Salmeterol
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Salmeterol: Respiratory malformation
One-Sentence Summary
Salmeterol is a long-acting beta2-adrenergic agonist that is marketed in Canada as an inhaled medicine. The TxGNN model predicts it may be useful for respiratory malformation, but no study directly addresses this disease. The only supporting material is 2 loosely related clinical trials and several publications on other airway conditions, so the evidence is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Respiratory malformation |
| TxGNN Prediction Score | 0.9991 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 12 of 12) |
| Number of DINs | 12 (marketed: 12) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Salmeterol belongs to the long-acting beta2-agonist class. These drugs relax airway smooth muscle and may also influence ciliary beat frequency and mucociliary clearance.
“Respiratory malformation” is a heterogeneous category with no single, direct mechanistic rationale for salmeterol. Any plausible link is indirect. Some conditions with abnormal ciliary function or impaired airway clearance, such as primary ciliary dyskinesia and cystic fibrosis, might respond to agents that modulate ciliary activity. This evidence is not specific to malformation. The high TxGNN score should therefore be treated as a hypothesis-generating signal, not as proof of benefit.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00005110 | Not applicable | Suspended | Not reported | Six-month comparison of inhaled salmeterol with albuterol or placebo for long-term bronchodilator benefit in cystic fibrosis. This is a related airway disease, not a malformation. |
| NCT01681979 | Not applicable | Completed | 1 | Study of asthma treatment in pregnancy and adverse pregnancy outcomes. Not related to respiratory malformation. |
Neither trial studies respiratory malformation directly.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 34902004 | 2022 | RCT | JAMA Pediatrics | Inhaled corticosteroids alone or with long-acting beta2-agonists for reduced lung function in preterm-born children. This is a related population, not malformation. |
| 15293609 | 2004 | Randomized crossover study | European Respiratory Journal | In 23 patients with COPD, salmeterol reduced lung hyperinflation and changed the ventilatory response to exercise. |
| 26229457 | 2015 | Review | Int J Chron Obstruct Pulmon Dis | Role of dual bronchodilation in COPD management. |
| 20528601 | 2010 | Review | Journal of Asthma | Review of a combined inhaled corticosteroid and long-acting beta2-agonist inhaler in persistent asthma. |
| 22608352 | 2012 | Observational | Respiratory Medicine | Nasal ciliary beating is depressed in COPD, which provides context for ciliary function. |
| 30021361 | 2018 | Preclinical | Biomedicine & Pharmacotherapy | Thyme extract increased mucociliary beating frequency in cells from COPD patients. Salmeterol was not tested. |
| 20703071 | 2010 | Case report | Arerugi | A patient with primary ciliary dyskinesia who had previously been diagnosed with asthma. |
None of these publications studies salmeterol in respiratory malformation.
Canada Market Information
Health Canada records show 12 valid licences, with none cancelled. Five are listed below. Several are products that combine salmeterol with fluticasone propionate, so they do not describe the approval of salmeterol alone.
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02231129 | SEREVENT DISKUS (50MCG/DOSE) | Not listed | Not listed |
| 02245127 | ADVAIR | Not listed | Not listed |
| 02240837 | ADVAIR 500 DISKUS | Not listed | Not listed |
| 02495600 | WIXELA INHUB | Not listed | Not listed |
| 02494523 | PMS-FLUTICASONE PROPIONATE/SALMETEROL DPI | Not listed | Not listed |
Safety Considerations
- Key Warnings and Contraindications: Please refer to the package insert for safety information.
- Drug Interactions: The interaction screening found 100 interacting drugs. Notable examples:
- Major: clarithromycin.
- Moderate: epinephrine, famotidine, isometheptene, diethylpropion, dolasetron, and several antidiabetic agents (acarbose, alogliptin, canagliflozin, chlorpropamide, dapagliflozin, empagliflozin, albiglutide, dulaglutide).
- Minor: several corticosteroids (hydrocortisone, triamcinolone, dexamethasone, beclomethasone, betamethasone, budesonide).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but no trial or publication studies respiratory malformation directly. The mechanistic link is indirect and non-specific, so the evidence level is L5.
To proceed, the following is needed:
- Clear definition of which respiratory malformation subtypes, if any, might benefit, and a mechanistic rationale for each.
- Mechanism-of-action data for salmeterol.
- Preclinical or clinical studies directly in the target condition.
- Review of the Health Canada package insert for warnings and contraindications.
- Assessment of formulation and route suitability for the target population, including paediatric use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.