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.
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| 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.
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| 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.
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| 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.
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| 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:
|