Terbutaline
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Terbutaline: From Asthma to Obstructive Lung Disease
One-Sentence Summary
Terbutaline is a selective beta-2 adrenergic agonist, originally used to treat asthma, bronchitis and emphysema. The TxGNN model predicts it may be effective for obstructive lung disease, a category that largely overlaps with its existing uses. The data compiled for this report include 15 clinical trials (9 of them completed Phase 3 studies) and 20 publications supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Asthma, bronchitis and emphysema (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, terbutaline is a selective beta-2 adrenergic agonist. It relaxes bronchial smooth muscle through the cAMP pathway, which directly matches the pathophysiology of reversible airflow obstruction.
The predicted indication overlaps with terbutaline's established uses in asthma, bronchitis and emphysema. This is therefore closer to an on-label or near-label category than true repurposing. Several large Phase 3 trials used terbutaline as the as-needed reliever comparator, which supports its efficacy and safety profile. Note that in those studies terbutaline was the active comparator and not the investigational arm.
Among the other predictions, chronic obstructive pulmonary disease (COPD) (score 96.81%) also has strong support, including a Phase 3 trial (NCT00421122) and several randomized studies. Anaphylaxis has only preclinical and animal evidence. The remaining predictions (respiratory malformation, Rienhoff syndrome, laryngotracheitis, bronchial neoplasm, food-dependent exercise-induced anaphylaxis, nasolacrimal duct disease, lacrimal atrophy) have no meaningful supporting evidence and appear to be model artefacts. Their recommendation is Hold.
Clinical Trial Evidence
The 10 most relevant trials for obstructive lung disease:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02322788 | Phase 3 | Completed | 95 | Bricanyl Turbuhaler M3 vs M2: protection against methacholine-induced bronchoconstriction in mild to moderate asthma (4-way crossover) |
| NCT06626620 | Phase 3 | Completed | 120 | IV magnesium sulfate vs terbutaline in children with acute asthma exacerbation |
| NCT02224157 | Phase 3 | Completed | 4215 | Symbicort as needed vs Pulmicort twice daily plus as-needed terbutaline in asthma |
| NCT02149199 | Phase 3 | Completed | 3850 | Symbicort as needed vs as-needed terbutaline vs Pulmicort plus as-needed terbutaline |
| NCT00849095 | Phase 3 | Completed | 860 | As-needed vs regular budesonide/formoterol plus as-needed terbutaline in mild-moderate persistent asthma |
| NCT00839800 | Phase 3 | Completed | 2091 | Symbicort SMART vs Symbicort plus as-needed terbutaline 0.4 mg in asthma |
| NCT00252863 | Phase 3 | Completed | 1600 | Symbicort single inhaler therapy vs conventional best practice in persistent asthma |
| NCT01096017 | Phase 3 | Completed | 24 | Terbutaline Turbuhaler 0.4 mg vs salbutamol pMDI 200 μg in Japanese adults with asthma |
| NCT00837967 | Phase 3 | Completed | 25 | Tolerability of 10 inhalations of Symbicort vs terbutaline on top of Symbicort in Japanese asthma patients |
| NCT00421122 | Phase 3 | Completed | 315 | Symbicort plus Bricasol pMDI vs Pulmicort plus Bricasol pMDI in Chinese COPD patients |
Several trials (for example NCT00849095, NCT02224157, NCT02149199) use terbutaline as a reliever comparator, not as the main study drug. One Phase 2/3 terbutaline exposure-response study (NCT04973345) was withdrawn with no participants enrolled.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29768149 | 2018 | RCT | N Engl J Med | As-needed budesonide-formoterol as an alternative to conventional strategies in mild asthma |
| 30156361 | 2019 | RCT | Acad Emerg Med | Nebulized terbutaline plus ipratropium vs terbutaline alone in acute COPD exacerbation requiring noninvasive ventilation |
| 3073804 | 1988 | RCT | Br J Dis Chest | Oral terbutaline increased diaphragmatic contraction force vs placebo in COPD |
| 6988343 | 1980 | RCT | Int J Clin Pharmacol Ther Toxicol | Oral clenbuterol vs terbutaline in chronic obstructive lung disease (two-week double-blind study) |
| 36227333 | 2023 | Systematic Review | Naunyn-Schmiedeberg's Arch Pharmacol | Clinical pharmacokinetics of terbutaline in humans |
| 23348973 | 2013 | Review | Am J Respir Crit Care Med | Beta-2 agonist therapy in lung disease; terbutaline provides rapid as-needed symptom relief |
| 25515181 | 2015 | Guideline | Basic Clin Pharmacol Toxicol | Finnish guideline on diagnosis and pharmacotherapy of stable COPD |
| 10384064 | 1999 | Randomized crossover study | Lung | Single-dose terbutaline Turbuhaler on lung function and exercise capacity in COPD |
| 1615190 | 1992 | Randomized crossover study | Respir Med | Inhaled terbutaline on FEV1, FVC, dyspnoea and walking distance in chronic obstructive lung disease |
| 33065789 | 2020 | Clinical study | Ann Palliat Med | N-acetylcysteine combined with terbutaline in elderly COPD patients |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN08075P | BUTYLIN SYRUP 1.5 mg/5 ml | Syrup | Not stated in the licence record |
| SIN07055P | ASMALIN SYRUP 1.5 mg/5 ml | Syrup | Not stated in the licence record |
| SIN06420P | ASMALIN TABLET 2.5 mg | Tablet | Not stated in the licence record |
All three registrations are valid single-ingredient products (oral syrup and tablet). No inhaled or injectable forms are registered in the compiled data.
Safety Considerations
- Contraindications and disease-related cautions (from the TxGNN knowledge graph, not label text): hypertension, epilepsy, hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, potassium deficiency, sudden cardiac arrest, heart conduction disease, respiratory failure, hyperthyroidism (Graves disease, thyrotoxicosis), pulmonary oedema, myocardial ischaemia, coronary artery disease, and placental abruption.
- Drug Interactions: 100 interactions were found. The sample reviewed includes mostly Moderate and some Minor interactions.
- Moderate: antidiabetic drugs (acarbose, alogliptin, pioglitazone, canagliflozin, chlorpropamide, albiglutide), epinephrine, isometheptene, famotidine, clarithromycin, loperamide, and laxative or bowel-preparation agents (bisacodyl, picosulfuric acid, polyethylene glycol with electrolytes).
- Minor: corticosteroids (hydrocortisone, triamcinolone, dexamethasone, beclomethasone, betamethasone, budesonide).
- Guardrails from the evidence review: monitor for tachycardia, arrhythmia, hypokalaemia and tremor, particularly in elderly patients with comorbidities.
Please also refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Terbutaline's bronchodilator mechanism fits obstructive airway disease, and multiple completed Phase 3 trials plus randomized studies support its use in asthma and COPD. Because this is essentially an on-label or near-label category, the main uncertainty is about practical positioning and safety, not efficacy. In the large Phase 3 trials terbutaline was a comparator, and long-acting agents are preferred for COPD maintenance, so its role is mainly short-acting or rescue use.
To proceed, the following is needed:
- The Singapore package insert (warnings, contraindications and approved indications), since the licence records have no indication text
- Detailed mechanism of action data
- A cardiovascular and metabolic monitoring plan (heart rate and rhythm, potassium, glucose) for patients with the comorbidities listed above
- Confirmation of terbutaline's role (study drug vs comparator) in the Phase 3 trials, especially NCT00421122 in COPD
- A decision on whether inhaled formulations are needed, since only oral forms are registered locally
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.