1. Clinical Overview
Entecavir is a potent, selective, and orally administered guanosine nucleoside analogue with activity against hepatitis B virus (HBV). It is a first-line antiviral agent for the treatment of chronic hepatitis B (CHB) in adults and children (≥2 years) with compensated liver disease and evidence of active viral replication, persistently elevated serum ALT levels, or histologically active disease. It is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits all three steps of the HBV replication process: base priming, reverse transcription of the negative strand from the pregenomic mRNA, and synthesis of the positive strand of HBV DNA.
| Onset | Duration | Bioavailability |
|---|---|---|
| Virologic response (reduction in HBV DNA) is typically observed within 1-2 weeks of initiation. | The antiviral effect is sustained with continued daily dosing. Upon discontinuation, a rebound in HBV DNA levels is common. | Approximately 100% when taken on an empty stomach (at least 2 hours before or after a meal). High-fat meals reduce bioavailability by 18-20%. |
2. Mechanism of Action
Entecavir is a guanosine nucleoside analogue that is phosphorylated intracellularly to its active triphosphate form. Entecavir triphosphate competes with the natural substrate deoxyguanosine triphosphate (dGTP) to inhibit all three functions of the HBV polymerase (reverse transcriptase): (1) base priming of the HBV DNA polymerase, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. This results in potent inhibition of HBV replication.
3. Indications & Uses
- Chronic hepatitis B virus (HBV) infection in adults with compensated liver disease and evidence of active viral replication (detectable HBV DNA), persistent elevation in serum ALT levels, or histologically active disease.
- Chronic hepatitis B virus (HBV) infection in pediatric patients 2 years of age and older with compensated liver disease and evidence of active viral replication (detectable HBV DNA), persistent elevation in serum ALT levels, or histologically active disease.
4. Dosage & Administration
Adult Dosage: For nucleoside-naïve patients: 0.5 mg orally once daily. For patients with a history of lamivudine resistance or known lamivudine-refractory viremia: 1 mg orally once daily.
Administration: Must be administered on an empty stomach, at least 2 hours before or 2 hours after a meal. Tablet should be swallowed whole with a glass of water. For the oral solution, use the provided calibrated dosing spoon or oral syringe. Missed Dose: If a dose is missed, it should be taken as soon as possible on the same day. Do not double the next day's dose.
5. Side Effects
Common side effects may include:
- Headache
- Fatigue
- Dizziness
- Nausea
- Dyspepsia
- Upper respiratory tract infection
- Increased serum ALT (alanine aminotransferase) levels (flare)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Drugs that reduce renal function or compete for active tubular secretion (e.g., Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir, Tenofovir, Aminoglycosides) | May increase serum concentrations of entecavir. Monitor for entecavir-associated adverse effects. | Moderate |
| Lamivudine or Telbivudine | No significant pharmacokinetic interaction, but cross-resistance is a therapeutic concern. | Major (Therapeutic) |
| HIV Protease Inhibitors (e.g., Atazanavir, Lopinavir/ritonavir) when used with Tenofovir | May increase tenofovir levels, potentially exacerbating renal risk; entecavir is not a concern for CYP interaction. | Moderate (Indirect) |
| Immunosuppressants (e.g., Cyclosporine, Tacrolimus) | No direct interaction, but both require renal monitoring. Entecavir is used in transplant settings under careful supervision. | Moderate |
7. Patient Counselling
- DO take the medicine exactly as prescribed, at the same time each day.
- DO take it on an empty stomach (at least 2 hours before or after a meal).
- DO NOT stop taking entecavir without consulting your doctor, as this can cause a severe flare-up of hepatitis.
- DO NOT share your medicine with anyone else.
- DO inform all your doctors and dentists that you are taking entecavir.
8. Toxicology & Storage
Overdose: Limited data. Expected effects would be an extension of its adverse reaction profile, particularly gastrointestinal symptoms (nausea) and dizziness. Lactic acidosis is a theoretical risk with massive overdose.
Storage: Store at room temperature (15°C to 30°C). Protect from light and moisture. Keep the bottle tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the label. For oral solution: Use within the period specified after opening (e.g., 2 months), and do not freeze.