Montelukast
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Montelukast: From Allergic Rhinitis and Asthma to Bronchitis
One-Sentence Summary
Montelukast is a leukotriene receptor antagonist, originally used for allergic rhinitis and asthma. The TxGNN model predicts it may be effective for bronchitis, with 17 clinical trials and 20 publications retrieved. However, most of this evidence concerns related conditions (bronchiolitis, bronchiolitis obliterans, eosinophilic bronchitis), not typical bronchitis.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, intrinsic asthma, allergic asthma (from the knowledge graph; the Singapore registration records contain no indication text) |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L2 (one completed Phase 3 RCT, but in the related condition of RSV bronchiolitis) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. The retrieved literature describes montelukast as a selective antagonist of the cysteinyl leukotriene 1 (CysLT1) receptor. By blocking this receptor, it reduces bronchoconstriction, airway swelling and eosinophilic inflammation. This explains its established use in asthma and allergic rhinitis.
Bronchitis and its related airway diseases share parts of this biology. Cysteinyl leukotrienes are released during RSV infection and contribute to airway inflammation. They are also implicated in eosinophilic airway disease that causes chronic cough. This gives a plausible mechanistic reason to test montelukast in bronchitis-type conditions.
The clinical evidence is not specific, though. "Bronchitis" is a broad term, and the studies found cover bronchiolitis in infants, bronchiolitis obliterans after transplant, non-asthmatic eosinophilic bronchitis, and recurrent obstructive bronchitis in children. The data compiled for this report do not show clear benefit in ordinary acute or chronic bronchitis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00076973 | Phase 3 | Completed | 1125 | Two montelukast doses vs placebo for respiratory symptoms of RSV bronchiolitis in children aged 3–24 months |
| NCT00863317 | N/A | Completed | 141 | Daily montelukast vs placebo on illness duration in infants with first-time viral bronchiolitis |
| NCT00524693 | N/A | Completed | 51 | Placebo-controlled trial in acute RSV bronchiolitis, assessing clinical course and cytokine profiles |
| NCT01370187 | N/A | Completed | 146 | Montelukast for acute bronchiolitis and post-bronchiolitis wheezing in infants aged 3–12 months |
| NCT04613180 | Phase 4 | Unknown | 100 | Treatment and prevention of recurrent obstructive bronchitis in children aged 1–7 years |
| NCT01121016 | Phase 4 | Unknown | 63 | Add-on montelukast to inhaled budesonide for cough from non-asthmatic eosinophilic bronchitis |
| NCT00656058 | Phase 2 | Completed | 25 | Montelukast for bronchiolitis obliterans after stem cell transplant |
| NCT01307462 | Phase 2 | Completed | 36 | Fluticasone, azithromycin and montelukast combination for bronchiolitis obliterans after stem cell transplant |
| NCT01211509 | Phase 4 | Completed | 30 | Placebo-controlled trial for bronchiolitis obliterans syndrome after lung transplant |
| NCT00394160 | Phase 2 | Completed | 12 | Safety and plasma levels of montelukast granules in infants aged 1–3 months with bronchiolitis |
These are the 10 most relevant of the 17 trials retrieved. Relevance grading for these trials has not been completed, and the table does not include study results.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25773054 | 2015 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Reviews leukotriene inhibitors such as montelukast for bronchiolitis in infants and young children |
| 24118637 | 2014 | Systematic review | Pediatr Allergy Immunol | Assesses montelukast for preventing wheezing after RSV bronchiolitis |
| 25563311 | 2015 | Clinical study | Chin Med J | Montelukast plus budesonide vs budesonide alone in non-asthmatic eosinophilic bronchitis, looking at cough, airway eosinophilia and quality of life |
| 38504551 | 2024 | Review | Ther Adv Respir Dis | Therapeutic potential and possible mechanisms of montelukast in bronchiolitis obliterans syndrome after lung or stem cell transplant |
| 29704475 | 2018 | Expert panel report | Chest | Systematic reviews on treating chronic cough after acute viral bronchiolitis in children |
| 38485149 | 2024 | Guideline | Eur Respir J | ERS/EBMT guidelines on pulmonary chronic graft-versus-host disease in adults |
| 40926299 | 2025 | Consensus statement | Br J Haematol | Taiwan consensus on diagnosing and managing pulmonary chronic GVHD |
| 14766663 | 2004 | Commentary | Am J Respir Crit Care Med | Commentary on montelukast in RSV bronchiolitis |
| 40702225 | 2025 | Review | Lung | Mast cells and cough hypersensitivity in eosinophilic bronchitis |
| 28545478 | 2017 | Preclinical (rat) | J Cardiothorac Surg | LTB4 and montelukast in transplant-related bronchiolitis obliterans |
The literature is mostly reviews and guidelines, and none of the retrieved papers has been formally classified as an RCT for bronchitis.
Singapore Market Information
Montelukast has 20 valid registrations in Singapore, all single-ingredient oral tablets. The five main ones are listed below. The registration records do not contain approved-indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09769P | Singulair Tablet 10 mg | Tablet | — |
| SIN09768P | Singulair Chewable Tablet 5 mg | Tablet | — |
| SIN11641P | Singulair Chewable Tablet 4 mg | Tablet, film coated | — |
| SIN14383P | Montelukast Sandoz Chewable Tablets 5 mg | Tablet, chewable | — |
| SIN14385P | Montelukast Sandoz Film Coated Tablet 10 mg | Tablet, film coated | — |
Safety Considerations
- Contraindications flagged in the knowledge graph (these come from graph relationships, not from label text): anxiety disorder, neurotic disorder, dysthymic disorder, anxiety, hypereosinophilic syndrome, cutaneous vasculitis.
- Neuropsychiatric events: The retrieved literature notes that the US FDA issued a boxed warning in 2020 on mental health adverse effects of montelukast. Several systematic reviews and cohort studies examine this risk, particularly in children, with some conflicting results. This is especially relevant here because many of the studied populations are infants and children.
- Drug interactions: 100 interactions were found. The moderate-level interactions include dexamethasone, metronidazole, miconazole, nateglinide, nitisinone and troglitazone. Others, such as pantoprazole, omeprazole, metformin and morphine, have unclassified severity.
Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The one completed Phase 3 RCT is in RSV bronchiolitis, not bronchitis, and the other studies are small, early-phase or of unknown status. Package insert warnings and contraindications are also not yet available, so safety screening cannot proceed. For comparison, the same data set shows much stronger evidence for asthma (an existing labeled use), which is not a new indication.
To proceed, the following is needed:
- Define the target condition precisely (acute bronchitis, chronic bronchitis, eosinophilic bronchitis, or pediatric obstructive bronchitis), since the evidence differs for each
- Review the efficacy conclusions of the Cochrane review and the completed trials (NCT00076973, NCT00863317, NCT04613180) in full
- Obtain the Singapore package insert warnings and contraindications
- Detailed mechanism of action data (MOA)
- A neuropsychiatric safety monitoring plan, especially for children
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.