Salbutamol
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Salbutamol: From Asthma to Papillary Conjunctivitis
One-Sentence Summary
Salbutamol is a short-acting beta-2 agonist bronchodilator, originally used for asthma and bronchial disease. The TxGNN model predicts it may be effective for papillary conjunctivitis (rank 1), but no clinical trials and no publications were found for this prediction, so it rests on the model score alone. Among the other top-ranked predictions, obstructive lung disease has the strongest support (Phase 3 evidence), though it is close to the existing asthma/bronchial indication and is not a true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Asthma, bronchial disease (approved indication text is not listed in the Singapore licence records) |
| Predicted New Indication | Papillary conjunctivitis |
| TxGNN Prediction Score | 99.996% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 17 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known pharmacology, salbutamol is a selective beta-2 adrenergic receptor agonist. It relaxes airway smooth muscle, which explains its efficacy in asthma and bronchial disease. Beta-2 agonism may also reduce mast cell mediator release and vascular permeability.
For papillary conjunctivitis, this offers only a speculative link, through possible suppression of allergic mediator release in the eye. Papillary conjunctivitis is often mechanically or contact-lens induced, so the benefit of a bronchodilator is uncertain. Preclinical work in other conjunctival models (guinea-pig allergic conjunctivitis and topical conjunctival anti-inflammatory activity of beta-2 agonists) is listed under the related prediction "atopic conjunctivitis", not papillary conjunctivitis itself.
The table below shows how the other top-ranked predictions compare:
| Predicted Indication | Evidence Level | Summary |
|---|---|---|
| Obstructive lung disease | L1 | Phase 3 trial of ipratropium/salbutamol in COPD (n=1,118), but the partner drug confounds attribution, and the indication is effectively the original one |
| Anaphylaxis | L2 | Phase 3 RCT (NCT05653024) of inhaled salbutamol vs placebo, terminated with n=24; underpowered |
| Bronchitis / bronchiolitis | L2 | Several trials and reviews; guidelines and meta-analyses generally do not support routine bronchodilator use in infants |
| Common cold | L3 | One small double-blind RCT of cough in children (PMID 26859020) |
| Atopic conjunctivitis | L4 | Preclinical animal data only |
| Nasal cavity disease, acute laryngopharyngitis, anorectal stricture | L5 | Prediction only |
| Pharyngitis | L5 | Prediction only; retrieved papers do not evaluate salbutamol for this condition |
Clinical Trial Evidence
Currently no related clinical trials registered for papillary conjunctivitis.
For reference, the most relevant trials among the other top predictions are:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02177253 | Phase 3 | Completed | 1118 | Ipratropium/salbutamol Respimat vs COMBIVENT in COPD (obstructive lung disease) |
| NCT05653024 | Phase 3 | Terminated | 24 | Inhaled salbutamol vs placebo for abdominal pain in food-induced allergic reactions (anaphylaxis) |
| NCT00114478 | N/A | Unknown | 600 | Epinephrine vs albuterol in bronchiolitis |
| NCT00696540 | Phase 2 | Unknown | 74 | Salbutamol in hypertonic vs normal saline in bronchiolitis |
| NCT06665711 | N/A | Not yet recruiting | 100 | 3% hypertonic saline vs salbutamol in bronchiolitis |
| NCT01721291 | Phase 4 | Completed | 64 | Inhaler treatment and small-airways assessment in COPD |
| NCT02686086 | N/A | Completed | 60 | Bronchodilator via vibrating mesh vs jet nebuliser in COPD |
Literature Evidence
Currently no related literature available for papillary conjunctivitis.
For reference, key publications for the other top predictions:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33893229 | 2021 | Network meta-analysis | Pediatrics | Comparative efficacy of bronchiolitis interventions in acute care |
| 24937099 | 2014 | Systematic review | Cochrane Database Syst Rev | Bronchodilators for bronchiolitis |
| 11983033 | 2002 | Review | Critical Care | 12 RCTs (843 infants) of salbutamol/albuterol in bronchiolitis; 9 showed no effect |
| 2019938 | 1991 | RCT | J Pediatr | Nebulized salbutamol vs saline in 83 children with acute bronchiolitis |
| 24687251 | 2014 | RCT | Eur J Pediatr | Salbutamol, magnesium sulfate and combination in moderate bronchiolitis |
| 36765418 | 2023 | Guideline | Ital J Pediatr | 2022 Italian guidelines on bronchiolitis in infants |
| 34366098 | 2021 | Review | J Allergy Clin Immunol Pract | Salbutamol for gastrointestinal anaphylaxis |
| 26859020 | 2014 | RCT | East Afr Med J | Honey, salbutamol and placebo for cough in children with common cold |
| 1729064 | 1992 | RCT | Chest | Theophylline and salbutamol in irreversible COPD |
| 3666475 | 1987 | Preclinical | Graefes Arch Clin Exp Ophthalmol | Topical salbutamol suppressed allergic conjunctivitis in guinea pigs |
Singapore Market Information
Salbutamol has 17 valid single-ingredient registrations. The approved indication text is not recorded for these licences.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11359P | Ventolin Evohaler 100 mcg | Aerosol, spray | Not recorded |
| SIN08675P | Buventol Easyhaler 200 mcg/inhalation dose | Powder, metered | Not recorded |
| SIN13980P | Azmasol HFA Inhalation Aerosol 100 mcg | Aerosol, metered | Not recorded |
| SIN02913P | Asmol Tablet 4 mg | Tablet | Not recorded |
| SIN02539P | Ventolin Solution for Intravenous Infusion 5 mg/5 ml | Injection | Not recorded |
Available forms include oral (tablet, syrup, suspension), inhaled (aerosol, powder, solution) and injectable products. No ophthalmic formulation is registered, which matters for any conjunctivitis indication.
Safety Considerations
- Contraindications / cautions (from knowledge-graph drug-disease links, not label text): hypertension, long QT syndrome, epilepsy, potassium deficiency, diabetes mellitus and diabetic ketoacidosis, metabolic acidosis, benign prostatic hyperplasia and bladder neck obstruction, ocular hypertension, angle-closure glaucoma, hyperthyroidism/Graves disease/thyrotoxicosis, sudden cardiac arrest, heart conduction disease, myocardial ischemia and coronary artery disease. The glaucoma and ocular hypertension links deserve particular attention for any ocular use.
- Drug Interactions: 100 interactions were identified. Examples of moderate-level ones include epinephrine, clarithromycin, cisapride, famotidine, and several antidiabetic agents (acarbose, alogliptin, canagliflozin, dapagliflozin, chlorpropamide). Corticosteroids (hydrocortisone, budesonide, dexamethasone, and others) are minor.
- Other signals: Anaphylaxis to salbutamol has been reported (case report, PMID 18447148). A meta-analysis of maternal drug use and anorectal malformations (PMID 29747656) raises a possible teratogenicity question, not a therapeutic signal.
For label warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, papillary conjunctivitis, has a very high model score but no trials or literature, and its mechanistic link is speculative. The only strongly supported prediction (obstructive lung disease) is essentially the existing asthma/bronchial indication, not a new use. Anaphylaxis and bronchiolitis are the more genuine repurposing candidates, but the anaphylaxis trial was terminated at n=24 and the bronchiolitis literature is largely negative.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA, plus approved indication text for the Singapore licences
- Mechanism of action data
- For papillary conjunctivitis: preclinical or early clinical studies, and a feasibility assessment of an ophthalmic formulation, as none is registered
- For anaphylaxis: results or a re-powered trial of inhaled salbutamol as an adjunct to epinephrine
- For bronchiolitis: a review of whether new evidence would overturn guideline recommendations against routine bronchodilator use
- Safety review of the cardiovascular, metabolic and glaucoma-related cautions for any new population or route
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.