Generic Name

Bicalutamide

Mechanism

• Selective androgen receptor (AR) antagonist: Bicalutamide competitively binds to the ligand‑binding domain of the AR with high affinity, blocking dihydrotestosterone (DHT) and testosterone from activating the receptor.
• Inhibition of AR translocation to the nucleus → ↓ transcription of AR‑responsive genes (e.g., prostate‑specific antigen, PSA).
• Does not stimulate androgen production; rather, it decreases androgen‑mediated oncogenic signaling in prostate tissue.

Pharmacokinetics

• Absorption: Oral bioavailability ~50–70 % (peak plasma conc. at ~1–3 h). Food decreases peak level by ~40 % but total exposure remains unchanged.
• Distribution: Highly protein‑bound (~87 % to albumin). Large volume of distribution (~70 L).
• Metabolism: Primarily hepatic via CYP3A4 to inactive metabolites (bicalutamide N‑oxide).
• Elimination: Biliary excretion of unchanged drug and metabolites; half‑life ~6 weeks at steady‑state due to long peripheral tissue binding.
• Drug interactions: CYP3A4 inhibitors (e.g., ketoconazole) ↑ plasma levels; inducers (e.g., rifampin) ↓ levels.

Indications

• Locally advanced or metastatic prostate cancer as monotherapy or in combination with:
• Gonadotropin‑releasing hormone (GnRH) agonists/antagonists (hormone deprivation therapy).
• Androgen‑deprivation after initial therapy (e.g., radiotherapy).
• Non‑metastatic castration‑resistant prostate cancer in selected patients.

Contraindications

• Contraindications:
• Known hypersensitivity to bicalutamide or any excipients (e.g., lactose, starch).
• Severe hepatic impairment (Child‑Pugh C).
• Warnings:
• Hepatotoxicity: Elevated transaminases (≥3× ULN) require dose reduction or discontinuation.
• Liver metastasis: Liver function monitoring essential; therapy may be unsafe in advanced hepatic disease.
• Fluid retention: Rare cases of edema; avoid in patients with heart failure.
• Photosensitivity: Occurs in <5 % of patients; use sunscreen during sunlight exposure.

Dosing

• Initial dose: 50 mg orally once daily.
• Maintenance: Continue 50 mg daily; may increase to 100 mg/d if PSA rises and liver function remains normal.
• Administration:
• Take orally with food to reduce GI upset.
• Swallow capsule whole; do NOT crush or chew.
• Rebound: Stop abruptly after long‑term use may induce androgen surge; taper gradually if switching to alternative therapy.

Adverse Effects

• Common (≥10 %)
• Nausea, vomiting, anorexia
• Hot flashes, sweating
• Breast tenderness or gynecomastia
• Headache
• Fatigue, weight gain
• Less common (1–10 %)
• Elevated liver enzymes
• Diarrhea, abdominal pain
• Hypothyroidism (rare)
• Serious (≤1 %)
• Severe hepatotoxicity → jaundice, hepatic failure
• Severe allergic reactions (anaphylaxis)
• Severe fluid retention (pulmonary edema)
• Severe thrombocytopenia (rare)

Monitoring

• Baseline: CBC, CMP (including bilirubin), PSA, liver enzymes.
• Follow‑up:
• Liver function tests every 4–8 weeks for first 6 months, then every 3–6 months.
• PSA every 4–8 weeks to gauge response.
• Monitor for signs of edema, skin rash, or allergic reactions.
• Imaging: Repeat CT/MRI annually or as clinically indicated.

Clinical Pearls

• Steady‑state lag: PSA falls gradually; clinicians should anticipate a 3‑month lag before meaningful PSA reduction, preventing premature discontinuation.
• Combination therapy: Adding bicalutamide to an LHRH agonist often improves progression‑free survival versus LHRH alone, particularly in patients with high‑volume disease.
• Hepatotoxicity vigilance: Patients on chronic corticosteroids or other hepatotoxic drugs (e.g., tamoxifen) should be monitored more frequently.
• Pregnancy caution: Though no data in humans, teratogenic in animal models; ensure effective contraception in all reproductive‑age patients.
• Drug‑drug interactions: For patients on multiple CYP3A4 inhibitors, consider therapeutic drug monitoring or dose adjustment; conversely, if on strong inducers, consider increasing dose under watchful monitoring.

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• References: UpToDate, FDA prescribing information, NCCN guidelines (2024).