New drug marks advance in treatment of hepatitis B

May 2, 2005

The Food & Drug Administration recently approved entecavir (Baraclude, Bristol-Myers Squibb) for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and evidence of either persistent elevations in serum aminotransferases or histologically active disease. Entecavir Tablets are currently available in U.S. pharmacies. Entecavir Oral Solution will be launched at a later date.

According to the Hepatitis B Foundation, approximately 1.2 million Americans are currently infected with HBV, and another 100,000 become infected annually.

Entecavir is a guanosine nucleoside analog that inhibits base priming, reverse transcription of the negative strand from the pregenomic messenger RNA, and synthesis of the positive strand of HBV DNA, said Robert Gish, M.D., medical director of the Liver Transplant Program at California Pacific Medical Center in San Francisco. He went on to say that the inhibitory concentration of entecavir is in the nano-molar range, whereas the inhibitory concentration of adefovir (Hepsera, Gilead Sciences) and lamivudine (Epivir-HBV, GlaxoSmithKline) is in the micromolar range. Gish said that less entecavir is required to achieve viral suppression because very high concentrations of entecavir triphosphate exist in hepatocytes, and entecavir inhibits three functions of HBV polymerase, not just one or two.

The recommended dose for chronic HBV infection in nucleoside treatment-naive adults and adolescents 16 years of age or older is 0.5 mg taken once daily. The recommended dose of entecavir in adults and adolescents with a history of hepatitis B viremia while receiving lamivudine or with known lamivudine resistance mutations is 1.0 mg taken once daily.

Gish said that entecavir is primarily renally excreted by glomerular filtration and net tubular secretion. Dosage adjustment is recommended for patients with creatinine clearance less than 50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.

Gish said that entecavir is primarily renally excreted by glomerular filtration and net tubular secretion. Dosage adjustment is recommended for patients with creatinine clearance less than 50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.

Bristol-Myers Squibb said that renal function must be monitored both before and during entecavir treatment in liver transplant recipients who have received or are receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus (Prograf, Astellas Pharma US).

A black box warning has been added to the product labeling regarding severe, acute exacerbations of HBV after the discontinuation of entecavir therapy, said Rivkin. The warning also cautions healthcare professionals about the risk of lactic acidosis and severe hepatomegaly with steatosis, she said.

Pharmacists are frequently asked about drug-drug interactions and adverse effects, noted Gish. He said entecavir really has no known drug-drug interactions. He also said entecavir is as safe as lamivudine in that both drugs have minimal adverse effects. According to the manufacturer, the most common adverse effects associated with entecavir use in clinical trials were headache, fatigue, dizziness, and nausea.

Rivkin agreed that educating patients about the adverse effects of therapy and discussing the pros and cons of available therapeutic options can all be a part of pharmacotherapeutic counseling.

Pharmacists can also become involved in prevention efforts to decrease the transmission of HBV and serve as advocates for HBV vaccination, said Rivkin.