Zileuton Advanced Drug Monograph

Zileuton Report

Name: Zileuton Name (English): Zileuton DrugBank ID: DB00744 Type: Small Molecule CAS Number: 111406-87-2

Indication: Prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. May have applications in aspirin-induced asthma, exercise-induced asthma, aspirin-exacerbated respiratory disease, chronic obstructive pulmonary disease, and certain dermatological conditions.

Mechanism of Action: Inhibits 5-lipoxygenase, the enzyme responsible for the synthesis of leukotrienes (LTB4, LTC4, LTD4, and LTE4). By reducing leukotriene production, zileuton helps to decrease inflammation, edema, mucus secretion, and bronchoconstriction in the airways.

Dosage:

• Immediate-release tablets: 600 mg four times daily.
• Extended-release tablets: 1.2 g twice daily (within 1 hour after morning and evening meals).

Contraindications: Active liver disease or serum aminotransferase concentrations ≥3 times the upper limit of normal (ULN). Known hypersensitivity to zileuton or any ingredient in the formulation.

Warnings and Precautions: Not for the relief of acute bronchospasm. May cause elevations in liver transaminases; monitoring is recommended. Use with caution in patients with a history of liver disease or excessive alcohol consumption. May interact with theophylline and warfarin, requiring dose adjustments and monitoring.

Adverse Reactions: Common side effects include headache, upper respiratory tract infections, diarrhea, myalgia, dyspepsia, nausea, and sinusitis. Less common but potentially serious adverse reactions include hepatotoxicity and hypersensitivity reactions. Neuropsychiatric events have been noted in postmarketing surveillance.

Pharmacokinetics:

• Absorption: Rapidly absorbed after oral administration, with peak plasma concentration reached in approximately 1.7 hours.
• Distribution: High plasma protein binding (93%). Apparent volume of distribution is approximately 1.2 L/kg.
• Metabolism: Primarily metabolized in the liver via glucuronidation and oxidation.
• Elimination: Primarily excreted in the urine (94.5%) as zileuton and its metabolites.

Drug Interactions:

• Increases theophylline levels.
• Increases warfarin levels, potentially increasing prothrombin time.
• May interact with propranolol.

Special Populations:

• Hepatic Impairment: Contraindicated in active liver disease.
• Renal Impairment: Dosage adjustment not required.
• Pregnancy: Advised against based on animal data; human data lacking.
• Lactation: Not recommended.
• Pediatric Use: Safety and efficacy established in children ≥12 years of age.
• Geriatric Use: Dosage adjustment not required.

Hepatotoxicity: Associated with mild-to-moderate serum aminotransferase elevations. Rare cases of clinically apparent liver injury with jaundice have been reported. Monitoring of liver enzymes is recommended.

Note: This report provides a summary of information available about zileuton and should not be considered exhaustive. Healthcare professionals should consult the full prescribing information for complete details.