VIR

• Chronic hepatitis B

Entecavir is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older with evidence of active viral replication and either evidence of persistent elevation in serum aminotransferases (ALT or AST) or histologically active disease.

N/A

Entecavir is contraindicated in patients with previously demonstrated hypersensitivity to Entecavir or any component of the product.

By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): Base priming, Reverse transcription of the negative strand from the pregenomic messenger RNA, and Synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity.

Co-administration of Entecavir with Lamivudine or Adefovir dipivoxil did not result in significant drug interactions. The effects of co-administration of Entecavir with other drugs that are eliminated through renal or are known to affect renal function have not been evaluated and patients should be monitored closely for adverse events when coadministered with such drugs.

The most common adverse events are headache, fatigue, dizziness and nausea.

There is no experience of Entecavir overdosage reported in patients. Healthy subjects who received up to 20 mg daily for up to 14 days and single doses up to 40 mg had no unexpected adverse events. If overdosage occurs, the patient must be monitored for evidence of toxicity and standard supportive treatment as necessary.

There are no data on the effect of Entecavir on the transmission of HBV from mother to infant. Therefore, appropriate care should be taken. It is not known whether it is excreted in human milk. Mothers should be instructed not to breastfeed if they are taking Entecavir.

Lactic acidosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals. Exacerbations of hepatitis after discontinuation of treatment: Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including Entecavir.

Pediatric: Safety and effectiveness of Entecavir in pediatric patients below the age of 2 years have not been established.Geriatric: Clinical studies of Entecavir did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. But care should be taken in dose selection, and it may be useful to monitor renal function. Dose adjustment in renal impairment: Dose adjustment is recommended for patients with CrCl <50 ml/min including patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) as shown below: 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