Generic Name

Montelukast

Mechanism

• CysLT1 receptor blockade: Montelukast competitively inhibits leukotriene D4 (LTD₄) binding to the CysLT1 receptor on bronchial smooth muscle and mucosal cells.
• ↓ Bronchoconstriction, vascular permeability, mucus secretion, and eosinophilic infiltration.
• ↓ Production of pro-inflammatory cytokines (IL‑4, IL‑5, IL‑13) and chemokines.
• Result: reduced airway inflammation and improved bronchodilation, especially in late‑phase asthma responses.

Pharmacokinetics

| Drug interactions | CYP3A4 inhibitors (e.g., ketoconazole) ↑ montelukast levels; CYP3A4 inducers (e.g., rifampin) ↓ levels.

Indications

• Chronic persistent asthma (all age groups).
• Exercise‑induced bronchospasm (children & adults).
• Allergic rhinitis (with or without asthma).
• Aspirin‑induced asthma (secondary prevention).
• Chronic rhinosinusitis (off‑label, moderate benefit).

Contraindications

• Contraindicated: known hypersensitivity to montelukast or any excipient.
• Warnings:
• Not indicated for acute severe or life‑threatening asthma attacks.
• Use with caution in patients with pre‑existing liver disease (monitor LFTs).
• Potential neuropsychiatric effects: agitation, depression, suicidal ideation—monitor mood changes, especially in children/adolescents.
• Pregnancy Category C – use only if benefits outweigh risks.
• Avoid concomitant use of strong CYP3A4 inhibitors or inducers without dose adjustment.

Dosing

• Take with or without food.
• Continue daily even during symptom remission; added as maintenance or rescue for exercise‑induced asthma.

Adverse Effects

Common (≤10 %)
• Headache, upper‑respiratory‑tract infections, nasal congestion, abdominal pain, nausea.
• Mild insomnia, rash.

Serious (≤1 %)
• Severe hepatotoxicity (ALT/AST ↑ >5× ULN) → discontinue.
• Eosinophilic granulomatosis with polyangiitis.
• Neuropsychiatric: aggression, depression, suicidal thoughts.
• Rare allergic reactions (anaphylaxis).

Monitoring
• Baseline liver function tests (ALT, AST, bilirubin) and repeat after 4–6 wk or if symptoms arise.
• CBC if eosinophilia or vasculitis suspected.
• Observe for mood or behavior changes; report promptly.

Monitoring

• Liver function: baseline, week 4, then monthly for chronic therapy if clinically indicated.
• Renal function: baseline for patients >65 yrs or with CKD.
• Clinical response: symptom diary, peak flow variability.
• Adverse event reporting for neuropsychiatric changes.

Clinical Pearls

1. Timing matters – bedtime dosing aligns with the circadian peak of leukotriene production, enhancing efficacy.

2. Add‑on therapy – Montelukast can reduce inhaled steroid doses by up to 20 % in pediatric asthma with minimal adverse effects.

3. Exercise‑induced asthma – Oral montelukast 4 mg pre‑exercise (30 min prior) is effective in both adults and children.

4. Aspirin‑induced asthma – Continuation of montelukast during aspirin desensitization improves long‑term control.

5. No rescue role – Never use as first‑line acute bronchodilator; treat severe attacks with β₂‑agonists or systemic steroids.

6. Psychiatric vigilance – Particularly in adolescents, screen for mood changes at each visit; consider early referral if negative mood trends present.

7. Drug interactions – Concomitant CYP3A4 inhibitors (ketoconazole, erythromycin) may require dose adjustment or monitoring.

8. Long‑term safety – The protracted receptor occupancy means drug effects can persist for up to a week after stopping; counsel patients on this.

9. Pregnancy – Limited data; use only if no safer alternatives exist; counsel regarding potential risk to fetus.

10. Labeling updates – Recent FDA updates emphasize psychiatric warning; keep up‑to‑date with prescribing information changes.

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• Key Takeaway: *Montelukast* is a well‑established leukotriene receptor antagonist that provides sustained anti‑inflammatory benefit in asthma and allergic rhinitis, with a favorable safety profile when monitored appropriately.