Entecavir
| Evidence Level: L4 | Predicted Indications: 9 |
Table of Contents
Entecavir: Chronic hepatitis C virus infection
One-Sentence Summary
Entecavir is an antiviral drug originally used to treat chronic hepatitis B virus (HBV) infection. The TxGNN model predicts it may be effective for chronic hepatitis C virus infection, but the evidence is weak: 2 clinical trials and 20 publications are linked to this prediction, and none shows entecavir treating hepatitis C. They address HBV in patients who have both infections.
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 | L4 |
| Canada Market Status | Marketed (marketed DINs: 10 of 10) |
| Number of DINs | 10 (marketed: 10) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on established pharmacology, entecavir is a guanosine nucleoside analogue. Inside cells it is converted to its triphosphate form, which competes with the natural nucleotide dGTP and blocks the HBV polymerase.
Hepatitis B and C are both chronic viral liver infections, so the similarity the model learned between them is understandable. The mechanisms differ, though. HCV replicates with its own RNA-dependent RNA polymerase (NS5B), and entecavir has no known direct activity against it. The high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence of an antiviral effect on HCV.
The one plausible clinical link is co-infection. In people with both HBV and HCV, entecavir can suppress HBV replication or prevent HBV reactivation during HCV direct-acting antiviral (DAA) therapy. That is an HBV benefit, not treatment of HCV.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02555943 | Phase 2/3 | Completed | 23 | Tracks HBV reactivation during HCV DAA therapy in HCV/HBV co-infected patients. It does not test entecavir against HCV. |
| NCT04405011 | Not applicable | Unknown | 60 | Tests whether prophylactic nucleos(t)ide analogues, with 12 vs 24 weeks of prophylaxis, prevent HBV reactivation in co-infected patients on DAA therapy. This supports HBV prophylaxis, not HCV efficacy. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 34864158 | 2022 | RCT | Clin Gastroenterol Hepatol | Entecavir prevents HBV reactivation during DAA treatment of HCV/HBV dual infection (an HBV-protective effect). |
| 25027705 | 2014 | Review | Minerva Gastroenterol Dietol | Antiviral drugs for hepatitis B and C and their effects on kidney function. |
| 24773464 | 2014 | Review | Expert Opin Pharmacother | Advances in treating HBV/HCV co-infection. |
| 16937041 | 2006 | Review | Wien Med Wochenschr | Current treatment and future prospects for chronic hepatitis B and C. |
| 36146665 | 2022 | Cohort | Viruses | HCV reactivation in anti-HCV-positive chronic hepatitis B patients (66 patients) on nucleos(t)ide analogue therapy for HBV. |
| 35108715 | 2022 | Not classified | Dig Dis | Incidence and course of HBV reactivation in patients treated with DAAs for hepatitis C. |
| 28230928 | 2017 | Not classified | J Gastroenterol Hepatol | HBV reactivation risk in chronic hepatitis C patients with HBV infection treated with DAAs. |
| 32173307 | 2020 | Not classified | Clin Res Hepatol Gastroenterol | Present and future management of viral hepatitis B and C in children. |
| 24868325 | 2014 | Not classified | World J Hepatol | Management of hepatitis B and C before and after liver and kidney transplantation. Entecavir and tenofovir are described for HBV. |
| 28487602 | 2017 | Not classified | World J Gastroenterol | HBV infection and alcohol consumption as causes of hepatocellular carcinoma. |
Canada Market Information
Entecavir has 10 valid single-ingredient licenses in Canada, and no cancelled ones. The first 5 are listed below. Dosage form and approved-indication text were not available for these licenses.
| DIN | Product Name |
|---|---|
| 02485907 | MINT-ENTECAVIR |
| 02448777 | AURO-ENTECAVIR |
| 02396955 | APO-ENTECAVIR |
| 02282224 | BARACLUDE |
| 02467232 | JAMP ENTECAVIR |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): impaired renal function, fatty liver disease, non-alcoholic steatohepatitis, and lactic acidosis.
- Monitoring points from the evidence review: lactic acidosis, renal function, thrombocytopenia (a case report exists, PMID 34823407), and hepatitis flares after stopping treatment.
- Drug interactions: 44 interactions were recorded, and all those shown are Moderate. The main ones are:
- Acid-suppressing H2 blockers: famotidine, ranitidine, cimetidine.
- Metformin.
- Potentially nephrotoxic agents: amphotericin B (several formulations), vancomycin, kanamycin, neomycin, polymyxin B.
- Levofloxacin, amoxicillin, and orlistat.
- Aminosalicylates: mesalazine, balsalazide, olsalazine, sulfasalazine.
Please also refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The TxGNN score is very high (0.9998), but there is no evidence that entecavir treats hepatitis C. Entecavir targets the HBV polymerase, not HCV NS5B.
- The linked trials and publications concern HBV reactivation in HBV/HCV co-infected patients, which is an HBV indication.
- HCV already has highly effective, specific direct-acting antivirals, so there is little need for this repurposing.
To proceed, the following is needed:
- In vitro evidence of anti-HCV activity, such as replicon assays.
- Detailed mechanism of action data to support or refute a link to HCV.
- If the co-infection use is of interest, a separate evaluation framed as HBV reactivation prophylaxis during HCV DAA therapy, not HCV treatment.
- The package insert warnings and contraindications from Health Canada, which were missing from the data compiled for this report.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.