Montelukast

Montelukast: Comprehensive Overview

Montelukast is a selective leukotriene receptor antagonist (LTRA) widely employed for the prophylactic and maintenance treatment of asthma and the alleviation of allergic rhinitis symptoms. It acts by competitively inhibiting leukotriene binding to receptors on airway smooth muscles and vascular endothelium. Leukotrienes are potent inflammatory mediators that contribute to asthma by promoting bronchoconstriction, mucus secretion, and airway oedema. By mitigating these effects, Montelukast reduces airway inflammation, improves airflow, and provides symptomatic relief, serving as a vital oral adjunct or alternative to inhaled therapies.

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Uses

Montelukast is primarily indicated for long-term management of mild to moderate persistent asthma and for the treatment of seasonal and perennial allergic rhinitis. It is also used to prevent exercise-induced bronchospasm and to manage chronic urticaria refractory to antihistamines. Emerging evidence supports its off-label use in conditions like eosinophilic oesophagitis, atopic dermatitis, and chronic obstructive pulmonary disease (COPD), though further research is necessary.

Dosage and Administration

Montelukast is administered orally once daily, regardless of food intake. Standard dosages are as follows:

• 10 mg film-coated tablets for adults and adolescents aged 15 years and older.

• 5 mg chewable tablets for children aged 6–14 years.

• 4 mg chewable tablets or oral granules for children aged 2–5 years.

• 4 mg granules for infants aged 6 months to 2 years. Strict adherence to the prescribed dosing schedule is crucial for optimal efficacy.

Dose Adjustment in Different Diseases

• Renal Impairment: No adjustment is necessary, as Montelukast is metabolised hepatically with minimal renal excretion.

• Hepatic Impairment: Use with caution in mild to moderate hepatic dysfunction; avoid in severe hepatic impairment due to extensive liver metabolism.

• Pregnancy: Classified as Pregnancy Category B. While animal studies show no harm, Montelukast should be used during pregnancy only when clearly needed, following thorough counselling.

Effects and Side Effects

Montelukast is generally well tolerated. Common adverse effects include headache, gastrointestinal upset, and fatigue. More serious, though rare, neuropsychiatric effects such as agitation, aggression, depression, hallucinations, and suicidal ideation have been reported. Prompt recognition and intervention are critical, especially in paediatric and vulnerable populations.

How Montelukast Works

Montelukast selectively antagonises cysteinyl leukotriene receptor type 1 (CysLT1) found on airway smooth muscle and immune cells. By blocking leukotriene D4 activity, it reduces bronchoconstriction, mucosal oedema, and eosinophilic infiltration, thereby stabilising airway function and ameliorating allergic symptoms. Its action makes it highly suitable for maintenance therapy in chronic respiratory disorders.

Drug Combinations in Use

Montelukast is often used alongside inhaled corticosteroids (ICS) to improve asthma control. It may also be combined with antihistamines such as cetirizine or loratadine for allergic rhinitis. During acute exacerbations requiring corticosteroid infusions, Montelukast should be continued to maintain baseline asthma management. It must not replace short-acting bronchodilators during acute asthma attacks.

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Presentation and Dosage Forms

Form	Strength	Target Group
Film-coated tablet	10 mg	Adults and adolescents (15+ years)
Chewable tablet	5 mg	Children 6–14 years
Chewable tablet	4 mg	Children 2–5 years
Oral granules	4 mg	Infants 6 months–2 years

Pharmacokinetics and Pharmacodynamics

Montelukast is rapidly absorbed, reaching peak plasma concentrations within 3–4 hours. It binds extensively to plasma proteins (>99%) and is metabolised mainly by CYP3A4, CYP2C8, and CYP2C9 enzymes. Elimination occurs primarily via biliary excretion. Pharmacodynamically, it antagonises the CysLT1 receptor without affecting prostaglandin or thromboxane pathways. While not directly antimicrobial, it may reduce infection susceptibility by controlling airway inflammation.

Drug Interaction

Montelukast levels may be influenced by agents affecting cytochrome P450 enzymes. Rifampicin and phenobarbital (enzyme inducers) can lower Montelukast levels, reducing its efficacy. Conversely, inhibitors like gemfibrozil can increase plasma concentrations, raising the risk of adverse effects. Periodic medication reviews are advised when co-administered with such drugs.

Comparison with Other LTRAs

Drug	Mechanism	Clinical Indication	Advantages	Disadvantages
Montelukast	LTRA	Asthma, allergic rhinitis	Oral, once daily	Neuropsychiatric risks
Zafirlukast	LTRA	Asthma	Useful in aspirin-sensitive asthma	Must be taken on an empty stomach
Pranlukast	LTRA	Asthma (primarily Asia)	Effective for allergic rhinitis	Limited availability outside Asia

Precautions and Special Considerations

Patients must not discontinue corticosteroids abruptly after starting Montelukast. Monitoring for signs of Churg-Strauss syndrome is essential, particularly during corticosteroid dose reductions. Psychiatric evaluation and vigilant monitoring are recommended, particularly in patients with pre-existing mental health conditions.

Toxicity or Overdose and Antidote

Symptoms of Montelukast overdose include hyperactivity, somnolence, polydipsia, vomiting, and abdominal pain. Treatment is primarily supportive, as there is no specific antidote. Activated charcoal may be considered if the overdose is recent.

Recent Updates and Guidelines (2025)

The 2025 Global Initiative for Asthma (GINA) guidelines reaffirm Montelukast's role as a second-line option for mild persistent asthma and allergic rhinitis, especially where inhaled therapies are impractical. Emphasis has been placed on psychiatric screening and monitoring due to concerns about neuropsychiatric side effects.

Key Facts to Remember

• Montelukast is a maintenance therapy and should not be used for acute symptom relief.

• Daily adherence is crucial to maintain symptom control.

• Close monitoring for mental health changes is essential.

Did You Know?

Since its launch in 1998, Montelukast has revolutionised asthma care by offering a convenient, once-daily oral alternative to inhaled treatments. Exciting research is underway exploring its potential neuroprotective effects in diseases like Alzheimer's.

References

1. Global Initiative for Asthma (GINA) 2025 Report.

2. Montelukast Prescribing Information - FDA.

3. British National Formulary (BNF) 2025.

4. NICE Guidelines on Asthma Management 2025.

5. Drugs.com. Montelukast Professional Information.

6. EMA (European Medicines Agency) Review on Montelukast Safety 2025.