Entecavir 0.5 mg Tablet

Entecavir tablets are indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. Entecavir tablets are a hepatitis B virus nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of chronic hepatitis B virus infection in adults and children at least 2 years of age with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. ( 1 )

• Nucleoside-inhibitor-treatment-naïve with compensated liver disease (greater than or equal to 16 years old): 0.5 mg once daily
• Nucleoside-inhibitor-treatment-naïve and lamivudine-experienced
• Pediatric patients at least 2 years of age and weighing at least 10 kg: dosing is based on weight
• Lamivudine-refractory or known lamivudine or telbivudine resistance substitutions (greater than or equal to 16 years old): 1 mg once daily
• Decompensated liver disease (adults): 1 mg once daily
• Renal impairment: Dosage adjustment is recommended if creatinine clearance is less than 50 mL/min
• Entecavir tablets should be administered on an empty stomach
• Timing of Administration Entecavir tablets should be administered on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal)
• Recommended Dosage
• In Adults Compensated Liver Disease The recommended dose of entecavir tablets for chronic hepatitis B virus infection in nucleoside-inhibitor-treatment-naïve
• Adults and adolescents 16 years of age and older is 0.5 mg once daily
• The recommended dose of entecavir tablets
• In adults and adolescents (at least 16 years of age) with a history of hepatitis B viremia while receiving lamivudine or known lamivudine or telbivudine resistance substitutions rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L is 1 mg once daily
• Decompensated Liver Disease The recommended dose of entecavir tablets for chronic hepatitis B virus infection

Entecavir tablets, USP 0.5 mg are white to off-white, oval, film-coated, biconvex bevel edged, unscored tablets, debossed with “AN” on one side and “446” on the other side. Entecavir tablets, USP 1 mg are pink, oval, film-coated, biconvex bevel edged, unscored tablets, debossed with “AN” on one side and “449” on the other side. Tablets: 0.5 mg and 1 mg (3, 16)

• Entecavir was evaluated in two clinical trials of pediatric subjects 2 years of age and older with HBeAg-positive chronic HBV infection and compensated liver disease
• The exposure of entecavir in nucleoside-inhibitor-treatment-naïve and lamivudine-experienced pediatric subjects 2 years of age and older with HBeAg-positive chronic HBV infection and compensated liver disease receiving 0.015 mg/kg (up to 0.5 mg once daily) or 0.03 mg/kg (up to 1 mg once daily), respectively, was evaluated in Study AI463028. …

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. …

• See FDA-approved patient labeling (Patient Information)
• Severe Acute Exacerbation of Hepatitis after Discontinuation of Treatment Inform patients that discontinuation of anti-hepatitis B therapy, including entecavir, may result in severe acute exacerbations of hepatitis B
• Advise the patient to not discontinue entecavir without first informing their healthcare provider [see Warnings and Precautions ] . …

• None
• None

Since entecavir is primarily eliminated by the kidneys [see Clinical Pharmacology (12.3) ] , co-administration of entecavir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the co-administered drug. Co-administration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir disoproxil fumarate did not result in significant drug interactions. The effects of co-administration of entecavir with other drugs that are renally eliminated or are known to affect renal function have not been evaluated, and patients should be monitored closely for adverse events when entecavir is co-administered with such drugs.

Severe acute exacerbations of hepatitis B virus infection after discontinuation: Monitor hepatic function closely for at least several months. (5.1, 6.1) Co-infection with HIV: Entecavir is not recommended unless the patient is also receiving HAART. (5.2) Lactic acidosis and severe hepatomegaly with steatosis: If suspected, treatment should be suspended. (5.3) 5.1 Severe Acute Exacerbations of Hepatitis B Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir [see Adverse Reactions (6.1) ] . …

The following adverse reactions are discussed in other sections of the labeling: Exacerbations of hepatitis after discontinuation of treatment [see Boxed Warning , Warnings and Precautions (5.1) ] . Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning , Warnings and Precautions (5.3) ] . In adults, the most common adverse reactions (≥3%, all severity grades) are headache, fatigue, dizziness, and nausea. The adverse reactions observed in pediatric patients were consistent with those observed in adults. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to entecavir during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. …

There is limited experience of entecavir overdosage reported in patients. Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. Following a single 1 mg dose of entecavir, a 4-hour hemodialysis session removed approximately 13% of the entecavir dose.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.