EULEXIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EULEXIN (EULEXIN).
Nonsteroidal antiandrogen that competitively inhibits the binding of dihydrotestosterone to androgen receptors in target tissues, thereby blocking androgen action.
| Metabolism | Extensively metabolized in the liver via hydroxylation and reduction, primarily by CYP1A2 and CYP3A4, to active and inactive metabolites including 2-hydroxyflutamide. |
| Excretion | Renal: 28% (as unchanged drug and metabolites, mainly 2-hydroxyflutamide), Biliary/Fecal: 4.2% (as metabolites) |
| Half-life | 5-6 hours for flutamide; 8-10 hours for active metabolite 2-hydroxyflutamide; requires three times daily dosing |
| Protein binding | 94-96% (primarily to albumin, minor to alpha-1-acid glycoprotein) |
| Volume of Distribution | Flutamide: approximately 10 L/kg; 2-hydroxyflutamide: approximately 25 L/kg; extensive tissue distribution, especially in prostate |
| Bioavailability | Oral: nearly 100% for flutamide; active metabolite achieves higher AUC than parent drug |
| Onset of Action | Oral: 2-4 hours for detectable serum levels; clinical effect (e.g., androgen blockade) within 2 weeks |
| Duration of Action | Serum levels maintained for 8-10 hours; clinical effect persists with continuous dosing; no data for single dose |
250 mg orally three times daily (every 8 hours).
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based dose adjustments are recommended; use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class C cirrhosis. For Child-Pugh Class A or B, use with caution and monitor hepatic function; no specific dose reduction guidelines established. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients. |
| Geriatric use | No specific dose adjustment based on age alone; monitor for increased risk of cardiovascular events and hepatic toxicity in elderly patients with comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EULEXIN (EULEXIN).
| Breastfeeding | Not recommended. Flutamide is excreted in breast milk in rats; unknown in humans. M/P ratio not determined. Potential for adverse effects in nursing infant due to antiandrogenic activity. |
| Teratogenic Risk | EULEXIN (flutamide) is contraindicated in pregnancy. First trimester: Risk of fetal harm based on animal studies showing feminization of male fetuses. Second/Third trimester: Potential for antiandrogenic effects on fetal development, including hypospadias. No adequate human studies. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to flutamide or any component of the formulation.","Severe hepatic impairment (baseline ALT >2 times upper limit of normal)."]
| Precautions | ["Hepatotoxicity (including hepatic failure, cholestatic hepatitis, jaundice, and hepatic encephalopathy); monitor liver function tests frequently.","Gynecomastia and breast tenderness.","Decreased libido and impotence.","Anemia and leukopenia.","Potential for increased bleeding time.","Interference with prothrombin time in patients on anticoagulants."] |
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| Pregnancy test prior to initiation. Monitor hepatic function (LFTs) due to risk of hepatotoxicity. Monitor for signs of fetal distress if inadvertent exposure. No specific fetal monitoring guidelines due to contraindication. |
| Fertility Effects | Flutamide may impair spermatogenesis and cause reversible infertility in males. In females, menstrual irregularities and reduced fertility due to the hormonal effects of castration levels of testosterone. Return to baseline after discontinuation is variable. |