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, 2024. Written by ASHP.

Introduction

Antineoplastic agent; a nonsteroidal antiandrogen.^{1 2 3 5 6 7 9 11 16 19 23 24 25 26 27}

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.^{1 3 5 6 7 20 22 23}

Treatment of locally confined (stage B2 or C)^{1 20 22 23} and metastatic (stage D2) prostate cancer;^{1 3 5 6 7 20} should be used in conjunction with an LHRH analog.^{1 3 5 6 7 20 22 23}

Flutamide Dosage and Administration

General

• In patients with stage B2 or C prostate cancer, initiate flutamide and LHRH analog 8 weeks prior to and continue during radiation therapy.¹

• In patients with stage D2 metastatic prostate cancer, initiate flutamide and LHRH analog concomitantly and continue until disease progression.¹

Administration

Oral Administration

Administer orally 3 times daily at 8-hour intervals^{1 2 3 5 6 7 12 14 17} without regard to meals²⁹ .

Dosage

Adults

Prostate Cancer

Oral

250 mg 3 times daily, at 8-hour intervals.^{1 2 3 5 6 7 12 14 17 24 25 27 28}

Cautions for Flutamide

Contraindications

• Known hypersensitivity to flutamide or any ingredient in the formulation.¹

• Severe hepatic impairment.¹

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.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm if used in pregnant women.¹

Aniline Toxicity

Metabolized in part to 4-nitro-3-fluoro-methylaniline; toxicities associated with aniline exposure (i.e., methemoglobinemia, hemolytic anemia, cholestatic jaundice) reported.¹

Monitor methemoglobin concentrations periodically in susceptible patients (e.g., those with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease, smokers).¹

Sensitivity Reactions

Photosensitivity

Photosensitivity reactions (i.e., erythema, ulceration, bullous eruptions, epidermal necrolysis) reported.¹

General Precautions

Endocrine Effects

Possible gynecomastia.^{1 27}

Laboratory Monitoring

Regularly monitor serum PSA to assess response; if PSA increases, evaluate possible disease progression.¹

For patients with objective progression of disease and elevated serum PSA, consider temporarily withdrawing flutamide while continuing LHRH analog.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Warnings.)

Lactation

Not intended for use in women.¹

Pediatric Use

Not studied in pediatric patients.¹

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment. (See Boxed Warning.)¹

Women

Not intended for use in women, particularly for nonserious or nonlife-threatening conditions.¹

Common Adverse Effects

Combined therapy with LHRH analog: hot flashes, loss of libido, impotence, diarrhea, nausea, vomiting, gynecomastia.¹

Cystitis, rectal bleeding, proctitis, skin rash, hematuria also frequent when flutamide combined with LHRH analog and radiation therapy.¹

Drug Interactions

Specific Drugs

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.^{1 27}

Food

Food does not affect bioavailability.¹

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.¹

Distribution

Plasma Protein Binding

Flutamide: 94–96%; 2-hydroxyflutamide: 92–94%.^{1 27}

Elimination

Metabolism

Rapidly and extensively metabolized to ≥6 metabolites, including an active α-hydroxylated derivative, 2-hydroxyflutamide.^{1 27}

Elimination Route

Excreted principally in urine and to lesser extent in feces (4.2%) as unchanged drug and metabolites.¹

Half-life

2-Hydroxyflutamide: about 6 hours after a single 250-mg dose.¹

Special Populations

In patients with renal impairment (Cl_cr <29 mL/minute), half-life of active metabolite was slightly prolonged; no dosage adjustment necessary in chronic renal impairment.¹

In geriatric patients, half-life of active metabolite is about 8 hours after a single 250-mg dose.¹

Pharmacokinetics not studied in patients with hepatic impairment, women, or pediatric patients.¹

Stability

Storage

Oral

Capsules

2–30°C.¹ Protect unit dose packages from excessive moisture.¹

Actions

• A selective antiandrogen with no estrogenic, antiestrogenic, progestational, antiprogestational, antigonadotropic, or adrenocortical activity in various animal models.³

• Competitively blocks nuclear androgen receptors in target tissues (e.g., prostate, seminal vesicles, adrenal cortex).^{1 3 8 9 10 11 12 24 25}

• Blockade of androgen receptors in the hormone-sensitive tumor cells may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis.^{1 3 8 9 10 11 12 24 25}

• Inhibits initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) associated with the first month of LHRH analog therapy.^{6 10 11 18}

Advice to Patients

• Risk of liver toxicity.¹ Importance of adhering to schedule for laboratory monitoring of serum transaminases and reporting signs or symptoms of hepatic toxicity to clinician immediately.¹

• Importance of initiating flutamide concomitantly with LHRH analog and of not interrupting or discontinuing therapy without consulting a clinician.¹

• Risk of facial flushing, particularly if used in conjunction with alcohol.³¹ Avoidance of alcohol recommended if flushing occurs.³¹

• Not intended for use in women.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

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

Frequently asked questions

• How does flutamide work in prostate cancer?

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