Eltrombopag

Evidence Level: L3

Predicted Indications: 1

Eltrombopag

Pharmacist Assessment Report

Eltrombopag: From Autoimmune Thrombocytopenia to HIV Infectious Disease

One-Sentence Summary

Eltrombopag is a thrombopoietin receptor agonist, originally used to treat autoimmune thrombocytopenia. The TxGNN model predicts it may be useful for HIV infectious disease. The supporting evidence is limited: 1 clinical trial (whose relevance to HIV is unconfirmed) and 8 publications, mostly case reports, case series and reviews. Any benefit is likely to be supportive care for HIV-related low blood counts, not antiviral activity.

Quick Overview

Item	Content
Original Indication	Autoimmune thrombocytopenia
Predicted New Indication	HIV infectious disease
TxGNN Prediction Score	0.9926
Evidence Level	L3
Canada Market Status	Marketed (marketed DINs: 4 of 4)
Number of DINs	4 (marketed: 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, eltrombopag is a thrombopoietin receptor agonist. Its efficacy in immune thrombocytopenia is established, and it may be applicable to HIV-related blood-count problems.

The most plausible link is symptomatic. Eltrombopag raises platelet counts in HIV-associated immune thrombocytopenia, including thrombocytopenia after immune reconstitution. It may also support blood-cell production in HIV-associated marrow failure such as aplastic anaemia. This is supportive-care benefit for HIV-related cytopenias, not antiviral activity.

The very high TxGNN score (0.9926) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence of an effect on HIV itself. One 2020 screen of FDA-approved compounds (PMID 32977702) reported modulation of HIV-1 proviral transcription. It is preclinical and only hypothesis-generating.

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 transfusions in thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures. The record does not confirm an HIV-specific population, and the study was terminated early.

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 immune thrombocytopenic purpura
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 eltrombopag; possible immunomodulatory role
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 screen	Viruses	Screen of FDA-approved drugs for modulators of HIV-1 proviral transcription (preclinical)
24128106	2013	Case report	Farm Hosp	Eltrombopag for thrombocytopenia in chronic hepatitis C (indirect relevance to HIV)
28043314	2016	Case report	J Coll Physicians Surg Pak	Hepatitis B leading to megaloblastic anaemia and severe thrombocytopenia (indirect relevance)

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02361833	REVOLADE	Not specified	Not specified
02361825	REVOLADE	Not specified	Not specified
02506742	APO-ELTROMBOPAG	Not specified	Not specified
02506769	APO-ELTROMBOPAG	Not specified	Not specified

Safety Considerations

Disease-related cautions (from the knowledge graph, not label text): The TxGNN knowledge graph links eltrombopag to cautions in these conditions: kidney disease, liver disease (including acute liver failure and hepatitis), gallbladder disease, hepatic vein thrombosis and Budd-Chiari syndrome, anaemia, leukopenia, myelodysplastic syndrome, thrombocytosis, and hyperbilirubinaemia (including Gilbert syndrome). These should be checked against the official labelling.
Drug Interactions: 100 interactions were identified. The ones shown include:
- Major: eluxadoline.
- Moderate: polyvalent cation products, including calcium salts (phosphate, acetate, carbonate, citrate, gluconate, lactate), magnesium salts (oxide, carbonate, chloride, citrate, gluconate, hydroxide), aluminium hydroxide, magaldrate, kaolin, attapulgite and iron. Also glyburide.

For label warnings and contraindications, please refer to the package insert.

Conclusion and Next Steps

Decision: Hold

Rationale: The evidence for HIV is limited to case reports, a case series, reviews and one preclinical screen. The single clinical trial is in chronic liver disease, was terminated early, and is not confirmed as HIV-specific. The high TxGNN score probably reflects shared thrombocytopenia biology, and any benefit is supportive care for HIV-related cytopenias, not antiviral activity.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
Mechanism of action data
Confirmation of the population, endpoints and termination reason of NCT00678587
Prospective or controlled studies of eltrombopag in HIV-associated thrombocytopenia or marrow failure
Dosage form and approved indication details for the Canadian licences
Review of safety in patients with liver disease and of interactions with commonly co-prescribed antiretrovirals and cation-containing products
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.