Singulair - Drug Monograph

Introduction

Singulair (montelukast sodium) is a leukotriene receptor antagonist (LTRA) medication primarily used in the management of asthma and allergic rhinitis. Developed by Merck & Co., it was first approved by the FDA in 1998. As a maintenance medication, Singulair works by blocking inflammatory pathways different from those targeted by corticosteroids, offering an alternative approach to respiratory disease management.

Mechanism of Action

Singulair selectively binds to and blocks cysteinyl leukotriene type 1 (CysLT1) receptors in the respiratory tract. Leukotrienes are inflammatory mediators derived from arachidonic acid metabolism that cause bronchoconstriction, increased vascular permeability, mucus secretion, and eosinophil recruitment. By competitively inhibiting these receptors, montelukast prevents leukotriene-induced bronchoconstriction and reduces airway inflammation without possessing bronchodilator properties.

Indications

FDA-approved indications include:

• Chronic asthma management and prophylaxis in adults and children ≥12 months
• Prevention of exercise-induced bronchoconstriction in patients ≥6 years
• Relief of symptoms of allergic rhinitis (seasonal and perennial) in patients ≥2 years

Dosage and Administration

• Adults and adolescents ≥15 years: 10 mg once daily
• Children 6-14 years: 5 mg chewable tablet once daily
• Children 2-5 years: 4 mg chewable tablet or oral granules once daily
• Children 12-23 months: 4 mg oral granules once daily

• Tablets: Swallow whole with water
• Chewable tablets: Chew completely before swallowing
• Oral granules: Administer directly in mouth or mixed with certain soft foods
• Evening administration recommended for asthma
• Timing flexible for allergic rhinitis
• Not for acute asthma attacks

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: Use with caution in moderate to severe impairment
• Elderly: No dosage adjustment required

Pharmacokinetics

Contraindications

• Hypersensitivity to montelukast or any component of the formulation
• Patients with acute asthma attacks (not for rescue therapy)

Warnings and Precautions

• Agitation, aggressive behavior, anxiety
• Depression, disorientation, hallucinations
• Insomnia, irritability, memory impairment
• Obsessive-compulsive symptoms, restlessness
• Stuttering, suicidal thoughts and behavior
• Tremor, sleepwalking

Patients should be monitored for neuropsychiatric symptoms, and discontinuation considered if such symptoms occur.

• Not a substitute for inhaled or systemic corticosteroids
• Do not abruptly substitute for corticosteroid therapy
• Systemic eosinophilia may occur (Churg-Strauss syndrome)
• Phenylketonuria: Chewable tablets contain aspartame
• Patients with aspirin sensitivity: May not be fully protective

Drug Interactions

• CYP enzyme inducers (rifampin, phenobarbital, carbamazepine): May decrease montelukast concentrations
• Gemfibrozil: Increases montelukast exposure approximately 4.5-fold
• CYP2C8 inhibitors: May increase montelukast concentrations
• No clinically important interactions with prednisone, theophylline, or oral contraceptives

Adverse Effects

• Headache (18-19%)
• Influenza (4-5%)
• Abdominal pain (2-4%)
• Cough (2-4%)
• Dyspepsia (2-3%)
• Upper respiratory infection (2-3%)
• Fever (1-3%)
• Dizziness (1-2%)

• Neuropsychiatric events (see Boxed Warning)
• Systemic eosinophilia with vasculitis (Churg-Strauss syndrome)
• Hepatic eosinophilic infiltration
• Severe hepatic reactions
• Suicidal ideation and behavior

Monitoring Parameters

• Asthma control assessment (symptom frequency, nighttime awakenings)
• Pulmonary function tests (FEV1, peak flow)
• Need for rescue medication
• Neuropsychiatric symptoms (baseline and periodic assessment)
• Hepatic function in patients with symptoms of liver dysfunction
• Eosinophil count if systemic vasculitis suspected
• Growth velocity in pediatric patients

Patient Education

• Take medication daily as prescribed, even during symptom-free periods
• Not for treatment of acute asthma attacks (keep rescue inhaler available)
• Report any changes in behavior or mood, including agitation, aggression, depression, or suicidal thoughts
• Do not stop taking without consulting healthcare provider
• Chewable tablets contain phenylalanine (aspartame)
• Oral granules should be taken within 15 minutes of opening packet
• Continue other asthma medications unless instructed to change
• Report any symptoms of liver problems (jaundice, dark urine, right upper quadrant pain)
• Inform all healthcare providers about Singulair use

References

1. US Food and Drug Administration. (2020). Singulair (montelukast sodium) prescribing information. 2. Drugs.com. (2023). Montelukast Professional Monograph. 3. Global Initiative for Asthma. (2023). GINA Report, Global Strategy for Asthma Management and Prevention. 4. Philip, G., et al. (2004). "Montelukast for asthma in children." Journal of Pediatrics, 144(2), 231-235. 5. Micromedex Solutions. (2023). Montelukast Drug Information. 6. US National Library of Medicine. (2023). DailyMed - Singulair label. 7. Clinical Pharmacology [database online]. (2023). Montelukast. 8. Journal of Allergy and Clinical Immunology. (2019). "Leukotriene receptor antagonists in asthma therapy." 143(2), 659-670.