indication

For the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate

pharmacology

Flutamide is a nonsteroidal antiandrogen. 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.

mechanism of action

Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.

toxicity

In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.

biotransformation

Flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration.

absorption

Rapidly and completely absorbed.

half life

The plasma half-life for the alpha-hydroxylated metabolite of flutamide (an active metabolite) is approximately 6 hours.

route of elimination

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.

drug interactions

Telithromycin: Telithromycin may reduce clearance of Flutamide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Flutamide if Telithromycin is initiated, discontinued or dose changed.

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Flutamide by decreasing Flutamide metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Flutamide if Thiabendazole is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of flutamide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of flutamide if voriconazole is initiated, discontinued or dose changed.