Entecavir
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Entecavir: From Chronic Hepatitis B to Chronic Hepatitis C Virus Infection
One-Sentence Summary
Entecavir is an oral antiviral originally used to treat chronic hepatitis B virus (HBV) infection. The TxGNN model predicts it may be effective for chronic hepatitis C virus (HCV) infection. The evidence is indirect: 2 clinical trials and 20 publications were retrieved, but they address HBV management in patients who also have HCV, not HCV treatment itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis B virus infection |
| Predicted New Indication | Chronic hepatitis C virus infection |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L4 (indirect evidence only) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 17 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Entecavir is known to be a guanosine nucleoside analogue that inhibits the HBV polymerase. Its efficacy in chronic hepatitis B is well established.
The prediction looks like a network association rather than a true pharmacological link. HCV is an RNA virus with no DNA polymerase or reverse transcription step, which are the steps entecavir blocks. The model's signal most likely reflects HBV/HCV co-infection and shared hepatitis-related associations. The trials and publications retrieved are about preventing or managing HBV in patients who also have HCV, usually while they receive direct-acting antivirals (DAAs) for HCV. Any anti-HCV effect in these studies comes from the DAAs, not from entecavir.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02555943 | Phase 2/3 | Completed | 23 | Studies HBV reactivation during DAA therapy in HCV/HBV co-infected patients. Any HCV efficacy comes from the DAAs, not entecavir. |
| NCT04405011 | Not applicable | Unknown | 60 | Randomized, open-label study of whether prophylactic nucleos(t)ide analogues (12 vs 24 weeks) prevent HBV reactivation in co-infected patients on DAA therapy. The endpoint is HBV, not HCV. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 34864158 | 2022 | Randomized trial | Clin Gastroenterol Hepatol | Entecavir prevents HBV reactivation during DAA treatment of HCV/HBV dual infection. |
| 24773464 | 2014 | Review | Expert Opin Pharmacother | Advances in treating HBV/HCV co-infection, a group at high risk of cirrhosis and liver cancer. |
| 25027705 | 2014 | Review | Minerva Gastroenterol Dietol | Antiviral drugs for hepatitis B and C and their effects on kidney function. |
| 16937041 | 2006 | Review | Wien Med Wochenschr | Current treatment and future prospects for chronic hepatitis B and C. |
| 36146665 | 2022 | Cohort | Viruses | HCV reactivation in 66 anti-HCV-positive chronic hepatitis B patients on nucleos(t)ide analogue therapy. |
| 28230928 | 2017 | Not classified | J Gastroenterol Hepatol | Risk of HBV reactivation when HCV patients with HBV infection receive DAAs. |
| 35108715 | 2022 | Not classified | Dig Dis | Incidence and clinical course of HBV reactivation in HBV-exposed patients treated with DAAs for HCV. |
| 32173307 | 2020 | Not classified | Clin Res Hepatol Gastroenterol | Current and future management of hepatitis B and C in children. |
| 24868325 | 2014 | Not classified | World J Hepatol | Management of hepatitis B and C around liver and kidney transplantation. Entecavir and tenofovir are described as high-barrier agents for HBV. |
| 18808207 | 2008 | Not classified | Drugs Aging | Prevention and management of viral hepatitis in elderly haemodialysis patients. |
Singapore Market Information
Entecavir has 17 valid single-ingredient registrations in Singapore, all film-coated oral tablets. Approved indication text is not available for these registrations. Five of them are listed below.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| SIN13165P | BARACLUDE TABLET 0.5mg | Film-coated tablet | AstraZeneca Pharmaceuticals LP and others |
| SIN13167P | BARACLUDE TABLET 1mg | Film-coated tablet | AstraZeneca Pharmaceuticals LP and others |
| SIN15548P | ENTECAVIR SANDOZ FILM-COATED TABLET 0.5MG | Film-coated tablet | Novartis Pharmaceutical Manufacturing LLC |
| SIN16094P | PMS-ENTECAVIR FILM COATED TABLET 0.5mg | Film-coated tablet | Pharmascience Inc |
| SIN16092P | ENTECAVIR-TEVA FC TABLETS 0.5MG | Film-coated tablet | Remedica Ltd. |
Safety Considerations
- Conditions flagged in a drug-disease knowledge graph (not package insert text): impaired renal function, fatty liver disease, non-alcoholic steatohepatitis, and lactic acidosis.
- Drug Interactions: 44 interactions were recorded, and those listed in detail are all rated Moderate. They include:
- Acid suppressants: famotidine, ranitidine, cimetidine.
- Metformin.
- Amphotericin B (including lipid, liposomal and cholesteryl sulfate formulations).
- Antibiotics: vancomycin, kanamycin, neomycin, levofloxacin, amoxicillin, polymyxin B.
- Mesalazine, balsalazide, olsalazine and sulfasalazine.
- Orlistat.
- Additional safety notes: please refer to the package insert for key warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Entecavir has no recognised activity against HCV. The retrieved trials and publications concern HBV management in HCV co-infected patients, not HCV treatment. The high model score therefore appears to reflect network association rather than a genuine anti-HCV effect. The established use of entecavir in HBV/HCV co-infection is for HBV reactivation prophylaxis, which is an HBV indication.
To proceed, the following is needed:
- Mechanism of action data and in vitro evidence of anti-HCV activity, if any exists.
- Package insert warnings and contraindications from the Singapore regulator, for a full safety review.
- A controlled study with an HCV efficacy endpoint (for example, sustained virological response) showing an effect from entecavir itself.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.