|Systematic (IUPAC) name|
|Biological half-life||~56 hours|
|CAS Registry Number|
|Molecular mass||317.221 g/mol|
Nilutamide (synthetic, non-steroidal, pure antiandrogen used in the treatment of advanced-stage (metastatic) prostate cancer. It was developed by Roussel, introduced in 1987, and was the second non-steroidal antiandrogen to be marketed after flutamide. Nilutamide acts as a potent and selective competitive silent antagonist of the androgen receptor (AR), which prevents testosterone and other androgens from activating the AR. Because most prostate cancer cells rely on activation of the AR for growth and survival, nilutamide can extend life in men with prostate cancer.
Nilutamide is used in prostate cancer in combination with a GnRH analogue at a dosage of 300 mg daily for the first 4 weeks of treatment, and 150 mg once daily thereafter. It is not indicated as a monotherapy in prostate cancer. Nilutamide has a half-life of approximately two days, which allows for once-daily administration. In addition to prostate cancer, nilutamide has also been studied in and used as a component of hormone replacement therapy in trans women.
General side effects of non-steroidal antiandrogens, including nilutamide, include gynecomastia, breast pain/tenderness, hot flashes, depression, fatigue, and sexual dysfunction. In addition, relative to other non-steroidal antiandrogens, nilutamide has been uniquely associated with mild and reversible visual disturbances (31%), a disulfiram-like alcohol intolerance (19%), and interstitial pneumonitis (1–2%) (which can progress to pulmonary fibrosis), and has a higher incidence of nausea (27%) and vomiting than other non-steroidal antiandrogens. There is also a risk of hepatoxicity with nilutamide, though occurrence is very rare and the risk is significantly less than with flutamide. The unique adverse effects of nilutamide, and especially its risk of interstitial pneumonitis, have limited its clinical use relative to other non-steroidal antiandrogens. From a safety standpoint, bicalutamide is clinically preferred over both nilutamide (due to interstitial pneumonitis) and flutamide (due to hepatotoxicity) in regards to choice of non-steroidal antiandrogen.
Like other non-steroidal antiandrogens such as flutamide and bicalutamide, nilutamide, without concomitant GnRH analogue therapy, increases serum androgen (by two-fold in the case of testosterone), estrogen, and prolactin levels due to inhibition of AR-mediated suppression of steroidogenesis via negative feedback on the hypothalamic-pituitary-gonadal axis. As such, though nilutamide is still highly effective as an antiandrogen as a monotherapy, it is given in combination with a GnRH analogue such as leuprorelin in prostate cancer to suppress androgen concentrations to castrate levels in order to attain maximal androgen blockade (MAB).
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