Montelukast

證據等級: L5

預測適應症: 5 個

Montelukast: From Asthma to Bronchitis

One-Sentence Summary

Montelukast is a leukotriene receptor antagonist originally used to control asthma and allergic rhinitis. The TxGNN model predicts it may also be effective for Bronchitis (a category that in this evidence set spans infectious/eosinophilic bronchitis and post-transplant bronchiolitis obliterans), currently supported by 23 clinical trials and 20 publications, though a substantial share of the retrieved trials are ontology-matching noise rather than true montelukast evidence.

Quick Overview

Item	Content
Original Indication	Asthma / Allergic Rhinitis (no local market license record found in this jurisdiction)
Predicted New Indication	Bronchitis
TxGNN Prediction Score	99.95%
Evidence Level	L2
US Market Status	✗ Not Marketed
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

A structured mechanism-of-action record was not available for this drug in the current evidence pack. However, other parts of the same evidence set (the mechanistic rationale attached to the “asthma” candidate) confirm that montelukast is a selective cysteinyl leukotriene receptor 1 (CysLT1) antagonist: it blocks the bronchoconstrictive, mucus-hypersecretory, and eosinophil-recruiting effects of cysteinyl leukotrienes. This is the established mechanism behind its approved use in asthma and allergic rhinitis.

Bronchitis, as retrieved here, is not a single homogeneous disease — the underlying trials cluster into three sub-groups: (1) viral/RSV-induced bronchiolitis in infants, (2) non-asthmatic eosinophilic bronchitis, and (3) bronchiolitis obliterans (BO) following lung or hematopoietic stem-cell transplantation. Leukotriene-mediated inflammation has reasonable biological plausibility in the eosinophilic-bronchitis and post-transplant BO subtypes (both show measurable CysLT activity), which is where the highest-quality trial evidence (Phase 3/4 RCTs) actually concentrates. For general infectious bronchitis, the mechanistic link is comparatively weak.

Data-quality caveat: this evidence pack separately lists “asthma” (rank 3) as a predicted new indication for montelukast, with an evidence level of L1 and 50 clinical trials. Asthma is in fact montelukast’s well-established, decades-old core indication — not a genuine repurposing signal. This indicates the underlying ranking pipeline is not filtering out already-approved indications, and the disease-matching for “bronchitis” and “obstructive lung disease” pulls a similarly large volume of unrelated or duplicated trials (sepsis, ruxolitinib/belumosudil GVHD studies, STEMI, probiotics). All quantitative counts in this report should be read with that caveat in mind.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00863317	N/A	Completed	141	Double-blind placebo-controlled RCT of daily montelukast for viral bronchiolitis in infants; primary endpoint was duration of acute illness.
NCT01211509	Phase 4	Completed	30	Double-blind placebo-controlled RCT testing whether montelukast slows chronic rejection (bronchiolitis obliterans syndrome) after lung transplantation.
NCT01307462	Phase 2	Completed	36	Fluticasone + azithromycin + montelukast (FAM) combination in bronchiolitis obliterans after stem cell transplant.
NCT00394069	Phase 2	Completed	14	Safety, tolerability and plasma concentration of montelukast oral granules in infants 3–6 months with bronchiolitis.
NCT00076973	Phase 3	Completed	1125	Large 2-period RCT of two montelukast (MK0476) doses vs. placebo for respiratory symptoms of RSV-induced bronchiolitis in children 3–24 months.
NCT00656058	Phase 2	Completed	25	Multi-institutional prospective study of montelukast for bronchiolitis obliterans after allogeneic/autologous stem cell transplant.
NCT01121016	Phase 4	Unknown	63	Randomized double-blind add-on montelukast vs. inhaled budesonide alone in non-asthmatic eosinophilic bronchitis.
NCT04613180	Phase 4	Unknown	100	Evaluated effectiveness of montelukast for treatment/prevention of recurrent obstructive bronchitis in children 1–7 years.
NCT00524693	N/A	Completed	51	Double-blind placebo-controlled RCT of montelukast in acute RSV bronchiolitis, assessing clinical progress and cytokine profiles.
NCT01370187	N/A	Completed	146	Montelukast for acute bronchiolitis and post-bronchiolitis viral-induced wheezing in infants 3–12 months.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
25563311	2015	RCT	Chinese Medical Journal	Montelukast + budesonide improved life quality and suppressed airway eosinophilia vs. budesonide alone in non-asthmatic eosinophilic bronchitis.
20976161	2010	RCT	PLoS ONE	Compared fish oil and montelukast, alone and combined, on airway inflammation and hyperpnea-induced bronchoconstriction.
38504551	2024	Review	Ther Adv Respir Dis	Reviews therapeutic potential and mechanisms of montelukast in bronchiolitis obliterans syndrome after lung/HSC transplantation.
30038355	2019	Review	Bone Marrow Transplant	Reviews diagnosis and treatment challenges of bronchiolitis obliterans syndrome, a manifestation of chronic GVHD.
21486501	2011	Review	BMJ Clinical Evidence	General clinical-evidence review of bronchiolitis in infants.
38485149	2024	Guideline	Eur Respir J	ERS/EBMT joint clinical practice guideline on treatment of pulmonary chronic GVHD (includes BO management context).
35114411	2022	Phase II Trial	Transplant Cell Ther	Prospective Phase II trial of montelukast for BOS after hematopoietic cell transplantation; investigates BOS pathogenesis.
26475726	2016	Phase II Trial	Biol Blood Marrow Transplant	FAM (fluticasone/azithromycin/montelukast) regimen for new-onset BOS after HCT (publication of NCT01307462).
27229850	2016	Clinical Study	Respiratory Research	Budesonide/formoterol + montelukast + N-acetylcysteine for BOS after HSCT.
28545478	2017	Preclinical (rat model)	J Cardiothoracic Surgery	Investigated LTB4 and montelukast in transplantation-related bronchiolitis obliterans in a rat model.

US Market Information

Montelukast currently has no marketing license or NDA on record in this jurisdiction (market status: Not Marketed; 0 licenses returned by the regulatory query). No product-level formulation or approved-indication text is available to summarize.

Safety Considerations

Please refer to the package insert for safety information.

Additional signal noted in the literature evidence (not part of the formal DDI/label data queried for this candidate): multiple publications retrieved for related montelukast indications (e.g., PMID 37758273, 35608857, 36948487, 39836401, 39578088) discuss the FDA’s 2020 boxed warning on neuropsychiatric adverse events associated with montelukast. This is not sourced from the structured safety block and should be independently verified against the current label before use in any clinical evaluation.

Conclusion and Next Steps

Decision: Hold

Rationale: The drug has no local marketing authorization, and the blocking data gap (TFDA label/warnings, DG001) means no formal safety review is currently possible. The “bronchitis” evidence itself is a mixed bag — real signal exists only in specific subtypes (post-transplant bronchiolitis obliterans, eosinophilic bronchitis), while much of the raw trial count reflects ontology-matching noise unrelated to montelukast or to bronchitis at all.

To proceed, the following is needed:

TFDA-equivalent label, warnings, and contraindications (DG001, blocking)
Structured mechanism-of-action data from DrugBank (DG002)
Manual disease-subtype triage: separate infectious bronchitis, eosinophilic bronchitis, and bronchiolitis obliterans into distinct candidates, since they have very different evidence strength and mechanistic rationale
Re-run/audit the ranking pipeline — the “asthma” candidate in this same batch is montelukast’s existing approved indication, not a new use, indicating disease-matching needs review before any candidate in this batch is trusted at face value
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.