Flutamide

Flutamide is a nonsteroidal antiandrogen used primarily in the treatment of androgen-dependent prostate cancer. It acts as a competitive antagonist at the androgen receptor, blocking the effects of testosterone and dihydrotestosterone at the receptor level. Unlike surgical or chemical castration, it does not itself reduce circulating testosterone but inhibits its action in target tissues such as the prostate.

Clinically, flutamide is approved for the treatment of metastatic prostate cancer, typically in combination with a gonadotropin-releasing hormone (LHRH) agonist to prevent an initial testosterone surge known as flare. It has also been used off-label for other androgen-dependent conditions, but its use in those indications has diminished because of safety concerns, particularly liver toxicity.

Adverse effects and safety considerations include hot flashes, gynecomastia and breast tenderness, diarrhea, and nausea. A major and potentially serious risk is hepatotoxicity, which can progress to hepatic failure; liver function tests should be monitored before and during therapy. Other effects may include impotence, edema, rash, and rarely severe hypersensitivity. Flutamide is teratogenic and contraindicated in pregnancy; caution is advised in women of childbearing potential.

Pharmacologically, flutamide is administered orally and is rapidly metabolized in the liver to the active metabolite 4-hydroxyflutamide, which contributes to antiandrogen activity. The parent drug has a relatively short half-life, while the active metabolite remains pharmacologically active for a longer period. Excretion occurs mainly via the urine and feces.

In the market, flutamide has been marketed under the brand name Eulexin among others. Its use has declined in some regions due to safety concerns and the availability of newer antiandrogens.