Eptifibatide
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Eptifibatide: From Acute Coronary Syndrome to Rheumatoid Arthritis
One-Sentence Summary
Eptifibatide is a glycoprotein IIb/IIIa antagonist originally used to treat acute coronary syndrome. The TxGNN model’s top-ranked prediction is rheumatoid arthritis, but this prediction rests on the model alone, with no clinical trials and no publications supporting it. The best-supported alternative direction is hemoglobinopathy (sickle cell disease), backed by 1 clinical trial and 4 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute coronary syndrome |
| Predicted New Indication | Rheumatoid arthritis |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L5 (model prediction only) |
| 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 | 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, eptifibatide is a GP IIb/IIIa (αIIbβ3 integrin) antagonist that blocks platelet aggregation. Its efficacy in acute coronary syndrome is established, and mechanistically it may be applicable to conditions in which platelet activation drives disease.
For rheumatoid arthritis, the link is speculative: platelets contribute to synovial inflammation, but no trials or literature support this use. Patients with rheumatoid arthritis often take NSAIDs and corticosteroids, which adds to the bleeding risk of an antiplatelet drug.
Among the other predictions, hemoglobinopathy (sickle cell disease) has the most coherent rationale. Activated platelets and GP IIb/IIIa-mediated adhesion contribute to microvascular occlusion and inflammation during vaso-occlusive crises, and eptifibatide blocks this pathway. Several other sickle cell genotypes (HbSD, HbSE, HbSC, HbF-persistence, sickle-beta-thalassemia) share this biology but have no genotype-specific data. Female breast carcinoma has preclinical support only. Beta-thalassemia has only a speculative link through hypercoagulability. Partial deletion of the short arm of chromosome 16 has no plausible pharmacological mechanism, and its high score likely reflects network proximity.
Clinical Trial Evidence
No clinical trials are registered for the top-ranked indication (rheumatoid arthritis). The only related trial was found for hemoglobinopathy (sickle cell disease):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00834899 | Phase 1/2 | Terminated | 13 | Randomized, double-blind, placebo-controlled safety study of eptifibatide for acute pain episodes in sickle cell disease. Directly relevant, but terminated early and underpowered, so it cannot establish efficacy. |
Literature Evidence
No publications are linked to rheumatoid arthritis. The following are linked to the related predictions:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17916103 | 2007 | Phase I study | Br J Haematol | Safety and pharmacodynamics of eptifibatide in four steady-state sickle cell anaemia patients, based on the rationale that platelet reactivity and CD40L play a role similar to that in ACS. |
| 23973010 | 2013 | Pilot clinical study | Thromb Res | Pilot evaluation of safety and efficacy of eptifibatide during acute painful episodes in sickle cell disease. |
| 29322543 | 2018 | Biomarker study (secondary analysis) | Am J Hematol | Effect of eptifibatide on inflammation markers during acute pain episodes in sickle cell disease. |
| 22156199 | 2012 | In vitro model | J Clin Invest | Microfluidic model of microvascular occlusion and thrombosis in hematologic diseases such as sickle cell disease. |
| 25090985 | 2015 | In vitro cell-line study | Curr Drug Targets | Eptifibatide and abciximab showed proapoptotic effects in MCF-7 breast cancer cells. |
| 33522559 | 2021 | Preclinical organ-on-chip | Lab Chip | Inhibition of integrin β3 affected breast cancer cell extravasation in a metastatic niche model. |
| 24678072 | 2005 | Tolerability/feasibility study | Curr Ther Res | Eptifibatide in ACS patients at high cardiovascular risk. It does not test HbSC disease and is not direct evidence for that indication. |
India Market Information
Eptifibatide is marketed in India under 20 valid single-ingredient registrations. Approved indication text is not listed for these products. The main authorizations are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 109891 | Integrilin Injection (Merck Ltd) | Bottle of 100 ml infusion | Not listed |
| 77081 | Eptifab 0.75mg/ml Infusion (Abbott) | Bottle of 100 ml infusion | Not listed |
| 83357 | Eptide 20mg Injection (Sun Pharmaceutical) | Vial of 10 ml injection | Not listed |
| 108424 | Intiflo 20mg Injection (Cipla) | Vial of 10 ml injection | Not listed |
| 83167 | Eptigrilin 20mg Injection (Zydus Cadila) | Vial of 10 ml injection | Not listed |
All products are injectable or infusion forms.
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): thrombocytopenia, blood coagulation disease, impaired renal function disease.
- Drug Interactions: 100 interactions were identified. Notable ones:
- Major: deferasirox, ibritumomab tiuxetan, tositumomab (I-131)
- Moderate: acetylsalicylic acid, dexfenfluramine, fenfluramine, sibutramine
- Bleeding risk: this is the key concern for any new use, especially in rheumatoid arthritis (concurrent NSAIDs and corticosteroids) and oncology patients.
Package insert warnings and contraindications were not available. Please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, rheumatoid arthritis, is supported only by the model score (L5), with no trials or literature. The sickle cell direction is mechanistically coherent (L2) but rests on small early-phase studies, and the only randomized trial was terminated with 13 participants.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India product labels (a blocking gap for safety screening)
- Detailed mechanism of action data from DrugBank
- For rheumatoid arthritis: any preclinical or clinical evidence, plus a bleeding-risk assessment with NSAIDs and corticosteroids
- For sickle cell disease: a better-powered efficacy trial and a bleeding-safety plan, as a possible research question
- Assessment of route compatibility (the drug is available only as injection or infusion) for each candidate indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.