Linked Life Data

Flutamide (Capsule)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2130

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PredicateObject
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Flutamide (Capsule)
dailymed-instance:dosage
The recommended dosage is 2 capsules 3 times a day at 8 hour intervals for a total daily dose of 750 mg.
dailymed-instance:descripti...
Flutamide capsules contain flutamide, an acetanilid, nonsteroidal, orally active antiandrogen having the chemical name,��,��,��-trifluoro-2-methyl-4'-nitrom-propionotoluidide. Each capsule contains 125 mg flutamide. The compound is a buff to yellow powder with a molecular weight of 276.22 and the following structural formula: CHFNO In addition, each capsule contains the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, povidone, and sodium lauryl sulfate. Gelatin capsule shells may contain gelatin, silicon dioxide, sodium lauryl sulfate, titanium dioxide, FDA/E172 Red Iron Oxide, FDA/E172 Yellow Iron Oxide, and black ink containing pharmaceutical glaze (modified) in SD-45, synthetic blackiron oxide, N-butyl alcohol, SDA-3A alcohol, FD&C Blue No.2 Aluminum Lake, FD&C Red No.40 Aluminum Lake, FD&C Blue No.1 Aluminum Lake, and D&C Yellow No.10 Aluminum Lake.
dailymed-instance:clinicalP...
In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g., castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration. Pharmacokinetics Absorption Analysis of plasma, urine, and feces following a single oral 200 mg dose of tritium-labeled flutamide to human volunteers showed that the drug is rapidly and completely absorbed. Following a single 250 mg oral dose to normal adult volunteers, the biologically active alpha-hydroxylated metabolite reaches maximum plasma concentrations in about 2 hours, indicating that it is rapidly formed from flutamide. Food has no effect on the bioavailability of flutamide. Distribution In male rats administered an oral 5 mg/kg dose ofC-flutamide neither flutamide nor any of its metabolites is preferentially accumulated in any tissue except the prostate. Total drug levels were highest 6 hours after drug administration in all tissues. Levels declined at roughly similar rates to low levels at 18 hours. The major metabolite was present at higher concentrations than flutamide in all tissues studied. Following a single 250 mg oral dose to normal adult volunteers, low plasma concentrations of flutamide were detected. The plasma half-life for the alpha-hydroxylated metabolite of flutamide is approximately 6 hours. Flutamide,in vivo, at steady-state plasma concentrations of 24 to 78 ng/mL, is 94% to 96% bound to plasma proteins. The active metabolite of flutamide, in vivo, at steady-state plasma concentrations of 1556 to 2284 ng/mL, is 92% to 94% bound to plasma proteins. Metabolism The composition of plasma radioactivity, following a single 200 mg oral dose of tritium-labeled flutamide to normal adult volunteers, showed that flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration. At least six metabolites have been identified in plasma. The major plasma metabolite is a biologically active alpha-hydroxylated derivative which accounts for 23% of the plasma tritium 1 hour after drug administration. The major urinary metabolite is 2-amino-5nitro-4-(trifluoromethyl)phenol. Excretion Flutamide and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours. Plasma Pharmacokinetics of Flutamide and Hydroxyflutamide in Geriatric Volunteers (mean��SD) Special Populations GeriatricFollowing multiple oral dosing of 250 mg t.i.d. in normal geriatric volunteers, flutamide and its active metabolite approached steady-state plasma levels (based on pharmacokinetic simulations) after the fourth flutamide dose. The half-life of the active metabolite in geriatric volunteers after a single flutamide dose is about 8 hours and at steady-state in 9.6 hours. RaceThere are no known alterations in flutamide absorption, distribution, metabolism, or excretion due to race. Renal ImpairmentFollowing a single 250 mg dose of flutamide administered to subjects with chronic renal insufficiency, there appeared to be no correlation between creatinine clearance and either Cor AUC of flutamide. Renal impairment did not have an effect on the Cor AUC of the biologically active alpha- hydroxylated metabolite of flutamide. In subjects with creatinine clearance of<29 mL/min, the half-life of the active metabolite was slightly prolonged. Flutamide and its active metabolite were not well dialyzed. Dose adjustment in patients with chronic renal insufficiency is not warranted. Hepatic ImpairmentNo information on the pharmacokinetics of flutamide in hepatic impairment is available (seeBOXED WARNING, Hepatic Injury). Women, PediatricsFlutamide has not been studied in women or pediatric subjects. Drug-Drug Interactions Interactions between flutamide capsules and LHRH-agonists have not occurred. Increases in prothrombin time have been noted in patients receiving warfarin therapy (seePRECAUTIONS).
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dailymed-instance:contraind...
Flutamide capsules are contraindicated in patients who are hypersensitive to flutamide or any component of this preparation. Flutamide capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment).
dailymed-instance:supply
Flutamide capsules USP, 125 mg, are available as opaque, beige/beige capsules, imprinted���93���-���7120���on the cap and body. They are available in bottle of 180 (NDC 49884-753-13) and 500 (NDC 49884-753-05). Store at 20��to 25��C (68��to 77��F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
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dailymed-instance:boxedWarn...
WARNINGS Hepatic Injury There have been postmarketing reports of hospitalization and rarely death due to liver failure in patients taking flutamide. Evidence of hepatic injury included elevated serum transaminase levels, jaundice, hepatic encephalopathy and death related to acute hepatic failure. The hepatic injury was reversible after discontinuation of therapy in some patients. Approximately halfof the reported cases occurred within the initial 3 months of treatment with flutamide. Serum transaminase levels should be measured prior to starting treatment with flutamide. Flutamide is not recommended in patients whose ALT values exceed twice the upper limit of normal. Serum transaminase levels should then be measured monthly for the first 4 months of therapy, and periodically thereafter. Liver function tests also should be obtained at the first signs and symptoms suggestive of liver dysfunction, e.g., nausea, vomiting, abdominal pain, fatigue, anorexia,���flu-like���symptoms, hyperbilirubinuria, jaundice or right upper quadrant tenderness. If at any time, a patient has jaundice, or their ALT rises above 2 times the upper limit of normal, flutamide should be immediately discontinued with close follow-up of liver function tests until resolution.
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dailymed-instance:overdosag...
In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia. Clinical trials have been conducted with flutamide in doses up to 1500 mg per day for periods up to 36 weeks with no serious adverse effects reported. Those adverse reactions reported included gynecomastia, breast tenderness, and some increases in SGOT. The single dose of flutamide ordinarily associated with symptoms of overdose or considered to be life-threatening has not been established. Flutamide is highly protein bound, and is not cleared by hemodialysis. As in the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken. If vomiting does not occur spontaneously, it should be induced if the patient is alert. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated.
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Flutamide
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Flutamide (Capsule)
dailymed-instance:adverseRe...
Stage B-C Prostatic Carcinoma Treatment with flutamide capsules and the goserelin acetate implant did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing flutamide + goserelin acetate implant + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below: Adverse Events During Acute Radiation Therapy (within first 90 days of radiation therapy) Adverse Events During Late Radiation Phase (after 90 days of radiation therapy) Additional adverse event data were collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%). Stage DMetastatic Carcinoma The following adverse experiences were reported during a multicenter clinical trial comparing flutamide + LHRH agonist versus placebo + LHRH agonist. The most frequently reported (greater than 5%) adverse experiences during treatment with flutamide capsules in combination with an LHRH agonist are listed in the table below. For comparison, adverse experiences seen with an LHRH agonist and placebo are also listed in the following table. As shown in the table, for both treatment groups, the most frequently occurring adverse experiences (hot flashes, impotence, loss of libido) were those known to be associated with low serum androgen levels and known to occur with LHRH agonists alone. The only notable difference was the higher incidence of diarrhea in the flutamide + LHRH agonist group (12%), which was severe in 5% as opposed to the placebo + LHRH agonist (4%), which was severe in less than 1%. In addition, the following adverse reactions were reported during treatment with flutamide + LHRH agonist. Cardiovascular System:hypertension in 1% of patients. Central Nervous System: CNS (drowsiness/confusion/depression/anxiety/nervousness) reactions occurred in 1% of patients. Gastrointestinal System: anorexia 4%, and other GI disorders occurred in 6% of patients. Hematopoietic System: anemia occurred in 6%, leukopenia in 3%, and thrombocytopenia in 1% of patients. Liver and Biliary System: hepatitis and jaundice in less than 1% of patients. Skin: irritation at the injection site and rash occurred in 3% of patients. Other:edema occurred in 4%, genitourinary and neuromuscular symptoms in 2%, and pulmonary symptoms in less than 1% of patients. In addition, the following spontaneous adverse experiences have been reported during the marketing of flutamide: hemolytic anemia,macrocytic anemia,methemoglobinemia, sulfhemoglobinemia, photosensitivity reactions (including erythema, ulceration, bullous eruptions, and epidermal necrolysis) and urine discoloration. The urine was noted to change to an amber or yellow-green appearance which can be attributed to the flutamide and/or its metabolites. Also reported were cholestatic jaundice, hepatic encephalopathy, and hepatic necrosis. The hepatic conditions were often reversible after discontinuing therapy; however, there have been reports of death following severe hepatic injury associated with use of flutamide. Malignant breast neoplasms have occurred rarely in male patients being treated with flutamide capsules. Abnormal Laboratory Test Values: Laboratory abnormalities including elevated SGOT, SGPT, bilirubin values, SGGT, BUN, and serum creatinine have been reported.
dailymed-instance:indicatio...
Flutamide capsules are indicated for use in combination with LHRH-agonists for the management of locally confined Stage B-C and Stage Dmetastatic carcinoma of the prostate. Stage B-C Prostatic Carcinoma Treatment with flutamide capsules and the goserelin acetate implant should start eight weeks prior to initiating radiation therapy and continue during radiation therapy. Stage DMetastatic Carcinoma To achieve benefit from treatment, flutamide capsules should be initiated with the LHRH-agonist and continued until progression.
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Flutamide