FLUTAMIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Nonsteroidal antiandrogen; competitively inhibits androgen binding to androgen receptors, thereby blocking androgen action in target tissues.

What the body does with it

Metabolism	Hepatic; primarily via CYP1A2 to active metabolite 2-hydroxyflutamide.
Excretion	Primarily renal (approximately 98% of absorbed dose as metabolites, with ~4.5% as the active metabolite 2-hydroxyflutamide); less than 1% excreted unchanged; biliary/fecal elimination is minimal (<1%).
Half-life	Flutamide has an initial half-life of about 5–6 hours; its active metabolite, 2-hydroxyflutamide, has a terminal elimination half-life of 8–10 hours, supporting twice-daily dosing for steady-state concentrations.
Protein binding	Flutamide is >94% bound to plasma proteins (primarily albumin); 2-hydroxyflutamide is approximately 94–96% protein bound.
Volume of Distribution	Apparent volume of distribution for flutamide is approximately 1.5–2.0 L/kg; for 2-hydroxyflutamide, Vd is about 0.5–0.7 L/kg, indicating extensive tissue distribution.
Bioavailability	Flutamide is well absorbed after oral administration, with absolute bioavailability approximately 80–90%, though it undergoes extensive first-pass metabolism to the active metabolite.
Onset of Action	After oral administration, clinical effects (e.g., suppression of androgen-dependent symptoms) are typically observed within 2–3 weeks; more rapid decrease in serum PSA may be seen within 2–4 weeks.
Duration of Action	Duration of action is approximately 24 hours based on twice-daily dosing; steady-state concentrations of active metabolite are achieved within 2–4 days.

Classification & Brands

Action Class	Androgen receptor antagonist
Brand Substitutes	Flutatec 250mg Tablet, Ticum 250mg Tablet, Prostamid 250mg Tablet, Flutacare 250mg Tablet, Flutide 250mg Tablet

Dosing & administration

250 mg orally every 8 hours. Total daily dose: 750 mg.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for renal impairment. Flutamide is not significantly renally excreted.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; consider dose reduction or discontinuation if liver function deteriorates. Monitor transaminases frequently.
Pediatric use	Not recommended for use in pediatric patients. Safety and efficacy have not been established.
Geriatric use	No specific dose adjustment required. Monitor liver function and potential drug interactions more frequently due to age-related changes in hepatic function and polypharmacy.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Warfarin metabolism is inhibited increasing INR Can cause hepatotoxicity and gynecomastia.

Breastfeeding	Excretion into human milk is unknown; however, due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended. M/P ratio not available.
Teratogenic Risk	Pregnancy Category D. There is positive evidence of human fetal risk. Androgen receptor blockade may interfere with sexual differentiation in male fetuses during the first trimester. Hypospadias and other urogenital abnormalities have been reported. Use is contraindicated in pregnant women.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hepatic impairment.","Hypersensitivity to flutamide or any component."]

Clinical Precautions

Precautions

["Hepatotoxicity including hepatic failure, jaundice, hepatic encephalopathy; monitor liver function tests.","Gynecomastia and breast tenderness.","Methemoglobinemia in CYP1A2 poor metabolizers."]

Clinical Tips & Counseling

Drug interactions

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