Papaverine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Papaverine: From Peripheral Vascular Disease to Ischemic Disease
One-Sentence Summary
Papaverine is a vasodilator originally used for peripheral vascular disease, intermittent claudication, peripheral arterial disease, brain ischemia and transient ischemic attack. The TxGNN model predicts it may be effective for ischemic disease, but support is thin: 1 clinical trial (an observational registry that does not test papaverine as a therapy) and 20 publications, mostly reviews, diagnostic studies and case reports.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Peripheral vascular disease, intermittent claudication, peripheral arterial disease, brain ischemia, transient ischemic attack (the Indian licence records contain no approved-indication text) |
| Predicted New Indication | Ischemic disease |
| TxGNN Prediction Score | 0.9991 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (4 of 4) – CDSCO approval status is not included in this data |
| Number of Listed Products | 4 (valid: 4) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, papaverine is a non-selective phosphodiesterase inhibitor that relaxes vascular smooth muscle. This is consistent with a benefit in ischemic states caused by vasospasm.
Its original indications (peripheral vascular disease, cerebral ischemia, TIA) already sit within the broader category of ischemic disease, so the prediction is a natural extension. The literature shows papaverine used in mesenteric ischemia, spinal cord ischemia, renal artery vasospasm and intracoronary flow-reserve measurement. These are mainly diagnostic or adjunct uses, not controlled efficacy trials.
Other high-scoring predictions are weaker. Intracranial arteriosclerosis and Raynaud disease have a plausible vasodilation rationale but only old or case-level evidence. Vascular ectasia, angiodysplasia, venous thromboembolism and Monckeberg arteriosclerosis have no clear therapeutic rationale, and vasodilation could be harmful in some of them.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06125392 | N/A | Recruiting | 1000 | Multicenter registry of chronic angina without obstructive coronary stenosis, aiming to refine the definition of acetylcholine-induced spasm. It is observational and does not test papaverine as a therapy. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 3661361 | 1987 | Clinical physiological study | Am Heart J | Intracoronary papaverine was superior to radiographic contrast for measuring coronary flow reserve in ischemic heart disease (a diagnostic use). |
| 8293164 | 1993 | Review | Curr Opin Neurol | Interventional neuroradiology, including superselective papaverine infusion for vasospasm after aneurysm rupture. |
| 21761272 | 2011 | Guideline / review | Neurocrit Care | Critical care guidelines on endovascular management of cerebral vasospasm. |
| 7590571 | 1995 | Review | Hepato-Gastroenterology | Non-occlusive mesenteric ischemia. |
| 11341865 | 2001 | Review | Curr Treat Options Cardiovasc Med | Mesenteric vascular disease: medical and endovascular treatment options. |
| 16368347 | 2006 | Comparative study | Ann Thorac Surg | Papaverine versus glyceryl-trinitrate/verapamil solution as topical and intraluminal vasodilators for internal thoracic artery spasm. |
| 28455799 | 2018 | Case report | J Robot Surg | Periarterial papaverine treated renal artery vasospasm during robot-assisted partial nephrectomy. |
| 28832798 | 2017 | Experimental (rat) | Braz J Cardiovasc Surg | Papaverine and ascorbic acid studied for liver ischemia-reperfusion injury after aortic cross-clamping. |
| 23076900 | 2012 | Cochrane review (indirect) | Cochrane Database Syst Rev | Cerebrospinal fluid drainage in aortic aneurysm surgery to reduce spinal cord ischemia; not specific to papaverine. |
| 1291208 | 1992 | Clinical report | Chin Med J | Ligusticum chuanxiong preparations were comparable or better than controls such as papaverine in ischemic stroke. |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 174192 | Papaverine 60mg Injection (Mercury Laboratories Ltd) | Ampoule of 2 ml injection | Not stated in the licence record |
| 188635 | Repaverine 30mg Injection (Retort Pharma Pvt Ltd) | Vial of 2 ml injection | Not stated in the licence record |
| 174506 | Paparin 2 ml Injection (Troikaa Pharmaceuticals Ltd) | Vial of 2 ml injection | Not stated in the licence record |
| 179631 | Papavar 30mg Injection (Chandra Bhagat Pharma Pvt Ltd) | Ampoule of 5 injections | Not stated in the licence record |
All four licences are valid, single-ingredient injectable products.
Safety Considerations
- Disease-level cautions (knowledge graph, not label text): Papaverine is linked to contraindication or caution in liver disease, gallbladder disease, hypotensive disorder, coronary artery disease, myocardial infarction, coronary thrombosis, hemoglobinopathy, sudden cardiac arrest, heart conduction disease, atrioventricular block and glaucoma. These are especially relevant when considering use in ischemic heart conditions.
- Drug Interactions: 238 interactions were identified. Major-level examples include abiraterone, tramadol, adenosine, salbutamol, alfuzosin, amiodarone, amisulpride, amitriptyline, anagrelide, propofol, loperamide, apalutamide, apomorphine, arsenic trioxide, lumefantrine, asenapine and atomoxetine. Moderate-level examples include amifostine, apraclonidine and aripiprazole.
- Other signals from the literature: Older reports describe antagonism of levodopa by papaverine (relevant in Parkinson’s disease) and ischemic priapism after intracavernosal injection.
Please refer to the package insert for label warnings and contraindications; they were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (0.9991), and the vasodilator mechanism is plausible for ischemic states. However, the evidence is L4: no trial tests papaverine as a therapy, and the literature consists of reviews, diagnostic or adjunct uses, animal studies and case reports. The listed cardiac contraindications (coronary artery disease, myocardial infarction, conduction disease) also conflict with some ischemic settings.
To proceed, the following is needed:
- Specify which ischemic subtype to pursue (for example cerebral vasospasm, mesenteric ischemia, or Raynaud-type vasospasm). “Ischemic disease” is too broad to study as a single indication.
- Obtain the package insert warnings and contraindications from the Indian regulator to complete safety screening.
- Obtain detailed mechanism of action data to support mechanistic analysis.
- Review controlled efficacy data for papaverine in the chosen subtype. Raynaud disease and cerebral vasospasm are the more mechanistically plausible candidates.
- Assess route and dose compatibility, since all marketed Indian products are injections.
- Develop a cardiac and drug-interaction risk management plan.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.