Streptokinase
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
Streptokinase: Prinzmetal angina
One-Sentence Summary
Streptokinase is a clot-dissolving (thrombolytic) enzyme given by injection, marketed in India under 20 valid registrations. Note that myocardial infarction is already an established use of streptokinase, so this is better described as confirming a known use than as true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Prinzmetal angina |
| TxGNN Prediction Score | 0.9980 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| 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 known pharmacology, streptokinase forms a complex with plasminogen that converts plasminogen to plasmin. Plasmin then breaks down fibrin, the protein mesh that holds a clot together.
In a heart attack, a clot blocks a coronary artery. Dissolving that clot restores blood flow and limits damage to heart muscle. This is why the mechanism fits the predicted indication directly.
The literature includes reviews of the large randomised trials (such as ISIS-2, GISSI and ISAM), which describe a survival benefit with intravenous streptokinase. Newer fibrin-specific agents and primary PCI (percutaneous coronary intervention) are now often preferred alternatives.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00000507 | Phase 3 | Completed | Not reported | Tested whether early intravenous streptokinase limits heart muscle damage in acute transmural MI |
| NCT01305226 | Phase 3 | Completed | 120 | Double-bolus recombinant staphylokinase (THR-100) vs streptokinase in acute MI |
| NCT00627809 | Phase 4 | Completed | 53 | Low-dose intracoronary streptokinase added to PCI in STEMI; effect on infarct size and left ventricular volumes |
| NCT00000503 | Phase 3 | Completed | Not reported | Randomised trial of non-surgical coronary reperfusion on infarct size (likely thrombolytic-based; streptokinase use not confirmed) |
| NCT02182011 | Phase 3 | Completed | 49 | Procoagulant effect of tenecteplase, alteplase and streptokinase in acute MI |
| NCT03677466 | Not applicable | Completed | 60 | Intramyocardial haemorrhage in primary STEMI under different reperfusion strategies |
| NCT02893280 | Not applicable | Withdrawn | 0 | Sri Lanka acute coronary syndrome audit project; no participants enrolled |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8130384 | 1994 | Review | Drugs & Aging | Large randomised trials show a survival benefit from intravenous streptokinase in older MI patients (ISIS-2) |
| 2191849 | 1990 | Review | Drugs | Reappraisal of intravenous streptokinase; GISSI, ISIS-2 and ISAM (over 30,000 patients) |
| 3312370 | 1987 | Review | J Am Coll Cardiol | Review of randomised trials of intracoronary and intravenous streptokinase in MI |
| 10572811 | 1999 | Review | J Accid Emerg Med | Outcomes of accelerated alteplase vs streptokinase in acute MI |
| 481511 | 1979 | Controlled trial | N Engl J Med | European trial of 24-hour streptokinase infusion vs glucose; lower six-month mortality in the streptokinase group |
| 2146913 | 1990 | Meta-analysis | Ann Intern Med | Effect of intravenous streptokinase on early mortality by infarct location |
| 3396164 | 1988 | Randomised trial analysis | Circulation | Western Washington trial; higher infarct artery patency with streptokinase and effects on ventricular function |
| 10163575 | 1996 | Review | PharmacoEconomics | Streptokinase is as effective as alteplase given as a 3-hour infusion; economic appraisal |
| 9339259 | 1997 | Review | Arch Mal Coeur Vaiss | Anti-streptokinase antibodies arise after administration |
| 10454969 | 1999 | Review | Eur Heart J | Commentary “Streptokinase…never again” arguing against its continued use |
India Market Information
All 20 registrations are valid single-ingredient injections. The data compiled for this report contain no approved indication text for any of them. The table below lists five of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 204083 | Streptase 1500000IU Injection (Sanofi India Ltd) | Vial of 1 ml injection | Not stated |
| 209939 | Streptase 750000IU Injection (Sanofi India Ltd) | Vial of 1 ml injection | Not stated |
| 116831 | Klotbuster 1500000IU Injection (Alembic Pharmaceuticals Ltd) | Vial of 1 injection | Not stated |
| 220461 | Thromboflux 1500000IU Injection (Bharat Serums & Vaccines Ltd) | Vial of 10 ml injection | Not stated |
| 116650 | Kabikinase 1.5 MIU Injection (Pharmacia Health Care Ltd) | Vial of 1 injection | Not stated |
Safety Considerations
- Drug Interactions: 122 interactions are recorded. Several are rated Major, mostly with other agents that affect bleeding or clotting:
- Anticoagulants and antithrombotics: apixaban, betrixaban, bivalirudin and abciximab.
- Other Major pairings: acalabrutinib, avapritinib, deferasirox, ibritumomab tiuxetan and tositumomab (I-131).
- Moderate interactions include aspirin, NSAIDs (ibuprofen, ketorolac, celecoxib), aminocaproic acid, omega-3 fatty acids and ginger.
- Guardrails from the evidence review: bleeding and intracranial haemorrhage risk; anti-streptokinase antibodies and allergic reactions that limit repeat use; haemorrhagic infarction and septal rupture reported after thrombolysis in case-level and observational literature. Jaundice after streptokinase has also been reported in one case.
Package insert warnings and contraindications were not available in the data compiled for this report, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanism directly fits myocardial infarction, and several completed Phase 3 trials plus large randomised trial reviews support streptokinase in this setting. This is an established use rather than new repurposing, and the main concerns are bleeding, immunogenicity, and the availability of fibrin-specific agents and primary PCI.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Indian regulator and manufacturers, which are currently missing and block formal safety screening
- Approved indication text for the Indian registrations
- Mechanism of action data from DrugBank to complete the mechanistic analysis
- A bleeding-risk and re-administration (antibody) management plan
- A comparison of streptokinase with fibrin-specific agents and primary PCI in the intended care setting
Other Predicted Indications (Summary)
| Predicted Indication | Evidence Level | Decision | Comment |
|---|---|---|---|
| Coronary thrombosis | L1 | Proceed with Guardrails | Mechanism directly applies; the listed Phase 3 trial is in prosthetic valve thrombosis, not coronary |
| Peripheral arterial disease | L2 | Proceed with Guardrails | Literature only (Cochrane reviews, streptokinase vs urokinase); no registered trials; restrict to acute limb ischaemia |
| Peripheral vascular disease | L2 | Proceed with Guardrails | Overlaps with peripheral arterial occlusion; no registered trials |
| Septal, posteroinferior and posterolateral MI | L3 | Research Question | Subtypes of MI; no registered trials and mostly case-level literature |
| Prinzmetal angina | L5 | Hold | Mainly vasospasm, so weak mechanistic fit |
| Hemoglobinopathy | L5 | Hold | No clear mechanistic link |
| Partial deletion of the short arm of chromosome 16 | L5 | Hold | No supporting studies; likely a prediction artifact |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.