Generic Name

Flutamide

Mechanism

Flutamide is a *non‑steroidal anti‑androgen* that competitively binds to the androgen receptor (AR) in target tissues.
• Inhibits the binding of testosterone and dihydrotestosterone.
• Blocks downstream AR‑mediated transcription, thereby diminishing androgen‑driven cellular proliferation.
• Effective in tissues such as prostate, skin, and the breast.

Pharmacokinetics

• Absorption: Oral bioavailability ~ 70 %, peak plasma levels at ~1 h.
• Distribution: 95 % protein‑bound; crosses the placenta.
• Metabolism: Primary hepatic metabolism via CYP2C9 and CYP3A4 → glucuronide conjugates.
• Elimination: Renal excretion (≈ 45 %) and biliary (> 50 %).
• Half‑life: 2–3 h (parent drug), 30–40 h for metabolites.

Indications

• Metastatic or locally advanced prostate cancer (in combination with androgen deprivation).
• Hormone‑sensitive hirsutism or acne in women with elevated androgen levels.

Contraindications

• Severe hepatic impairment or elevated ALT/AST ≥ 3× ULN.
• Pregnancy and breastfeeding – contraindicated due to placental transfer.
• Known hypersensitivity to flutamide or related compounds.
• Concomitant use with strong CYP2C9 inhibitors (e.g., fluconazole) may elevate toxicity.

Dosing

• Prostate cancer: 250 mg orally twice daily, orally with or without food.
• Hirsutism: 500–750 mg daily (or 250 mg BID).
• Dose adjustment: Reduce to 125 mg BID if baseline liver enzymes are mildly elevated.
• Titration: No dose escalation guidelines; maintain stable dosing once therapeutic effect is reached.

Adverse Effects

• Common: nausea, vomiting, appetite loss, headache, fatigue, gynecomastia.
• Serious:
• Hepatotoxicity → elevated transaminases, jaundice.
• Severe fatigue or anemia (rare).
• Endocrine disturbances (e.g., breast tenderness).

Monitoring

• Baseline & periodic: ALT/AST, bilirubin, CBC.
• Liver monitoring: Every 4–8 weeks during the first 6 months.
• Dose‑dependent symptoms: Watch for peripheral edema or fluid retention.

Clinical Pearls

• Start low–hold high: Begin at 250 mg BID; monitor liver enzymes before any dose increase.
• Hepatotoxicity is dose‑related: Patients on >500 mg daily have a >2× risk; consider switching to a steroidal anti‑androgen if liver function deteriorates.
• Breast changes in men: Gynecomastia appears in ~ 15 % of patients; counseling is essential.
• Drug interactions: Avoid overlap with potent CYP2C9 inhibitors; consider alternative anti‑androgens (e.g., bicalutamide).
• Pregnancy safety: Flutamide crosses the placenta; abrupt discontinuation is advised if emergently needed, as it may precipitate abrupt withdrawal of anti‑androgen effects.