Specialty Formalary
Trade Name: 
Eulexin; Flutamin
In Treatment of: 
Flutamide is an oral, non-steroidal antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer cells to grow. Flutamide has been largely replaced by a newer member of this class, bicalutamide, due to a better side-effect profile. Flutamide may also be used to treat excess androgen levels in women - especially those with PolyCystic Ovarian Syndrome (PCOS).
Adverse Effects: 
Treatment with flutamide Capsules and the LHRH agonist did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing flutamide Capsules + LHRH-A +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 Acute Radiation Therapy (within first 90 days of radiation therapy) (n= 231) LHRH -A + EULEXIN (flutamide) Capsules + Radiation % All (n= 235) Radiation Only % All Rectum/Large Bowel 80 76 Bladder 58 60 Skin 37 37 Adverse Events During Late Radiation Phase (after 90 days of radiation therapy) (n= 231) LHRH-A +Flutamide Capsules + Radiation %All (n= 235) Radiation Only %All Diarrhea 36 40 Cystitis 16 16 Rectal Bleeding 14 20 Proctitis 8 8 Hematuria 7 12 Additional adverse event data was 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 D2 Metastatic Carcinoma The following adverse experiences were reported during a multi-center clinical trial comparing flutamide Capsules + 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. (n= 294) Flutamide + LHRH agonist %All (n= 285) Placebo + LHRA agonist %All Hot Flashes 61 57 Loss of Libido 36 31 Impotence 33 29 Diarrhea 12 4 Nausea/ Vomiting 11 10 Gynecomastia 9 11 Other 7 9 Other GI 6 4 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 than1%. In addition, the following adverse reactions were reported during treatment with flutamide + LHRH agonist. No causal relatedness of these reactions to drug treatment has been made, and some of the adverse experiences reported are those that commonly occur in elderly patients. 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, 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 usually reversible after discontinuing therapy; however, there have been reports of death following severe hepatic injury associated with use of flutamide. Malignant breast neoplasms have occured in male patients being treated with EULEXIN (flutamide) Capsules. Abnormal Laboratory Test Values: Laboratory abnormalities including elevated SGOT, SGPT, bilirubin values, SGGT, BUN, and serum creatinine have been reported.
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.
Special Precaution: 
General: In clinical trials, gynecomastia occurred in 9% of patients receiving flutamide together with medical castration. Laboratory Tests Regular assessment of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient's response. If PSA levels rise significantly and consistently during EULEXIN (flutamide) therapy the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated P.A. a treatment- free period of antiandrogen while continuing the LHRH analogue may be considered. Carcinogenesis, Mutagenesis, Impairment of Fertility In a 1-year dietary study in male rats, interstitial cell adenomas of the testes were present in 49% to 75% of all treated rats (daily oral doses of 10, 30, and 50 mg/kg/day were administered). These produce plasma Cmax values that are 1, 2-3, and 4-fold, respectively, those associated with therapeutic doses in humans. In male rats similarly dosed for 1 year, tumors were still present after 1 year of a drug-free period, but the incidences were 43% to 47%. In a 2-year carcinogenicity study in male rats, daily administration of flutamide at these same doses produced testicular interstitial cell adenomas in 91% to 95% of all treated rats as opposed to 11% of untreated control rats. Mammary adenomas, adenocarcinomas, and fibroadenomas were increased in treated male rats at exposure levels that were 1- to 4- fold those observed during therapeutic dosing in humans. There are likewise reports of malignant breast neoplasms in men treated with FLUTAMIDE Capsules Flutamide did not demonstrate DNA modifying activity in the Ames Salmonella/ microsome Mutagenesis Assay. Dominant lethal tests in rats were negative. Reduced sperm counts were observed during a 6-week study of flutamide monotherapy in normal human volunteers. Flutamide did not affect estrous cycles or interfere with the mating behavior of male and female rats when the drug was administered at 25 and 75 mg/kg/day prior to mating. Males treated with 150 mg/kg/day (30 times the minimum effective antiandrogenic dose) failed to mate; mating behavior returned to normal after dosing was stopped. Conception rates were decreased in all dosing groups. Suppression of spermatogenesis was observed in rats dosed for 52 weeks at approximately 3, 8, or 17 times the human dose and in dogs dosed for 78 weeks at 1.4, 2.3, and 3.7 times the human dose. Animal Toxicology: Serious cardiac lesions were observed in 2/10 beagle dogs receiving 25 mg/kg/day for 78 weeks and 3/16 receiving 40 mg/kg/day for 2-4 years. These lesions, indicative of chronic injury and repair processes, included chronic myxomatous degeneration, intraatrial fibrosis, myocardial acidophilic degeneration, vasculitis, and perivasculitis. The doses at which these lesions occurred were associated with 2-hydroxyflutamide levels that were 1- to 12-fold greater than those observed in humans at therapeutic levels. Pregnancy: Pregnancy Category D. There was decreased 24-hour survival in the offspring of pregnant rats treated with flutamide at doses of 30, 100, or 200 mg/kg/day (approximately 3, 9, and 19 times the human dose). A slight increase in minor variations in the development of the sternebrae and vertebrae was seen in fetuses of rats treated with two higher doses. Feminization of the male rats also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day, equal to 1.4 times the human dose).
Increases in prothrombin time have been noted in patients receiving long- term warfarin therapy after flutamide was initiated. Therefore, close monitoring of prothrombin time is recommended and adjustment of the anticoagulant dose may be necessary when EULEXIN (flutamide) Capsules are administered concomitantly with warfarin.
The recommended dosage is 2 capsules 3 times a day at 8-hour intervals for a total daily dose of 750 mg.

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