A Comprehensive Monograph on Nilutamide (DB00665): From Clinical Utility to Therapeutic Obsolescence

Executive Summary and Drug Identification

Nilutamide is a pure, nonsteroidal antiandrogen (NSAA) that functions as a competitive antagonist of the androgen receptor (AR). As a first-generation agent in its class, it was developed to provide a more targeted approach to hormone therapy for androgen-sensitive malignancies. Its primary approved indication is for the treatment of metastatic prostate cancer, where it is used in combination with surgical castration to achieve a state of maximal androgen blockade (MAB). The therapeutic rationale is to block the effects of residual androgens, primarily of adrenal origin, that are not eliminated by orchiectomy. Despite this clear mechanism of action, the clinical utility of Nilutamide is severely limited by a distinct and unfavorable safety profile. This profile is characterized by risks of potentially fatal interstitial pneumonitis and significant hepatotoxicity, which necessitate rigorous patient monitoring. Furthermore, Nilutamide is associated with a unique constellation of side effects, including impaired dark adaptation and a disulfiram-like alcohol intolerance, which can significantly impact patient quality of life. These substantial risks, coupled with the development of better-tolerated and more potent agents like bicalutamide and subsequent second-generation antiandrogens, have rendered Nilutamide largely obsolete in modern clinical practice.[1] It now serves primarily as a subject of historical and pharmacological interest, illustrating the evolution of androgen receptor-targeted therapies.