Entekor 1.0

Product Description Description: 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 [see WARNINGS AND PRECAUTIONS] Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus.) nucleoside reverse transcriptase inhibitors if ENTEKOR is used to treat chronic hepatitis B virus (HBV) infection in patients with HIV infection that is not being treated. Therapy with ENTEKOR is not recommended for HIV/HBV co-infected patients who are not also Receiving highly active antiretroviral therapy (HEART) [see WARNING AND PRECAUTIONS].Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretroviral [see WARNING AND PRECAUTIONS]. Warning: Severe Acute Exagerbations of Hepatitis B.patient Co-infected With Hiv and Hbv and Lactic Acidosis and Hepatomegaly. Pharmacokinetics: The single- and multiple-dose pharmacokinetics of Entecavir were evaluated in healthy subjects And subjects with chronic HBV infection. Absorption. Following oral administration in healthy Subjects, Entecavir peak plasma concentration occurred between 0.5 and 1.5 hours. Following Multiple daily doses ranging from 0.1to 1.0 mg. CMAX and area under the concentration-time curve (AUC) at steady state increased in proportion to dose. Steady state was achieved after 6 to 10 days of once-daily administration with approximately 2-fold accumulation. for a 0.5 mg oral Dose, CMAX at steady state was 4.2ng/ML.and trough plasma concentration (C1rough) was 0.3 ng/ML.for a 1mg oral dose. CMAX at steady state was 4.2ng/ML and trough plasma concentration( CMAX ) was 0.3 ng/ml for a 1 mg oral dose CMAX was 8.2ng/ml and C1rough was 0.5ng.ml. Effects of Food on Oral Absorption: Oral administration of 0.5 mg of Entecavir with a Standard high-fat meal (945 kcal,54.6 g fat)or a light meal(379 kcal.8.2 g fat) resulted in a delay In absorption (1.0-1.5 hours fed versus 0.75 hours fasted).a decrease in AUC of 18-20%[see DOSAGE ANDADMINISTRATION]. Distribution: Based on the pharmacokinetic profile of entecavir after oral dosing, the estimated apparent volume of distribution is in excess of total body water, suggesting that entecavir is extensively Distributed into tissues. Binding of entecavir to human serum proteins in vitro was approximate 13%. Metabolism and Elimination: Following administration of 14C-entecavir in humans, no oxidative of acetylated metabolism were observed. Minor amounts of phase II metabolites (glucuronide and sulfate Conjugates) were observed entecavir is not a substrate, inhibitor, or include the cytochrome P450 (CYP450) enzyme system [see Drug Interactions]. After reaching peak concentration entecavir plasma concentrations decreased in a biexponential manner with a terminal elimination half-life of approximately 128-149 hours. The observed drug accumulation index is approximately 2-fold with once-daily dosing. Suggesting an Effective accumulation half-life of approximately 24 hours. Entecavir is predominantly eliminated by the kidney, with a unary recovery of the unchanged drug at steady state ranging from 62% to 73% of the administered dose. Renal clearance is independent of dose and ranges from 360 to 471 ml/min, suggesting that entecavir undergoes both glomerular filtration and net tubular secretion [see Drug Interactions.]