosensitivity reaction, maculopapular rash; Rare: follicular rash, eczema, dermatitis, contact dermatitis, bullous eruption, hypertrichosis, skin discoloration, pustular rash.<br/>Endocrine Disorders-: Rare: exophthalmos, gynecomastia.<br/>Gastrointestinal Disorders-: Frequent: appetite increased; Infrequent: dysphagia, tooth caries aggravated, eructation, esophagitis, gastroenteritis; Rare: melena, glossitis, gum hyperplasia, hiccup, stomatitis, tenesmus, colitis, diverticulitis, fecal incontinence, gastritis, rectum hemorrhage, hemorrhagic peptic ulcer, proctitis, ulcerative stomatitis, tongue edema, tongue ulceration.<br/>General-: Frequent: back pain, asthenia, malaise, weight increase; Infrequent: fever, rigors, generalized edema; Rare: face edema, aphthous stomatitis.<br/>Hearing and Vestibular Disorders-: Rare: hyperacusis, labyrinthine disorder.<br/>Hematopoietic and Lymphatic-: Rare: anemia, anterior chamber eye hemorrhage.<br/>Liver and Biliary System Disorders-: Rare: abnormal hepatic function.<br/>Metabolic and Nutritional Disorders-: Infrequent: thirst; Rare: hypoglycemia, hypoglycemia reaction.<br/>Musculoskeletal System Disorders-: Frequent: myalgia; Infrequent: arthralgia, dystonia, arthrosis, muscle cramps, muscle weakness.<br/>Psychiatric Disorders-: Frequent: yawning, other male sexual dysfunction, other female sexual dysfunction; Infrequent: depression, amnesia, paroniria, teeth-grinding, emotional lability, apathy, abnormal dreams, euphoria, paranoid reaction, hallucination, aggressive reaction, aggravated depression, delusions; Rare: withdrawal syndrome, suicide ideation, libido increased, somnambulism, illusion.<br/>Reproductive-: Infrequent: menstrual disorder, dysmenorrhea, intermenstrual bleeding, vaginal hemorrhage, amenorrhea, leukorrhea; Rare: female breast pain, menorrhagia, balanoposthitis, breast enlargement, atrophic vaginitis, acute female mastitis.<br/>Respiratory System Disorders-: Frequent: rhinitis; Infrequent: coughing, dyspnea, upper respiratory tract infection, epistaxis, bronchospasm, sinusitis; Rare: hyperventilation, bradypnea, stridor, apnea, bronchitis, hemoptysis, hypoventilation, laryngismus, laryngitis.<br/>Special Senses-: Frequent: tinnitus; Infrequent: conjunctivitis, earache, eye pain, abnormal accommodation; Rare: xerophthalmia, photophobia, diplopia, abnormal lacrimation, scotoma, visual field defect.<br/>Urinary System Disorders-: Infrequent: micturition frequency, polyuria, urinary retention, dysuria, nocturia, urinary incontinence; Rare: cystitis, oliguria, pyelonephritis, hematuria, renal pain, strangury.<br/>Laboratory Tests-: In man, asymptomatic elevations in serum transaminases (SGOT [or AST] and SGPT [or ALT]) have been reported infrequently (approximately 0.8%) in association with sertraline hydrochloride tablets administration. These hepatic enzyme elevations usually occurred within the first 1 to 9 weeks of drug treatment and promptly diminished upon drug discontinuation. Sertraline hydrochloride tablets therapy was associated with small mean increases in total cholesterol (approximately 3%) and triglycerides (approximately 5%), and a small mean decrease in serum uric acid (approximately 7%) of no apparent clinical importance.<br/>Other Events Observed During the Postmarketing Evaluation of Sertraline Hydrochloride Tablets-: Reports of adverse events temporally associated with sertraline hydrochloride tablets that have been received since market introduction, that are not listed above and that may have no causal relationship with the drug, include the following: acute renal failure, anaphylactoid reaction, angioedema, blindness, optic neuritis, cataract, increased coagulation times, bradycardia, AV block, atrial arrhythmias, QT-interval prolongation, ventricular tachycardia(including torsade de pointes-type arrhythmias), hypothyroidism, agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness, hyperglycemia, galactorrhea, hyperprolactinemia, neuroleptic malignant syndrome-like events, extrapyramidal symptoms, oculogyric crisis, serotonin syndrome, psychosis, pulmonary hypertension, severe skin reactions, which potentially can be fatal, such as Stevens-Johnson syndrome, vasculitis, photosensitivity and other severe cutaneous disorders, rare reports of pancreatitis, and liver events���clinical features (which in the majority of cases appeared to be reversible with discontinuation of sertraline hydrochloride tablets) occurring in one or more patients include: elevated enzymes, increased bilirubin, hepatomegaly, hepatitis, jaundice, abdominal pain, vomiting, liver failure and death.
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Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions. Chemotoxic reactions result from the physio-chemical properties of the contrast media, the dose and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast medium are included in this category. Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40 years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the speed of injection, the mode of injection and the radiographic procedure. Idiosyncratic reactions are subdivided into minor, intermediate and severe. The minor reactions are self-limited and of short duration; the severe reactions are life-threatening and treatment is urgent and mandatory. Fatalities have been reported following the administration of iodine-containing contrast agents. Based upon clinical literature, the incidence of death is reported to range from one in 10,000 (0.01 percent) to less than one in 100,000 (0.001 percent). The following adverse reactions have been observed in conjunction with the use of iodine-containing contrast agents. The most frequent adverse reactions are nausea, vomiting, facial flush and a feeling of body warmth. These are usually of brief duration. Other reactions include the following: Hypersensitivity reactions���Dermal manifestations of urticaria with or without pruritus, erythema and maculopapular rash. Dry mouth. Sweating. Conjunctival symptoms. Facial, peripheral and angioneurotic edema. Symptoms related to the respiratory system include sneezing, nasal stuffiness, coughing, choking, dyspnea, chest tightness and wheezing, which may be initial manifestations of more severe and infrequent reactions including asthmatic attack, laryngospasm and bronchospasm with or without edema, pulmonary edema, apnea and cyanosis. Rarely, these allergic-type reactions can progress into anaphylaxis with loss of consciousness and coma and severe cardiovascular disturbances. Cardiovascular reactions���Generalized vasodilation, flushing and venospasm. Occasionally, thrombosis or rarely, thrombophlebitis. Red blood cell clumping and agglutination, crenation and interference in clot formation. Extremely rare cases of disseminated intravascular coagulation resulting in death have been reported. Severe cardiovascular responses include rare cases of hypotensiveshock, coronary insufficiency, cardiac arrhythmia, fibrillation and arrest. These severe reactions are usually reversible with prompt and appropriate management; however, fatalities have occurred. Technique reactions���Extravasation with burning pain, hematomas, ecchymosis and tissue necrosis, paresthesia or numbness, vascular constriction due to injection rate, thrombosis and thrombophlebitis. Neurological reactions���Spasm, convulsions, aphasia, syncope, paresis, paralysis resulting from spinal cord injury and pathology associated with syndrome of transverse myelitis, visual field losses which are usually transient but may be permanent, coma and death. Other reactions���Headache, trembling, shaking, chills without fever and lightheadedness. Temporary renal shutdown or other nephropathy. (Adverse reactions to specific procedures receive comment under that procedure.)
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Due to oral doxycycline's virtually complete absorption, side effects to the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines: Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Hepatotoxicity has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medications immediately before going to bed . Skin: Maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above . Renal toxicity: Rise in BUN has been reported and is apparently dose-related . Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus. Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Other: Bulging fontanels in infants and benign intracranial hypertension in adults . When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur.
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The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA AND OTHER BLOOD DYSCRASIAS .<br/>Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.<br/>Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported.<br/>Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.<br/>Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine.<br/>Metabolic and Nutritional: Hyperkalemia (see PRECAUTIONS: Use in the Treatment of and Prophylaxis for Pneumocystis Carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS).<br/>Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.<br/>Psychiatric: Hallucinations, depression, apathy, nervousness.<br/>Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.<br/>Musculoskeletal: Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported with sulfamethoxazole and trimethoprim, mainly in AIDS patients.<br/>Respiratory: Cough, shortness of breath and pulmonary infiltrates .<br/>Miscellaneous: Weakness, fatigue, insomnia.
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Data from a large, 28-week,
placebo-controlled US study that compared the safety of salmeterol
(SEREVENT Inhalation Aerosol) or placebo added to usual asthma therapy
showed an increase in asthma-related deaths in patients receiving
salmeterol (see WARNINGS and CLINICAL TRIALS: Asthma: Salmeterol Multi-center Asthma Research Trial).<br/>Asthma: Two multicenter, 12-week, controlled studies have
evaluated twice-daily doses of SEREVENT DISKUS in patients 12 years
of age and older with asthma. Table 4 reports the incidence of adverse
events in these 2 studies. Table 4 includes all events (whether considered
drug-related or nondrug-related by the investigator) that occurred
at a rate of 3% or greater in the group receiving SEREVENT DISKUS
and were more common than in the placebo group. Pharyngitis, sinusitis, upper respiratory tract infection, and cough
occurred at���3% but were more common in the placebo group.
However, throat irritation has been described at rates exceeding that
of placebo in other controlled clinical trials. Other adverse events that occurred in the group receiving SEREVENT
DISKUS in these studies with an incidence of 1% to 3% and that occurred
at a greater incidence than with placebo were:<br/>Ear, Nose, and Throat: Sinus headache.<br/>Gastrointestinal: Nausea.<br/>Mouth and Teeth: Oral mucosal abnormality.<br/>Musculoskeletal: Pain in joint.<br/>Neurological: Sleep disturbance, paresthesia.<br/>Skin: Contact dermatitis, eczema.<br/>Miscellaneous: Localized aches and pains, pyrexia of unknown origin. Two multicenter, 12-week, controlled studies have evaluated
twice-daily doses of SEREVENT DISKUS in patients aged 4 to 11 years
with asthma. Table 5 includes all events (whether considered drug-related
or nondrug-related by the investigator) that occurred at a rate of
3% or greater in the group receiving SEREVENT DISKUS and were more
common than in the placebo group. The following events were reported at an incidence
of 1% to 2% (3 to 4 patients) in the salmeterol group and with a higher
incidence than in the albuterol and placebo groups: gastrointestinal
signs and symptoms, lower respiratory signs and symptoms, photodermatitis,
and arthralgia and articular rheumatism. In
clinical trials evaluating concurrent therapy of salmeterol with inhaled
corticosteroids, adverse events were consistent with those previously
reported for salmeterol, or with events that would be expected with
the use of inhaled corticosteroids.<br/>Chronic Obstructive Pulmonary Disease: Two multicenter, 24-week, controlled studies have
evaluated twice-daily doses of SEREVENT DISKUS in patients with COPD.
For presentation (Table 6), the placebo data from a third trial, identical
in design, patient entrance criteria, and overall conduct but comparing
fluticasone propionate with placebo, were integrated with the placebo
data from these 2 studies (total N = 341 for salmeterol
and 576 for placebo). Other events occurring in the group receiving
SEREVENT DISKUS that occurred at a frequency of 1% to<3% and were
more common than in the placebo group were as follows:<br/>Endocrine and Metabolic: Hyperglycemia.<br/>Eye: Keratitis and conjunctivitis.<br/>Gastrointestinal: Candidiasis mouth/throat, dyspeptic symptoms, hyposalivation,
dental discomfort and pain, gastrointestinal infections.<br/>Lower Respiratory: Lower respiratory signs and symptoms.<br/>Musculoskeletal: Arthralgia and articular rheumatism; muscle pain;
bone and skeletal pain; musculoskeletal inflammation; muscle stiffness,
tightness, and rigidity.<br/>Neurology: Migraines.<br/>Non-Site Specific: Pain, edema and swelling.<br/>Psychiatry: Anxiety.<br/>Skin: Skin rashes. Adverse reactions
to salmeterol are similar in nature to those seen with other selective
beta-adrenoceptor agonists, i.e., tachycardia; palpitations;
immediate hypersensitivity reactions, including urticaria, angioedema,
rash, bronchospasm (see WARNINGS); headache; tremor; nervousness;
and paradoxical bronchospasm (see WARNINGS).<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical
trials, the following events have been identified during postapproval
use of salmeterol. Because they are reported voluntarily from a population
of unknown size, estimates of frequency cannot be made. These events
have been chosen for inclusion due to either their seriousness, frequency
of reporting, or causal connection to salmeterol or a combination
of these factors. In extensive US and worldwide
postmarketing experience with salmeterol, serious exacerbations of
asthma, including some that have been fatal, have been reported. In
most cases, these have occurred in patients with severe asthma and/or
in some patients in whom asthma has been acutely deteriorating (see
WARNINGS), but they have also occurred in a few patients with less
severe asthma. It was not possible from these reports to determine
whether salmeterol contributed to these events.<br/>Respiratory: Reports of upper airway symptoms of laryngeal spasm,
irritation, or swelling such as stridor or choking; oropharyngeal
irritation.<br/>Cardiovascular: Arrhythmias (including atrial fibrillation, supraventricular
tachycardia, extrasystoles), and anaphylaxis.<br/>Non-Site Specific: Very rare anaphylactic reaction in patients with
severe milk protein allergy.
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Allergic Rhinitis: In controlled US and international clinical studies, a total of 3210 adult and adolescent patients ages 12 years and older with allergic rhinitis received treatment with NASONEX Nasal Spray, 50 mcg at doses of 50 to 800 mcg/day. The majority of patients (n = 2103) were treated with 200 mcg/day. In controlled US and international studies, a total of 990 pediatric patients (ages 3 to 11 years) with allergic rhinitis received treatment with NASONEX Nasal Spray, 50 mcg, at doses of 25 to 200 mcg/day. The majority of pediatric patients (720) were treated with 100 mcg/day. A total of 513 adult, adolescent, and pediatric patients have been treated for 1 year or longer. The overall incidence of adverse events for patients treated with NASONEX Nasal Spray, 50 mcg was comparable to patients treated with the vehicle placebo. Also, adverse events did not differ significantly based on age, sex, or race. Three percent or less of patients in clinical trials discontinued treatment because of adverse events; this rate was similar for the vehicle and active comparators. All adverse events (regardless of relationship to treatment) reported by 5% or more of adult and adolescent patients ages 12 years and older who received NASONEX Nasal Spray, 50 mcg, 200 mcg/day and by pediatric patients ages 3 to 11 years who received NASONEX Nasal Spray, 50 mcg, 100 mcg/day in clinical trials vs placebo and that were more common with NASONEX Nasal Spray, 50 mcg than placebo, are displayed in the table below. Other adverse events which occurred in less than 5% but greater than or equal to 2% of mometasone furoate adult and adolescent patients (ages 12 years and older) treated with 200-mcg doses (regardless of relationship to treatment), and more frequently than in the placebo group included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, earache, flu-like symptoms, myalgia, nausea, and rhinitis. Other adverse events which occurred in less than 5% but greater than or equal to 2% of mometasone furoate pediatric patients ages 3 to 11 years treated with 100-mcg doses vs placebo (regardless of relationship to treatment) and more frequently than in the placebo group included: diarrhea, nasal irritation, otitis media, and wheezing. The adverse event (regardless of relationship to treatment) reported by 5% of pediatric patients ages 2 to 5 years who received NASONEX Nasal Spray, 50 mcg, 100 mcg/day in a clinical trial vs placebo including 56 subjects (28 each NASONEX Nasal Spray, 50 mcg and placebo) and that was more common with NASONEX Nasal Spray, 50 mcg than placebo, included: upper respiratory tract infection (7% vs 0%, respectively). The other adverse event which occurred in less than 5% but greater than or equal to 2% of mometasone furoate pediatric patients ages 2 to 5 years treatedwith 100-mcg doses vs placebo (regardless of relationship to treatment) and more frequently than in the placebo group included: skin trauma.<br/>Nasal Polyps: In controlled clinical studies, the types of adverse events observed in patients with nasal polyps were similar to those observed for patients with allergic rhinitis. A total of 594 adult patients (ages 18 to 86 years) received NASONEX Nasal Spray, 50 mcg, at doses of 200 mcg once or twice daily for up to 4 months for treatment of nasal polyps. The overall incidence of adverse events for patients treated with NASONEX Nasal Spray, 50 mcg was comparable to patients treated with the placebo except for epistaxis, which was 9% for 200 mcg once daily, 13% for 200 mcg twice daily, and 5%for placebo. Rare cases of nasal ulcers and nasal and oral candidiasis were also reported in patients treated with NASONEX Nasal Spray, 50 mcg, primarily in patients treated for longer than 4 weeks. In postmarketing surveillance of this product, cases of nasal burning and irritation, anaphylaxis and angioedema, and rare cases of nasal septal perforation have been reported. Disturbances of taste and smell have been reported very rarely.
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Herpes Simplex SHORT-TERM ADMINISTRATION The most frequent adverse events reported during clinical trials of treatment of genital herpes with acyclovir 200 mg administered orally five times daily every 4 hours for 10 days were nausea and/or vomiting in 8 of 298 patient treatments (2.7%). Nausea and/or vomiting occurred in 2 of 287 (0.7%) patients who received placebo. LONG-TERM ADMINISTRATION The most frequent adverse events reported in a clinical trial for the prevention of recurrences with continuous administration of 400 mg (two 200 mg capsules) two times daily for 1 year in 586 patients treated with acyclovir were nausea (4.8%) and diarrhea (2.4%). The 589 control patients receiving intermittent treatment of recurrences with acyclovir for 1 year reported diarrhea (2.7%), nausea (2.4%), and headache (2.2%). Herpes Zoster The most frequent adverse event reported during three clinical trials of treatment of herpes zoster (shingles) with 800 mg of oral acyclovir five times daily for 7 to 10 days in 323 patients was malaise (11.5%). The 323 placebo recipients reported malaise (11.1%). Chickenpox The most frequent adverse event reported during three clinical trials of treatment of chickenpox with oral acyclovir at doses of 10 to 20 mg/kg four times daily for 5 to 7 days or 800 mg four times daily for 5 days in 495 patients was diarrhea (3.2%). The 498 patients receiving placebo reported diarrhea (2.2%). Observed During Clinical Practice In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of acyclovir. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to acyclovir, or a combination of these factors: ���General: anaphylaxis, angioedema, fever, headache, pain, peripheral edema. ���Nervous: aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium, dizziness, dysarthria, encephalopathy, hallucinations, paresthesia, psychosis, seizure, somnolence, tremors. These symptoms may be marked, particularly in older adults or in patients with renal impairment (see PRECAUTIONS). ���Digestive: diarrhea, gastrointestinal distress, nausea. ���Hematologic and Lymphatic: anemia, leukocytoclastic vasculitis, leukopenia, lymphadenopathy, thrombocytopenia. ���Hepatobiliary Tract and Pancreas: elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice. ���Musculoskeletal: myalgia. ���Skin: alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. ���Special Senses: visual abnormalities. ���Urogenital: renal failure, elevated blood urea nitrogen, elevated creatinine, hematuria (see WARNINGS).
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The information included in the subsection on Adverse Events Observed in Short-Term, Placebo-Controlled Trials with Alprazolam XR tablets is based on pooled data of five 6- and 8-week placebo-controlled clinical studies in panic disorder. Adverse event reports were elicited either by general inquiry or by checklist, and were recorded by clinical investigators using terminology of their own choosing. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergentif it occurred for the first time or worsened during therapy following baseline evaluation. In the tables and tabulations that follow, standard MedDRA terminology (version 4.0) was used to classify reported adverse events.<br/>Adverse Events Observed in Short-Term, Placebo-Controlled Trials of Alprazolam XR:<br/>Adverse Events Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials: Approximately 17% of the 531 patients who received Alprazolam XR in placebo-controlled clinical trials for panic disorder had at least one adverse event that led to discontinuation compared to 8% of 349 placebo-treated patients. The most common events leading to discontinuation and considered to be drug-related (ie, leading to discontinuation in at least 1% of the patients treated with Alprazolam XR at a rate at least twice that of placebo) are shown in the following table.<br/>Adverse Events Occurring at an Incidence of 1% or More Among Patients Treated with Alprazolam XR: The prescriber should be aware that adverse event incidence cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with event incidence obtained from other clinical investigations involving different treatments, uses, and investigators. The cited values, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The following table shows the incidence of treatment-emergent adverse events that occurred during 6- to 8-week placebo-controlled trials in 1% or more of patients treated with Alprazolam XR where the incidence in patients treated with Alprazolam XR was greater than the incidence in placebo-treated patients. The most commonly observed adverse events in panic disorder patients treated with Alprazolam XR (incidence of 5% or greater and at least twice the incidence in placebo patients) were: sedation, somnolence, memory impairment, dysarthria, coordination abnormal, ataxia, libido decreased (see table).<br/>Other Adverse Events Observed During the Premarketing Evaluation of Alprazolam XR tablets: Following is a list of MedDRA terms that reflect treatment-emergent adverse events reported by 531 patients with panic disorder treated with Alprazolam XR. All potentially important reported events are included except those already listed in the above table or elsewhere in labeling, those events for which a drug cause was remote, those event terms that were so general as to be uninformative, and those events that occurred at rates similar to background rates in the general population. It is important to emphasize that, although the events reported occurred during treatment with Alprazolam XR, they were not necessarily caused by the drug. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least l/l00 patients; infrequent adverse events are those occurring in less than l/100 patients but at least l/1000 patients; rare events are those occurring in fewer than l/1000 patients. Cardiac disorders: Frequent: palpitation; Infrequent: sinus tachycardia Ear and Labyrinth disorders: Frequent: Vertigo; Infrequent: tinnitus, ear pain Eye disorders: Frequent: blurred vision; Infrequent: tmydriasis, photophobia Gastrointestinal disorders: Frequent: diarrhea, vomiting, dyspepsia, abdominal pain; Infrequent: dysphagia, salivary hypersecretion General disorders and administration site conditions: Frequent: malaise, weakness, chest pains; Infrequent: fall, pyrexia, thirst, feeling hot and cold, edema, feeling jittery, sluggishness, asthenia, feeling drunk, chest tightness, increased energy, feeling of relaxation, hangover, loss of control of legs, rigors Musculoskeletal and connective tissue disorders: Frequent: back pain, muscle cramps, muscle twitching Nervous system disorders: Frequent: headache, dizziness, tremor; Infrequent: amnesia, clumsiness, syncope, hypotonia, seizures, depressed level of consciousness, sleep apnea syndrome, sleep talking, stupor Psychiatric system disorders: Frequent: irritability, insomnia, nervousness, derealization, libido increased, restlessness, agitation, depersonalization, nightmare; Infrequent: abnormal dreams, apathy, aggression, anger, bradyphrenia, euphoric mood, logorrhea, mood swings, dysphonia, hallucination, homicidal ideation, mania, hypomania, impulse control, psychomotor retardation, suicidal ideation Renal and urinary disorders: Frequent: difficulty in micturition; Infrequent: urinary frequency, urinary incontinence Respiratory, thoracic, and mediastinal disorders: Frequent: nasal congestion, hyperventilation; Infrequent: choking sensation, epistaxis, rhinorrhea Skin and subcutaneous tissue disorders: Frequent: sweating increased; Infrequent: clamminess, rash, urticaria Vascular disorders: Infrequent: hypotension The categories of adverse events reported in the clinical development program for Alprazolam tablets in the treatment of panic disorder differ somewhat from those reported for Alprazolam XR tablets because the clinical trials with Alprazolam tablets and Alprazolam XR tablets used different standard medical nomenclature for reporting the adverse events. Nevertheless, the types of adverse events reported in the clinical trials with Alprazolam tablets were generally the same as those reported in the clinical trials with Alprazolam XR tablets.<br/>Discontinuation-Emergent Adverse Events Occurring at an Incidence of 5% or More Among Patients Treated with Alprazolam XR: The following table shows the incidence of discontinuation-emergent adverse events that occurred during short-term, placebo-controlled trials in 5% or more of patients treated with Alprazolam XR where the incidence in patients treated with Alprazolam XR was two times greater than the incidence in placebo-treated patients. There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam . To discontinue treatment in patients taking Alprazolam XR tablets, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of Alprazolam XR tablets be decreased by no more than 0.5 mg every three days . Some patients may benefit from an even slower dosage reduction. In a controlled postmarketing discontinuation study of panic disorder patients which compared this recommended taper schedule with a slower taper schedule, no difference was observed between the groups in theproportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. As with all benzodiazepines, paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations, and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with posttraumatic stress disorder.<br/>Post Introduction Reports: Various adverse drug reactions have been reported in association with the use of Alprazolam tablets since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of Alprazolam tablets cannot be readily determined. Reported events include: liver enzyme elevations, hepatitis, hepatic failure, Stevens-Johnson syndrome, hyperprolactinemia, gynecomastia, and galactorrhea.
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In clinical trials of nitrofurantoin monohydrate/macrocrystals, the most frequent clinical adverse events that were reported as possibly or probably drug-related were nausea (8%), headache (6%), and flatulence (1.5%). Additional clinical adverse events reported as possibly or probably drug-related occurred in less than 1% of patients studied and are listed below within each body system in order of decreasing frequency: Gastrointestinal: Diarrhea, dyspepsia, abdominal pain, constipation, emesis Neurologic: Dizziness, drowsiness, amblyopia Respiratory: Acute pulmonary hypersensitivity reaction Allergic: Pruritus, urticaria Dermatologic: Alopecia Miscellaneous: Fever, chills, malaise The following additional clinical adverse events have been reported with the use of nitrofurantoin: Gastrointestinal: Sialadenitis, pancreatitis. There have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment. Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy. Asthenia, vertigo, and nystagmus also have been reported with the use of nitrofurantoin. Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions have been reported rarely. Bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely.<br/>Respiratory: CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR WITH THE USE OF NITROFURANTOIN. CHRONIC PULMONARY REACTIONS GENERALLY OCCUR IN PATIENTS WHO HAVE RECEIVED CONTINUOUS TREATMENT FOR SIX MONTHS OR LONGER. MALAISE, DYSPNEA ON EXERTION, COUGH, AND ALTERED PULMONARY FUNCTION ARE COMMON MANIFESTATIONS WHICH CAN OCCUR INSIDIOUSLY. RADIOLOGIC AND HISTOLOGIC FINDINGS OF DIFFUSE INTERSTITIAL PNEUMONITIS OR FIBROSIS, OR BOTH, ARE ALSO COMMON MANIFESTATIONS OF THE CHRONIC PULMONARY REACTION. FEVER IS RARELY PROMINENT. THE SEVERITY OF CHRONIC PULMONARY REACTIONS AND THEIR DEGREE OF RESOLUTION APPEAR TO BE RELATED TO THE DURATION OF THERAPY AFTER THE FIRST CLINICAL SIGNS APPEAR. PULMONARY FUNCTION MAY BE IMPAIRED PERMANENTLY, EVEN AFTER CESSATION OF THERAPY. THE RISK IS GREATER WHEN CHRONIC PULMONARY REACTIONS ARE NOT RECOGNIZED EARLY. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. If the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution often is dramatic. Changes in EKG (e.g., non-specific ST/T wave changes, bundle branch block) have been reported in association with pulmonary reactions. Cyanosis has been reported rarely.<br/>Hepatic: Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely.<br/>Allergic: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; anaphylaxis; arthralgia; myalgia; drug fever; and chills have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations.<br/>Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.<br/>Hematologic: Cyanosis secondary to methemoglobinemia has been reported rarely.<br/>Miscellaneous: As with other antimicrobial agents, superinfections caused by resistant organisms, e.g., Pseudomonas species or Candida species, can occur. In clinical trials of nitrofurantoin monohydrate/macrocrystals, the most frequent laboratory adverse events (1 to 5%), without regard to drug relationship, were as follows: eosinophilia, increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus. The following laboratory adverse events also have been reported with the use of nitrofurantoin:glucose-6-phosphate dehydrogenase deficiency anemia , agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia. In most cases, these hematologic abnormalities resolved following cessation of therapy. Aplastic anemia has been reported rarely.
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ULTRAM ER was administered to a total of 3108 patients during studies conducted in the U.S. These included four double-blind studies in patients with osteoarthritis and/or chronic low back pain and one open-label study in patients with chronic non-malignant pain. A total of 901 patients were 65 years or older. The frequency of adverse events generallyincreased with doses from 100 mg to 400 mg in the two pooled, twelve-week, randomized, double-blind, placebo-controlled studies in patients with chronic non-malignant pain (see Table 2). The following adverse events were reported from all the chronic pain studies (N=3108). The lists below include adverse events not otherwise noted in Table 2. Adverse events with incidence rates of 1.0% to<5.0% Eye disorders: vision blurred Gastrointestinal disorders: abdominal pain upper, dyspepsia, abdominal pain, sore throat General disorders: weakness, pain, feeling hot, influenza like illness, fall, rigors, lethargy, pyrexia, chest pain Infections and infestations: nasopharyngitis, upper respiratory tract infection, sinusitis, influenza, gastroenteritis viral, urinary tract infection, bronchitis Investigations: blood creatine phosphokinase increased, weight decreased Metabolism and nutrition disorders: appetite decreased Musculoskeletal, connective tissue and bone disorders: arthralgia, back pain, pain in limb, neck pain Nervous system disorders: tremor, paresthesia, hypoesthesia Psychiatric disorders: nervousness, anxiety, depression, restlessness Respiratory, thoracic and mediastinal disorders: sneezing, cough, rhinorrhea, nasal congestion, dyspnea, sinus congestion Skin and subcutaneous tissue disorders: sweating increased, dermatitis Vascular disorders: hot flushes, vasodilatation Adverse events with incidence rates of 0.5% to<1.0% and serious adverse events reported in at least 2 patients. Cardiac disorders: palpitations, myocardial infarction Ear and labyrinth disorders: tinnitus, vertigo Gastrointestinal disorders: flatulence, toothache, constipation aggravated, appendicitis, pancreatitis General disorders: feeling jittery, edema lower limb, shivering, joint swelling, malaise, drug withdrawal syndrome, peripheral swelling Hepato-biliary disorders: cholelithiasis, cholecystitis Infections and infestations: cellulitis, ear infection, gastroenteritis, pneumonia, viral infection Injury and poisoning: joint sprain, muscle injury Investigations: alanine aminotransferase increased, blood pressure increased, aspartate aminotransferase increased, heart rate increased, blood glucose increased, liver function tests abnormal , Musculoskeletal, connective tissue and bone disorders: muscle cramps, muscle spasms, joint stiffness, muscle twitching, myalgia, osteoarthritis aggravated Nervous system disorders: migraine, sedation, syncope, disturbance in attention, dizziness aggravated Psychiatric disorders: euphoric mood, irritability, libido decreased, sleep disorder, agitation, disorientation, abnormal dreams Renal and urinary disorders: difficulty in micturition, urinary frequency, hematuria, dysuria, urinary retention Respiratory, thoracic and mediastinal disorders: yawning Skin and subcutaneous tissue disorders: contusion, piloerection, clamminess, night sweats, urticaria Vascular disorders: hypertension aggravated, hypertension, peripheral ischemia
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Adverse reactions are rare following oral administration of bethanechol, but are more common following subcutaneous injection. Adverse reactions are more likely to occur when dosage is increased. The following adverse reactions have been observed: Body as a Whole: malaise; Digestive: abdominal cramps or discomfort, colicky pain, nausea and belching, diarrhea, borborygmi, salivation; Renal: urinary urgency; Nervous System: headache; Cardiovascular: a fall in blood pressure with reflex tachycardia, vasomotor response; Skin: flushing producing a feeling of warmth, sensation of heat about the face, sweating; Respiratory: bronchial constriction, asthmatic attacks; Special Senses: lacrimation, miosis.<br/>Causal Relationship Unknown: The following adverse reactions have been reported, and a causal relationship to therapy with bethanechol has not been established: Body as a Whole: malaise; Nervous System: seizures.
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Adverse reactions are rare following oral administration of bethanechol, but are more common following subcutaneous injection. Adverse reactions are more likely to occur when dosage is increased. The following adverse reactions have been observed: Body as a Whole: malaise; Digestive: abdominal cramps or discomfort, colicky pain, nausea and belching, diarrhea, borborygmi, salivation; Renal: urinary urgency; Nervous System: headache; Cardiovascular: a fall in blood pressure with reflex tachycardia, vasomotor response; Skin: flushing producing a feeling of warmth, sensation of heat about the face, sweating; Respiratory: bronchial constriction, asthmatic attacks; Special Senses: lacrimation, miosis.<br/>Causal Relationship Unknown: The following adverse reactions have been reported, and a causal relationship to therapy with bethanechol has not been established: Body as a Whole: malaise; Nervous System: seizures.
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In controlled clinical trials, the most frequent adverse reactions reported for Dovonex were burning, itching and skin irritation, which occurred in approximately 10-15% of patients. Erythema, dry skin, peeling, rash, dermatitis, worsening of psoriasis including development of facial/scalp psoriasis were reported in 1 to 10% of patients. Other experiences reported in less than 1% of patients included skin atrophy, hyperpigmentation, hypercalcemia, and folliculitis. Once daily dosing has not been shown to be superior in safety to twice daily dosing.
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Side effects to alprazolam tablets, if they occur, are generally observed at the beginning of therapy and usually disappear upon continued medication. In the usual patient, the most frequent side effects are likely to be an extension of the pharmacological activity of alprazolam, eg, drowsiness or light-headedness. The data cited in the two tables below are estimates of untoward clinical event incidence among patients who participated under the following clinical conditions: relatively short duration (ie, four weeks) placebo-controlled clinical studies with dosages up to 4 mg/day of alprazolam (for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety) and short-term (up to ten weeks) placebo-controlled clinical studies with dosages up to 10 mg/day of alprazolam in patients with panic disorder, with or without agoraphobia. These data cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics, and other factors often differ from those in clinical trials. These figures cannot be compared with those obtained from other clinical studies involving related drug products and placebo as each group of drug trials are conducted under a different set of conditions. Comparison of the cited figures, however, can provide the prescriber with some basis for estimating the relative contributions of drug and non-drug factors to the untoward event incidence in the population studied. Even this use must be approached cautiously, as a drug may relieve a symptom in one patient but induce it in others. (For example, an anxiolytic drug may relieve dry mouth [a symptom of anxiety] in some subjects but induce it [an untoward event] in others.) Additionally, for anxiety disorders the cited figures can provide the prescriber with an indication
as to the frequency with which physician intervention (eg, increased surveillance, decreased dosage
or discontinuation of drug therapy) may be necessary because of the untoward clinical event. In addition to the relatively common (ie, greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of benzodiazepines: dystonia, irritability, concentration difficulties, anorexia, transient amnesia or memory impairment, loss of coordination, fatigue, seizures, sedation, slurred speech, jaundice, musculoskeletal weakness, pruritus, diplopia, dysarthria, changes in libido, menstrual irregularities, incontinence and urinary retention. In addition to the relatively common (ie, greater than 1%) untoward events enumerated in the table above, the following adverse events have been reported in association with the use of alprazolam: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated bilirubin, elevated hepatic enzymes, and jaundice. There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam tablets . To discontinue treatment in patients taking alprazolam, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every three days . Some patients may benefit from an even
slower dosage reduction. In a controlled postmarketing discontinuation study of panic disorder patients which
compared this recommended taper schedule with a slower taper schedule, no difference was observed
between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was
associated with a reduction in symptoms associated with a withdrawal syndrome. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Therefore, the same precaution must be exercised when using doses of alprazolam greater than 4 mg/day in treating patients with panic disorders as is exercised with the
use of any psychotropic drug in treating depressed patients or those in whom there is reason to expect concealed
suicidal ideation or plans. As with all benzodiazepines, paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects , patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol orsubstance abuse
may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with post-traumatic stress disorder. Laboratory analyses were performed on patients participating in the clinical program for alprazolam. The following incidences of abnormalities shown below were observed in patients receiving alprazolam and in patients in the corresponding placebo group. Few of these abnormalities were considered to be of physiological significance. When treatment with alprazolam is protracted, periodic blood counts, urinalysis and blood chemistry analyses are advisable. Minor changes in EEG patterns, usually low-voltage fast activity have been observed in patients during therapy with alprazolam and are of no known significance.<br/>Post Introduction Reports: Various adverse drug reactions have been reported in association with the use of alprazolam since market introduction. The majority of these reactions were reported through the medical event voluntary reporting system. Because of the spontaneous nature of the reporting of medical events and the lack of controls, a causal relationship to the use of alprazolam cannot be readily determined. Reported events include: liver enzyme elevations hepatitis, hepatic failure , Stevens-Johnson syndrome, hyperprolactinemia, gynecomastia and galactorrhea.
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As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. GH antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. In clinical studies of pediatric patients that were treated with Nutropin [somatropin (rDNA origin) for injection] for the first time, 0/107 growth hormone���deficient (GHD) patients, 0/125 CRI patients, and 0/112 Turner syndrome, and 0/117 ISS patients screened for antibody production developed antibodies with binding capacities���2 mg/L at six months. In a clinical study of patients that were treated with Nutropin AQ for the first time, 0/38 GHD patients screened for antibody production for up to 15 months developed antibodies with binding capacities���2 mg/L. Additional short���term immunologic and renal function studies were carried out in a group of patients with CRI after approximately one year of treatment to detect other potential adverse effects of antibodies to GH. Testing included measurements of C1q, C3, C4, rheumatoid factor, creatinine, creatinine clearance, and BUN. No adverse effects of GH antibodies were noted. In addition to an evaluation of compliance with the prescribed treatment program and thyroid status, testing for antibodies to GH should be carried out in any patient who fails to respond to therapy. In a post marketing surveillance study, the National Cooperative Growth Study, the pattern of adverse events in over 8000 patients with idiopathic short stature was consistent with the known safety profile of GH, and no new safety signals attributable to GH were identified. The frequency of protocol-defined targeted adverse eventsis described in the table, below. Injection site discomfort has been reported. This is more commonly observed in children switched from another GH product to Nutropin AQ. Experience with Nutropin AQ in adults is limited. Leukemia has been reported in a small number of GHD patients treated with GH. It is uncertain whether this increased risk is related to the pathology of GH deficiency itself, GH therapy, or other associated treatments such as radiation therapy for intracranial tumors. On the basis of current evidence, experts cannot conclude that GH therapy is responsible for these occurrences. The risk to GHD, CRI, or Turner syndrome patients, if any, remains to be established. Other adverse drug reactions that have been reported in GH-treated patients include the following:
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The following reactions have been reported:<br/>Gastrointestinal:: Diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia, and pseudomembranous colitis. Onset of
pseudomembranous colitis symptoms may occur during or after antibiotic treatment . Nausea and vomiting have been reported rarely.<br/>Allergic:: Anaphylaxis, eosinophilia, itching, drug fever, skin rash, Stevens-Johnson syndrome.<br/>Hematologic:: Neutropenia, leukopenia, thrombocytopenia, thrombocythemia.<br/>Hepatic:: Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. As with other cephalosporins, reports of
hepatitis have been received.<br/>Renal:: As with other cephalosporins, reports of increased BUN and creatinine levels, as well as renal failure, have been
received.<br/>Local Reactions:: Rare instances of phlebitis have been reported at site of injection.<br/>Other Reactions:: Genital and anal pruritus (including vulvar pruritus, genital moniliasis, and vaginitis).
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Adults: The safety of NORVIR alone
and in combination with nucleoside reverse transcriptase inhibitors
was studied in 1270 adult patients. Table 7 lists treatment-emergent
adverse events (at least possibly related and of at least moderate
intensity) that occurred in 2% or greater of adult patients receiving
NORVIR alone or in combination with nucleoside reverse transcriptase
inhibitors in Study 245 or Study 247 and in combination with saquinavir
in study 462. In that study, 141 protease inhibitor-naive, HIV-infected
patients with mean baseline CDof 300 cells/��L were
randomized to one of four regimens of NORVIR + saquinavir, including
NORVIR 400 mg twice-daily + saquinavir 400 mg twice-daily. Overall
the most frequently reported clinical adverse events, other than asthenia,
among adult patients receiving NORVIR were gastrointestinal and neurological
disturbances including nausea, diarrhea, vomiting, anorexia, abdominal
pain, taste perversion, and circumoral and peripheral paresthesias.
Similar adverse event profiles were reported in adult patients receiving
ritonavir in other trials. Adverse events occurring in less than
2% of adult patients receiving NORVIR in all phase II/phase III
studies and considered at least possibly related or of unknown relationship
to treatment and of at least moderate intensity are listed below by
body system.<br/>Body as a Whole: Abdomen enlarged,
accidental injury, allergic reaction, back pain, cachexia, chest pain,
chills, facial edema, facial pain, flu syndrome, hormone level altered,
hypothermia, kidney pain, neck pain, neck rigidity, pelvic pain, photosensitivity
reaction, and substernal chest pain.<br/>Cardiovascular System: Cardiovascular disorder,
cerebral ischemia, cerebral venous thrombosis, hypertension, hypotension,
migraine, myocardial infarct, palpitation, peripheral vascular disorder,
phlebitis, postural hypotension, tachycardia and vasospasm.<br/>Digestive System: Abnormal stools,
bloody diarrhea, cheilitis, cholestatic jaundice, colitis, dry mouth,
dysphagia, eructation, esophageal ulcer, esophagitis, gastritis, gastroenteritis,
gastrointestinal disorder, gastrointestinal hemorrhage, gingivitis,
hepatic coma, hepatitis, hepatomegaly, hepatosplenomegaly, ileus,
liver damage, melena, mouth ulcer, pancreatitis, pseudomembranous
colitis, rectal disorder, rectal hemorrhage, sialadenitis, stomatitis,
tenesmus, thirst, tongue edema, and ulcerative colitis.<br/>Endocrine System: Adrenal cortex insufficiency
and diabetes mellitus.<br/>Hemic and Lymphatic System: Acute myeloblastic
leukemia, anemia, ecchymosis, leukopenia, lymphadenopathy, lymphocytosis,
myeloproliferative disorder, and thrombocytopenia.<br/>Metabolic and Nutritional Disorders: Albuminuria, alcohol
intolerance, avitaminosis, BUN increased, dehydration, edema, enzymatic
abnormality, glycosuria, gout, hypercholesteremia, peripheral edema,
and xanthomatosis.<br/>Musculoskeletal System: Arthritis, arthrosis,
bone disorder, bone pain, extraocular palsy, joint disorder, leg cramps,
muscle cramps, muscle weakness, myositis, and twitching.<br/>Nervous System: Abnormal dreams,
abnormal gait, agitation, amnesia, aphasia, ataxia, coma, convulsion,
dementia, depersonalization, diplopia, emotional lability, euphoria,
grand mal convulsion, hallucinations, hyperesthesia, hyperkinesia,
hypesthesia, incoordination, libido decreased, manic reaction, nervousness,
neuralgia, neuropathy, paralysis, peripheral neuropathic pain, peripheral
neuropathy, peripheral sensory neuropathy, personality disorder, sleep
disorder, speech disorder, stupor, subdural hematoma, tremor, urinary
retention, vertigo, and vestibular disorder.<br/>Respiratory System: Asthma, bronchitis,
dyspnea, epistaxis, hiccup, hypoventilation, increased cough, interstitial
pneumonia, larynx edema, lung disorder, rhinitis, and sinusitis.<br/>Skin and Appendages: Acne, contact dermatitis,
dry skin, eczema, erythema multiforme, exfoliative dermatitis, folliculitis,
fungal dermatitis, furunculosis, maculopapular rash, molluscum contagiosum,
onychomycosis, pruritus, psoriasis, pustular rash, seborrhea, skin
discoloration, skin disorder, skin hypertrophy, skin melanoma, urticaria,
and vesiculobullous rash.<br/>Special Senses: Abnormal electro-oculogram,
abnormal electroretinogram, abnormal vision, amblyopia/blurred vision,
blepharitis, conjunctivitis, ear pain, eye disorder, eye pain, hearing
impairment, increased cerumen, iritis, parosmia, photophobia, taste
loss, tinnitus, uveitis, visual field defect, and vitreous disorder.<br/>Urogenital System: Acute kidney failure,
breast pain, cystitis, dysuria, hematuria, impotence, kidney calculus,
kidney failure, kidney function abnormal, kidney pain, menorrhagia,
penis disorder, polyuria, urethritis, urinary frequency, urinary tract
infection, and vaginitis.<br/>Post-Marketing Experience: The following adverse
events have been reported during post-marketing use of NORVIR. Because
these reactions are reported voluntarily from a population of unknown
size, it is not possible to reliably estimate their frequency or establish
a causal relationship to NORVIR exposure.<br/>Laboratory Abnormalities: Table 8 shows the
percentage of adult patients who developed marked laboratory abnormalities.<br/>Pediatrics:<br/>Treatment-Emergent Adverse Events: NORVIR has been studied in 265 pediatric patients>1 month to 21 years of age. The adverse event profile observed
during pediatric clinical trials was similar to that for adult patients. Vomiting, diarrhea, and skin rash/allergy were the only
drug-related clinical adverse events of moderate to severe intensity
observed in���2% of pediatric patients enrolled in NORVIR clinical
trials.<br/>Laboratory Abnormalities: The following Grade 3-4 laboratory abnormalities
occurred in>3% of pediatric patients who received treatment with
NORVIR either alone or in combination with reverse transcriptase inhibitors:
neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia
(4%), and elevated AST (3%).
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Adverse Reactions in Adult Patients: During clinical investigations with oral and parenteral ciprofloxacin, 49,038 patients received courses of the drug. Most of the adverse events reported were described as only mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Ciprofloxacin was discontinued because of an adverse event in 1.8% of intravenously treated patients. The most frequently reported drug related events, from clinical trials of all formulations, all dosages, all drug-therapy durations, and for all indications of ciprofloxacin therapy were nausea (2.5%), diarrhea (1.6%), liver function tests abnormal (1.3%), vomiting (1.0%), and rash (1.0%). In clinical trials the following events were reported, regardless of drug relationship, in greater than 1% of patients treated with intravenous ciprofloxacin: nausea, diarrhea, central nervous system disturbance, local I.V. site reactions, liver function tests abnormal, eosinophilia, headache, restlessness, and rash. Many of these events were described as only mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Local I.V. site reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions which resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen. Additional medically important events, without regard to drug relationship or route of administration, that occurred in 1% or less of ciprofloxacin patients are listed below: BODY AS A WHOLE: abdominal pain/discomfort, foot pain, pain, pain in extremities CARDIOVASCULAR: Cardiovascular collapse, cardiopulmonary arrest, myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina pectoris, atrial flutter, ventricular ectopy, (thrombo)- phlebitis, vasodilation, migraine CENTRAL NERVOUS SYSTEM: Convulsive seizures, paranoia, toxic psychosis, depression, dysphasia, phobia, depersonalization, manic reaction, unresponsiveness, ataxia, confusion, hallucinations, dizziness, lightheadedness, paresthesia, anxiety, tremor, insomnia, nightmares, weakness, drowsiness, irritability, malaise, lethargy, abnormal gait, grand mal convulsion, anorexia GASTROINTESTINAL: Ileus, jaundice, gastrointestinal bleeding, C. difficile associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis, intestinal perforation, dyspepsia, epigastric pain, constipation, constipation, oral ulceration, oral candidiasis, mouth dryness, anorexia, dysphagia, flatulence, hepatitis, painful oral mucosa HEMIC/LYMPHATIC: Agranulocytosis, prolongation of prothrombin time, lymphadenopathy, petechia METABOLIC/NUTRITIONAL: Amylase increase, lipase increase MUSCULOSKELETAL: Arthralgia, jaw, arm or back pain, joint stiffness, neck and chest pain, achiness, flare up of gout, myasthenia gravis. RENAL/UROGENITAL: Renal failure, interstitial nephritis, nephritis, hemorrhagic cystitis, renal calculi, frequent urination, acidosis, urethral bleeding, polyuria, urinary retention, gynecomastia, candiduria, vaginitis, breast pain. Crystalluria, cylindruria, hematuria and albuminuria have also been reported. RESPIRATORY: Respiratory arrest, pulmonary embolism, dyspnea, laryngeal or pulmonary edema, respiratory distress, pleural effusion, hemoptysis, epistaxis, hiccough, bronchospasm SKIN/HYPERSENSITIVITY: Allergic reactions, anaphylactic reactions including life-threatening anaphylactic shock, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or lower extremities, purpura, fever, chills, flushing, pruritus, urticaria, cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation, erythema nodosum, thrombophlebitis, burning, paresthesia, erythema, swelling, photosensitivity/phototoxicity reaction SPECIAL SENSES: Decreased visual acuity, blurred vision, disturbed vision (flashing lights, change in color perception, overbrightness of lights, diplopia), eye pain, anosmia, hearing loss, tinnitus, nystagmus, chromatopsia, a bad taste. In several instances, nausea, vomiting, tremor, irritability, or palpitation were judged by investigators to be related to elevated serum levels of theophylline possibly as a result of drug interaction with ciprofloxacin. In randomized, double-blind controlled clinical trials comparing ciprofloxacin (I.V. and I.V. P.O. sequential) with intravenous beta-lactam control antibiotics, the CNS adverse event profile of ciprofloxacin was comparable to that of the control drugs.<br/>Adverse Reactions in Pediatric Patients: Ciprofloxacin, administered I.V. and /or orally, was compared to a cephalosporin for treatment of complicated urinary tract infections (cUTI) or pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6��4 years). The trial was conducted in the US, Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). The primary objective of the study was to assess musculoskeletal and neurological safety within 6 weeks of therapy and through one year of follow-up in the 335 ciprofloxacin- and 349 comparator-treated patients enrolled. An Independent Pediatric Safety Committee (IPSC) reviewed all cases of musculoskeletal adverse events as well as all patients with an abnormal gait or abnormal joint exam (baseline or treatment-emergent). These events were evaluated in a comprehensive fashion and included such conditions as arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint. The affected joints included: knee, elbow, ankle, hip, wrist, and shoulder. Within 6 weeks of treatment initiation, the rates of these events were 9.3% (31/335) in the ciprofloxacin-treated group versus 6.0 % (21/349) in comparator-treated patients. The majority of these events were mild or moderate in intensity. All musculoskeletal events occurring by 6 weeks resolved (clinical resolution of signs and symptoms), usually within 30 days of end of treatment. Radiological evaluations were not routinely used to confirm resolution of the events. The events occurred more frequently in ciprofloxacin-treated patients than control patients, regardless of whether they received I.V. or oral therapy. Ciprofloxacin-treated patients were more likely to report more than one event and on more than one occasion compared to control patients. These events occurred in all age groups and the rates were consistently higher in the ciprofloxacin group compared to the control group. At the end of 1 year, the rate of these events reported at any time during that period was 13.7% (46/335) in the ciprofloxacin-treated group versus 9.5% (33/349) comparator-treated patients. An adolescent female discontinued ciprofloxacin for wrist pain that developed during treatment. An MRI performed 4 weeks later showed a tear in the right ulnar fibrocartilage. A diagnosis of overuse syndrome secondary to sports activity was made, but a contribution from ciprofloxacin cannot be excluded. The patient recovered by 4 months without surgical intervention. The incidence rates of neurological events within 6 weeks of treatment initiation were 3% (9/335) in the ciprofloxacin group versus 2% (7/349) in the comparator group and included dizziness, nervousness, insomnia, and somnolence. In this trial, the overall incidence rates of adverse events regardless of relationship to study drug and within 6 weeks of treatment initiation were 41% (138/335) in the ciprofloxacin group versus 31% (109/349) in the comparator group. The most frequent events were gastrointestinal: 15% (50/335) of ciprofloxacin patients compared to 9% (31/349) of comparator patients. Serious adverse events were seen in 7.5% (25/335) of ciprofloxacin-treated patients compared to 5.7% (20/349) of control patients. Discontinuation of drug due to an adverse event was observed in 3% (10/335) of ciprofloxacin-treated patients versus 1.4% (5/349) of comparator patients. Other adverse events that occurred in at least 1% of ciprofloxacin patients were diarrhea 4.8%, vomiting 4.8%, abdominal pain3.3%, accidental injury 3.0%, rhinitis 3.0%, dyspepsia 2.7%, nausea 2.7%, fever 2.1%, asthma 1.8% and rash 1.8%. In addition to the events reported in pediatric patients in clinical trials, it should be expected that events reported in adults during clinical trials or post-marketing experience may also occur in pediatric patients.<br/>Post-Marketing Adverse Events: The following adverse events have been reported from worldwide marketing experience with quinolones, including ciprofloxacin. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, or (3) strength of causal connection to the drug. Agitation, agranulocytosis, albuminuria, anosmia, candiduria, cholesterol elevation (serum), confusion, constipation, delirium, dyspepsia, dysphagia, erythema multiforme, exfoliative dermatitis, fixed eruption, flatulence, glucose elevation (blood), hemolytic anemia, hepatic failure, hepatic necrosis, hyperesthesia, hypertonia, hypesthesia, hypotension (postural), jaundice, marrow depression (life threatening), methemoglobinemia, moniliasis (oral, gastrointestinal, vaginal) myalgia, myasthenia, myasthenia gravis (possible exacerbation), myoclonus, nystagmus, pancreatitis, pancytopenia (life threatening or fatal outcome), peripheral neuropathy, phenytoin alteration (serum), photosensitivity/phototoxicity reaction, potassium elevation (serum), prothrombin time prolongation or decrease,pseudomembranous colitis (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.), psychosis (toxic), renal calculi, serum sickness like reaction, Stevens-Johnson syndrome, taste loss, tendinitis, tendon rupture, torsade de pointes, toxic epidermal necrolysis (Lyell's Syndrome), triglyceride elevation (serum), twitching, vaginal candidiasis, and vasculitis. Adverse events were also reported by persons who received ciprofloxacin for anthrax post-exposure prophylaxis following the anthrax bioterror attacks of October 2001 .<br/>Adverse Laboratory Changes: The most frequently reported changes in laboratory parameters with intravenous ciprofloxacin therapy, without regard to drug relationship are listed below: Other changes occurring infrequently were: decreased leukocyte count, elevated atypical lymphocyte count, immature WBCs, elevated serum calcium, elevation of serum gamma-glutamyl transpeptidase (��GT), decreased BUN, decreased uric acid, decreased total serum protein, decreased serum albumin, decreased serum potassium, elevated serum potassium, elevated serum cholesterol. Other changes occurring rarely during administration of ciprofloxacin were: elevation of serum amylase, decrease of blood glucose, pancytopenia, leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased prothrombin time, hemolytic anemia, and bleeding diathesis.
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Adverse event information for Lexapro was collected from 715 patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The adverse event information for Lexapro in patients with GAD was collected from 429 patients exposed to escitalopram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.<br/>Adverse Events Associated with Discontinuation of Treatment:<br/>Major Depressive Disorder: Among the 715 depressed patients who received Lexapro in placebo-controlled trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies, the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro was not significantly different from the rate of discontinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of 20 mg/day Lexapro was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at leasttwice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients).<br/>Generalized Anxiety Disorder: Among the 429 GAD patients who received Lexapro 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%).<br/>Incidence of Adverse Events in Placebo-Controlled Clinical Trials:<br/>Major Depressive Disorder: Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 715 depressed patients who received Lexapro at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients. The prescriber should be aware that these figures can not be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied. The most commonly observed adverse events in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue, and somnolence (see TABLE 2).<br/>Generalized Anxiety Disorder: Table 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received Lexapro 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients. The most commonly observed adverse events in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia, fatigue, decreased libido, and anorgasmia (see TABLE 3).<br/>Dose Dependency of Adverse Events: The potential dose dependency of common adverse events (defined as an incidence rate of���5% in either the 10 mg or 20 mg Lexapro groups) was examined on the basis of the combined incidence of adverse events in two fixed-dose trials. The overall incidence rates of adverse events in 10 mg Lexapro-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day Lexapro-treated patients was greater (86%). Table 4 shows common adverse events that occurred in the 20 mg/day Lexapro group with an incidence that was approximately twice that of the 10 mg/day Lexapro group and approximately twice that of the placebo group.<br/>Male and Female Sexual Dysfunction with SSRIs: Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence. Table 5 shows the incidence rates of sexual side effects in patients with major depressive disorder and GAD in placebo-controlled trials. There are no adequately designed studies examining sexual dysfunction with escitalopram treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.<br/>Vital Sign Changes: Lexapro and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with Lexapro treatment. In addition, a comparison of supine and standing vital sign measures in subjects receiving Lexapro indicated that Lexapro treatment is not associated with orthostatic changes.<br/>Weight Changes: Patients treated with Lexapro in controlled trials did not differ from placebo-treated patients with regard to clinically important change in body weight.<br/>Laboratory Changes: Lexapro and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with Lexapro treatment.<br/>ECG Changes: Electrocardiograms from Lexapro (N=625), racemic citalopram (N=351), and placebo (N=527) groups were compared with respect to (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed (1) a decrease in heart rate of 2.2 bpm for Lexapro and 2.7 bpm for racemic citalopram, compared to an increase of 0.3 bpm for placebo and (2) an increase in QTc interval of 3.9 msec for Lexapro and 3.7 msec for racemic citalopram, compared to 0.5 msec for placebo. Neither Lexapro nor racemic citalopram were associated with the development of clinically significant ECG abnormalities.<br/>Other Events Observed During the Premarketing Evaluation of Lexapro: Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by the 1428 patients treated with Lexapro for periods of up to one year in double-blind or open-label clinical trials during its premarketing evaluation. All reported events are included except those already listed in Tables 2&3 , those occurring in only one patient, event terms that are so general as to be uninformative, and those that are unlikely to be drug related. It is important to emphasize that, although the events reported occurred during treatment with Lexapro, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients. Cardiovascular - Frequent: palpitation, hypertension. Infrequent: bradycardia, tachycardia, ECG abnormal, flushing, varicose vein. Central and Peripheral Nervous System Disorders - Frequent: light-headed feeling, migraine. Infrequent: tremor, vertigo, restless legs, shaking, twitching, dysequilibrium, tics, carpal tunnel syndrome, muscle contractions involuntary, sluggishness, coordination abnormal, faintness, hyperreflexia, muscular tone increased. Gastrointestinal Disorders - Frequent: heartburn, abdominal cramp, gastroenteritis. Infrequent: gastroesophageal reflux, bloating, abdominal discomfort, dyspepsia, increased stool frequency, belching, gastritis, hemorrhoids, gagging, polyposis gastric, swallowing difficult. General - Frequent: allergy, pain in limb, fever, hot flushes, chest pain. Infrequent: edema of extremities, chills, tightness of chest, leg pain, asthenia, syncope, malaise, anaphylaxis, fall. Hemic and Lymphatic Disorders - Infrequent: bruise, anemia, nosebleed, hematoma, lymphadenopathy cervical. Metabolic and Nutritional Disorders - Frequent: increased weight. Infrequent: decreased weight, hyperglycemia, thirst, bilirubin increased, hepatic enzymes increased, gout, hypercholesterolemia. Musculoskeletal System Disorders - Frequent: arthralgia, myalgia. Infrequent: jaw stiffness, muscle cramp, muscle stiffness, arthritis, muscle weakness, back discomfort, arthropathy, jaw pain, joint stiffness. Psychiatric Disorders - Frequent: appetite increased, lethargy, irritability, concentration impaired. Infrequent: jitteriness, panic reaction, agitation, apathy, forgetfulness, depression aggravated, nervousness, restlessness aggravated, suicide attempt, amnesia, anxiety attack, bruxism, carbohydrate craving, confusion, depersonalization,disorientation, emotional lability, feeling unreal, tremulousness nervous, crying abnormal, depression, excitability, auditory hallucination, suicidal tendency. Reproductive Disorders/Female* - Frequent: menstrual cramps, menstrual disorder. Infrequent: menorrhagia, breast neoplasm, pelvic inflammation, premenstrual syndrome, spotting between menses. *% based on female subjects only: N= 905 Respiratory System Disorders - Frequent: bronchitis, sinus congestion, coughing, nasal congestion, sinus headache. Infrequent: asthma, breath shortness, laryngitis, pneumonia, tracheitis. Skin and Appendages Disorders - Frequent: rash. Infrequent: pruritus, acne, alopecia, eczema, dermatitis, dry skin, folliculitis, lipoma, furunculosis, dry lips, skin nodule. Special Senses - Frequent: vision blurred, tinnitus. Infrequent: taste alteration, earache, conjunctivitis, vision abnormal, dry eyes, eye irritation, visual disturbance, eye infection, pupils dilated, metallic taste. Urinary System Disorders - Frequent: urinary frequency, urinary tract infection. Infrequent: urinary urgency, kidney stone, dysuria, blood in urine. Events Reported Subsequent to the Marketing of Escitalopram- Although no causal relationship to escitalopram treatment has been found, the following adverse events have been reported to have occurred in patients and to be temporally associated with escitalopram treatment during post marketing spontaneous and clinical trial experience and were not observed during the premarketing evaluation of escitalopram: Blood and Lymphatic System Disorders: hemolytic anemia, leukopenia, thrombocytopenia. Cardiac Disorders: atrial fibrillation, cardiac failure, myocardial infarction, torsade de pointes, ventricular arrhythmia, ventricular tachycardia. Endocrine Disorders: diabetes mellitus, hyperprolactinemia, SIADH. Eye Disorders: diplopia, glaucoma. Gastrointestinal Disorder: gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage. General Disorders and Administration Site Conditions: abnormal gait. Hepatobiliary Disorders: fulminant hepatitis, hepatic failure, hepatic necrosis, hepatitis. Immune System Disorders: allergic reaction. Investigations: electrocardiogram QT prolongation, INR increased, prothrombin decreased. Metabolism and Nutrition Disorders: hypoglycemia, hypokalemia. Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis. Nervous System Disorders: akathisia, choreoathetosis, dysarthria, dyskinesia, dystonia, extrapyramidal disorders, grand mal seizures (or convulsions), hypoaesthesia, myoclonus, neuroleptic malignant syndrome, nystagmus, seizures, serotonin syndrome, tardive dyskinesia. Pregnancy, Puerperium and Perinatal Conditions: spontaneous abortion. Psychiatric Disorders: acute psychosis, aggression, anger, delirium, delusion, nightmare, paranoia, visual hallucinations. Renal and Urinary Disorders: acute renal failure. Reproductive System and Breast Disorders: priapism. Respiratory, Thoracic and Mediastinal Disorders: pulmonary embolism. Skin and Subcutaneous Tissue Disorders: angioedema, ecchymosis, erythema multiforme, photosensitivity reaction, Stevens Johnson Syndrome, toxic epidermal necrolysis, urticaria. Vascular Disorders: deep vein thrombosis, hypotension, orthostatic hypotension, phlebitis thrombosis.
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As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria. The following adverse reactions have been reported asassociated with the use of penicillins: Gastrointestinal: Nausea, vomiting, diarrhea, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. Hypersensitivity Reactions: Serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported. NOTE: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is lifethreatening and amenable only to amoxicillin therapy. Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported. Renal: Crystalluria has also been reported . Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely. Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.<br/>Combination Therapy with Clarithromycin and Lansoprazole: In clinical trials using combination therapy with amoxicillin plus clarithromycin and lansoprazole, and amoxicillin plus lansoprazole, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxicillin, clarithromycin, or lansoprazole.<br/>Triple Therapy:<br/>Amoxicillin/Clarithromycin/Lansoprazole: The most frequently reported adverse events for patients who received triple therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen.<br/>Dual Therapy:<br/>Amoxicillin/Lansoprazole: The most frequently reported adverse events for patients who received amoxicillin three times daily plus lansoprazole three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with amoxicillin three times daily plus lansoprazole three times daily dual therapy than with lansoprazole alone. For more information on adverse reactions with clarithromycin or lansoprazole, refer to their package inserts, ADVERSE REACTIONS.
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Most adverse reactions occurring during therapy
with Seromycin involve
the nervous system or are manifestations of drug hypersensitivity. The following
side effects have been observed in patients receiving Seromycin:
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Adverse reactions were relatively frequent, with over 50% of patients reporting at least one. Most (30% to 40%) involved the gastrointestinal tract. Most adverse effects are mild, but 21% of patients discontinued therapy because of an adverse event, principally diarrhea, rash, nausea, vomiting, Gl pain, and neutropenia. Most adverse effects occur early in the course of treatment, but a new onset of adverse effects can occur after several months. The incidence rates of adverse events listed in the following table were derived from multicenter, controlled clinical trials in stroke patients described above comparing ticlopidine hydrochloride, placebo, and aspirin over study periods of up to 5.8 years. Adverse events considered by the investigator to be probably drug-related that occurred in at least 1% of patients treated with ticlopidine hydrochloride are shown in the following table:<br/>Hematological: Neutropenia/thrombocytopenia, TTP, aplastic anemia (see BOXED WARNING and WARNINGS), leukemia, agranulocytosis, eosinophilia, pancytopenia, thrombocytosis, and bone marrow depression have been reported.<br/>Gastrointestinal: Ticlopidine hydrochloride therapy has been associated with a variety of gastrointestinal complaints including diarrhea and nausea. The majority of cases are mild, but about 13% of patients discontinued therapy because of these. They usually occur within 3 months of initiation of therapy and typically are resolved within 1 to 2 weeks without discontinuation of therapy. If the effect is severe or persistent, therapy should be discontinued. In some cases of severe or bloody diarrhea, colitis was later diagnosed.<br/>Hemorrhagic: Ticlopidine hydrochloride has been associated with increased bleeding, spontaneous post-traumatic bleeding, and perioperative bleeding including, but not limited to, gastrointestinal bleeding. It has also been associated with a number of bleeding complications such as ecchymosis, epistaxis, hematuria, and conjunctival hemorrhage. Intracerebral bleeding was rare in clinical trials with ticlopidine hydrochloride, with an incidence no greater than that seen with comparator agents (ticlopidine 0.5%, aspirin 0.6%, placebo 0.75%). It has also been reported postmarketing.<br/>Rash: Ticlopidine has been associated with a maculopapular or urticarial rash (often with pruritus). Rash usually occurs within 3 months of initiation of therapy, with a mean onset time of 11 days. If drug is discontinued, recovery occurs within several days. Many rashes do not recur on drug rechallenge. There have been rare reports of severe rashes, including Stevens-Johnson syndrome, erythema multiforme, and exfoliative dermatitis.<br/>Less Frequent Adverse Reactions (Probably Related): Clinical adverse experiences occurring in 0.5% to 1.0% of patients in the controlled trials include: ���Digestive System: Gl fullness ���Body as a Whole: asthenia, pain ���Skin and Appendages: urticaria ���Hemostatic System: epistaxis ���Nervous System: headache ���Special Senses: tinnitus In addition, rarer, relatively serious and potentially fatal events associated with the use of ticlopidine hydrochloride have also been reported from postmarketing experience: Hemolytic anemia with reticulocytosis, immune thrombocytopenia, hepatitis, hepatocellular jaundice, cholestatic jaundice, hepatic necrosis, hepatic failure, peptic ulcer, renal failure, nephrotic syndrome, hyponatremia, vasculitis, sepsis, allergic reactions (including angioedema, allergic pneumonitis, and anaphylaxis), systemic lupus (positive ANA), peripheral neuropathy, serum sickness, arthropathy, and myositis.
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