Entecavir
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Entecavir: Chronic hepatitis C virus infection
One-Sentence Summary
Entecavir is a guanosine nucleoside analogue that inhibits hepatitis B virus polymerase. The TxGNN model predicts it may be relevant to chronic hepatitis C virus infection, but none of the 2 clinical trials and 20 publications compiled for this report tests entecavir as a treatment for hepatitis C. The evidence is indirect and limited to HBV/HCV co-infection management.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Chronic hepatitis C virus infection |
| TxGNN Prediction Score | 0.9998 |
| 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 | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this report. Entecavir is known to act on the polymerase of hepatitis B virus, a DNA virus. Hepatitis C virus is an RNA virus that replicates through its own NS5B RNA-dependent RNA polymerase. Entecavir has no recognized direct activity against that target.
The only plausible link is clinical rather than pharmacological. Some patients carry both hepatitis viruses, and during direct-acting antiviral treatment for hepatitis C the hepatitis B virus can reactivate. Entecavir has been studied as a way to prevent that reactivation. This is management of the co-infection, not evidence that entecavir treats hepatitis C. The high TxGNN score most likely reflects the closeness of the hepatitis viruses in the model’s network, and should not be read as evidence of anti-HCV efficacy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02555943 | Phase 2/3 | Completed | 23 | Direct-acting antivirals in HCV/HBV co-infected patients, studying how often HBV reactivates during anti-HCV therapy. The intervention is the HCV antiviral, not entecavir. |
| NCT04405011 | Not applicable | Unknown | 60 | Three-arm open-label randomized study of whether nucleos(t)ide analogue prophylaxis (12 vs 24 weeks) prevents HBV reactivation during anti-HCV therapy. It targets HBV prophylaxis, not HCV treatment. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 34864158 | 2022 | Randomized trial | Clin Gastroenterol Hepatol | Entecavir prevents HBV reactivation during direct-acting antiviral therapy in HCV/HBV dual infection. It does not show an anti-HCV effect. |
| 28230928 | 2017 | Study | J Gastroenterol Hepatol | Risk of HBV reactivation in chronic hepatitis C patients with HBV infection treated with direct-acting antivirals. |
| 35108715 | 2022 | Study | Dig Dis | Incidence and clinical course of HBV reactivation in patients treated with direct-acting antivirals for hepatitis C. |
| 36146665 | 2022 | Cohort | Viruses | HCV reactivation in 66 anti-HCV-positive chronic hepatitis B patients receiving anti-HBV nucleos(t)ide analogues. |
| 24773464 | 2014 | Review | Expert Opin Pharmacother | Advances in treating HBV/HCV coinfection. |
| 25027705 | 2014 | Review | Minerva Gastroenterol Dietol | Antivirals for hepatitis B and C and their effects on kidney function. |
| 16937041 | 2006 | Review | Wien Med Wochenschr | Treatment and future prospects for chronic hepatitis B and C. |
| 32173307 | 2020 | Review | Clin Res Hepatol Gastroenterol | Present and future management of viral hepatitis B and C in children. |
| 24868325 | 2014 | Review | World J Hepatol | Management of hepatitis B and C before and after liver and kidney transplantation. |
| 35327336 | 2022 | Review | Biomedicines | Overview of therapy for chronic viral hepatitis. |
India Market Information
Entecavir is marketed in India, with 20 valid single-ingredient licences and no cancelled licences. The records may be partial. The approved indication text is not recorded in the local data. Five main authorizations are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 75964 | Entarica 0.5 Tablet (Fibrica Healthcare) | Strip of 10 tablets | Not available |
| 77463 | Entabest 0.5 Tablet (Shelton Pharmaceuticals) | Bottle of 30 tablets | Not available |
| 72382 | Entavir 0.5mg Tablet (Cipla) | Strip of 10 tablets | Not available |
| 72781 | Entehep 0.5 Tablet (Zydus Cadila) | Bottle of 30 tablets | Not available |
| 105508 | Hepalo 0.5 Tablet (Emcure Pharmaceuticals) | Strip of 10 tablets | Not available |
Safety Considerations
- Drug Interactions: 44 interactions were found. The ones listed here are all moderate-level: famotidine, ranitidine, cimetidine, metformin, amphotericin B (including lipid, cholesteryl sulfate and liposomal forms), amoxicillin, mesalazine, balsalazide, olsalazine, sulfasalazine, vancomycin, kanamycin, neomycin, polymyxin B, levofloxacin and orlistat.
For warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: Entecavir has no recognized activity against hepatitis C virus. The only related studies use it to prevent hepatitis B reactivation during hepatitis C therapy. The evidence level is L5, because no study tests entecavir as a treatment for hepatitis C.
To proceed, the following is needed:
- Mechanism of action data and any laboratory evidence of anti-HCV activity
- A study that directly tests entecavir against hepatitis C virus, if a mechanistic basis is found
- Package insert warnings and contraindications for the Indian products
- Clarification of whether the co-infection prophylaxis use is the actual clinical question, since it is a different question from treating hepatitis C
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.