Reteplase
| Evidence Level: L5 | Predicted Indications: 7 |
Table of Contents
Reteplase: Congenital coronary artery anomaly
One-Sentence Summary
Reteplase is a recombinant tissue plasminogen activator (a clot-dissolving drug) originally used to treat myocardial infarction and coronary thrombosis. Evidence is thin: 0 registered clinical trials and 1 publication (a case report), so the support is essentially model prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Congenital coronary artery anomaly |
| TxGNN Prediction Score | 0.9980 |
| Evidence Level | L5 |
| 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?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, reteplase is a recombinant tissue plasminogen activator that converts plasminogen to plasmin and dissolves fibrin clots in occluded coronary arteries. Its efficacy in acute myocardial infarction is established, and mechanistically it applies to any infarction caused by a thrombus in a coronary artery.
Posterolateral myocardial infarction is defined by the part of the heart wall affected, not by a different disease process. It therefore falls under the existing myocardial infarction indication. For this reason it is not a true repurposing candidate.
Other predictions in the list are weaker still:
- Coronary stenosis has the most reteplase-specific literature, but this comes from the facilitated-PCI era, and that strategy has since fallen out of favor.
- Septal myocardial infarction is another subtype of the approved indication.
- Thrombophilias (heparin cofactor 2 deficiency, antithrombin deficiency type 2) would benefit from thrombolysis only during an acute thrombotic event, not for the underlying disorder.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21351226 | 2011 | Case report | Catheter Cardiovasc Interv | Primary PCI of an unprotected left main with mini-crush drug-eluting stents, facilitated by intracoronary reteplase, in a patient with posterolateral acute MI. It does not evaluate reteplase efficacy. |
Related literature for other predicted indications (not for posterolateral MI) includes:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15800019 | 2005 | Cohort (secondary analysis of trial data) | Eur Heart J | GUSTO-V: relationship between aPTT and outcomes after standard-dose reteplase or half-dose reteplase plus abciximab (coronary stenosis). |
| 11079647 | 2000 | Clinical trial | J Am Coll Cardiol | SPEED (GUSTO-4 pilot): early PCI after reteplase with or without abciximab in acute MI (coronary stenosis). |
| 16786798 | 2005 | Case report | Przegl Lek | Reteplase plus abciximab in a patient with inferior and right ventricular MI and congenital atrial septal defect (septal MI). Context is only indirect. |
| 34512848 | 2021 | Review/case report | Pan Afr Med J | De Winter ECG pattern in spontaneous coronary artery dissection (congenital coronary anomaly). Not a reteplase study. |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 185024 | Retefast 18mg Injection (Cipla Ltd) | Vial of 10 ml injection | Not stated in the data compiled |
| 236830 | Vascium 18mg Injection (Emcure Pharmaceuticals Ltd) | Vial of 1 injection | Not stated in the data compiled |
| 184768 | Retefuse 18mg Injection (Lupin Ltd) | Packet of 1 injection | Not stated in the data compiled |
| 186122 | Retefast Kit (Cipla Ltd) | Box of 1 injection | Not stated in the data compiled |
All four registrations are valid single-ingredient injectable products.
Safety Considerations
Drug Interactions: 137 interactions were identified. Examples with a Major level include:
- Abciximab
- Apixaban
- Betrixaban
- Acalabrutinib
- Avapritinib
- Deferasirox
- Ibritumomab tiuxetan
- Tositumomab
Examples with a Moderate level include:
- Acetylsalicylic acid
- Ibuprofen
- Ketorolac
- Celecoxib
- Aminocaproic acid
- Omega-3 fatty acids
- Fenfluramine, dexfenfluramine and sibutramine
Most of these involve additive bleeding risk with anticoagulants, antiplatelets and NSAIDs.
For warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The top predictions are subtypes of myocardial infarction, which reteplase already covers, so they add little as repurposing opportunities. No clinical trials were found, and the literature consists mainly of case reports and older facilitated-PCI studies. The more distant predictions have no plausible mechanism.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Indian products (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- A decision on whether the subtype predictions need separate evaluation, since they fall under the existing label
- Reteplase-specific trial or registry evidence for any indication that is genuinely outside the current label
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.