Introduction
Eulexin (flutamide) is a nonsteroidal oral antiandrogen medication primarily used in the treatment of prostate cancer. It belongs to the first-generation antiandrogen class and works by competitively inhibiting androgen uptake and nuclear binding in target tissues. Originally approved by the FDA in 1989, Eulexin is typically used in combination with a luteinizing hormone-releasing hormone (LHRH) agonist for maximal androgen blockade in advanced prostate cancer.
Mechanism of Action
Eulexin exerts its therapeutic effects through competitive inhibition of androgen binding to androgen receptors in target tissues. The drug and its active metabolite (2-hydroxyflutamide) bind to androgen receptors in the prostate gland and other androgen-sensitive tissues, preventing the binding of dihydrotestosterone (DHT) and testosterone. This receptor blockade inhibits androgen-stimulated cell proliferation and leads to apoptosis of prostate cancer cells. Unlike some other antiandrogens, flutamide does not suppress gonadotropin secretion and may actually increase testosterone levels when used as monotherapy.
Indications
- Treatment of metastatic prostate cancer (stage D2) in combination with an LHRH agonist
- Advanced prostate cancer as part of maximal androgen blockade therapy
- Off-label uses include: treatment of hirsutism in women, precocious puberty, and as component of feminizing hormone therapy (Note: These uses are not FDA-approved)
Dosage and Administration
Standard dosing: 250 mg orally three times daily (every 8 hours) Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution; consider dosage reduction or alternative therapy
- Elderly patients: No specific dosage adjustment required
- Pediatric patients: Not indicated for use in children
- Should be administered with or without food
- Consistent timing of doses is important for maintaining therapeutic effect
- When used with LHRH agonists, both medications should be initiated simultaneously
Pharmacokinetics
Absorption: Rapidly and completely absorbed following oral administration; bioavailability is approximately 94% Distribution: Widely distributed throughout body tissues; protein binding >94% Metabolism: Extensive first-pass metabolism in liver via hydroxylation to active metabolite (2-hydroxyflutamide) Elimination: Half-life of parent compound is 5-6 hours; half-life of active metabolite is 8-10 hours Excretion: Primarily renal (≈90%) with minor fecal excretionContraindications
- Hypersensitivity to flutamide or any component of the formulation
- Severe hepatic impairment
- Pregnancy (Category D) - may cause fetal harm
- Women who are or may become pregnant
Warnings and Precautions
Black Box Warning: Eulexin has been associated with fatal hepatotoxicity including hepatic necrosis. Liver function tests should be monitored regularly. Additional precautions:- Monitor for signs of liver injury (jaundice, dark urine, fatigue, abdominal pain)
- Risk of gynecomastia and breast tenderness
- Potential for diarrhea and gastrointestinal disturbances
- May cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Caution in patients with pre-existing cardiac disease
- Monitor for adrenal insufficiency when discontinuing therapy
Drug Interactions
Significant interactions:- Warfarin: Increased anticoagulant effect; monitor INR closely
- Other hepatotoxic drugs: Increased risk of liver damage
- Drugs metabolized by CYP1A2: Flutamide may inhibit CYP1A2 metabolism
- LHRH agonists: Additive therapeutic effect (intended combination)
- Important: The active metabolite of flutamide may interfere with 17-hydroxycorticosteroid measurements in urine
Adverse Effects
Common adverse reactions (≥10%):- Hot flashes (61%)
- Loss of libido (36%)
- Impotence (33%)
- Diarrhea (12%)
- Nausea (9%)
- Gynecomastia (9%)
- Hepatotoxicity (including fatal hepatic necrosis)
- Hemolytic anemia
- Pulmonary fibrosis/interstitial pneumonitis
- Cardiovascular effects (edema, hypertension)
- Visual disturbances
- Thrombocytopenia
Monitoring Parameters
Baseline assessment:- Complete blood count
- Comprehensive metabolic panel (including liver function tests)
- Prostate-specific antigen (PSA)
- Testosterone levels
- Liver function tests: Monthly for first 4 months, then periodically
- PSA levels: Every 3-6 months
- CBC: Periodically
- Clinical signs of disease progression
- Symptoms of hepatotoxicity
- Cardiovascular status
- Breast examination for gynecomastia
Patient Education
Key points for patients taking Eulexin:- Take exactly as prescribed, typically three times daily at evenly spaced intervals
- Do not stop taking medication without consulting your healthcare provider
- Report any signs of liver problems immediately: yellowing of skin/eyes, dark urine, severe fatigue, abdominal pain
- Be aware of potential side effects including hot flashes, breast tenderness, and sexual dysfunction
- Use effective contraception as the drug can harm an unborn baby
- Inform all healthcare providers about all medications you're taking, including over-the-counter drugs
- Regular follow-up appointments and blood tests are essential for safe treatment
- Maintain adequate hydration, especially if experiencing diarrhea
References
1. FDA Prescribing Information: Eulexin (flutamide) 2. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer (2023) 3. Scher HI, et al. "Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group." J Clin Oncol. 2008;26(7):1148-1159. 4. McLeod DG. "Hormonal therapy: historical perspective to future directions." Urology. 2003;61(2 Suppl 1):3-7. 5. Oh WK, Kantoff PW. "Management of hormone refractory prostate cancer: current standards and future prospects." J Urol. 1998;160(4):1220-1229. 6. Bennett CL, et al. "Fatal hepatotoxicity associated with flutamide therapy for prostate cancer." J Urol. 1999;161(6):1913-1914. 7. Drugdex® Evaluations: Flutamide. Micromedex Solutions. Truven Health Analytics.