Eltrombopag
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Eltrombopag: From Autoimmune Thrombocytopenia to HIV Infectious Disease
One-Sentence Summary
Eltrombopag is a thrombopoietin receptor agonist, originally used to treat autoimmune thrombocytopenia (immune thrombocytopenia, ITP). The TxGNN model predicts it may be useful for HIV infectious disease. In practice, the plausible benefit is for HIV-associated thrombocytopenia rather than for the infection itself. Support currently comes from 1 clinical trial (terminated, with an indirect link to HIV) and 8 publications, mostly case reports and reviews.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Autoimmune thrombocytopenia (the India licence entries carry no indication text) |
| Predicted New Indication | HIV infectious disease |
| TxGNN Prediction Score | 0.9926 |
| Evidence Level | L5 by the strict rules, with weak supporting case-level data (see note below) |
| 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 |
Note on evidence level: The data compiled for this report assigns L2. The only trial found is terminated and its link to HIV is inferred, not stated. The literature consists of reviews, case reports, one case series and an in vitro screen. Under the stated rules, no completed Phase 2/3 RCT in HIV supports an L2 rating, so this report treats the evidence as weak, between L3 and L5.
Why is This Prediction Reasonable?
Eltrombopag stimulates the thrombopoietin receptor to increase platelet production. Detailed mechanism of action data is not available in the compiled data. Based on its known drug class, its efficacy in immune thrombocytopenia is established.
Thrombocytopenia is a common complication of HIV infection. It arises from immune-mediated platelet destruction, similar to ITP, and from impaired platelet production in the bone marrow. Stimulating the thrombopoietin receptor could therefore plausibly raise platelet counts in HIV-associated thrombocytopenia.
Case reports also describe benefit in HIV-related aplastic anaemia. One report noted immunomodulatory changes (reduced Th1 and Th17 cells, higher regulatory T-cell ratio). A separate in vitro screen reported modulation of HIV-1 proviral transcription, but this is preclinical and does not support antiviral claims. The high TxGNN score reflects this overlap but is a computational prediction, not clinical evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00678587 | Phase 3 | Terminated | 292 | Randomised, double-blind, placebo-controlled study of eltrombopag to reduce platelet transfusion need in thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures. The link to HIV is indirect and should be verified. |
Early termination limits the reliability of any conclusions. The termination reason and any posted results should be checked.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25504472 | 2015 | Case series | J Int Assoc Provid AIDS Care | Initial experience with thrombopoietin receptor agonists in refractory HIV-associated ITP |
| 22992580 | 2012 | Case report | AIDS | Eltrombopag used successfully without splenectomy in refractory HIV-related immune reconstitution thrombocytopenia |
| 25333665 | 2014 | Case report | AIDS | Successful treatment of HIV-associated aplastic anaemia, with signs of an immunomodulatory effect |
| 19932434 | 2009 | Review | Hematol Oncol Clin North Am | Infectious causes of chronic immune thrombocytopenia, including HIV, HCV and H. pylori |
| 19245929 | 2009 | Review | Semin Hematol | Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias |
| 32977702 | 2020 | In vitro screening | Viruses | FDA-approved drug library screen for modulators of HIV-1 proviral transcription |
| 24128106 | 2013 | Case report | Farm Hosp | Eltrombopag for thrombocytopenia in chronic hepatitis C (two cases) |
| 28043314 | 2016 | Case report | J Coll Physicians Surg Pak | Hepatitis B leading to megaloblastic anaemia and severe thrombocytopenia (background, not eltrombopag-specific) |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 214967 | Trombopag 50mg Tablet (Natco Pharma Ltd) | Strip of 7 tablets | Not specified |
| 215030 | Trombopag 25 Tablet (Natco Pharma Ltd) | Strip of 7 tablets | Not specified |
| 184283 | Revolade 25mg Tablet (Novartis India Ltd) | Strip of 7 tablets | Not specified |
| 184195 | Revolade 50mg Tablet (Novartis India Ltd) | Strip of 7 tablets | Not specified |
All four licences are valid single-ingredient oral products.
Safety Considerations
- Knowledge-graph contraindication signals (not label text): kidney disease, liver disease, acute liver failure, hepatitis, gallbladder disease, hyperbilirubinaemia (including Gilbert syndrome), anaemia, leukopenia, myelodysplastic syndrome, thrombocytosis, hepatic vein thrombosis and Budd-Chiari syndrome. These should be confirmed against the official package insert.
- Drug Interactions: 135 interactions were identified. The one Major interaction among those listed is eluxadoline. Moderate interactions include polyvalent cation products (calcium, magnesium and aluminium salts, iron, kaolin, attapulgite, magaldrate), which may reduce absorption, and glyburide.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic link to HIV-associated thrombocytopenia is plausible, and case-level reports are encouraging. However, there is no completed controlled trial in HIV, the only registered trial is terminated and indirectly related, and the benefit would be for the haematologic complication rather than HIV infection. The package insert safety data is also missing.
To proceed, the following is needed:
- Review of the termination reason and any results for NCT00678587, and confirmation of its relevance to HIV
- Controlled studies in HIV-associated thrombocytopenia
- Detailed mechanism of action data
- Package insert warnings and contraindications from the India licences, and the approved indication text
- Safety assessment in HIV populations, including liver function and interactions with antiretroviral therapy
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.