Recommended Leukotriene Inhibitor for Asthma Management
Montelukast (Singulair) is the recommended leukotriene inhibitor for asthma, dosed once daily at 10 mg for adults and adolescents ≥15 years, 5 mg for children 6-14 years, and 4 mg for children 2-5 years. 1, 2
Primary Leukotriene Inhibitor Options
Montelukast is the preferred leukotriene receptor antagonist due to its once-daily dosing, approval for patients older than one year, and superior compliance rates compared to other agents in its class. 1, 3
Alternative Leukotriene Modifiers
Zafirlukast (Accolate) is the alternative leukotriene receptor antagonist, approved for patients ≥7 years old and dosed twice daily, making it less convenient than montelukast. 1, 4
Zileuton (5-lipoxygenase inhibitor) is available for patients ≥12 years old but is less desirable because it requires liver function monitoring. 4
Clinical Context and Positioning
When to Use Leukotriene Inhibitors
Leukotriene receptor antagonists are appropriate in these specific scenarios:
Alternative therapy for mild persistent asthma in patients who are unable or unwilling to use inhaled corticosteroids. 1, 3
Add-on therapy for moderate persistent asthma (Step 3-4) when combined with inhaled corticosteroids, though this is less preferred than adding a long-acting beta-agonist. 1
Patients requiring ease of use where the oral once-daily formulation provides advantages in compliance over inhaled medications. 1, 3
Critical Limitation: Inferior to Inhaled Corticosteroids
Low-dose inhaled corticosteroids are significantly more effective than montelukast for asthma control and should be the preferred first-line treatment for mild persistent asthma. 4, 5
Meta-analysis in school-aged children demonstrates inhaled fluticasone superiority over montelukast with a weighted mean difference of 4.6% predicted FEV1 (95% CI: 3.5-5.5) and 5.6% more asthma control days (95% CI: 4.3-6.9). 6
Inhaled corticosteroids consistently improve lung function, symptom control, and exacerbation reduction more effectively than leukotriene receptor antagonists in both children and adults. 4, 6
Dosing Algorithm by Age
Adults and adolescents ≥15 years: Montelukast 10 mg once daily 1, 2
Children 6-14 years: Montelukast 5 mg once daily (chewable tablet) 1, 2
Children 2-5 years: Montelukast 4 mg once daily (chewable tablet or oral granules) 2
Children 12-23 months (asthma only): Montelukast 4 mg oral granules once daily 2
Important Clinical Caveats
Timing and Administration
Efficacy is demonstrated when montelukast is administered in the evening without regard to food for asthma, though morning or evening dosing shows similar pharmacokinetics. 2
Clinical benefits are typically seen within one day of treatment, with no development of tolerance over time. 7
When Montelukast Fails
If asthma is not adequately controlled within 4-6 weeks of montelukast monotherapy, discontinue and initiate inhaled corticosteroids as the preferred medication. 6
Patient Selection Considerations
Approximately 25% of patients benefit more from montelukast than fluticasone, though this cannot be predicted prospectively. 6
More severe disease or markers of allergic inflammation are associated with more favorable response to inhaled corticosteroids over montelukast. 6
Drug Interactions
Phenobarbital and rifampin (potent CYP450 inducers) decrease montelukast AUC by approximately 40%, though no dosage adjustment is officially recommended. 2
Montelukast does not significantly interact with theophylline, warfarin, digoxin, oral contraceptives, or prednisone. 2
Stepwise Treatment Algorithm
For Step 2 (mild persistent asthma): Low-dose inhaled corticosteroid is preferred; montelukast is an alternative option. 1, 5
For Step 3 (moderate persistent asthma): Low-dose inhaled corticosteroid plus long-acting beta-agonist is preferred; low-dose inhaled corticosteroid plus montelukast is an alternative. 1, 4
Never use montelukast as monotherapy for moderate-to-severe asthma where inhaled corticosteroids with or without long-acting beta-agonists are required. 5