Ephedrine
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Ephedrine: From Sympathomimetic (Original Indication Not Listed) to Nasal Cavity Disease
One-Sentence Summary
Ephedrine is a marketed sympathomimetic drug, and the supplied US label data does not list its approved indications. The TxGNN model predicts it may be effective for nasal cavity disease (nasal congestion), but none of the 17 registered trials and 8 publications retrieved for this prediction confirms ephedrine as the intervention. Evidence is indirect and mostly preclinical.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the supplied US label data |
| Predicted New Indication | Nasal cavity disease |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (the listed authorizations are ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the supplied data. Based on general pharmacology, ephedrine is a mixed direct and indirect sympathomimetic. Alpha-adrenergic vasoconstriction of nasal mucosal vessels plausibly reduces mucosal swelling and congestion, which fits the predicted indication. This link comes from general pharmacology, not from the supplied data.
Nasal decongestion is also a long-established use of ephedrine and related agents. This prediction may therefore reflect a known use rather than true repurposing. No supplied trial confirms ephedrine as the studied drug.
The strongest supporting signals are a human comparison of related oral and topical decongestants (PMID 11345158) and several animal nasal congestion models. A 1964 clinical test of a nasal preparation containing ephedrine (PMID 14211229) is directly relevant but historical.
Clinical Trial Evidence
The trials below were matched to the indication, not to ephedrine. The two B-grade trials need manual review, and none can currently support L2.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00562120 | Phase 2 | Completed | 21 | Placebo-controlled four-way crossover of an H3 antagonist (PF-03654746) on congestion after nasal allergen challenge. Ephedrine or another decongestant as a comparator cannot be confirmed. |
| NCT01886768 | N/A | Unknown | 212 | Randomized trial of double vs single pledget nasal anesthesia and decongestion for transnasal endoscopy. The ephedrine link is unverified. |
| NCT03620513 | Phase 4 | Completed | 160 | Double-blind randomized study of topical anesthesia and/or decongestant before fiberoptic laryngoscopy. The specific agents are not stated in the summary. |
| NCT00517946 | N/A | Completed | 21 | MRI as a measure of anti-allergy drug effects on nasal mucosa after allergen challenge. |
| NCT06580210 | N/A | Recruiting | 114 | Seawater decongestant spray (device) for acute rhinitis with nasal obstruction. No ephedrine relevance. |
| NCT05494346 | N/A | Recruiting | 101 | Seawater decongestant spray pocket valve for acute rhinitis. No ephedrine relevance. |
| NCT06457100 | Phase 1/2 | Active, not recruiting | 60 | IV esmolol vs lidocaine for recovery quality after sinus surgery. Different drug question. |
| NCT01854619 | N/A | Unknown | 48 | Photodisinfection for chronic rhinosinusitis. Non-drug intervention. |
| NCT04048174 | N/A | Completed | 27 | Lactococcus lactis probiotic for refractory chronic rhinosinusitis. Unrelated to ephedrine. |
| NCT05131958 | N/A | Unknown | 30 | Observational study of nasality in nasal polyposis. No ephedrine intervention. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11345158 | 2001 | Comparative clinical study | Am J Rhinol | Compared oral and topical nasal decongestant effects of phenylpropanolamine and d-pseudoephedrine (related sympathomimetics) using acoustic rhinometry. |
| 14211229 | 1964 | Historical clinical test | Svenska Lakartidningen | Experimental clinical testing of a nasal preparation combining an antihistamine (Aprobit) with ephedrine hydrochloride. No abstract available. |
| 1541887 | 1992 | Clinical comparative study | J Laryngol Otol | Compared nasal packing and spraying for pre-operative nasal preparation. No abstract available, so the agents used are unconfirmed. |
| 12962193 | 2003 | Animal model | Am J Rhinol | Allergic nasal congestion model in ragweed-sensitized dogs, measured by acoustic rhinometry. |
| 12387934 | 2002 | Animal model | J Pharmacol Toxicol Methods | Pharmacological characterization of a chronic dog model for studying nasal decongestant mechanisms. |
| 11895194 | 2002 | Animal model | Am J Rhinol | Dog model of nasal congestion induced by compound 48/80, with nasal patency measured by acoustic rhinometry. |
| 11789239 | 2000 | Clinical observation | Zhongguo Zhong Xi Yi Jie He Za Zhi | Preliminary clinical observation of a rhinitis spray for chronic rhinitis. Not ephedrine-specific. |
| 8283338 | 1993 | Case series | Nihon Jibiinkoka Gakkai Kaiho | Congenital nasal stenosis case series. Peripheral relevance. |
US Market Information
Five of the 20 authorizations are shown below. All are injection products, and the supplied data has no approved indication text for them. Other listed dosage forms include injectable solution and film-coated oral tablet.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA212932 | Ephedrine Sulfate (Medical Purchasing Solutions, LLC) | Injection | Not listed in supplied data |
| ANDA214579 | Ephedrine Sulfate (Eugia US LLC) | Injection | Not listed in supplied data |
| ANDA212932 | Ephedrine Sulfate (NorthStar Rx LLC) | Injection | Not listed in supplied data |
| ANDA216146 | Ephedrine Sulfate (REMEDYREPACK INC.) | Injection | Not listed in supplied data |
| ANDA215825 | Ephedrine Sulfate (Medical Purchasing Solutions, LLC) | Injection | Not listed in supplied data |
Safety Considerations
Please refer to the package insert for safety information. No warnings, contraindications, or drug interaction records were available. As a sympathomimetic stimulant, ephedrine could plausibly cause cardiovascular stimulation, and the data set’s lowest-ranked prediction (trigeminal autonomic cephalalgia) raises a possible headache-worsening concern. Safety screening cannot proceed until the label is reviewed.
Conclusion and Next Steps
Decision: Hold
Rationale: The model score is very high (99.90%), but no supplied trial or publication tests ephedrine for nasal cavity disease. The support is indirect and mostly comes from animal models and related decongestants. The safety data is also missing, and that gap blocks safety screening.
The other two predictions, acute laryngopharyngitis and trigeminal autonomic cephalalgia, have no trials or literature (L5) and are also on Hold.
To proceed, the following is needed:
- Download and review the FDA package insert (warnings, contraindications, approved indications).
- Obtain mechanism of action data from DrugBank.
- Manually review NCT00562120, NCT01886768 and NCT03620513 to confirm whether ephedrine was studied.
- Check whether nasal decongestion is already a known ephedrine use, and whether a nasal or oral ephedrine product is marketed in the US, since the listed products are injections.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.