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Flutamide (Monograph)

Brand name: Eulexin
Drug class: Antineoplastic Agents
- Antiandrogens
VA class: AN900
Chemical name: 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide
Molecular formula: C11H11F3N2O3
CAS number: 13311-84-7

Medically reviewed by Drugs.com on Jun 21, 2023. Written by ASHP.

Warning

    Hepatotoxicity
  • Severe liver injury (i.e., increased serum transaminase concentrations, jaundice, hepatic encephalopathy, acute hepatic failure) reported, sometimes resulting in hospitalization and/or rarely death; manifestations generally occurred within first 3 months and in some patients, were reversible after discontinuance.

  • Measure serum transaminase concentrations prior to initiation of therapy, monthly during first 4 months, and periodically thereafter.

  • Immediately measure serum transaminase (especially ALT) concentrations if manifestations suggestive of liver dysfunction (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, flu-like symptoms, hyperbilirubinuria, jaundice, right upper quadrant tenderness) occur.

  • Immediately discontinue if jaundice develops or serum ALT concentration is >2 times ULN; monitor liver function closely until resolves.

Introduction

Antineoplastic agent; a nonsteroidal antiandrogen.

Uses for Flutamide

Prostate Cancer

First-line therapy in combination with a luteinizing hormone-releasing hormone (LHRH) analog (e.g., goserelin, leuprolide acetate, triptorelin) for prostate cancer.

Treatment of locally confined (stage B2 or C) and metastatic (stage D2) prostate cancer; should be used in conjunction with an LHRH analog.

Flutamide Dosage and Administration

General

Administration

Oral Administration

Administer orally 3 times daily at 8-hour intervals without regard to meals .

Dosage

Adults

Prostate Cancer
Oral

250 mg 3 times daily, at 8-hour intervals.

Cautions for Flutamide

Contraindications

Warnings/Precautions

Warnings

Hepatic Effects

For warnings regarding hepatotoxicity, see Boxed Warning.

Use in Women

Not intended for use in women, particularly for nonserious or nonlife-threatening conditions.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm if used in pregnant women.

Aniline Toxicity

Metabolized in part to 4-nitro-3-fluoro-methylaniline; toxicities associated with aniline exposure (i.e., methemoglobinemia, hemolytic anemia, cholestatic jaundice) reported.

Monitor methemoglobin concentrations periodically in susceptible patients (e.g., those with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease, smokers).

Sensitivity Reactions

Photosensitivity

Photosensitivity reactions (i.e., erythema, ulceration, bullous eruptions, epidermal necrolysis) reported.

General Precautions

Endocrine Effects

Possible gynecomastia.

Laboratory Monitoring

Regularly monitor serum PSA to assess response; if PSA increases, evaluate possible disease progression.

For patients with objective progression of disease and elevated serum PSA, consider temporarily withdrawing flutamide while continuing LHRH analog.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Warnings.)

Lactation

Not intended for use in women.

Pediatric Use

Not studied in pediatric patients.

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment. (See Boxed Warning.)

Women

Not intended for use in women, particularly for nonserious or nonlife-threatening conditions.

Common Adverse Effects

Combined therapy with LHRH analog: hot flashes, loss of libido, impotence, diarrhea, nausea, vomiting, gynecomastia.

Cystitis, rectal bleeding, proctitis, skin rash, hematuria also frequent when flutamide combined with LHRH analog and radiation therapy.

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Alcohol

Increased risk of facial flushing

Avoid alcohol consumption during therapy

LHRH analog (e.g., goserelin, leuprolide)

Pharmacokinetic interaction unlikely

Warfarin

Increased PT reported

Closely monitor PT; adjust anticoagulant dosage as needed

Flutamide Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed following oral administration, with peak plasma concentrations of active metabolite (2-hydroxyflutamide) attained within about 2 hours.

Food

Food does not affect bioavailability.

Special Populations

In patients with chronic renal impairment, there appears to be no correlation between creatinine clearance and maximum plasma concentrations or AUC of flutamide; renal impairment did not affect maximum plasma concentrations or AUC of active metabolite.

Distribution

Plasma Protein Binding

Flutamide: 94–96%; 2-hydroxyflutamide: 92–94%.

Elimination

Metabolism

Rapidly and extensively metabolized to ≥6 metabolites, including an active α-hydroxylated derivative, 2-hydroxyflutamide.

Elimination Route

Excreted principally in urine and to lesser extent in feces (4.2%) as unchanged drug and metabolites.

Half-life

2-Hydroxyflutamide: about 6 hours after a single 250-mg dose.

Special Populations

In patients with renal impairment (Clcr <29 mL/minute), half-life of active metabolite was slightly prolonged; no dosage adjustment necessary in chronic renal impairment.

In geriatric patients, half-life of active metabolite is about 8 hours after a single 250-mg dose.

Pharmacokinetics not studied in patients with hepatic impairment, women, or pediatric patients.

Stability

Storage

Oral

Capsules

2–30°C. Protect unit dose packages from excessive moisture.

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Flutamide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

125 mg*

Eulexin (with parabens and povidone;)

Schering

Flutamide Capsules

Barr

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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Frequently asked questions