Terbutaline
| Evidence Level: L1 | Predicted Indications: 3 |
Table of Contents
Terbutaline: From Asthma to Obstructive Lung Disease
One-Sentence Summary
Terbutaline is a short-acting bronchodilator originally used for asthma, bronchitis and pulmonary emphysema. The TxGNN model predicts it may be effective for obstructive lung disease, with 14 clinical trials and 20 publications currently supporting this direction. Most of the trials use terbutaline as a comparator or reliever, so this is better read as confirmation of an existing use than as true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Asthma (other listed uses: intrinsic and allergic asthma, bronchitis, pulmonary emphysema; the regulatory record contains no approved indication text) |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L1 |
| New Zealand Market Status | ✗ Cancelled only |
| Number of Authorizations | 1 (cancelled) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on established pharmacology, terbutaline is a selective beta2-adrenergic agonist. It relaxes bronchial smooth muscle and produces bronchodilation.
Obstructive lung disease covers asthma, chronic bronchitis, emphysema and COPD. Terbutaline's original indications (asthma, bronchitis, pulmonary emphysema) already fall within this group. The prediction therefore largely confirms an existing use. Reviews and trials in the literature also describe terbutaline use in COPD.
The market status is "Cancelled only", so product availability must be verified before any further development.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02224157 | Phase 3 | Completed | 4215 | Symbicort as-needed vs Pulmicort twice daily plus as-needed terbutaline in asthma (terbutaline is the reliever in the comparator arm) |
| NCT02149199 | Phase 3 | Completed | 3850 | Symbicort as-needed vs as-needed terbutaline vs Pulmicort plus terbutaline in asthma (terbutaline is the active reliever comparator) |
| NCT06626620 | Phase 3 | Completed | 120 | IV magnesium sulfate vs terbutaline in children with acute asthma exacerbation (terbutaline directly tested) |
| NCT00839800 | Phase 3 | Completed | 2091 | Symbicort SMART vs Symbicort plus as-needed terbutaline 0.4 mg in asthma |
| NCT00849095 | Phase 3 | Completed | 860 | As-needed vs regular budesonide/formoterol plus as-needed terbutaline in mild-moderate asthma (indirect evidence) |
| NCT00252863 | Phase 3 | Completed | 1600 | Symbicort single inhaler therapy vs conventional best practice that includes terbutaline as reliever |
| NCT02322788 | Phase 3 | Completed | 95 | Bricanyl Turbuhaler M3 vs M2: protection against methacholine-induced bronchoconstriction in mild to moderate asthma (terbutaline's role not confirmed from the supplied data) |
| 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 Symbicort inhalations vs 10 terbutaline inhalations on top of Symbicort in Japanese adults with asthma |
| NCT00421122 | Phase 3 | Completed | 315 | Symbicort plus Bricasol (terbutaline) pMDI vs Pulmicort plus Bricasol pMDI in Chinese COPD patients |
Four further trials were retrieved but contribute little: NCT04973345 (withdrawn, 0 enrolled), NCT00244608, NCT00259766 and NCT00567476 (terbutaline peripheral or comparator only).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29768149 | 2018 | RCT | N Engl J Med | As-needed budesonide-formoterol in mild asthma as an alternative to conventional strategies that use a short-acting β2-agonist |
| 3073804 | 1988 | RCT | Br J Dis Chest | Oral terbutaline increased diaphragmatic contraction force vs placebo in COPD (n=10) |
| 6988343 | 1980 | RCT | Int J Clin Pharmacol Ther Toxicol | Oral clenbuterol vs terbutaline bronchodilator effects in chronic obstructive lung disease |
| 6107217 | 1980 | RCT | Chest | Interaction of beta-blockers (metoprolol, propranolol) with oral terbutaline in COLD with ischemic heart disease or hypertension |
| 10384064 | 1999 | Crossover trial | Lung | Single dose of terbutaline Turbuhaler on lung function and exercise capacity in COPD (double-blind, placebo-controlled, n=26) |
| 30156361 | 2019 | RCT | Acad Emerg Med | Nebulized terbutaline plus ipratropium vs terbutaline alone in acute COPD exacerbation requiring noninvasive ventilation |
| 36227333 | 2023 | Systematic Review | Naunyn-Schmiedebergs Arch Pharmacol | Pharmacokinetics of terbutaline in humans; used for bronchospasm in asthma, bronchitis, emphysema and COPD |
| 23348973 | 2013 | Review | Am J Respir Crit Care Med | β2-agonist therapy in lung disease; short-acting agents including terbutaline give rapid as-needed relief |
| 33065789 | 2020 | Clinical study | Ann Palliat Med | N-acetylcysteine combined with terbutaline in elderly COPD patients |
| 2951811 | 1986 | Randomized study | Respiration | Fenoterol-ipratropium vs inhaled terbutaline in chronic obstructive lung disease |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2578417 (Cancelled) | Bricanyl Turbuhaler | Powder for inhalation, 200 mcg per dose (equivalent to 250 mcg metered dose), breath activated | Not available |
Safety Considerations
- Contraindications / cautions (knowledge-graph associations, not label text): hypertension, epilepsy, hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, potassium deficiency, sudden cardiac arrest, heart conduction disease, myocardial ischaemia, coronary artery disease, respiratory failure, pulmonary oedema, hyperthyroidism (Graves disease, thyrotoxicosis) and placental abruption.
- Drug Interactions: 407 interactions were identified. Examples:
- Moderate: epinephrine, antidiabetic agents (acarbose, alogliptin, pioglitazone, canagliflozin, chlorpropamide, albiglutide), clarithromycin, famotidine, loperamide, isometheptene, and laxatives or bowel preparations (bisacodyl, picosulfuric acid, polyethylene glycol).
- Minor: corticosteroids (hydrocortisone, dexamethasone, budesonide, beclomethasone, betamethasone, triamcinolone).
- A beta-blocker interaction study in COPD patients with cardiac disease is also in the literature (PMID 6107217).
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several large completed Phase 3 trials in asthma include terbutaline as an active or reliever arm, and COPD studies support its bronchodilator effect. However, the evidence is mostly indirect, the use overlaps the existing indications, and the only New Zealand authorization is cancelled.
To proceed, the following is needed:
- Confirmation of current product availability and regulatory status in New Zealand
- Package insert warnings and contraindications (not yet retrieved)
- Detailed mechanism of action data from DrugBank
- A safety monitoring plan for patients with cardiovascular disease, diabetes, hyperthyroidism or hypokalaemia risk
Other Predicted Indications (Not Recommended)
- Respiratory malformation (score 99.52%, L4, Hold): The retrieved evidence concerns asthma, bronchitis and unrelated topics, and none of it shows an effect on structural malformation. The high score probably reflects network proximity to respiratory disease terms.
- Rienhoff syndrome (score 99.38%, L5, Hold): No trials or literature were found and no plausible mechanistic link can be established. The prediction should not be acted on without independent validation.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.