Flutamide

INDICATIONS AND USAGE Eulexin ® capsules are indicated for use in combination with LHRH-agonists for the management of locally confined Stage B 2 -C and Stage D 2 metastatic carcinoma of the prostate. Stage B 2 -C Prostatic Carcinoma Treatment with Eulexin ® capsules and the goserelin acetate implant should start eight weeks prior to initiating radiation therapy and continue during radiation therapy. Stage D 2 Metastatic Carcinoma To achieve benefit from treatment, Eulexin ® capsules should be initiated with the LHRH-agonist and continued until progression.

ADVERSE REACTIONS Stage B 2 -C Prostatic Carcinoma Treatment with Eulexin ® 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 Eulexin ® + goserelin acetate implant + radiation versus radiation alone.

Pregnancy Pregnancy Category D There was decreased 24 hour survival in the offspring of pregnant rats treated with Eulexin ® 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).

WARNINGS Hepatic Injury There have been postmarketing reports of hospitalization and rarely death due to liver failure in patients taking Eulexin ® . 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 half of the reported cases occurred within the initial 3 months of treatment with Eulexin ® . WARNINGS Hepatic Injury SEE BOXED WARNINGS Use in Women Eulexin ® capsules are for use only in men. This product has no indication for women and should not be used in this population, particularly for nonserious or nonlife-threatening conditions. Fetal toxicity Eulexin ® may cause fetal harm when administered to a pregnant woman (see Pregnancy ). Aniline toxicity One metabolite of Eulexin ® is 4-nitro-3-fluoro-methylaniline. Several toxicities consistent with aniline exposure, including methemoglobinemia, hemolytic anemia and cholestatic jaundice have been observed in both animals and humans after Eulexin ® administration. In patients susceptible to aniline toxicity (e.g. CONTRAINDICATIONS Eulexin ® capsules are contraindicated in patients who are hypersensitive to Eulexin ® or any component of this preparation. Eulexin ® capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment).