• 5-Lipoxygenase (5-LO) Inhibitor
• Leukotriene synthesis inhibitor

Parent class:

• Leukotriene Modifiers

Zileuton inhibits the 5-lipoxygenase enzyme.

Normal pathway:

Arachidonic acid
    ↓ (5-lipoxygenase)
Leukotrienes (LTA4 → LTC4, LTD4, LTE4)

Zileuton:

• Blocks leukotriene synthesis at the source
• Reduces ALL leukotrienes (not just receptor activation)

Effects:

• ↓ Bronchoconstriction
• ↓ Airway inflammation
• ↓ Mucus production
• ↓ Eosinophilic activity

Unlike montelukast and zafirlukast, zileuton blocks production rather than receptor binding.

• Oral administration
• Immediate-release: four times daily
• Extended-release: twice daily
• Hepatic metabolism (CYP1A2, CYP2C9, CYP3A4)
• Eliminated via liver

Requires liver function monitoring.

• Asthma (maintenance therapy)

Not used for:

• Acute asthma exacerbations

Less commonly used due to liver toxicity risk.

• Immediate-release: 600 mg PO four times daily
• Extended-release: 1200 mg PO twice daily

Monitor liver function tests before initiation and periodically during therapy.

Common:

• Headache
• Dyspepsia
• Nausea

Serious:

• Hepatotoxicity
• Elevated liver enzymes

Black box warning for liver injury.

Inhibits CYP enzymes:

• ↑ Theophylline levels
• ↑ Warfarin levels
• ↑ Propranolol levels

Monitor INR and drug levels when applicable.

Compared to receptor blockers:

• Broader leukotriene suppression
• More drug interactions
• Requires liver monitoring
• More frequent dosing

Because of safety concerns and complexity, it is rarely first choice.

May be considered in:

• Aspirin-exacerbated respiratory disease
• Select refractory asthma cases

See:

• Asthma Management

• Only leukotriene drug that blocks synthesis.
• Requires liver monitoring.
• Significant CYP drug interactions.
• Not commonly used in current practice.
• Not a rescue medication.
• More mechanistically comprehensive but less convenient.

• Leukotriene Modifiers
• Montelukast
• Corticosteroids
• Histamine & Antihistamines