What is the recommended use and dosage of Zafirukast (leukotriene receptor antagonist) for asthma treatment?

Zafirlukast for Asthma Treatment: Recommended Use and Dosage

Zafirlukast is recommended as an alternative, but not preferred, therapy for mild persistent asthma at a dosage of 20 mg twice daily for adults and children 12 years and older, and 10 mg twice daily for children 7-11 years of age. 1

Mechanism of Action and Classification

• Zafirlukast is a leukotriene receptor antagonist (LTRA) that selectively and competitively blocks cysteinyl leukotrienes (LTC4, LTD4, and LTE4), which are important mediators in asthma pathogenesis 2, 3
• LTRAs interfere with the pathway of leukotriene mediators released from mast cells, eosinophils, and basophils 1

Recommended Dosage

• Adults and children ≥12 years: 20 mg twice daily 2, 4
• Children 7-11 years: 10 mg twice daily 5
• Administration should be at least 1 hour before or 2 hours after meals, as food decreases bioavailability 1

Clinical Position in Asthma Management

• Zafirlukast is positioned as an alternative, not preferred, therapy for:
  • Step 2 care (mild persistent asthma) 1
  • Adjunctive therapy with inhaled corticosteroids (ICS) in moderate persistent asthma 1
• Inhaled corticosteroids remain the preferred first-line controller medication for persistent asthma due to superior efficacy 1

Efficacy

• Zafirlukast improves lung function, symptom control, and reduces short-acting beta-agonist use in mild to moderate asthma 2, 3
• Reduces risk of asthma exacerbations by approximately 50% compared to placebo 6
• Can attenuate exercise-induced bronchoconstriction 1, 3
• Less effective than inhaled corticosteroids for improving morning peak flow, FEV1, and daytime symptom scores 4, 3

Special Considerations and Monitoring

• Monitor hepatic enzymes, particularly with higher doses, as elevated liver enzymes have been reported 1, 3
• Zafirlukast is a microsomal P450 enzyme inhibitor that can affect metabolism of:
  • Warfarin (increased anticoagulant effect)
  • Theophylline
  • Erythromycin 1, 2
• Patients should discontinue use if they experience signs of liver dysfunction 1
• Careful monitoring is required when reducing oral corticosteroids in patients taking zafirlukast due to rare reports of Churg-Strauss syndrome 2, 4

Advantages and Potential Benefits

• Oral administration may improve compliance in patients with poor inhaler technique 2, 3
• Once or twice daily dosing simplifies treatment regimen 1, 4
• Well-tolerated with adverse event profile similar to placebo at recommended doses 4, 5

Common Pitfalls and Caveats

• Zafirlukast should never be used as monotherapy for moderate or severe persistent asthma 1
• Long-acting beta-agonists (LABAs) are preferred over LTRAs as add-on therapy to ICS in patients ≥12 years 1
• Dosages exceeding 40 mg twice daily are not recommended due to risk of elevated liver enzymes 2
• The drug may have limited efficacy in certain genetic populations, particularly those with variations in leukotriene pathway genes 1
• Zafirlukast is not approved for children under 7 years of age 1