Introduction
Nilandron (nilutamide) is a nonsteroidal antiandrogen medication used in the treatment of metastatic prostate cancer. It belongs to the class of antiandrogens that competitively inhibit androgen binding at androgen receptors. Nilandron is typically administered as adjunctive therapy following surgical castration to achieve complete androgen blockade.
Mechanism of Action
Nilandron exerts its therapeutic effect through competitive inhibition of androgen binding to androgen receptors in target tissues. Unlike steroidal antiandrogens, it does not possess other hormonal activities. The drug specifically blocks the effects of testosterone and dihydrotestosterone (DHT) at the cellular level, thereby inhibiting the growth of androgen-dependent prostate cancer cells. Nilandron does not lower serum testosterone levels but prevents androgens from stimulating cancer cell proliferation.
Indications
Nilandron is FDA-approved for use in combination with surgical castration for the treatment of metastatic prostate cancer (Stage D2). It is indicated as adjunctive therapy to achieve complete androgen blockade by inhibiting the effects of adrenal androgens that persist after orchidectomy.
Dosage and Administration
Standard dosing: 300 mg orally once daily for 30 days, followed by 150 mg once daily thereafter Initiation: Begin within 24 hours after surgical castration or on the same day Administration: Tablets should be swallowed whole with water, with or without food Special populations:- Renal impairment: Use with caution in severe renal impairment
- Hepatic impairment: Contraindicated in severe hepatic impairment
- Elderly: No dosage adjustment required based on age alone
Pharmacokinetics
Absorption: Well absorbed orally with bioavailability of approximately 80-100% Distribution: Extensive tissue distribution; protein binding ~80-84% Metabolism: Hepatic metabolism via cytochrome P450 system (CYP2C19 and CYP3A4) Elimination: Primarily renal excretion (approximately 62% in urine, 10% in feces) Half-life: Approximately 38-59 hours Steady-state: Reached within 14 days of continuous dosingContraindications
- Severe hepatic impairment (baseline serum transaminases >2-3 times upper limit of normal)
- Severe respiratory insufficiency
- Hypersensitivity to nilutamide or any component of the formulation
- Concomitant use with certain medications metabolized by CYP2C19
Warnings and Precautions
Interstitial pneumonitis: Cases of interstitial pneumonitis have been reported, which may be fatal. Discontinue immediately if symptoms occur. Hepatotoxicity: Regular liver function monitoring required. Discontinue if transaminases exceed 2-3 times upper limit of normal. Visual adaptation: May cause delayed adaptation to darkness (3-25% of patients). Patients should be cautioned about driving at night or through tunnels. Alcohol intolerance: Approximately 5-20% of patients experience alcohol intolerance (flushing, hypotension, malaise). Monitoring: Regular ophthalmologic examinations and liver function tests recommended.Drug Interactions
CYP2C19 substrates: Increased exposure to drugs metabolized by CYP2C19 (e.g., phenytoin, warfarin) CYP2C19 inhibitors: May increase nilutamide concentrations Vitamin K antagonists: Enhanced anticoagulant effect requiring INR monitoring Theophylline: Potential for increased theophylline concentrations Phenytoin: May require dosage adjustment Alcohol: Increased risk of intolerance reactionsAdverse Effects
Common (>10%):- Hot flashes (20-68%)
- Visual disturbances (13-25%)
- Alcohol intolerance (5-20%)
- Nausea (10-32%)
- Constipation (5-17%)
- Dizziness (5-15%)
- Interstitial pneumonitis (2%)
- Hepatotoxicity (1-2%)
- Severe visual impairment
- Cardiovascular effects (angina, heart failure)
Monitoring Parameters
Baseline:- Complete blood count
- Liver function tests (ALT, AST, bilirubin)
- Respiratory assessment
- Visual acuity and dark adaptation testing
- Monthly liver function tests for first 4 months, then periodically
- Regular respiratory assessment
- Visual function monitoring
- PSA levels to assess treatment response
- Periodic chest X-ray if respiratory symptoms develop
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 intolerance reactions
- Use caution when driving at night or in low-light conditions
- Inform all healthcare providers about Nilandron therapy
- Report any yellowing of skin or eyes, dark urine, or unusual fatigue
- Maintain regular follow-up appointments for monitoring
- Do not stop medication without consulting your physician
References
1. FDA prescribing information for Nilandron (nilutamide) 2. Mahler C, Verhelst J, Denis L. Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. Clin Pharmacokinet. 1994;26(2):145-161. 3. Decensi AU, Boccardo F, Guarneri D, et al. Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. J Urol. 1991;146(2):377-381. 4. Janknegt RA, Abbou CC, Bartoletti R, et al. Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol. 1993;149(1):77-83. 5. McLeod DG. Tolerability of nonsteroidal antiandrogens in the treatment of advanced prostate cancer. Oncologist. 1997;2(1):18-27. 6. Schellhammer PF, Sharifi R, Block NL, et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997;50(3):330-336.