Monograph: |
Entecavir
Adverse Effects
The most common adverse effects of entecavir have been headache, fatigue, dizziness, and nausea.
Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been associated with treatment with nucleoside reverse transcriptase inhibitors.
Entecavir is carcinogenic in rodents.
Precautions
Severe exacerbation of hepatitis B has been reported after stopping treatment with entecavir and hepatic function should be monitored closely, with both clinical and laboratory follow-up for several months, after treatment is discontinued. Dosage reduction may be necessary in patients with renal impairment.
Antiviral Action
Entecavir is phosphorylated intracellularly to the active triphosphate form which competes with deoxyguanosine triphosphate, the natural substrate of hepatitis B virus reverse transcriptase, thereby inhibiting every stage of the enzyme's activity.
Entecavir has no activity against HIV.
Pharmacokinetics
Entecavir is absorbed from the gastrointestinal tract after oral doses. Peak plasma concentrations occur 30 to 90 minutes after a dose and steady state concentrations after 6 to 10 days of treatment. Absorption is both delayed and reduced by administration with food; entecavir should therefore be taken on an empty stomach. Bioavailability of the tablet formulation is equal to that of the oral solution and they may be given interchangeably. Binding of entecavir to plasma proteins is about 13% in vitro. Entecavir is not metabolised by the cytochrome P450 system. It is mainly eliminated by the kidneys by glomerular filtration and active tubular secretion, with a terminal elimination half-life of 128 to 149 hours. Minor amounts of glucuronide and sulfate conjugate metabolites occur. Entecavir is partially removed by haemodialysis.
Uses and Administration
Entecavir is a nucleoside reverse transcriptase inhibitor, structurally related to guanosine with selective antiviral activity against hepatitis B virus. It is used for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistently elevated liver enzyme values or of histologically active disease, including those resistant to lamivudine. The usual dose of entecavir in nucleoside treatment-naive patients is 500 micrograms once daily by mouth on an empty stomach. A dose of 1 mg once daily should be used in patients with a history of hepatitis B viraemia during lamivudine therapy or with known resistance to lamivudine.
Administration in renal impairment.
Doses of entecavir should be reduced in patients with renal impairment according to creatinine clearance (CC) as follows:
CC 30 to 49 mL/minute: 250 micrograms once daily in nucleoside treatment-naive patients; 500 micrograms once daily in lamivudine-refractory patients
CC 10 to 29 mL/minute: 150 micrograms once daily in nucleoside treatment-naive patients; 300 micrograms once daily in lamivudine-refractory patients
CC less than 10 mL/minute: 50 micrograms once daily in nucleoside treatment-naive patients; 100 micrograms once daily in lamivudine-refractory patients
Patients receiving haemodialysis should receive the appropriate dose after each dialysis session.
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