Montelukast
| Evidence Level: L2 | Predicted Indications: 5 |
Table of Contents
Montelukast: From Asthma to Bronchitis
One-Sentence Summary
Montelukast is a cysteinyl leukotriene receptor antagonist, best known for treating asthma and allergic airway disease. The TxGNN model predicts it may be effective for bronchitis, and the search returned 23 clinical trials and 20 publications. Only 2 trials (NCT04613180, NCT01121016) and 2 papers (PMID 25563311, 22819521) address bronchitis directly, so the evidence is thin and the disease mapping is imprecise. Most of the signal concerns bronchiolitis and bronchiolitis obliterans syndrome.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the Evidence Pack (US license entries carry no indication text). Asthma is the well-established use of montelukast |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L2 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (all listed products are generic ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the DrugBank record supplied. The literature in the pack describes montelukast as a selective, orally active CysLT1 receptor antagonist. Blocking this receptor can reduce leukotriene-driven airway inflammation, bronchoconstriction, mucus production and eosinophil recruitment.
Bronchitis is an inflammatory airway condition, so the mechanism is plausible. The best direct support comes from nonasthmatic eosinophilic bronchitis (NAEB), where two studies tested montelukast as add-on to inhaled budesonide (PMID 25563311, 22819521; NCT01121016). A trial in children with recurrent obstructive bronchitis (NCT04613180) is also listed, but its status is Unknown and no results are provided.
Much of the remaining evidence is about neighbouring diseases: viral or RSV bronchiolitis in infants and bronchiolitis obliterans syndrome (BOS) after transplant. These are different conditions from bronchitis. One BOS regimen (fluticasone, azithromycin, montelukast) is a combination, so the effect of montelukast alone cannot be isolated. The high TxGNN score most likely reflects closeness to these related respiratory diseases, not proven efficacy in bronchitis.
Clinical Trial Evidence
The pack contains no results or effect sizes. The findings below summarize each trial’s stated objective.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04613180 | Phase 4 | Unknown | 100 | Montelukast to treat and prevent recurrent obstructive bronchitis in children aged 1–7 |
| NCT01121016 | Phase 4 | Unknown | 63 | Randomized, double-blind, placebo-controlled add-on montelukast to inhaled budesonide for nonasthmatic eosinophilic bronchitis (primary endpoint: cough VAS) |
| NCT00076973 | Phase 3 | Completed | 1125 | Two montelukast doses vs placebo for respiratory symptoms of RSV bronchiolitis in children aged 3–24 months |
| NCT00863317 | NA | Completed | 141 | Randomized, double-blind, placebo-controlled daily montelukast for viral bronchiolitis (bronchiolitis, not bronchitis) |
| NCT00524693 | NA | Completed | 51 | Placebo-controlled trial of montelukast in acute RSV bronchiolitis, with cytokine profiles |
| NCT01370187 | NA | Completed | 146 | Montelukast in acute bronchiolitis and post-bronchiolitis wheezing, infants 3–12 months |
| NCT01211509 | Phase 4 | Completed | 30 | Randomized, double-blind, placebo-controlled montelukast for BOS after lung transplant |
| NCT00656058 | Phase 2 | Completed | 25 | Montelukast for bronchiolitis obliterans after stem cell transplant |
| NCT01307462 | Phase 2 | Completed | 36 | Fluticasone + azithromycin + montelukast combination for post-transplant bronchiolitis obliterans (montelukast effect cannot be isolated) |
| NCT02479074 | Phase 4 | Completed | 49 | Cough response to montelukast or prednisolone in chronic cough with raised exhaled NO |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25563311 | 2015 | RCT | Chin Med J | Montelukast plus budesonide vs budesonide alone in NAEB, assessing airway inflammation, cough and quality of life |
| 22819521 | 2012 | Pilot study | Respir Med | Add-on montelukast vs double-dose budesonide in NAEB |
| 24118637 | 2014 | Systematic review | Pediatr Allergy Immunol | Montelukast for preventing wheezing after bronchiolitis |
| 38504551 | 2024 | Review | Ther Adv Respir Dis | Therapeutic potential and mechanisms of montelukast in BOS after lung or stem cell transplant |
| 35114411 | 2022 | Phase II trial | Transplant Cell Ther | Single-arm, open-label trial of montelukast for BOS after hematopoietic cell transplant |
| 26475726 | 2016 | Phase II trial | Biol Blood Marrow Transplant | Fluticasone, azithromycin and montelukast (FAM) in 36 patients with new-onset BOS |
| 25846070 | 2016 | Clinical study | World J Pediatr | RSV bronchiolitis with Mycoplasma co-infection, with add-on montelukast |
| 18296556 | 2008 | PK/safety study | J Clin Pharmacol | Pharmacokinetics and tolerability of montelukast granules in 12 infants aged 1–3 months with bronchiolitis |
| 20442434 | 2010 | Preclinical (mouse) | Am J Respir Crit Care Med | Montelukast during primary RSV infection prevented airway hyperresponsiveness and inflammation on reinfection |
| 28545478 | 2017 | Preclinical (rat) | J Cardiothorac Surg | LTB4 and montelukast in transplant-related bronchiolitis obliterans |
US Market Information
The license records contain no approved-indication text, so that column is omitted.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA200405 | Montelukast Sodium | Chewable tablet | AvPAK |
| ANDA202468 | Montelukast Sodium | Film-coated tablet | PD-Rx Pharmaceuticals, Inc. |
| ANDA090984 | Montelukast Sodium | Chewable tablet | Proficient Rx LP |
| ANDA202717 | Montelukast Sodium | Film-coated tablet | Accord Healthcare Inc. |
| ANDA203037 | Montelukast | Chewable tablet | Proficient Rx LP |
Only the first 5 of 20 licenses are shown. All listed forms are oral.
Safety Considerations
- Neuropsychiatric events: The literature in the pack states that the US FDA issued a boxed warning on neuropsychiatric adverse effects of montelukast in 2020 (PMID 37758273). Observational studies in children and adults report mixed findings (PMIDs 39836401, 35608857, 36948487, 39578088).
- Paediatric use: The bronchitis and bronchiolitis evidence is largely in infants and young children, the population where neuropsychiatric monitoring matters most.
The package insert warnings, contraindications and drug interaction data were not retrieved. Please refer to the package insert for complete safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and there are small add-on studies in eosinophilic bronchitis. But there is no Phase 3 RCT in bronchitis, the strongest signals are in neighbouring conditions (bronchiolitis, BOS), and the safety data needed for screening are missing. It is best treated as a research question until these gaps are closed.
To proceed, the following is needed:
- Package insert warnings and contraindications (blocking data gap)
- Mechanism of action data from DrugBank
- Extraction of outcomes and effect sizes from NCT04613180, NCT01121016 and PMID 25563311
- A decision on whether “bronchitis” means NAEB, recurrent obstructive bronchitis in children or another subtype, followed by an adequately powered RCT in that population
- A neuropsychiatric risk-monitoring plan, especially for paediatric use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.