Entecavir Accord

Therapy should be initiated by a physician experienced in the management of chronic hepatitis B infection. 5 and 1 mg film-coated tablets. For patients who are not able to swallow tablets or for whom a dose reduction is recommended, other entecavir-containing products with more suitable formulations may be available.

5 mg once daily, with or without food. e. 2). ). 2). 1. Duration of therapy The optimal duration of treatment is unknown. 4). • In HBeAg negative adult patients, treatment should be administered at least until HBs seroconversion or there is evidence of loss of efficacy.

With prolonged treatment for more than 2 years, regular reassessment is recommended to confirm that continuing the selected therapy remains appropriate for the patient. In patients with decompensated liver disease or cirrhosis, treatment cessation is not recommended.

5 mg an oral solution may be available. 4 The decision to treat paediatric patients should be based on careful consideration of individual patient needs and with reference to current paediatric treatment guidelines including the value of baseline histological information.

The benefits of long-term virologic suppression with continued therapy must be weighed against the risk of prolonged treatment, including the emergence of resistant hepatitis B virus. Serum ALT should be persistently elevated for at least 6 months prior to treatment of paediatric patients with compensated liver disease due to HBeAg positive chronic hepatitis B; and for at least 12 months in patients with HBeAg negative disease.

5 mg tablet with or without food. 6 kg. There are no recommendations for entecavir in children less than 2 years of age or weighing less than 10 kg. Duration of therapy for paediatric patients The optimal duration of treatment is unknown.

In accordance with current paediatric practice guidelines, treatment discontinuation may be considered as follows: • In HBeAg positive paediatric patients, treatment should be administered for at least 12 months after achieving undetectable HBV DNA and HBeAg seroconversion (HBeAg loss and anti- HBe detection on two consecutive serum samples at least 3-6 months apart) or until HBs seroconversion or there is loss of efficacy.

4). • In HBeAg negative paediatric patients, treatment should be administered until HBs seroconversion or there is evidence of loss of efficacy. Pharmacokinetics in paediatric patients with renal or hepatic impairment have not been studied.

a. Summary of the safety profile In clinical trials in patients with compensated liver disease, the most common adverse reactions of any severity with at least a possible relation to entecavir were headache (9%), fatigue (6%), dizziness (4%) and nausea (3%).

4 and c. Description of selected adverse reactions). b. 1). 5 mg daily (679 nucleoside-naive HBeAg positive or negative patients treated for a median of 53 weeks), entecavir 1 mg daily (183 lamivudine-refractory patients treated for a median of 69 weeks), and lamivudine.

Adverse reactions considered at least possibly related to treatment with entecavir are listed by body system organ class. Frequency is defined as very common ( 1/10); common ( 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 4). Treatment beyond 48 weeks: continued treatment with entecavir for a median duration of 96 weeks did not reveal any new safety signals.

c.

Description of selected adverse reactions Laboratory test abnormalities:

In clinical trials with nucleoside-naive patients, 5% had ALT elevations > 3 times baseline, and < 1% had ALT elevations > 2 times baseline together with total bilirubin > 2 times upper limit of normal (ULN) and > 2 times baseline.

5 g/dl occurred in < 1% of patients, amylase levels > 3 times baseline in 2%, lipase levels > 3 times baseline in 11% and platelets < 50,000/mm3 in < 1%. 9 In clinical trials with lamivudine-refractory patients, 4% had ALT elevations > 3 times baseline, and < 1% had ALT elevations > 2 times baseline together with total bilirubin > 2 times ULN and > 2 times baseline.

Amylase levels > 3 times baseline occurred in 2% of patients, lipase levels > 3 times baseline in 18% and platelets < 50,000/mm3 in < 1%. Exacerbations during treatment: in studies with nucleoside naive patients, on treatment ALT elevations > 10 times ULN and > 2 times baseline occurred in 2% of entecavir treated patients vs 4% of lamivudine treated patients.

2). The proposed dose modifications are based on extrapolation of limited data, and their safety and effectiveness have not been clinically evaluated. Therefore, virological response should be closely monitored. Exacerbations of hepatitis: spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum ALT.

8). Among entecavir-treated patients on-treatment exacerbations had a median time of onset of 4-5 weeks. In patients with compensated liver disease, these increases in serum ALT are generally not accompanied by an increase in serum bilirubin concentrations or hepatic decompensation.

Patients with advanced liver disease or cirrhosis may be at a higher risk for hepatic decompensation following hepatitis exacerbation, and therefore should be monitored closely during therapy. 2). Post-treatment exacerbations are usually associated with rising HBV DNA, and the majority appears to be self-limited.

However, severe exacerbations, including fatalities, have been reported. 8). Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least 6 months after discontinuation of hepatitis B therapy.

If appropriate, resumption of hepatitis B therapy may be warranted. Patients with decompensated liver disease: a higher rate of serious hepatic adverse events (regardless of causality) has been observed in patients with decompensated liver disease, in particular in those with Child-Turcotte-Pugh (CTP) class C disease, compared with rates in patients with compensated liver function.

Also, patients with decompensated liver disease may be at higher risk for lactic acidosis and for specific renal adverse events such as hepatorenal syndrome. 1). Lactic acidosis and severe hepatomegaly with steatosis: occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues.

1.