Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/664
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Rescriptor (Tablet)
|
| dailymed-instance:dosage |
The recommended dosage for RESCRIPTOR Tablets is 400 mg (four 100 mg or two 200 mg tablets) three times daily. RESCRIPTOR should be used in combination with other antiretroviral therapy. The complete prescribing information for other antiretroviral agents should be consulted for information on dosage and administration. The 100 mg RESCRIPTOR Tablets may be dispersed in water prior to consumption. To prepare a dispersion, add four 100 mg RESCRIPTOR Tablets to at least 3 ounces of water, allow to stand for a few minutes, and then stir until a uniform dispersion occurs . The dispersion should be consumed promptly. The glass should be rinsed with water and the rinse swallowed to insure the entire dose is consumed. The 200 mg tablets should be taken as intact tablets, because they are not readily dispersed in water. Note: The 200 mg tablets are approximately one-third smaller in size than the 100 mg tablets. RESCRIPTOR Tablets may be administered with or without food . Patients with achlorhydria should take RESCRIPTOR with an acidic beverage (e.g., orange or cranberry juice). However, the effect of an acidic beverage on the absorption of delavirdine in patients with achlorhydria has not been investigated. Patients taking both RESCRIPTOR and antacids should be advised to take them at least one hour apart.
|
| dailymed-instance:descripti... |
RESCRIPTOR Tablets contain delavirdine mesylate, a synthetic non-nucleoside reverse transcriptase inhibitor of the human immunodeficiency virus type 1 (HIV-1). The chemical name of delavirdine mesylate is piperazine, 1-[3-[(1-methyl-ethyl)amino]-2-pyridinyl]-4-[[5-[(methylsulfonyl)amino]-1H-indol-2-yl]carbonyl]-, monomethanesulfonate. Its molecular formula is CHNOS���CHOS, and its molecular weight is 552.68. The structural formula is: Delavirdine mesylate is an odorless white-to-tan crystalline powder. The aqueous solubility of delavirdine free base at 23��C is 2942��g/mL at pH 1.0, 295��g/mL at pH 2.0, and 0.81��g/mL at pH 7.4. Each RESCRIPTOR Tablet, for oral administration, contains 100 or 200 mg of delavirdine mesylate (henceforth referred to as delavirdine). Inactive ingredients consist of lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, colloidal silicon dioxide, and carnauba wax. In addition, the 100 mg tablet contains Opadry White YS-1-7000-E and the 200 mg tablet contains hypromellose, Opadry White YS-1-18202-A and Pharmaceutical Ink Black.
|
| dailymed-instance:clinicalP... |
Pharmacokinetics:<br/>Absorption and Bioavailability: Delavirdine is rapidly absorbed following oral administration, with peak plasma concentrations occurring at approximately one hour. Following administration of delavirdine 400 mg tid (n=67, HIV-1���infected patients), the mean��SD steady-state peak plasma concentration (C) was 35��20��M (range 2 to 100��M), systemic exposure (AUC) was 180��100��M���hr (range 5 to 515��M���hr) and trough concentration (C) was 15��10��M (range 0.1 to 45��M). The single-dose bioavailability of delavirdine tablets relative to an oral solution was 85��25% (n=16, non-HIV���infected subjects). The single-dose bioavailability of delavirdine tablets (100 mg strength) was increased by approximately 20% when a slurry of drug was prepared by allowing delavirdine tablets to disintegrate in water before administration (n=16, non-HIV���infected subjects). The bioavailability of the 200 mg strength delavirdine tablets has not been evaluated when administered as a slurry, because they are not readily dispersed in water . Delavirdine may be administered with or without food. In a multiple-dose, crossover study, delavirdine was administered every eight hours with food or every eight hours, one hour before or two hours after a meal (n=13, HIV-1���infected patients). Patients remained on their typical diet throughout the study; meal content was not standardized. When multiple doses of delavirdine were administered with food, geometric mean Cwas reduced by approximately 25%, but AUC and Cwere not altered.<br/>Distribution: Delavirdine is extensively bound (approximately 98%) to plasma proteins, primarily albumin. The percentage of delavirdine that is protein-bound is constant over a delavirdine concentration range of 0.5 to 196��M. In five HIV-1���infected patients whose total daily dose of delavirdine ranged from 600 to 1200 mg, cerebrospinal fluid concentrations of delavirdine averaged 0.4%��0.07% of the corresponding plasma delavirdine concentrations; this represents about 20% of the fraction not bound to plasma proteins. Steady-state delavirdine concentrations in saliva (n=5, HIV-1���infected patients who received delavirdine 400 mg tid) and semen (n=5 healthy volunteers who received delavirdine 300 mg tid) were about 6% and 2%, respectively, of the corresponding plasma delavirdine concentrations collected at the end of a dosing interval.<br/>Metabolism and Elimination: Delavirdine is extensively converted to several inactive metabolites. Delavirdine is primarily metabolized by cytochrome P450 3A (CYP3A), but in vitro data suggest that delavirdine may also be metabolized by CYP2D6. The major metabolic pathways for delavirdine are N-desalkylation and pyridine hydroxylation. Delavirdine exhibits nonlinear steady-state elimination pharmacokinetics, with apparent oral clearance decreasing by about 22-fold as the total daily dose of delavirdine increases from 60 to 1200 mg/day. In a study ofC-delavirdine in six healthy volunteers who received multiple doses of delavirdine tablets 300 mg tid, approximately 44% of the radiolabeled dose was recovered in feces, and approximately 51% of the dose was excreted in urine. Less than 5% of the dose was recovered unchanged in urine. The parent plasma half-life of delavirdine increases with dose; mean half-life following 400 mg tidis 5.8 hours, with a range of 2 to 11 hours. In vitro and in vivo studies have shown that delavirdine reduces CYP3A activity and inhibits its own metabolism. In vitro studies have also shown that delavirdine reduces CYP2C9, CYP2D6, and CYP2C19 activity. Inhibition of hepatic CYP3A activity by delavirdine is reversible within 1 week after discontinuation of drug.<br/>Special Populations:<br/>Hepatic or Renal Impairment: The pharmacokinetics of delavirdine in patients with hepatic or renal impairment have not been investigated .<br/>Age: The pharmacokinetics of delavirdine have not been adequately studied in patients<16 years or>65 years of age.<br/>Gender: Data from population pharmacokinetics suggest that the plasma concentrations of delavirdine tend to be higher in females than in males. However, this difference is not considered to be clinically significant.<br/>Race: No significant differences in the mean trough delavirdine concentrations were observed between different racial or ethnic groups.<br/>Drug Interactions: Specific drug interaction studies were performed with delavirdine and a number of drugs. Table 1 summarizes the effects of delavirdine on the geometric mean AUC, Cand Cof coadministered drugs. Table 2 shows the effects of coadministered drugs on the geometric mean AUC, Cand Cof delavirdine. For information regarding clinical recommendations, see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: Drug Interactions.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:supply |
RESCRIPTOR Tablets are available as follows: 100 mg: white, capsule-shaped tablets marked with "U 3761".Bottles of 360 tablets NDC 63010-020-36200 mg: white, capsule-shaped tablets marked with "RESCRIPTOR 200 mg".Bottles of 180 tablets NDC 63010-021-18Store at controlled room temperature 20��to 25��C (68��to 77��F) [see USP]. Keep container tightly closed. Protect from high humidity.
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:overdosag... |
Human experience of acute overdose with RESCRIPTOR is limited.<br/>Management of Overdosage: Treatment of overdosage with RESCRIPTOR should consist of general supportive measures, including monitoring of vital signs and observation of the patient's clinical status. There is no specific antidote for overdosage with RESCRIPTOR. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Since delavirdine is extensively metabolized by the liver and is highly protein-bound, dialysis is unlikely to result in significant removal of the drug.
|
| dailymed-instance:genericMe... |
delavirdine mesylate
|
| dailymed-instance:fullName |
Rescriptor (Tablet)
|
| dailymed-instance:adverseRe... |
The safety of RESCRIPTOR Tablets alone and in combination with other therapies has been studied in approximately 6,000 patients receiving RESCRIPTOR. The majority of adverse events were of mild or moderate (i.e., ACTG grade 1 or 2) intensity. The most frequently reported drug-related adverse event (i.e., events considered by the investigatorto be related to the blinded study medication, or events with an unknown or missing causal relationship to the blinded medication) among patients receiving RESCRIPTOR was skin rash . Adverse events of moderate to severe intensity reported by at least 5% of evaluable patients in any treatment group in the pivotal trials, which includes patients receiving RESCRIPTOR in combination with zidovudine and/or lamivudine in Study 21 Part II for up to 98 weeks and in combination with zidovudine and either lamivudine, didanosine,or zalcitabine in Study 13C for up to 72 weeks are summarized in Table 9. Other adverse events that occurred in patients receiving RESCRIPTOR (in combination treatment) in all phase II and III studies, and considered possibly related to treatment, and of at least ACTG grade 2 in intensity are listed below by body system. Body as a Whole: Abdominal cramps, abdominal distention, abdominal pain (localized), abscess, allergic reaction, chills, edema (generalized or localized), epidermal cyst, fever, infection, infection viral, lip edema, malaise, Mycobacterium tuberculosis infection, neck rigidity, sebaceous cyst, and redistribution/accumulation of body fat . Cardiovascular System: Abnormal cardiac rate and rhythm, cardiac insufficiency, cardiomyopathy, hypertension, migraine, pallor, peripheral vascular disorder, and postural hypotension. Digestive System: Anorexia, bloody stool, colitis, constipation, decreased appetite, diarrhea (Clostridium difficile), diverticulitis, dry mouth, dyspepsia, dysphagia, enteritis at all levels, eructation, fecal incontinence, flatulence, gagging, gastroenteritis, gastroesophageal reflux, gastrointestinal bleeding, gastrointestinal disorder, gingivitis, gum hemorrhage, hepatomegaly, increased appetite, increased saliva, increased thirst, jaundice, mouth or tongue inflammation or ulcers, nonspecific hepatitis, oral/enteric moniliasis, pancreatitis, rectal disorder, sialadenitis, tooth abscess, and toothache. Hemic and Lymphatic System: Adenopathy, bruising, eosinophilia, granulocytosis, leukopenia, pancytopenia, purpura, spleen disorder, thrombocytopenia, and prolonged prothrombin time. Metabolic and Nutritional Disorders: Alcohol intolerance, amylase increased, bilirubinemia, hyperglycemia, hyperkalemia, hypertriglyceridemia, hyperuricemia, hypocalcemia, hyponatremia, hypophosphatemia, increased AST (SGOT), increased gamma glutamyl transpeptidase, increased lipase, increased serum alkaline phosphatase, increased serum creatinine, and weight increase or decrease. Musculoskeletal System: Arthralgia or arthritis of single and multiple joints, bone disorder, bone pain, myalgia, tendon disorder, tenosynovitis, tetany, and vertigo. Nervous System: Abnormal coordination, agitation, amnesia, change in dreams, cognitive impairment, confusion, decreased libido, disorientation, dizziness, emotional lability, euphoria, hallucination, hyperesthesia, hyperreflexia, hypertonia, hypesthesia, impaired concentration, manic symptoms, muscle cramp, nervousness, neuropathy, nystagmus, paralysis, paranoid symptoms, restlessness, sleep cycle disorder, somnolence, tingling, tremor, vertigo, and weakness. Respiratory System: Chest congestion, dyspnea, epistaxis, hiccups, laryngismus, pneumonia, and rhinitis. Skin and Appendages: Angioedema, dermal leukocytoclastic vasculitis, dermatitis, desquamation, diaphoresis, discolored skin, dry skin, erythema, erythema multiforme, folliculitis, fungal dermatitis, hair loss, herpes zoster or simplex, nail disorder, petechiae, non-application site pruritus, seborrhea, skin hypertrophy, skin disorder, skin nodule, Stevens-Johnson syndrome, urticaria, vesiculobullous rash, and wart. Special Senses: Blepharitis, blurred vision, conjunctivitis, diplopia, dry eyes, ear pain, parosmia, otitis media, photophobia, taste perversion, and tinnitus. Urogenital System: Amenorrhea, breast enlargement, calculi of the kidney, chromaturia, epididymitis, hematuria, hemospermia, impaired urination, impotence, kidney pain, metrorrhagia, nocturia, polyuria, proteinuria, testicular pain, urinary tract infection, and vaginal moniliasis.<br/>Postmarketing Experience: Adverse event terms reported from postmarketing surveillance that were not reported in the phase II and III trials are presented below. Digestive System: Hepatic failure. Hemic and Lymphatic System: Hemolytic anemia. Musculoskeletal System: Rhabdomyolysis. Urogenital System: Acute kidney failure.<br/>Laboratory Abnormalities: Marked laboratory abnormalities observed in at least 2% of patients during Studies 21 Part II and 13C are summarized in Table 10. Marked laboratory abnormalities are defined as any Grade 3 or 4 abnormality found in patients at any time during study.
|
| dailymed-instance:indicatio... |
RESCRIPTOR Tablets are indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. The following should be considered before initiating therapy with RESCRIPTOR in treatment-naive patients. There are insufficient data directly comparing RESCRIPTOR-containing antiretroviral regimens with currently preferred 3-drug regimens for initial treatment of HIV. In studies comparing regimens consisting of 2 NRTIs (currently considered suboptimal) to RESCRIPTOR plus 2 NRTIs, the proportion of patients receiving the RESCRIPTOR regimen who achieved and sustained an HIV-1 RNA level<400 copies/mL over one year of therapy was relatively low . Resistant virus emerges rapidly when RESCRIPTOR is administered as monotherapy. Therefore, RESCRIPTOR should always be administered in combination with other antiretroviral agents.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Rescriptor
|