Trade Names:Baraclude- Tablets 0.5 mg- Tablets 1 mg- Solution, oral 0.05 mg/mL
Inhibits hepatitis B virus (HBV) polymerase (reverse transcriptase) by competing with the natural substrate deoxyguanosine triphosphate.
Bioavailability of tablet is 100% relative to oral solution. T max is between 0.5 and 1.5 h. Steady state achieved after 6 to 10 days. For 0.5 mg dose, C max was 4.2 ng/mL and C trough was 0.3 ng/mL; for 1 mg dose, C max was 8.2 ng/mL and C trough was 0.5 ng/mL. Administration with food decreases C max by 44% to 46% and AUC by 18% to 20%.
Approximately 13% protein bound. Vd is in excess of total body water, suggesting extensive distribution into tissues.
No oxidative or acetylated metabolites found. Minor amounts of phase 2 metabolites (glucuronide, sulfate conjugates) noted.
Terminal elimination half-life is 128 to 149 h; accumulation half-life approximately 24 h. Eliminated predominantly by kidney (both glomerular filtration and tubular secretion), with 62% to 73% of dose recovered in the urine.
C max and AUC increased in patients with moderate to severe renal function impairment or with end-stage renal disease. Dose reduction recommended for patients with CrCl less than 50 mL/min.Hepatic Function Impairment
Pharmacokinetics similar between hepatically impaired patients and healthy patients.Elderly
AUC was 29.3% greater in elderly subjects; most likely due to differences in renal function. Base dose adjustment of entecavir on renal function of patient and not on age.Children
Pharmacokinetic studies have not been conducted.
Treatment of chronic HBV in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
PO 1 mg daily.Nucleoside Treatment–Naive PatientsAdults and Children 16 yr of age and older
PO 0.5 mg daily.Renal ImpairmentAdults and Children 16 yr of age and older
POFor CrCl 30 to 49 mL/min Nucleoside-naive patients
0.25 mg once daily or 0.5 mg every 48 h.Lamivudine-refractory patients
0.5 mg once daily or 1 mg every 48 h.For CrCl 10 to 29 mL/min Nucleoside-naive patients
0.15 mg once daily or 0.5 mg every 72 h.Lamivudine-refractory patients
0.3 mg once daily or 1 mg every 72 h.For CrCl less than 10 mL/min Hemodialysis or chronic peritoneal dialysis patients
If administered on a hemodialysis day, give entecavir after the hemodialysis session.Nucleoside-naive patients
0.05 mg once daily or 0.5 mg every 7 daysLamivudine-refractory patients
0.1 mg once daily or 1 mg every 7 days.
Store at controlled room temperature (59° to 86°F). Protect oral solution from light.
Serum concentrations of entecavir or the coadministered drug may be elevated, possibly increasing pharmacologic and adverse effects.
None well documented.
Headache (4%); fatigue (3%).
Diarrhea, dyspepsia (1%).
Exacerbation of hepatitis (12%).
Anaphylactoid reaction (postmarketing).
Elevated ALT (12%); hematuria (9%); increased lipase (7%); glucosuria (4%); fasting hyperglycemia, increased total bilirubin (3%); increased creatinine (2%).
WarningsCoinfected with HIV and HBV
There is a potential for development of resistance to HIV nucleoside reverse transcriptase inhibitors if entecavir is used to treat chronic hepatitis B infection in patients with HIV infection that is not being treated with highly active antiretroviral therapy.Hepatitis
Acute exacerbations have occurred in patients who have discontinued antihepatitis B therapy, including entecavir. Monitor hepatic function closely with clinical and laboratory follow-up for at least several months in patients who discontinue antihepatitis B therapy. Resumption of antihepatitis B therapy may be warranted.Lactic acidosis/hepatomegaly
Lactic acidosis and hepatomegaly with steatosis (including fatal cases) have been reported with use of nucleoside analogues alone or in combination with other antiretrovirals.
Monitor patients for evidence of lactic acidosis and hepatitis. Monitor closely for adverse reactions when entecavir is coadministered with drugs that are excreted renally or with drugs known to affect renal function (eg, cyclosporine). Monitor hepatic function for several months after discontinuing therapy. Monitor renal function carefully in liver transplant patients who have received or are receiving an immunosuppressant that may affect renal function (eg, cyclosporine, tacrolimus).
Category C .
Safety and efficacy in children younger than 16 yr of age not established.
Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.
Dosage adjustments are recommended for patients with CrCl less than 50 mL/min, including patients on hemodialysis.
No experience reported.
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