Montelukast - Drug Monograph

Introduction

Montelukast is a selective leukotriene receptor antagonist (LTRA) that represents a significant advancement in the management of asthma and allergic rhinitis. As a once-daily oral medication, it offers a convenient non-steroidal option for controlling inflammatory airway conditions. First approved by the FDA in 1998, montelukast has become a cornerstone in the stepwise approach to asthma management and is widely used across pediatric and adult populations.

Mechanism of Action

Montelukast selectively binds to and blocks the cysteinyl leukotriene type 1 (CysLT1) receptor. This prevents the action of leukotriene D4 (LTD4) and other cysteinyl leukotrienes, which are potent inflammatory mediators derived from arachidonic acid metabolism. By inhibiting leukotriene-mediated effects, montelukast reduces:

• Bronchial smooth muscle contraction
• Airway edema formation
• Eosinophil migration into airways
• Mucus secretion

This mechanism provides both bronchodilatory and anti-inflammatory effects without the systemic side effects associated with corticosteroids.

Indications

• Prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months and older
• Relief of symptoms of allergic rhinitis (seasonal and perennial) in adults and pediatric patients 2 years and older
• Prevention of exercise-induced bronchoconstriction (EIB) in patients 15 years and older

• Adjunctive treatment in chronic urticaria
• Management of aspirin-exacerbated respiratory disease (AERD)
• Prevention of bronchospasm in viral-induced wheezing

Dosage and Administration

• Adults and adolescents (≥15 years): 10 mg once daily in the evening
• Children 6-14 years: 5 mg chewable tablet once daily in the evening
• Children 2-5 years: 4 mg chewable tablet or oral granule packet once daily in the evening
• Children 12-23 months: 4 mg oral granule packet once daily in the evening

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: No dosage adjustment recommended for mild to moderate impairment; use caution in severe hepatic impairment
• Geriatric patients: No dosage adjustment required
• Exercise-induced bronchoconstriction: 10 mg at least 2 hours before exercise (not to be repeated within 24 hours)

• Tablets: Swallow whole with water
• Chewable tablets: Chew completely before swallowing
• Oral granules: May be administered directly in mouth, dissolved in 5mL of cold or room temperature formula or breast milk, or mixed with spoonful of soft foods

Pharmacokinetics

Contraindications

• Hypersensitivity to montelukast or any component of the formulation
• Treatment of acute asthma attacks (not a rescue medication)
• Patients with phenylketonuria (chewable tablets contain aspartame)

Warnings and Precautions

• Agitation, aggressive behavior, anxiety
• Depression, disorientation, dream abnormalities
• Hallucinations, insomnia, irritability
• Restlessness, suicidal ideation and behavior
• Tremor, sleepwalking

• Systemic eosinophilia: Rare cases of Churg-Strauss syndrome have been reported
• Not for use in reversal of acute bronchospasm
• Phenylketonuria: Chewable tablets contain phenylalanine
• Aspirin sensitivity: Use with caution in patients with aspirin-sensitive asthma
• Corticosteroid reduction: Do not abruptly substitute for inhaled or oral corticosteroids

Drug Interactions

• Phenobarbital: Decreases montelukast AUC by 40%
• Rifampin: Decreases montelukast AUC by 40%
• Gemfibrozil: Increases montelukast AUC by 45% (CYP2C8 inhibition)
• CYP2C9 inducers: May decrease montelukast concentrations

• Other CYP2C8 inhibitors (trimethoprim, clopidogrel)
• CYP3A4 inducers (carbamazepine, St. John's wort)

Adverse Effects

• Headache (18.4%)
• Influenza (4.2%)
• Abdominal pain (2.9%)
• Cough (2.8%)
• Dizziness (1.8%)
• Fatigue (1.5%)

• Neuropsychiatric events (see Boxed Warning)
• Eosinophilic conditions
• Hepatic dysfunction (elevated transaminases)
• Hypersensitivity reactions (angioedema, urticaria)
• Pulmonary eosinophilia

Monitoring Parameters

• Complete medical history with focus on psychiatric history
• Asthma control assessment (symptom frequency, rescue inhaler use)
• Liver function tests (consider in patients with hepatic impairment)
• Eosinophil count

• Asthma symptom control and quality of life measures
• Rescue bronchodilator use frequency
• Psychiatric symptoms (at each visit and as needed)
• Liver function (if symptoms suggest hepatic dysfunction)
• Growth monitoring in pediatric patients

• Seek immediate care for acute asthma exacerbations
• Report any neuropsychiatric symptoms immediately

Patient Education

• Take medication daily as prescribed, even during symptom-free periods
• Not for treatment of acute asthma attacks—keep rescue inhaler available
• Take in evening for optimal control of nighttime symptoms
• Report any mood changes, anxiety, depression, or unusual behaviors immediately
• Chewable tablets must be chewed completely; do not swallow whole
• Oral granules may be mixed with soft food but not liquids
• Do not stop taking without consulting healthcare provider
• Continue avoiding known asthma triggers
• For exercise-induced asthma: Take at least 2 hours before exercise

• Store at room temperature (15-30°C/59-86°F)
• Protect from moisture and light
• Keep granules in original foil pouch until use

References

1. US Food and Drug Administration. (2020). Singulair (montelukast sodium) prescribing information. 2. Global Initiative for Asthma. (2023). GINA Report, Global Strategy for Asthma Management and Prevention. 3. Philip, G., et al. (2022). "Montelukast for chronic asthma in adults and children." Cochrane Database of Systematic Reviews. 4. Meltzer, E. O., et al. (2021). "Montelukast in the treatment of allergic rhinitis: an evidence-based review." Drugs. 5. US National Library of Medicine. (2023). Montelukast: Drug Information. DailyMed. 6. Clinical Pharmacology [database online]. (2023). Montelukast. Elsevier. 7. Micromedex Solutions. (2023). Montelukast Drug Monograph. Truven Health Analytics.