What is the indication and mechanism of action of Montelukast (Singulair)?

Montelukast: Indications and Mechanism of Action

Montelukast (Singulair) is indicated for the treatment of asthma, prevention of exercise-induced bronchoconstriction, and relief of symptoms of both seasonal and perennial allergic rhinitis, with its primary mechanism of action being selective antagonism of cysteinyl leukotriene type-1 (CysLT1) receptors. 1

Mechanism of Action

Montelukast works through a targeted mechanism:

• Selectively binds with high affinity to the CysLT1 receptor, blocking the action of cysteinyl leukotrienes (LTC4, LTD4, LTE4) 1
• These leukotrienes are products of arachidonic acid metabolism released from inflammatory cells including mast cells and eosinophils 1, 2
• In the airways, leukotrienes cause:
  • Smooth muscle contraction (bronchoconstriction)
  • Increased vascular permeability leading to edema
  • Enhanced mucus production
  • Inflammatory cell recruitment 1, 3

FDA-Approved Indications

Montelukast is approved for:

1. Asthma management:

   • Prophylaxis and chronic treatment in adults and children ≥12 months of age 1
   • Not indicated for acute asthma attacks or status asthmaticus

2. Exercise-induced bronchoconstriction:

   • Prevention in patients ≥15 years of age 1, 4

3. Allergic rhinitis:

   • Seasonal allergic rhinitis in patients ≥2 years of age
   • Perennial allergic rhinitis in patients ≥6 months of age 1

Clinical Efficacy

Asthma

• Improves day-time asthma symptoms and lung function (FEV1)
• Increases percentage of symptom-free days
• Reduces need for rescue medications 5
• Can be used as monotherapy for mild persistent asthma when inhaled corticosteroids cannot be administered 5
• Serves as an alternative to long-acting beta-agonists as add-on therapy to inhaled corticosteroids 5

Allergic Rhinitis

• Produces statistically significant improvement in nasal symptoms 6
• Similar efficacy to antihistamines when used alone, but less effective than intranasal corticosteroids 6, 7
• Particularly effective when combined with antihistamines 6, 7
• Guidelines suggest montelukast over oral leukotriene receptor antagonists for seasonal allergic rhinitis (strong recommendation) 8

Exercise-Induced Bronchoconstriction

• Effective for prevention when taken before exercise 4
• Has a rapid onset of action within one hour 5

Special Considerations

• Dual benefit: Particularly valuable for patients with both allergic rhinitis and asthma 6
• Administration: Once-daily oral dosing improves patient compliance compared to inhaled medications 5
• Safety profile: Well-tolerated with minimal side effects 7
• Pregnancy: Classified as pregnancy category B; can be considered for recalcitrant asthma during pregnancy if the patient has shown favorable response prior to pregnancy 8
• Chronic rhinosinusitis: Not recommended for maintenance therapy during pregnancy due to lack of efficacy data and potential risks 8

Dosing

• Adults and adolescents ≥15 years: 10 mg tablet once daily
• Children 6-14 years: 5 mg chewable tablet once daily
• Children 1-5 years: 4 mg chewable tablet or oral granules once daily 1, 5

Montelukast represents an important option in the management of allergic and inflammatory airway diseases, particularly valuable when oral administration is preferred or when patients have comorbid asthma and allergic rhinitis.