FLUTAMIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Nonsteroidal antiandrogen; competitively inhibits androgen binding to androgen receptors, thereby blocking androgen action in target tissues.
| 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. |
| Molecular Weight | 276.29 |
| Action Class | Androgen receptor antagonist |
| Brand Substitutes | Flutatec 250mg Tablet, Ticum 250mg Tablet, Prostamid 250mg Tablet, Flutacare 250mg Tablet, Flutide 250mg Tablet |
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. |
| 1st trimester | Contraindicated: risk of pseudovaginal perineoscrotal hypospadias in male fetuses due to antiandrogen effects. |
| 2nd trimester | Contraindicated: continued risk of fetal harm; no safe dose established. |
| 3rd trimester | Contraindicated: risk of fetal harm persists. |
Clinical note
Warfarin metabolism is inhibited increasing INR Can cause hepatotoxicity and gynecomastia.
| Placental transfer | Crosses placenta; has teratogenic effects in animal studies. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse effects in nursing infants. Discontinue breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to flutamide or any componentPregnancySevere hepatic impairment
| Precautions | Hepatotoxicity including hepatic failure, jaundice, hepatic encephalopathy; monitor liver function tests., Gynecomastia and breast tenderness., Methemoglobinemia in CYP1A2 poor metabolizers. |
| Food/Dietary | No specific food interactions are reported. However, avoid alcohol due to potential additive hepatotoxicity. |
| Clinical Pearls | Flutamide is a nonsteroidal antiandrogen used in combination with a GnRH analog for metastatic prostate carcinoma. Monitor liver function tests (LFTs) monthly due to risk of hepatotoxicity, including fatal hepatic failure. Discontinue if ALT rises above 2x upper limit of normal or if jaundice appears. May cause an isolated elevation of serum aminotransferases; if this occurs, discontinue. Also monitor for diarrhea, which can be severe, and consider dose reduction or discontinuation. Flutamide can cause gynecomastia and hot flashes as part of its antiandrogen effect. |
Loading safety data…
| L5 (Contraindicated) |
| 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 | Monitor liver function tests (ALT, AST, bilirubin) regularly due to risk of hepatotoxicity. Monitor for signs of hepatic injury. In pregnancy, fetal ultrasound may be considered to assess for anomalies. |
| Fertility Effects | May impair spermatogenesis and reduce sperm count in males. In females, antiandrogen effects may disrupt ovulation. |
| Patient Advice | Take flutamide exactly as prescribed, typically three times daily. · Report any signs of liver problems: yellowing of skin or eyes, dark urine, severe nausea, or abdominal pain. · This drug may cause diarrhea; if severe, contact your healthcare provider. · Flutamide can cause breast tenderness or enlargement; discuss with your doctor if bothersome. · Avoid alcohol, as it may increase the risk of liver damage. · Use effective contraception if you are a female partner of a male patient taking flutamide, as it can harm a developing fetus. · Do not donate blood during treatment and for 1 month after stopping. · Inform all healthcare providers that you are taking flutamide. |