Nilutamide

Pronunciation: (nye-LOO-ta-mide)
Class: Antiandrogen, Antineoplastic agent

Trade Names

Nilandron
- Tablets 150 mg

Anandron (Canada)

Pharmacology

Nonsteroidal with antiandrogen activity. It blocks the effects of testosterone at the androgen receptor level.

Pharmacokinetics

Absorption

Nilutamide is rapidly and completely absorbed. Steady state is 2 to 4 wk (multiple dosing).

Distribution

Nilutamide is moderately bound to plasma proteins and has low binding to erythrocytes.

Metabolism

Nilutamide is extensively metabolized. Five metabolites have been isolated with several active.

Elimination

Nilutamide is excreted in urine 62% (2% as unchanged) and feces 1.4% to 7%. The half-life is 38 to 59.1 h.

Indications and Usage

Treatment of metastatic prostate cancer (stage D2) in combination with surgical castration.

Contraindications

Severe hepatic impairment; severe respiratory insufficiency; hypersensitivity to nilutamide or any component of this preparation.

Dosage and Administration

Prostate Cancer
Adults Initial dose

PO 300 mg once daily for 30 days.

Maintenance dose

PO 150 mg once daily.

Hepatic function impairment

Dosage adjustments may be necessary, although no specific guidelines are available.

General Advice

• Nilutamide is considered a potential teratogen. Follow safe handling procedures when preparing, administering, or dispensing nilutamide.
• Initiate therapy on day of surgical castration or the day after surgery. Nilutamide may be taken without regard to meals.

Storage/Stability

Store at 59° to 86°F; protect from light.

Drug Interactions

CYP-450 enzymes

May alter the elimination of agents metabolized by the CYP-450 system. Carefully monitor patients for increased drug serum concentrations and toxicity, especially when administering drugs with a narrow therapeutic index (eg, phenytoin, theophylline, warfarin).

Adverse Reactions

Adverse reactions are reported in patients treated with nilutamide in combination with leuprolide or orchiectomy.

Cardiovascular

Hypertension (5%); heart failure (3%); angina, syncope (2%).

CNS

Headache (14%); dizziness (7%); hypesthesia (5%); paresthesia (3%); malaise, nervousness (2%).

Dermatologic

Body hair loss, sweating (6%); dry skin (5%); pruritus (2%).

EENT

Impaired adaptation to dark (57%); chromatopsia (9%); abnormal vision, impaired adaptation to light (7%); cataract, photophobia, rhinitis (2%).

Endocrine

Hot flushes (28%).

GI

Anorexia (11%); abdominal pain, nausea (10%); constipation (7%); diarrhea, dry mouth, GI disorder, GI hemorrhage, melena (2%).

Genitourinary

Testicular atrophy (16%); decreased libido (11%); UTI (8%).

Hepatic

Increased ALT or AST (8%).

Lab Tests

Hyperglycemia (4%); alkaline phosphatase increased, leukopenia (3%); creatinine increased, increased BUN, increased haptoglobin (2%).

Metabolic

Alcohol intolerance (5%); edema, weight loss (2%).

Musculoskeletal

Arthritis (2%).

Respiratory

Dyspnea (11%); pneumonia (5%); lung disorder (4%); increased cough, intestinal pneumonitis (2%).

Miscellaneous

Hot flushes (67%); chest pain (7%).

Precautions

Warnings Interstitial pneumonitis Interstitial pneumonitis has been reported in 2% of patients in clinical trials. Reports of interstitial changes, including pulmonary fibrosis leading to hospitalization and death, have been rarely reported in postmarketing surveillance. Most cases were reversible with discontinuation and occurred within the first 3 mo of therapy.

Monitor Perform a routine chest x-ray prior to initiating treatment with nilutamide and consider baseline pulmonary function tests. Assess serum transaminase levels prior to starting treatment and at regular intervals for the first 4 mo of treatment and periodically thereafter. Obtain LFTs at the first sign or symptoms suggestive of liver dysfunction.

Pregnancy

Category C .

Lactation

Not indicated for use in women.

Children

Safety and efficacy in children have not been established.

Antiandrogen withdrawal syndrome

Patients with disease progression during treatment with an antiandrogen may experience clinical improvement with discontinuation of the antiandrogen.

Aplastic anemia

Isolated cases have been reported in foreign postmarketing surveillance; causal relationship with nilutamide could not be established.

Hepatic effects

Severe liver injury, including cases leading to death or hospitalization, has been reported. Hepatotoxicity in these reports generally occurred within the first 3 to 4 mo of treatment.

Women

Nilutamide has no indication for women.

Overdosage

Symptoms

Dizziness; GI disorders, including nausea and vomiting; headache; malaise.

Patient Information

• Instruct patients to start nilutamide tablets on the day of, or the day after, surgical castration. Advise patients not to interrupt their dosing of nilutamide or stop taking the medication without consulting their health care provider.
• Delays of visual adaptation when passing from light to dark may occur. Advise patients to use caution when driving at night or through tunnels. Patients can use tinted glasses to help decrease the problem.
• Nilutamide may cause alcohol intolerance. Advise patients to avoid alcohol if facial flushing, malaise, or hypotension occurs after consuming alcoholic beverages.
• Instruct patients to notify their health care provider at the first sign or symptoms suggestive of liver dysfunction (eg, abdominal pain, anorexia, dark urine, fatigue, flu-like symptoms, jaundice, nausea, right upper quadrant tenderness, vomiting).
• Instruct patients to report any new or worsening shortness of breath that they experience while on nilutamide. If symptoms occur, discontinue nilutamide immediately until it can be determined if the symptoms are drug-related.

Copyright © 2009 Wolters Kluwer Health.