NILUTAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NILUTAMIDE (NILUTAMIDE).
Nonsteroidal antiandrogen that competitively inhibits androgen binding to androgen receptors, blocking androgen action in target tissues.
| Metabolism | Hepatic via multiple pathways including cytochrome P450; active metabolites: nilutamide and metabolites. |
| Excretion | Nilutamide is extensively metabolized; less than 2% of the dose is excreted unchanged in urine. The majority of metabolites (approximately 70%) are excreted renally, with the remainder (about 30%) eliminated in feces via biliary excretion. |
| Half-life | The terminal elimination half-life is approximately 38–56 hours (mean ~49 hours), allowing once-daily dosing. Steady-state is achieved after about 7–10 days. |
| Protein binding | ≥98% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.7–1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | 82–96% following oral administration (well absorbed); food may slightly increase absorption. |
| Onset of Action | Oral administration: Clinical effects (androgen receptor blockade) begin within a few days, but full therapeutic response may take 2–4 weeks due to gradual suppression of androgen-dependent growth. |
| Duration of Action | With once-daily dosing, androgen receptor blockade is maintained throughout the 24-hour dosing interval. The drug's long half-life provides sustained action; after discontinuation, effects persist for several days. |
| Molecular Weight | 317.3 |
300 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR ≥30 mL/min; not recommended for GFR <30 mL/min due to lack of data |
| Liver impairment | Contraindicated in Child-Pugh Class C; caution in Child-Pugh Class B (reduce dose to 150 mg once daily) |
| Pediatric use | Safety and efficacy not established; no standard pediatric dosing |
| Geriatric use | No specific dose adjustment; monitor for increased risk of interstitial pneumonitis and hepatic toxicity |
| 1st trimester | Nilutamide is contraindicated in pregnancy. It may cause fetal harm based on its mechanism of action as an antiandrogen. Animal studies have shown teratogenic effects. |
| 2nd trimester | Contraindicated due to potential feminization of male fetuses and other adverse developmental effects. |
| 3rd trimester | Contraindicated; may cause oligohydramnios and other fetal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for NILUTAMIDE (NILUTAMIDE).
| Placental transfer | Nilutamide crosses the placenta in animal studies. Human data are not available, but placental transfer is expected due to its molecular weight and lipophilicity. |
| Breastfeeding | Excretion into breast milk is unknown. Due to potential for serious adverse effects in the nursing infant, breastfeeding is not recommended during nilutamide therapy and for at least 3 months after the last dose. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to nilutamide or any component of the formulationPregnancySevere hepatic impairment (Child-Pugh Class C)Previous history of disulfiram-like reaction with nilutamide
| Precautions | Interstitial pneumonitis (risk increased in Asian patients), hepatotoxicity, alcohol intolerance (disulfiram-like reaction), visual disturbances (impaired adaptation to dark), cardiovascular effects (hypertension), anemia. |
| Food/Dietary | No significant food interactions, but alcohol must be strictly avoided due to disulfiram-like reaction. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | NILUTAMIDE is contraindicated in pregnancy. Based on its antiandrogenic mechanism, there is a high risk of feminization of male fetuses, including ambiguous genitalia and hypospadias, particularly during the first trimester when sexual differentiation occurs. Animal studies have shown teratogenic effects at doses lower than human therapeutic doses. Use in women of childbearing potential requires effective contraception before, during, and for at least 5 months after treatment. |
| Fetal Monitoring | Pregnancy testing should be performed before initiating nilutamide in women of childbearing potential. If used inadvertently during pregnancy, monitor fetal development with ultrasound to detect signs of feminization in male fetuses. Monitor maternal liver function tests, pulmonary status (interstitial pneumonitis), and ocular symptoms (visual disturbances) as nilutamide can cause hepatotoxicity, interstitial pneumonitis, and optic neuritis. |
| Fertility Effects | Nilutamide is an antiandrogen that may impair spermatogenesis and reduce fertility in males. In females, it may disrupt ovulation due to hormonal antagonism. Use may lead to reversible infertility in both sexes during treatment. |
| Nilutamide is a nonsteroidal antiandrogen used in combination with surgical castration for metastatic prostate cancer. Monitor for interstitial pneumonitis (often within first 3 months; discontinue if dyspnea or cough develops). Advise patients about alcohol intolerance (disulfiram-like reaction: facial flushing, nausea, hypotension). Baseline and periodic liver function tests required due to risk of hepatotoxicity. Dose adjustment needed in moderate hepatic impairment (Child-Pugh B); contraindicated in severe impairment (Child-Pugh C). |
| Patient Advice | Avoid alcohol completely while taking nilutamide; it can cause severe facial flushing, nausea, and low blood pressure. · Report any new or worsening shortness of breath, cough, or chest pain immediately, as this may indicate a serious lung problem (interstitial pneumonitis). · Tell your doctor if you notice yellowing of skin or eyes, dark urine, or severe stomach pain (signs of liver injury). · Nilutamide may cause visual disturbances, especially difficulty adapting to darkness; use caution when driving at night or moving from bright to dark areas. · Take nilutamide exactly as prescribed, usually three times daily, with or without food. |