No

Antiandrogen

In combination therapy with LHRH agonist analogues in treatment of metastatic prostatic carcinoma. A study has shown that the addition of flutamide to leuprolide therapy in patients with advanced prostatic cancer increased median actuarial survival time to 34.9 months versus 27.9 months with leuprolide alone. To achieve benefit to combination therapy, both drugs need to be started simultaneously.

D

Known hypersensitivity to flutamide

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Animal data (based on using doses higher than recommended for humans) produced testicular interstitial cell adenoma. Do not discontinue therapy without physician's advice. May cause hepatic failure, which can be fatal. Serum transaminases should be monitored at baseline and monthly for the first four months of therapy, and periodically thereafter. These should also be repeated at the first sign and symptom of liver dysfunction. Use of flutamide is not recommended in patients with baseline elevation of transaminase levels (> twice the upper limit of normal). Flutamide should be discontinued immediately at any time if the patient develops jaundice or elevation in serum transaminase levels (>2 times upper limit of normal).

>10%:

Gastrointestinal: Nausea, vomiting, diarrhea

Genitourinary: Impotence

Endocrine & metabolic: Loss of libido, hot flashes

1% to 10%:

Endocrine & metabolic: Gynecomastia

Gastrointestinal: Anorexia

Neuromuscular & skeletal: Numbness in extremities

<1%: Hepatic failure, jaundice, flu-like syndrome, abdominal pain, hypertension, edema, drowsiness, nervousness, confusion, hepatitis

Symptoms of overdose include hypoactivity, ataxia, anorexia, vomiting, slow respiration, lacrimation

Management is supportive, dialysis not of benefit; induce vomiting

CYP3A3/4 enzyme substrate

Store at room temperature

Nonsteroidal antiandrogen that inhibits androgen uptake or inhibits binding of androgen in target tissues

Absorption: Rapid and complete

Metabolism: Extensively to more than 10 metabolites

Half-life: 5-6 hours

Elimination: All metabolites excreted primarily in urine

Adults: Oral: 2 capsules every 8 hours for a total daily dose of 750 mg

Serum transaminase levels should be measured prior to starting treatment and should be repeated monthly for the first 4 months of therapy, and periodically thereafter. LFTs should be checked at the first sign or symptom of liver dysfunction (eg, nausea, vomiting, abdominal pain, fatigue, anorexia, flu-like symptoms, hyperbilirubinuria, jaundice, or right upper quadrant tenderness). Other parameters include tumor reduction, testosterone/estrogen, and phosphatase serum levels.

May rarely cause nervousness or confusion

None reported

No information available to require special precautions

No effects or complications reported

Take as directed; do not discontinue without consulting prescriber. You may experience decreased libido, impotence, swelling of breasts, or decreased appetite (small frequent meals may help). Report chest pain or palpitation; acute abdominal pain; pain, tingling, or numbness of extremities; swelling of extremities or unusual weight gain; difficulty breathing; or other persistent adverse effects. Pregnancy precautions: This drug will cause fetal abnormalities - use barrier contraceptives.

Capsule: 125 mg

Brogden RN and Chrisp P, "Flutamide. A Reivew of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use in Advanced Prostatic Cancer," Drugs Aging, 1991, 1(2):104-15.

Brogden RN and Clissold SP, "Flutamide. A Preliminary Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Advanced Prostate Cancer," Drugs, 1989, 38(2):185-203.

Crawford ED, Eisenberger MA, McLeod DG, et al, "A Controlled Trial of Leuprolide With and Without Flutamide in Prostatic Carcinoma," N Engl J Med, 1989, 321(7):419-24.

Delaere KP and Van Thillo EL, "Flutamide Monotherapy as Primary Treatment in Advanced Prostatic Carcinoma," Semin Oncol, 1991, 18(5 Suppl 6):13-8.

Goldspiel BR and Kohler DR, "Flutamide: An Antiandrogen for Advanced Prostate Cancer," DICP Ann Pharmacother, 1990, 24(6):616-23.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Labrie F, "Mechanism of Action and Pure Antiandrogenic Properties of Flutamide," Cancer, 1993, 72(12 Suppl):3816-27.

Moller S, Iversen P, and Franzmann MB, "Flutamide-Induced Liver Failure," J Hepatol, 1990, 10(3):346-9.

Schott AM, Vial T, Gozzo I, et al, "Flutamide-Induced Methemoglobinemia," DICP, 1991, 25(4):600-1.

Yagoda A, "Flutamide-Induced Diarrhea Secondary to Lactose Intolerance," J Natl Cancer Inst, 1989, 81(23):1839-40.