Flutamide

Trade Names:Flutamide- Capsules 125 mg

Pharmacology

Flutamide inhibits androgen uptake or inhibits nuclear binding of androgen in target tissues or both.

Pharmacokinetics

Absorption

Flutamide is rapidly and completely absorbed. T _max is approximately 2 h (for the active metabolite).

Distribution

The parent drug and the active metabolite are 94% to 96% and 92% to 94% protein bound at steady state, respectively.

Metabolism

Flutamide is rapidly and extensively metabolized to at least 6 metabolites. The active metabolite is hydroxyflutamide.

Elimination

The t _½ is about 6 h (active metabolite). The drug is excreted primarily in the urine with 4.2% excreted in feces.

The parent drug and active metabolite are not well dialyzed.

Special Populations

The t _½ is slightly prolonged. No dosage adjustment is necessary.

The t _½ and T _max are slightly prolonged.

Indications and Usage

Metastatic prostate cancer, combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog (eg, goserelin, leuprolide).

Unlabeled Uses

Treatment of hirsutism in women (250 mg/day).

Contraindications

Patients with severe hepatic function impairment.

Dosage and Administration

PO 250 mg (2 capsules) every 8 h.

PO Start treatment at 8 wk prior to initiating radiation therapy and continue during radiation therapy.

PO Initiate flutamide capsules with the LHRH agonist and continue until progression.

General Advice

• For patients unable to swallow capsules, open the capsule and mix the contents with applesauce, pudding, or other semi-solid foods. Administer immediately.

Storage/Stability

Store between 2° and 30°C (36° and 86°F). Protect unit dose packages from excessive moisture.

Drug Interactions

Prothrombin time may increase when flutamide therapy is initiated in patients stabilized on chronic warfarin therapy.

Laboratory Test Interactions

Elevated AST, ALT, bilirubin, SGGT, BUN, and serum creatinine.

Adverse Reactions

CNS

Decreased libido.

Endocrine

Hot flashes, gynecomastia.

GI

Low potential for nausea and vomiting; diarrhea; hepatocellular necrosis; cholestatic jaundice; elevated LFTs.

Genitourinary

Impotence; reduced sperm count.

Precautions

Pregnancy

Category D .

Aniline exposure

A metabolite of flutamide, 4-nitro-3-fluoro-methylaniline, may cause methemoglobinemia, hemolytic anemia, and cholestatic jaundice in patients treated with flutamide.

Women

Flutamide is used only in men.

Overdosage

Symptoms

Hypoactivity; piloerection; slow respiration; ataxia; lacrimation; anorexia; tranquilization; emesis; methemoglobinemia.

Patient Information

• The urine was noted to change to an amber or yellow-green appearance.
• Photosensitization may occur.
• Flutamide and LHRH-agonists should be administered concomitantly; and do not interrupt dosing or stop taking these medications without consulting the health care provider.

Copyright © 2009 Wolters Kluwer Health.