Eulexin Information
Eulexin (Flutamide)
Eulexin (Flutamide) Description
Eulexin (Flutamide) Capsules contain flutamide, an acetanilid, nonsteroidal, orally active antiandrogen having the chemical name, 2-methyl--[4-nitro-3-(trifluoromethyl)phenyl]propanamide.
Each capsule contains 125 mg flutamide, USP. The compound is a buff to yellow powder with a molecular weight of 276.2 and the following structural formula:
The inactive ingredients for Eulexin (Flutamide) Capsules include: corn starch, lactose, magnesium stearate, povidone, and sodium lauryl sulfate. Gelatin capsule shells may also contain benzyl alcohol, butylparaben, colloidal silicon dioxide, edetate calcium disodium, methylparaben, propylparaben, and sodium propionate, and the following dye systems: FD&C Blue No. 1, FD&C Red No. 3, FD&C Yellow No. 6, titanium dioxide, black ink, and other inactive ingredients.
Eulexin (Flutamide) Indications And Usage
Eulexin (Flutamide) Capsules are indicated for use in combination with LHRH agonists for the management of locally confined Stage B-C and Stage D metastatic carcinoma of the prostate.
Eulexin (Flutamide) Contraindications
Eulexin (Flutamide) Capsules are contraindicated in patients who are hypersensitive to flutamide or any component of this preparation.
Eulexin (Flutamide) Capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment).
Eulexin (Flutamide) Precautions
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 doses of 10, 30, and 50 mg/kg/day were administered). These produced plasma C values that are 1-, 2- to 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, adeno carcinomas, 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 Eulexin (Flutamide) Capsules (see section).
Flutamide did not demonstrate DNA modifying activity in the Ames /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.
Eulexin (Flutamide) Adverse Reactions
Treatment with Eulexin (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.
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%).
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 Eulexin (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:
Central Nervous System:
Gastrointestinal System:
Hematopoietic System:
Liver and Biliary System:
Skin:
Other:
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 Eulexin (Flutamide) Capsules.
Eulexin (Flutamide) Overdosage
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.
Eulexin (Flutamide) Dosage And Administration
The recommended dosage is 2 capsules 3 times a day at 8-hour intervals for a total daily dose of 750 mg.
Eulexin (Flutamide) How Supplied
Eulexin (Flutamide) Capsules, 125 mg, are available as opaque, two-toned brown capsules, imprinted with "Schering 525". They are supplied as follows:
NDC 0085-0525-05 - Bottles of 500NDC 0085-0525-03 - Unit Dose packages of 100 (10 × 10's)NDC 0085-0525-06 - Bottles of 180
Eulexin (Flutamide)
