Montelukast
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Montelukast: From Asthma to Bronchitis
One-Sentence Summary
Montelukast is a leukotriene receptor antagonist marketed for asthma. The TxGNN model predicts it may help in bronchitis. The evidence is thin for bronchitis itself: 23 clinical trials and 20 publications were retrieved, but most concern related conditions (bronchiolitis, post-transplant bronchiolitis obliterans, non-asthmatic eosinophilic bronchitis).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Asthma (inferred from the pack’s asthma entry; the SAHPRA indication text was not captured) |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L2 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not formally recorded in the pack. Montelukast is known to block the cysteinyl leukotriene receptor 1 (CysLT1). This may reduce leukotriene-driven airway inflammation, bronchoconstriction and mucus secretion.
Asthma and bronchitis are both airway inflammatory conditions, so the link is plausible. It is most credible for eosinophilic and obstructive forms of bronchitis. It is also plausible for post-transplant bronchiolitis obliterans, where montelukast is used within combination regimens.
The evidence mixes several distinct diseases (bronchitis, bronchiolitis, bronchiolitis obliterans syndrome). No Phase 3 montelukast trial for bronchitis proper was found. The prediction is therefore best treated as a research question, not an established new use.
Clinical Trial Evidence
The 10 most relevant of 23 retrieved trials are shown. No results are posted for the bronchitis-specific trials. No SANCTR or PACTR registrations were found.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04613180 | Phase 4 | Unknown | 100 | Montelukast for treatment and prevention of recurrent obstructive bronchitis in children aged 1–7. Directly on target; no results available. |
| NCT01121016 | Phase 4 | Unknown | 63 | Randomised, double-blind trial of add-on montelukast to inhaled budesonide in non-asthmatic eosinophilic bronchitis. Outcome is cough severity. |
| NCT00863317 | NA | Completed | 141 | Randomised, double-blind, placebo-controlled trial of daily montelukast in infants with first-time viral bronchiolitis. Outcome is duration of acute illness. |
| NCT00076973 | Phase 3 | Completed | 1125 | Two doses of montelukast vs placebo for respiratory symptoms after RSV bronchiolitis in children aged 3–24 months. |
| NCT01370187 | NA | Completed | 146 | Montelukast in acute bronchiolitis and post-bronchiolitis wheezing in infants aged 3–12 months. |
| NCT00524693 | NA | Completed | 51 | Double-blind, placebo-controlled trial in acute RSV bronchiolitis, including cytokine profiles. |
| NCT01307462 | Phase 2 | Completed | 36 | Fluticasone + azithromycin + montelukast (FAM) for bronchiolitis obliterans after stem cell transplant. Montelukast’s contribution cannot be isolated. |
| NCT00656058 | Phase 2 | Completed | 25 | Montelukast for bronchiolitis obliterans after allogeneic or autologous stem cell transplant. |
| NCT01211509 | Phase 4 | Completed | 30 | Placebo-controlled trial of montelukast for bronchiolitis obliterans syndrome after lung transplant. |
| NCT03072849 | N/A | Completed | 23 | Early detection and FAM therapy after paediatric stem cell transplant. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25563311 | 2015 | RCT | Chin Med J | Add-on montelukast to budesonide vs budesonide alone in non-asthmatic eosinophilic bronchitis. Assessed quality of life, airway eosinophilia and cough. |
| 24118637 | 2014 | Systematic review | Pediatr Allergy Immunol | Montelukast for preventing wheezing after RSV bronchiolitis. |
| 22819521 | 2012 | Pilot study | Respir Med | Add-on montelukast vs double-dose budesonide in non-asthmatic eosinophilic bronchitis. |
| 38504551 | 2024 | Review | Ther Adv Respir Dis | Therapeutic potential and possible mechanisms of montelukast in bronchiolitis obliterans syndrome after lung or stem cell transplant. |
| 26475726 | 2016 | Phase 2, single-arm | Biol Blood Marrow Transplant | FAM regimen in 36 patients with new-onset bronchiolitis obliterans syndrome. Primary endpoint was treatment failure. |
| 35114411 | 2022 | Phase 2, single-arm | Transplant Cell Ther | Montelukast for bronchiolitis obliterans syndrome after transplant, with pathogenesis investigation. |
| 27229850 | 2016 | Cohort | Respir Res | Budesonide/formoterol, montelukast and N-acetylcysteine for post-transplant bronchiolitis obliterans syndrome. |
| 25846070 | 2016 | Clinical study | World J Pediatr | RSV bronchiolitis with Mycoplasma co-infection and add-on montelukast. |
| 20442434 | 2010 | Preclinical (mouse) | Am J Respir Crit Care Med | Montelukast during primary RSV infection in mice, examining airway hyperresponsiveness and inflammation after reinfection. |
| 28545478 | 2017 | Preclinical (rat) | J Cardiothorac Surg | LTB4 and montelukast in transplant-related bronchiolitis obliterans. |
South Africa Market Information
Approved indication text was not available in the retrieved records for any of these products. The dosage form “Chu” is reproduced as listed in the source.
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 44/10.2.2/0486 | Sintrine | Chu | — |
| Reg. No. 44/10.2.2/0823 | Lumont | Chu | — |
| Reg. No. 44/10.2.2/0829 | Sintair | Chu | — |
| Reg. No. 49/5.7.1/0551 | Glemolev | Tablet | — |
Safety Considerations
- Literature-derived signals (not label data): The retrieved literature notes a US FDA boxed warning (2020) on neuropsychiatric adverse events with montelukast (PMID 37758273). Further cohort studies address this risk in children (PMIDs 39836401, 36948487, 35608857). An anaphylaxis case report (19284938) and a case series on eosinophilic granulomatosis with polyangiitis (39959324) were also retrieved. A pregnancy meta-analysis is available (39129058).
Please refer to the SAHPRA-approved Professional Information (PI) for warnings, contraindications and drug interactions. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and there is a Phase 4 trial in paediatric recurrent obstructive bronchitis. However, that trial has unknown status and no results, and the other evidence concerns bronchiolitis or transplant-related disease. No completed Phase 3 trial exists for bronchitis itself. SAHPRA package insert data are also missing, which blocks safety screening.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications (download and parse the PI)
- Formal mechanism of action data from DrugBank
- Results or status confirmation for NCT04613180 and NCT01121016
- A neuropsychiatric safety monitoring plan, particularly for children
- Confirmation of the approved indication text for the four SAHPRA registrations
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.