Salmeterol
| Evidence Level: L1 | Predicted Indications: 7 |
Table of Contents
Salmeterol: From Established Asthma/COPD Use to Bronchitis
One-Sentence Summary
Salmeterol is a long-acting beta2-adrenergic agonist (LABA) bronchodilator, long used for asthma and COPD. The TxGNN model predicts it may be effective for Bronchitis, which here is largely chronic bronchitis as a COPD phenotype. Currently 16 clinical trials and 20 publications are linked to this prediction, but most trials test salmeterol/fluticasone combinations, so salmeterol’s own contribution is hard to isolate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the SAHPRA licence data. Salmeterol is an established asthma/COPD bronchodilator per the literature |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L1 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 6 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. Salmeterol is a long-acting beta2-agonist. It relaxes airway smooth muscle and may also improve mucociliary clearance, the airway’s self-cleaning mechanism (PMID 15970448).
Chronic bronchitis is a COPD phenotype, so this prediction reflects an established respiratory use rather than a novel repurposing. In practice, the finding supports existing practice.
Most trials test salmeterol together with fluticasone, an inhaled corticosteroid. The effect of salmeterol alone therefore cannot be cleanly separated from the combination.
Clinical Trial Evidence
Ten of the 16 linked trials are shown below, selected for relevance. All are COPD or chronic bronchitis studies. No SANCTR or PACTR registrations were found.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02173691 | Phase 3 | Completed | 584 | 6-month double-blind comparison of tiotropium, salmeterol and placebo in COPD. Direct salmeterol evidence |
| NCT00268177 | Phase 3 | Completed | 130 | Salmeterol/fluticasone 50/500 vs placebo for bronchial anti-inflammatory activity in COPD |
| NCT01110200 | Phase 4 | Completed | 639 | Salmeterol/fluticasone vs salmeterol alone on COPD exacerbation rate after hospitalisation |
| NCT00633217 | Phase 4 | Completed | 247 | Fluticasone/salmeterol HFA inhaler vs Diskus over 12 weeks in COPD |
| NCT00857766 | Phase 4 | Completed | 249 | Fluticasone/salmeterol vs placebo on arterial stiffness in COPD over 16 weeks |
| NCT00269087 | Phase 3 | Completed | 122 | 56-week long-term safety study of fluticasone/salmeterol 50/500 in COPD (chronic bronchitis, emphysema) |
| NCT01332409 | N/A | Completed | 2000 | Post-marketing safety and effectiveness investigation of salmeterol/fluticasone in COPD, with pneumonia as a priority item. Not randomised |
| NCT00064402 | Phase 3 | Completed | 741 | Arformoterol study in COPD, placebo- and active-controlled. Salmeterol is likely the comparator (title truncated) |
| NCT00403286 | Phase 2 | Completed | 457 | Dose-finding of fluticasone/formoterol against Advair Diskus (fluticasone/salmeterol) in COPD |
| NCT00269126 | Phase 3 | Completed | 150 | Comparison of two medicines in COPD. Title uninformative, relevance unconfirmed |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12970006 | 2003 | RCT | Chest | Fluticasone 250 µg/salmeterol 50 µg in one Diskus inhaler vs placebo and each component alone in COPD |
| 19124357 | 2008 | RCT | Ther Adv Respir Dis | 12-month safety and tolerance of arformoterol vs salmeterol in COPD |
| 9916607 | 1998 | RCT | Clin Ther | Open-label comparison of inhaled salmeterol and oral theophylline in mild-to-moderate COPD (efficacy, tolerability, quality of life) |
| 17196106 | 2006 | Meta-analysis | Respir Res | Salmeterol 50 mcg twice daily added to usual therapy vs placebo/usual therapy in COPD |
| 15970448 | 2006 | Clinical study | Pulm Pharmacol Ther | Acute effect of salmeterol vs placebo on mucociliary and cough clearance in 14 patients with chronic bronchitis |
| 19210134 | 2009 | Cohort | Curr Med Res Opin | Hospitalisation, ED visits and costs in chronic bronchitis after starting fluticasone/salmeterol vs other inhaled maintenance therapies |
| 15329047 | 2004 | Review | Drugs | Review of salmeterol/fluticasone propionate in COPD |
| 16915216 | 2006 | Patient experience trial | MedGenMed | Fluticasone/salmeterol 250/50 in COPD associated with chronic bronchitis |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish national guideline on diagnosis and pharmacotherapy of stable COPD |
South Africa Market Information
Six SAHPRA registrations are recorded, and five are shown here. The licence records do not include approved indication text. Several products are not obviously salmeterol products (for example Keppra and Med-lemon flu & congestion), so the licence-to-ingredient mapping should be checked.
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 47/21.5.4/1320 | Airflusal Forspiro 50/250 | Accuhaler (Acc) |
| Reg. No. A40/2.5/0587 | Keppra | Solution |
| Reg. No. 50/21.5.4/0731 | Duoasma 25/50 | Inhaler |
| Reg. No. 42/21.5.4/0218 | Sereflo 25/50 HFA 120 dose | Inhaler |
| Reg. No. 27/5.8/0430 | Med-lemon flu & congestion hot medication | Sachet |
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 3 trials in COPD/chronic bronchitis meet the L1 threshold, and salmeterol is an established respiratory bronchodilator. However, most evidence comes from fixed-dose combinations with fluticasone, and this is confirmation of existing practice rather than a new indication.
To proceed, the following is needed:
- Extraction of warnings and contraindications from the SAHPRA package inserts (blocking gap, so safety screening cannot proceed without it).
- Approved indication text from the SAHPRA licences, with the licence-to-ingredient mapping checked (Keppra and Med-lemon do not appear to be salmeterol products).
- Mechanism of action data from DrugBank.
- A guardrail that LABAs should not be used as monotherapy in asthma, and should be used with an inhaled corticosteroid, because of known safety concerns.
- Trials that isolate salmeterol monotherapy in chronic bronchitis.
Other predictions in the pack:
- Asthma and obstructive lung disease: established uses, also rated Proceed with Guardrails.
- Respiratory malformation, Rienhoff syndrome, asthma-related traits and atopic eczema: Hold. These have no or only indirect, preclinical evidence.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.