Introduction
Nilutamide is a nonsteroidal antiandrogen medication used primarily in the treatment of prostate cancer. It belongs to the class of pure antiandrogens that competitively inhibit androgen binding to androgen receptors. First approved in the 1980s, nilutamide is typically used in combination with surgical castration or gonadotropin-releasing hormone (GnRH) analogs for the treatment of metastatic prostate cancer.
Mechanism of Action
Nilutamide acts as a competitive antagonist at androgen receptors in target tissues. Unlike steroidal antiandrogens, it does not possess progestational, estrogenic, or glucocorticoid activity. The drug blocks the action of androgens (including testosterone and dihydrotestosterone) by preventing their binding to nuclear androgen receptors in prostate cancer cells, thereby inhibiting androgen-stimulated cancer growth.
Indications
- Adjuvant treatment of metastatic prostate cancer in combination with surgical castration
- Treatment of advanced prostate cancer in combination with luteinizing hormone-releasing hormone (LHRH) analogs
Dosage and Administration
Standard dosing: 300 mg orally once daily for the first 30 days, followed by 150 mg once daily thereafter Administration:- Initiate therapy on the day of or day after surgical castration
- When used with LHRH analogs, start nilutamide on the same day as LHRH initiation
- Can be taken with or without food
- Dosage adjustment required in hepatic impairment
- Renal impairment: No specific dosage adjustment recommended
- Hepatic impairment: Use with caution; consider dosage reduction
- Elderly: No specific dosage adjustment required
Pharmacokinetics
Absorption: Rapidly and completely absorbed after oral administration (bioavailability >80%) Distribution: Extensive tissue distribution; protein binding: 80-84% Metabolism: Extensively metabolized in the liver via multiple pathways including hydroxylation, dealkylation, and glucuronidation Elimination: Primarily renal excretion (78%) with minor fecal elimination (22%); elimination half-life: approximately 41-49 hours Steady-state: Reached within 10-14 days of continuous dosingContraindications
- Hypersensitivity to nilutamide or any component of the formulation
- Severe hepatic impairment (Child-Pugh Class C)
- Severe respiratory insufficiency
- Concomitant use with drugs that may prolong QT interval in patients with congenital long QT syndrome
Warnings and Precautions
Black Box Warning: Interstitial pneumonitis occurring within the first 3 months of treatment (monitor respiratory symptoms) Additional precautions:- Hepatotoxicity: Monitor liver function tests regularly
- Visual disturbances: May cause delayed adaptation to darkness; caution when driving at night
- Alcohol intolerance: Reports of facial flushing, malaise, and hypotension
- QT prolongation: Monitor in patients with cardiac risk factors
- Hematologic effects: Rare cases of hemolytic anemia reported
Drug Interactions
Significant interactions:- Warfarin: Increased anticoagulant effect (monitor INR closely)
- Drugs metabolized by CYP2C19: Nilutamide may inhibit metabolism
- Vitamin K antagonists: Enhanced anticoagulant effect
- Alcohol: May cause disulfiram-like reaction
- Drugs that prolong QT interval: Additive risk of QT prolongation
Adverse Effects
Common (≥10%):- Hot flashes (28-68%)
- Visual disturbances (impaired dark adaptation) (13-57%)
- Nausea (10-32%)
- Constipation (5-15%)
- Dizziness (5-13%)
- Interstitial pneumonitis (2%)
- Hepatotoxicity (1%)
- Hemolytic anemia
- QT prolongation
- Severe alcohol intolerance reactions
Monitoring Parameters
Baseline:- Complete blood count
- Liver function tests (ALT, AST, bilirubin)
- Electrolytes, particularly potassium and magnesium
- ECG (if cardiac risk factors present)
- Pulmonary function tests (if respiratory symptoms develop)
- Visual assessment
- Monthly LFTs for first 4 months, then periodically
- Respiratory status assessment (especially first 3 months)
- Regular symptom assessment for visual changes
- INR monitoring if on concomitant anticoagulants
- Periodic ECG monitoring in at-risk patients
Patient Education
- Take medication exactly as prescribed at the same time each day
- Report any new or worsening respiratory symptoms immediately
- Avoid alcohol consumption due to potential severe reactions
- Use caution when driving at night due to possible delayed dark adaptation
- Report visual changes, yellowing of skin/eyes, or unusual bleeding/bruising
- Inform all healthcare providers about nilutamide use
- Maintain regular follow-up appointments for monitoring
- Do not stop medication without consulting your oncologist
References
1. FDA prescribing information: Nilutamide tablets 2. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer Version 4.2023 3. European Association of Urology Guidelines on Prostate Cancer, 2023 4. Micromedex DrugDex Evaluation: Nilutamide 5. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023 6. Sartor O, et al. Androgen receptor inhibitors in prostate cancer. N Engl J Med. 2023;388(6):541-553 7. Teoh JYC, et al. Management of advanced prostate cancer: A comprehensive review. Lancet Oncol. 2022;23(12):e543-e558
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.