Entecavir

Entecavir is an oral guanosine nucleoside analogue with potent activity against hepatitis B virus. It is a first-line drug for chronic hepatitis B when tenofovir is unsuitable, particularly in kidney disease or low bone density. It has a high barrier to resistance in naive patients, but lamivudine resistance greatly reduces its activity. Stopping it can cause severe hepatitis flares, and it carries a boxed warning for lactic acidosis.

Class. Nucleoside analogue antiviral.

Mechanism. Phosphorylated to entecavir triphosphate, which inhibits the hepatitis B polymerase at priming, reverse transcription and DNA synthesis. Lamivudine-resistance mutations (rtM204V/I) reduce susceptibility.

Pharmacokinetics. Oral absorption reduced by food. Half life about 128 to 149 hours. Excreted unchanged by the kidney.

Chronic hepatitis B, nucleoside-naive (adults and adolescents 16 years and over). 0.5 mg orally once daily on an empty stomach (at least 2 hours after a meal and 2 hours before the next).

Lamivudine-refractory or decompensated liver disease. 1 mg once daily.

Children 2 years and over (weight 10 kg or more). 0.015 mg/kg once daily (maximum 0.5 mg), using oral solution.

Dose adjustment for kidney function (0.5 mg regimen).

• CrCl 30 to 49 mL/min: 0.25 mg daily or 0.5 mg every 48 hours.
• CrCl 10 to 29: 0.15 mg daily or 0.5 mg every 72 hours.
• CrCl under 10 or haemodialysis: 0.05 mg daily or 0.5 mg every 7 days, given after dialysis.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 1 mg daily.

Main alternative. Tenofovir disoproxil fumarate or tenofovir alafenamide.

Contraindications. Hypersensitivity.

Serious adverse effects. Severe acute exacerbation of hepatitis B after stopping, lactic acidosis with hepatic steatosis, and, in HIV co-infection without effective antiretroviral therapy, selection of the M184V mutation.

Common adverse effects. Headache, fatigue, dizziness and nausea.

Interactions. Few; additive kidney effects with nephrotoxins; do not give with lamivudine for hepatitis B in an attempt to improve efficacy.

Common prescribing errors. Taking with food, treating HIV co-infection without a fully suppressive antiretroviral regimen, and full dose in kidney impairment.

Special groups.

• Pregnancy: avoid unless essential; tenofovir is preferred.
• Breastfeeding: avoid.
• Children: from 2 years by weight.
• Older adults: adjust for kidney function.
• Kidney impairment: reduce the dose or lengthen the interval at CrCl under 50 mL/min.
• Liver impairment: usual dose in compensated disease; 1 mg daily in decompensated disease, with monitoring for lactic acidosis.

Regional points. Tenofovir disoproxil fumarate is the usual first-line drug for hepatitis B in East Africa because it is also active against HIV; entecavir is chosen for people with kidney disease who are HIV negative.

Formulations. Tablets 0.5 mg and 1 mg; oral solution 0.05 mg/mL.

Administration. Once daily on an empty stomach, at least 2 hours after and 2 hours before a meal.

Baseline. Hepatitis B surface antigen, HBV DNA, HBeAg, ALT, creatinine and eGFR, HIV test, hepatitis C and D status.

Monitoring. HBV DNA and ALT every 3 months in the first year and then every 6 months; creatinine; lactate if unwell; liver ultrasound every 6 months in cirrhosis.

Stopping thresholds. Stop only under specialist supervision; monitor ALT and HBV DNA for at least 6 months after stopping; stop for lactic acidosis.

Referral and escalation. Specialist review for decompensated cirrhosis, hepatitis flare, HIV co-infection and treatment failure.