Entecavir

• Chronic Hepatitis B
• HBV Infection
• Viral Hepatitis Treatment
• Antiviral Therapy for HBV

Entecavir is a nucleoside analog antiviral used for the treatment of chronic hepatitis B virus (HBV) infection. This potent antiviral offers high efficacy, a high genetic barrier to resistance, and favorable tolerability, making it a first-line treatment option for chronic hepatitis B.

Mechanism of Action

Entecavir is a guanosine nucleoside analog that is efficiently phosphorylated to its active triphosphate form within cells. Entecavir triphosphate competes with the natural substrate deoxyguanosine triphosphate (dGTP) and inhibits the HBV polymerase (reverse transcriptase) at three key steps: priming of the HBV polymerase, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA. This multi-step inhibition results in potent suppression of HBV replication. Entecavir has a high genetic barrier to resistance in nucleoside-naive patients due to the multiple mutations required for viral escape.

Available Formulations

Entecavir is available as film-coated tablets (0.5 mg, 1 mg) and as an oral solution (0.05 mg/mL). The medication should be taken on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal) because food significantly reduces absorption. The oral solution is calibrated for precise dosing in pediatric patients.

Medical Uses

Entecavir is FDA-approved for the treatment of chronic hepatitis B virus infection in adults and pediatric patients (2 years of age and older weighing at least 10 kg) with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. It is effective in both HBeAg-positive and HBeAg-negative patients and can be used in patients with compensated or decompensated liver disease. Entecavir is recommended as a first-line therapy by major guidelines.

Dosing Guidelines

For nucleoside-treatment-naive adults with compensated liver disease, the dose is 0.5 mg once daily. For patients with lamivudine-refractory or telbivudine-refractory virus (with known resistance mutations), the dose is 1 mg once daily. For decompensated liver disease, 1 mg once daily is recommended. Pediatric dosing is weight-based. Significant dose adjustments are required for renal impairment (CrCl less than 50 mL/min), including after hemodialysis. Treatment duration is indefinite for most patients.

Important Safety Information

Severe acute exacerbations of hepatitis B have been reported in patients who discontinue entecavir. Hepatic function should be monitored closely for at least several months after discontinuation; resumption of therapy may be warranted. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs. HIV resistance may emerge if entecavir is used without fully suppressive antiretroviral therapy in patients with unrecognized or untreated HIV infection. All patients should be tested for HIV before starting entecavir.

Drug Interactions

Entecavir is primarily eliminated by the kidneys through both glomerular filtration and active tubular secretion. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of entecavir or the coadministered drug. Monitor closely when used with tenofovir or other nephrotoxic agents. No significant CYP450 interactions are expected.

Special Populations

There are limited data on use during pregnancy; animal studies showed no teratogenicity but some effects at high doses. It should be used during pregnancy only if clearly needed; tenofovir may be preferred if treatment is needed during pregnancy. Entecavir is excreted in breast milk in rats; breastfeeding is not recommended. Safety and efficacy have been established in pediatric patients 2 years and older. Elderly patients should be monitored for renal function. Significant dose adjustment is required for renal impairment. No dose adjustment is needed for hepatic impairment, though patients with decompensated liver disease should receive the higher dose.