Flutamide

Class: Nonsteroidal antiandrogen (NSAA)

Mechanism of Action:

Competitively inhibits binding of testosterone and dihydrotestosterone (DHT) to androgen receptors in prostate cancer cells. Does not reduce androgen production—used in combination with ADT for maximal androgen blockade.

Indications

• Metastatic prostate cancer in combination with LHRH agonist/antagonist
• Prevention of tumor flare when starting LHRH agonist

Adult Dose

• 250 mg PO every 8 hours (TID)
• For flare prevention: Start ≥3 days before LHRH agonist and continue for 7 days after first dose of LHRH agonist.

Pharmacokinetics

• Absorption: Well absorbed orally
• Metabolism: Extensive hepatic metabolism to active metabolite (hydroxyflutamide)
• Half-life: Flutamide ~6 hours; active metabolite ~8 hours
• Excretion: Urine and feces

Toxicities / Adverse Effects

• High risk of hepatotoxicity (more frequent/severe than bicalutamide) → monitor LFTs closely
• GI upset, diarrhea (very common)
• Hot flashes, decreased libido, impotence
• Gynecomastia, breast tenderness
• Rare: methemoglobinemia, interstitial pneumonitis

Monitoring

• Baseline & periodic LFTs (monthly during first 4 months, then periodically)
• PSA and disease progression
• GI tolerance and adherence

Clinical Pearls

• TID dosing → less convenient than bicalutamide (QD)
• GI toxicity (esp. diarrhea) is often dose-limiting
• Due to toxicity profile and dosing inconvenience, largely replaced by bicalutamide in current practice
• Still referenced historically and in some guideline-based regimens for flare prevention