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. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Co-infection with HIV: Entecavir has not been evaluated in HIV/HBV co-infected patients who were not simultaneously receiving effective HIV treatment. Limited clinical experience suggests there is a potential for the development of resistance to HIV nucleoside reverse transcriptase inhibitors if entecavir is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therefore, therapy with entecavir is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). Before initiating entecavir therapy, HIV antibody testing should be offered to all patients. Entecavir has not been studied as a treatment for HIV infection and is not recommended for this use.
Lactic acidosis and severe hepatomegaly with steatosis: 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.
Use in Racial/Ethnic Groups: Clinical studies of Entecavir did not include sufficient numbers of subjects from some racial/ethnic minorities (Black/African American, Hispanic) to determine whether they respond differently to treatment with the drug. There are no significant racial differences in entecavir pharmacokinetics.
Use in Children: Safety and effectiveness of entecavir in pediatric patients below the age of 16 years have not been established.
Use in Elderly: 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. Entecavir is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.