Epinephrine
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Epinephrine
- Pharmacist Assessment Report
- Epinephrine: Obstructive lung disease
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Other Predicted Indications (Brief Note)
- Disclaimer
Epinephrine: Obstructive lung disease
One-Sentence Summary
Epinephrine (adrenaline) is a non-selective adrenergic agonist, originally used for anaphylaxis, asthma, bronchitis, bronchiectasis, pulmonary emphysema, hypotensive disorders and open-angle glaucoma. The TxGNN model predicts it may be effective for obstructive lung disease, with 16 clinical trials and 20 publications currently supporting this direction. Much of this is an on-label or near-label extension rather than true repurposing, and several Phase 3 trials concern an inhaled formulation, not the injectable product registered in Australia.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Obstructive lung disease |
| TxGNN Prediction Score | 0.9971 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, epinephrine is a non-selective alpha/beta-adrenergic agonist. Beta-2 receptor activation relaxes bronchial smooth muscle and produces bronchodilation, while alpha-1 activation reduces mucosal oedema.
Asthma, bronchiectasis and emphysema are already among epinephrine’s original indications, so extending to obstructive lung disease (which includes asthma and COPD) is largely a class effect. It is better seen as consolidation of existing use than as a new therapeutic direction.
An important caveat: the Phase 3 trials listed below mostly test an inhaled HFA metered-dose inhaler (E004), not the injectable epinephrine registered in Australia. The evidence therefore supports the drug’s pharmacology, but does not directly establish efficacy of the injectable product for this indication.
Clinical Trial Evidence
Ten of the 16 trials registered are shown below, prioritising those most relevant to obstructive airway disease.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01357642 | Phase 3 | Completed | 373 | 12-week efficacy and safety of epinephrine HFA inhaler vs placebo and Primatene Mist in adolescents and adults with asthma |
| NCT01476904 | Phase 3 | Completed | 208 | 3-month safety extension of the E004-C study, giving 6-month safety data |
| NCT01460511 | Phase 3 | Completed | 70 | 4-week placebo-controlled study of E004 in children aged 4-11 with asthma |
| NCT01737905 | Phase 3 | Completed | 28 | Single-dose crossover study of E004 in children with asthma (small sample) |
| NCT01705964 | Phase 4 | Completed | 49 | Intramuscular epinephrine as an adjunct to inhaled beta-2 agonists in severe paediatric asthma exacerbation |
| NCT04207840 | Phase 4 | Completed | 28 | Systemic exposure of Primatene Mist vs intramuscular epinephrine and ProAir in healthy adults (pharmacokinetic) |
| NCT01255709 | Phase 2 | Completed | 24 | Pharmacokinetics of inhaled epinephrine (E004) in healthy volunteers |
| NCT01834820 | Phase 4 | Completed | 120 | Epinephrine, dexamethasone and hypertonic saline in infant bronchiolitis |
| NCT00817466 | Phase 4 | Unknown | 500 | Optimal inhalation treatment for infants aged 0-12 months with acute bronchiolitis |
| NCT00114478 | N/A | Unknown | 600 | Epinephrine vs albuterol in bronchiolitis |
Literature Evidence
Ten of the 20 publications are shown, prioritising systematic reviews and randomised trials.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35093318 | 2022 | RCT | J Pediatr | Corticosteroids plus inhaled epinephrine vs standard care in children with bronchiolitis in intensive care |
| 33893229 | 2021 | Network meta-analysis | Pediatrics | Comparative efficacy of bronchiolitis interventions in acute care |
| 21678340 | 2011 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Epinephrine for bronchiolitis |
| 14974006 | 2004 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Earlier Cochrane review of epinephrine for bronchiolitis |
| 35953216 | 2022 | Review | Emerg Med Clin North Am | Evaluation and management of asthma and COPD exacerbations in the emergency department |
| 30488718 | 2019 | Review | Expert Rev Respir Med | Role of racemic epinephrine, corticosteroids, hypertonic saline and high-flow oxygen in infant bronchiolitis |
| 21157348 | 2011 | Review | Curr Opin Pediatr | Update on bronchiolitis management; no treatment conclusively alters disease course |
| 23393929 | 2012 | Review | Duodecim | Bronchiolitis overview, including inhaled racemic epinephrine when required |
| 11940264 | 2002 | Review | Crit Care | Clinical review of severe asthma |
| 20876171 | 2010 | Economic analysis | Pediatrics | Cost-effectiveness of epinephrine and dexamethasone in bronchiolitis |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1016L | Link Medical Products Pty Ltd | Injection 1 mg (as acid tartrate) in 1 mL (1 in 1,000) | Not stated in the data compiled for this report |
The only registered product is an injectable. No inhaled epinephrine product appears in the data, which limits the direct applicability of the inhaled-formulation trials.
Safety Considerations
Contraindications flagged in the TxGNN knowledge graph (these come from graph edges, not product label text, and should be verified against the Product Information):
- Cardiovascular: hypertension, coronary artery disease, myocardial infarction, atrial fibrillation, heart conduction disease, sudden cardiac arrest, other heart disease
- Metabolic and endocrine: diabetes mellitus, diabetic ketoacidosis, hyperthyroidism, potassium deficiency
- Neurological: epilepsy, myasthenia gravis and neuromuscular junction disease
- Ocular: angle-closure glaucoma
- Organ function: liver disease and failure, kidney disease, respiratory failure, gallbladder disease
- Other: benign prostatic hyperplasia, hemoglobinopathy, butyrylcholinesterase deficiency, pyoureter
Drug Interactions: 100 interactions were identified. Major-level examples include the tricyclic antidepressants amitriptyline and amoxapine. Moderate-level examples include other beta-agonists (formoterol, salbutamol, arformoterol), beta-blockers (atenolol, acebutolol, betaxolol), stimulants (amphetamine, methylphenidate, atomoxetine), antidiabetic agents (acarbose, alogliptin, acetohexamide, albiglutide) and antipsychotics (aripiprazole, asenapine, amisulpride).
Please refer to the TGA-approved Product Information (PI) for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale:
- Several completed Phase 3 trials support epinephrine in asthma, and the prediction largely overlaps with existing indications. However, those trials used an inhaled formulation not registered in Australia, and the injectable product’s ARTG entry carries no indication text.
To proceed, the following is needed:
- Review of the TGA Product Information to confirm approved indications, warnings and contraindications
- Clarification of route and formulation: whether the evidence applies to the injectable product or would require an inhaled product
- Mechanism of action data to complete the evidence summary
- A safety monitoring plan for patients with cardiovascular, metabolic and other comorbidities flagged above
- Review of high-risk interactions (tricyclic antidepressants, beta-blockers) before clinical use
Other Predicted Indications (Brief Note)
| Predicted Indication | Evidence Level | Suggested Status |
|---|---|---|
| Laryngotracheitis (croup) | L1 | Proceed with Guardrails (established rescue therapy; one Phase 4 trial of unknown status plus published RCT evidence) |
| Food-dependent exercise-induced anaphylaxis | L4 | Research Question (strong mechanistic rationale, but evidence is reviews and case reports only) |
| Pseudoallergy | L4 | Research Question (indirect support only) |
| Respiratory malformation | L3 | Research Question (single trial in transient tachypnoea of the newborn, which is not a structural malformation) |
| Dry eye syndrome | L5 | Hold (preclinical data suggest adrenergic stimulation may worsen the condition) |
| Headache disorder | L5 | Hold (observational data only; headache is a known adverse effect) |
| Trigeminal autonomic cephalalgia | L5 | Hold (observational pathophysiology only) |
| Rienhoff syndrome | L5 | Hold (no supporting data; likely a model artefact) |
| Anorectal stricture | L5 | Hold (no supporting data) |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.