Posology : מינונים

4.2      Posology and method of administration

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

U   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 andmore 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.

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.

Baraclude dosage*

Creatinine clearance      Nucleoside naïve patients            Lamivudine-refractory or (ml/min)                                                   decompensated liver disease

≥ 50                 0.5 mg once daily                    1 mg once daily 
30 - 49              0.25 mg once daily*                  0.5 mg once daily OR
0.5 mg every 48 hours

10 - 29                   0.15 mg once daily*                    0.3 mg once daily* OR                                   OR
0.5 mg every 72 hours                  0.5 mg every 48 hours
< 10                    0.05 mg once daily*                    0.1 mg once daily* Haemodialysis or                       OR                                   OR CAPD**                  0.5 mg every 5-7 days                  0.5 mg every 72 hours * 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 :
U                         U



Baraclude should be taken orally.