Generic Name

Firmagon

Mechanism

• Androgen‑receptor blockade:
• Flutamide competes with testosterone and dihydrotestosterone (DHT) for binding to the intracellular androgen receptor (AR).
• The flutamide‑AR complex fails to translocate to the nucleus, thus preventing the activation of androgen‑responsive genes.
• This results in suppression of mitogenic signals in hormone‑sensitive tissues such as prostate epithelium.
• Indirect effects:
• By blocking AR, flutamide disrupts the autocrine‑paracrine loops that sustain tumor growth and can enhance the efficacy of luteinizing hormone‑releasing hormone (LHRH) analogs.

Pharmacokinetics

Indications

• Advanced or metastatic prostate cancer (monotherapy or combined with LHRH analogs).
• Androgenic disorders in women (e.g., severe hirsutism, acne) when systemic therapy is needed.
• Adjunct to androgen deprivation therapy to overcome castration‑resistant prostate cancer (cancer cells often retain functional AR).
• Rarely used for testicular adrenal rest tumors or penile hyperemia.

Contraindications

• Severe hepatic impairment or cirrhosis – contraindicated.
• Marked hepatotoxicity – stop therapy if ALT/AST >5× ULN.
• Pregnancy – teratogenic; contraindicated.
• Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin).
• Patients with known hypersensitivity to flutamide or any excipients.

Dosing

• Standard regimen: 150 mg orally *once daily* (recommended 150 mg BID or TID in some formulations).
• Hirsutism (women): 150 mg PO twice daily.
• Combination therapy: Often paired with LHRH agonists (goserelin, leuprolide) at standard doses.
• Administration note: Take on an empty stomach or at least one hour after meals to minimize GI upset; but food reduces flutamide‑related nausea for some patients.

Special instructions:
• Start with a low dose in patients with mild hepatic impairment and titrate up cautiously.
• Monitor adherence, as poor compliance can lead to subclinical flare.

Adverse Effects

Common (≥10 %)
• Gastrointestinal: nausea, vomiting, abdominal pain, dyspepsia, constipation.
• General: fatigue, headache, dizziness, hot flashes.
• Endocrine: breast tenderness, gynecomastia in men, oligomenorrhea in pre‑menopausal women.

Serious (≤5 %)
• Hepatotoxicity: Elevated transaminases, jaundice, fulminant hepatic failure.
• Allergic reactions: Rash, pruritus, anaphylaxis rarely.
• Myelosuppression: Rare neutropenia or thrombocytopenia.

Monitoring

Clinical Pearls

1. Hepatic vigilance is paramount – Flutamide’s hepatotoxic profile can precipitate fatal liver failure; pre‑screen hepatic panels and monitor closely.

2. Gynecomastia is a dose‑related side effect – Educate patients about breast tenderness and provide NSAIDs or anti‑hormonal support as needed.

3. Synergy with LHRH agonists – In practice, combining flutamide with an LHRH analog increases overall survival in metastatic prostate cancer; use them concurrently rather than sequentially.

4. Metabolite buildup in renal failure – Though primarily hepatic metabolism, renal clearance of metabolites increases risk; caution in patients with CKD stage 3+.

5. Pregnancy test before prescribing to females of childbearing potential – Even if not indicated for women, inadvertent exposure can cause teratogenic effects; a negative pregnancy test is required.

6. Patient support for GI side effects – Taking flutamide with a light meal reduces nausea; consider antiemetics on a provisional basis for patients intolerant.

7. Drug interactions with CYP3A4 inhibitors – Travails should avoid concomitant strong inhibitors or monitor serum levels and hepatic enzymes closely.

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• This Firmagon drug card provides a concise, evidence‑based reference for students and practitioners, integrating mechanism, use, safety, and practical pearls for optimal patient care.