BARACLUDE Film-coated tablets Ref.[6761] Active ingredients: Entecavir

Therapy should be initiated by a physician experienced in the management of chronic hepatitis B infection.

Posology

Compensated liver disease

Nucleoside naïve patients

The recommended dose in adults is 0.5 mg once daily, with or without food.

Lamivudine-refractory patients (i.e. with evidence of viraemia while on lamivudine or the presence of lamivudine resistance [LVDr] mutations) (see sections 4.4 and 5.1)

The recommended dose in adults is 1 mg once daily, which must be taken on an empty stomach (more than 2 hours before and more than 2 hours after a meal) (see section 5.2). In the presence of LVDr mutations, combination use of entecavir plus a second antiviral agent (which does not share cross-resistance with either lamivudine or entecavir) should be considered in preference to entecavir monotherapy (see section 4.4.).

Decompensated liver disease

The recommended dose for adult patients with decompensated liver disease is 1 mg once daily, which must be taken on an empty stomach (more than 2 hours before and more than 2 hours after a meal) (see section 5.2). For patients with lamivudine-refractory hepatitis B, see sections 4.4 and 5.1.

Duration of therapy

The optimal duration of treatment is unknown. Treatment discontinuation may be considered as follows:

• In HBeAg positive adult patients, treatment should be administered at least until 12 months after achieving HBe seroconversion (HBeAg loss and HBV DNA loss with anti-HBe detection on two consecutive serum samples at least 3-6 months apart) or until HBs seroconversion or there is loss of efficacy (see section 4.4).
• 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.

Paediatric population

For appropriate dosing in the paediatric population, Baraclude oral solution or Baraclude 0.5 mg film-coated tablets are available.

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.

Paediatric patients with body weight of at least 32.6 kg, should be administered a daily dose of one 0.5 mg tablet or 10 ml (0.5 mg) of the oral solution, with or without food. The oral solution should be used for patients with body weight less than 32.6 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. Serum ALT and HBV DNA levels should be followed regularly after treatment discontinuation (see section 4.4).
• 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.

Elderly

No dosage adjustment based on age is required. The dose should be adjusted according to the patient’s renal function (see dosage recommendations in renal impairment and section 5.2).

Gender and race

No dosage adjustment based on gender or race is required.

Renal impairment

The clearance of entecavir decreases with decreasing creatinine clearance (see section 5.2). Dose adjustment is recommended for patients with creatinine clearance <50 ml/min, including those on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). A reduction of the daily dose using Baraclude oral solution, as detailed in the table, is recommended. As an alternative, in case the oral solution is not available, the dose can be adjusted by increasing the dosage interval, also shown in the table. 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.

* for doses <0.5 mg Baraclude oral solution is recommended.
** on haemodialysis days, administer entecavir after haemodialysis.

Hepatic impairment

No dose adjustment is required in patients with hepatic impairment.

Method of administration

Baraclude should be taken orally.

There is limited experience of entecavir overdose reported in patients. Healthy subjects who received up to 20 mg/day for up to 14 days, and single doses up to 40 mg had no unexpected adverse reactions. If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.

Shelf life: 2 years.

Blisters: Do not store above 30°C. Store in the original carton.

Bottles: Do not store above 25°C. Keep the bottle tightly closed.

Each carton contains either:

• 30 × 1 film-coated tablet; 3 blister cards of 10 × 1 film-coated tablet each in Alu/Alu perforated unit dose blisters, or
• 90 × 1 film-coated tablet; 9 blister cards of 10 × 1 film-coated tablet each in Alu/Alu perforated unit dose blisters.

High-density polyethylene (HDPE) bottle with child resistant polypropylene closure containing 30 film-coated tablets. Each carton contains one bottle.

Not all pack sizes and container types may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.