Entecavir is indicated for the treatment of chronic hepatitis B virus infection in adults and children aged 2 years and older who show active viral replication, along with either persistently elevated serum aminotransferases (ALT or AST) or histologically active liver disease.

Entecavir inhibits hepatitis B virus (HBV) polymerase by competing with the natural substrate deoxyguanosine triphosphate. It functionally blocks all three activities of HBV polymerase (reverse transcriptase):

• Base priming
• Reverse transcription of the negative strand from pregenomic messenger RNA
• Synthesis of the positive strand of HBV DNA Once activated by cellular kinases, entecavir is incorporated into viral DNA, ultimately inhibiting HBV polymerase activity and preventing viral replication.

The recommended dose of Entecavir for chronic hepatitis B virus infection in nucleoside-treatment-naive adults and adolescents 16 years of age is 0.5 mg once daily. For Lamivudine-refractory or known Lamivudine or Telbivudine resistance mutations, the recommended dose of Entecavir is 1 mg once daily. For patients with decompensated liver disease (adult) the recommended dose of Entecavir is 1 mg once daily. Entecavir should be administered on an empty stomach (at least 2 hours after a meal or 2 hours before the next meal).

Missed Dose: If it is almost time for next dose, skip the missed dose and take the next dose at the proper time. Nobody should take a double dose to make up for the missed dose.

Co-administration of Entecavir with Lamivudine or Adefovir dipivoxil has not shown any significant drug interactions. The effects of taking Entecavir with other medications that are eliminated through the kidneys or affect kidney function have not been studied. Patients receiving such combinations should be closely monitored for potential adverse effects.

Entecavir should not be used in patients who have shown hypersensitivity to Entecavir or any component of the product.

The most common side effects of Entecavir are headache, fatigue, dizziness, and nausea.

There is no information on the effect of Entecavir on mother-to-child transmission of HBV. Therefore, appropriate precautions should be taken. It is not known whether Entecavir is excreted in human breast milk. Mothers taking Entecavir should be advised not to breastfeed.

Lactic acidosis: Cases of lactic acidosis and severe hepatomegaly with steatosis, including fatal outcomes, have been reported with the use of nucleoside analogues alone or in combination with antiretroviral drugs.

Exacerbations of hepatitis after treatment discontinuation: Severe acute exacerbations of hepatitis B have been reported in patients who stopped anti-hepatitis B therapy, including Entecavir. Patients should be closely monitored when discontinuing treatment.

Pediatric: The safety and effectiveness of Entecavir in children under 2 years of age have not been established.

Geriatric: Clinical studies did not include enough patients aged 65 years or older to determine if their response differs from younger patients. Care should be taken when selecting doses, and renal function may need to be monitored.

Dose adjustment in renal impairment: Dose adjustment is recommended for patients with creatinine clearance (CrCl) below 50 ml/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), as follows:

• CrCl ≥ 50 ml/min: 0.5 mg every 24 hours
• CrCl 30 to <50 ml/min: 0.5 mg every 48 hours
• CrCl 10 to <30 ml/min: 0.5 mg every 72 hours
• CrCl <10 ml/min or Hemodialysis or CAPD: 0.5 mg every 7 days

There are no reported cases of Entecavir overdose in patients. In healthy volunteers, doses up to 20 mg daily for 14 days or single doses up to 40 mg did not cause unexpected adverse effects. If an overdose occurs, the patient should be monitored for signs of toxicity, and standard supportive treatment should be provided as needed.

Hepatic viral infections (Hepatitis B)

Store Entecavir in a dry place at a temperature below 30°C. Protect from light and keep out of the reach of children.