Generic Name

Nilutamide

Mechanism

• Competitive AR antagonist: Binds to the ligand‑binding domain of the androgen receptor with high affinity, preventing testosterone and dihydrotestosterone (DHT) from activating the receptor.
• Inhibition of nuclear translocation: Blocks AR‑ligand complex movement into the nucleus, thereby suppressing transcription of androgen‑responsive genes.
• Prolonged suppression of PSA levels: Due to sustained AR blockade, prostate‑specific antigen (PSA) declines rapidly and remains suppressed longer than with some other anti‑androgens.

Pharmacokinetics

Indications

• Metastatic prostate cancer (adenocarcinoma) following androgen‑deprivation therapy (ADT).
• Heterologous tumor growth with documented androgen sensitivity (rare).

*Off‑label* – used in some centers for recurrent or castration‑resistant prostate cancer in combination with other anti‑androgens.

Contraindications

• Hypersensitivity to nilutamide or other non‑steroidal anti‑androgens.
• Pregnancy and lactation – Category X; teratogenic.
• Severe hepatic impairment – reduced clearance leads to accumulation.
• Concurrent use with potent CYP3A4 inhibitors or inducers – may alter plasma levels (see drug interactions).
• Risk of Stevens‑Johnson syndrome (SJS) – especially when combined with other potent anti‑androgens; avoid in patients with a history of SJS/TEN.

Warnings:
• Liver function tests (LFT) must be monitored regularly; hepatotoxicity reported in <5 % of patients.
• Monitor serum testosterone—suppression to castrate levels (<50 ng/dL) is achieved, but very low levels may increase fracture risk.
• Bleeding diathesis – nilutamide may potentiate warfarin or NSAIDs; monitor INR and bleeding signs.

Dosing

• Standard dose: 150 mg orally once daily, taken on an empty stomach (30 min before or 2 h after meals).
• Duration: Continue as long as clinically indicated; usually for months to years.
• Re‑titration/withdrawal: Gradual taper may be considered if symptoms of withdrawal are observed (e.g., hot flashes).
• Administration in patients on ADT: Typically combined with LHRH agonists or orchiectomy; nilutamide alone insufficient for castration.

Adverse Effects

• Serious: Liver injury warrants immediate discontinuation.
• Management: Treat rash and gynecomastia symptomatically (e.g., topical steroids, NSAIDs).

Monitoring

• Baseline & periodic: Liver function tests (ALT, AST, bilirubin); CBC; serum electrolytes.
• PSA levels: Every 4–6 weeks to assess tumor response.
• Serum testosterone: Confirm castration (<50 ng/dL) at baseline and periodically.
• ECG (baseline and if QTc prolongation suspected).
• Bone density: Evaluate risk of osteoporosis in long‑term ADT; consider bisphosphonate therapy.
• Drug interactions: Monitor for interactions with CYP2C19 inhibitors (e.g., fluconazole) and CYP3A4 inhibitors (e.g., ketoconazole).

Clinical Pearls

• Empty‑stomach rule: Nilutamide’s absorption drops 55 % if taken with food. For optimal efficacy, advise patients to take it 30 min before breakfast or 2 h after dinner.
• Rapid PSA drop: Nilutamide produces a notable PSA decline within 2–3 weeks; if PSA doesn’t fall, review adherence or consider alternative therapy.
• Drug‑drug caution: Co‑administration with ketoconazole or itraconazole can increase nilutamide levels by >2‑fold; consider dose adjustment or avoid combos.
• Skin safety net: Mild maculopapular rash often resolves; however, a rapidly progressive or blistering rash should prompt immediate evaluation for SJS/TEN.
• Bone health: Continue calcium + vitamin D and monitor bone mineral density; nilutamide does not mitigate ADT‑induced bone loss.
• Re‑exposure risk: Patients who developed severe cutaneous reactions to any anti‑androgen (e.g., flutamide) should avoid nilutamide unless no alternatives exist.

--
• Key Takeaway: Nilutamide is a potent, orally‑active non‑steroidal anti‑androgen that complements androgen‑deprivation strategies in prostate cancer. Optimizing dosing (empty stomach), vigilant monitoring for hepatotoxicity and skin reactions, and careful drug‑interaction screening maximize therapeutic benefit while minimizing adverse events.