Montelukast

Generic Name

Montelukast sodium

Brand Names

Singulair

Airkast

Montelo-10

Monteair

Montiget

Ventair

Available in multiple forms including tablets, chewable tablets, and granules

Drug Class

Leukotriene receptor antagonist (LTRA)

Selective and orally active cysteinyl leukotriene receptor (CysLT1) antagonist

Anti-asthmatic and anti-allergic agent

Mechanism of Action

Montelukast blocks the action of leukotrienes (specifically LTC4, LTD4, and LTE4) by binding to the cysteinyl leukotriene receptor type 1 (CysLT1) in the lungs and bronchial tubes

Leukotrienes are inflammatory mediators released by mast cells and eosinophils during allergic and asthmatic reactions

Inhibition reduces bronchoconstriction, vascular permeability, mucus secretion, and eosinophilic infiltration

Leads to decreased airway inflammation and improved respiratory function

Unlike corticosteroids, it does not exert broad immunosuppressive effects

It does not provide immediate bronchodilation and should not be used for acute asthma attacks

Indications

Approved Uses

Prophylaxis and chronic treatment of asthma in adults and pediatric patients aged 12 months and older

Prevention of exercise-induced bronchoconstriction (EIB) in patients aged 6 years and older

Relief of symptoms of seasonal allergic rhinitis (SAR) in patients aged 2 years and older

Relief of symptoms of perennial allergic rhinitis (PAR) in patients aged 6 months and older

Used in aspirin-sensitive asthma (aspirin-exacerbated respiratory disease, AERD)

Off-Label Uses

Chronic urticaria (especially antihistamine-resistant cases)

Allergic conjunctivitis

Atopic dermatitis

COPD with eosinophilic phenotype (as adjunct)

Sleep-disordered breathing (e.g., pediatric obstructive sleep apnea)

Eosinophilic esophagitis (under specialist direction)

Dosage and Administration

Asthma (once daily, in the evening)

Adults and adolescents (15 years and older): 10 mg tablet

Children 6–14 years: 5 mg chewable tablet

Children 2–5 years: 4 mg chewable tablet

Children 6–23 months: 4 mg oral granules

Exercise-Induced Bronchoconstriction

10 mg tablet at least 2 hours before exercise (adults and children 15+)

Do not take another dose within 24 hours

Not a substitute for regular asthma medication

Allergic Rhinitis (seasonal or perennial)

Same age-based dosing as asthma

Can be taken at any time of the day

Duration based on symptom persistence

Administration Notes

Can be taken with or without food

Granules may be administered directly in the mouth, dissolved in a teaspoon of cold/room temperature baby formula or breast milk, or mixed with soft food (e.g., applesauce)

Use within 15 minutes of opening packet

Pharmacokinetics

Absorption

Rapidly absorbed

Bioavailability:

– 10 mg tablet: ~64%

– 5 mg chewable: ~73%

– 4 mg granules: similar

Peak plasma levels: 2–4 hours post-dose

Distribution

Plasma protein binding: >99%

Volume of distribution: ~8–11 L

Metabolism

Extensively metabolized in liver

Primary via CYP3A4, CYP2C9, and to a lesser extent CYP2C8

Main metabolites inactive

Elimination

Half-life: 2.7–5.5 hours (dose-dependent)

Excreted mainly in bile

Negligible renal excretion

Contraindications

Known hypersensitivity to montelukast or any component of the formulation

Not indicated for relief of acute bronchospasm or status asthmaticus

Do not substitute for inhaled or oral corticosteroids without medical supervision

Warnings and Precautions

Neuropsychiatric Events

Black Box Warning (FDA 2020): Serious behavior and mood-related changes including agitation, aggression, depression, suicidal thoughts, and completed suicide

Counsel patients and caregivers to monitor for behavioral changes

Use only if benefits outweigh risks, especially in allergic rhinitis

Eosinophilic Conditions

Systemic eosinophilia, vasculitis, or Churg-Strauss syndrome-like presentation may occur (often after corticosteroid reduction)

Careful monitoring advised in asthmatic patients with eosinophilia

Hepatic Impairment

Mild-to-moderate impairment: no dose adjustment required

Severe impairment: use with caution due to metabolism via liver

Phenylketonuria (PKU)

Chewable tablets contain aspartame

Not suitable for individuals with PKU

Pregnancy and Lactation

Pregnancy Category B (US)

No evidence of fetal harm in animal studies

Use in pregnancy if clearly needed

No known teratogenicity

Lactation

Excretion into human milk unknown

Animal data suggest low milk concentration

Consider risk-benefit analysis before use during breastfeeding

Adverse Effects

Common (≥1%)

Headache

Abdominal pain

Cough

Diarrhea

Dizziness

Fatigue

Fever

Rash

Nasal congestion

Otitis media (in children)

Less Common

Elevated liver enzymes

Dyspepsia

Myalgia

Sleep disturbances

Rare but Serious

Neuropsychiatric symptoms: hallucinations, suicidal ideation, depression

Churg-Strauss syndrome

Stevens-Johnson syndrome

Thrombocytopenia

Anaphylaxis or angioedema

Hepatitis

Pediatric-Specific Effects

Hyperactivity

Nightmares

Aggression

Behavioral disturbances

Closely monitor children for mood or sleep changes

Overdose

Symptoms

Generally mild

Abdominal pain

Somnolence

Thirst

Headache

Vomiting

Hyperactivity

Management

No specific antidote

Symptomatic and supportive treatment

Activated charcoal may be considered in recent ingestion

Drug Interactions

CYP Enzyme Modulators

Rifampin: may reduce plasma levels by enhancing metabolism

Phenobarbital and phenytoin: potential enzyme inducers, reduce effectiveness

CYP Inhibitors (e.g., ketoconazole, fluconazole)

Minimal clinical significance due to wide therapeutic index

Gemfibrozil

May increase montelukast levels slightly

No dose adjustment required

Theophylline and warfarin

No significant interactions observed

Other Anti-Asthmatic Drugs

Can be used in combination with inhaled corticosteroids or β2-agonists

Do not replace fast-acting bronchodilators

Use in Special Populations

Children

Approved for use from 6 months of age (granules)

Behavioral monitoring required in pediatric population

Elderly

No overall difference in safety observed

Use standard adult dosing

Renal Impairment

No dose adjustment necessary due to biliary excretion

Hepatic Impairment

Mild/moderate: safe

Severe: caution advised

Monitoring Parameters

Asthma control (symptom frequency, rescue inhaler use, peak flow)

Behavior and mood changes

Signs of hypersensitivity or eosinophilia

Liver function tests in long-term therapy or hepatically impaired patients

Formulations Available

Tablets

10 mg (film-coated): adults and adolescents

Chewable Tablets

4 mg: for children 2–5 years

5 mg: for children 6–14 years

Oral Granules

4 mg sachets: for children 6 months to 5 years

Comparative Pharmacology

Montelukast vs Zafirlukast

Zafirlukast must be taken on an empty stomach

Montelukast has once-daily dosing and superior adherence

Montelukast has fewer drug interactions

Montelukast vs Inhaled Corticosteroids (ICS)

ICS are more effective in controlling persistent asthma

Montelukast useful for mild asthma or patients with ICS intolerance

Combination often used in moderate cases

Montelukast vs Antihistamines

Less effective than intranasal corticosteroids for allergic rhinitis

More beneficial when combined with antihistamines in seasonal allergies

Montelukast vs Biologics (e.g., omalizumab)

Biologics are used in severe asthma

Montelukast is an oral agent for mild to moderate cases

Used as step 2–3 controller per asthma guidelines

Legal and Regulatory Status

Prescription-only medicine in most countries

Black Box Warning (US FDA) for neuropsychiatric risks (2020)

Listed on the WHO Model List of Essential Medicines