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FDA recently approved revisions in the labeling for Baraclude (entecavir) 0.5 mg and 1 mg Tablets and 0.05 mg/mL Oral Solution. The Specific Populations section of the Package Insert (Sections 8.6 and 8.8) have been revised to include data from Studies AI463109 (postliver transplant population) and AI463085 (Black/African American population).
The label revisions are as follows for the respective sections:
8.6 Racial/Ethnic Groups There are no significant racial differences in entecavir pharmacokinetics. The safety and efficacy of BARACLUDE 0.5 mg once daily were assessed in a single-arm, open-label trial of HBeAgpositive or -negative, nucleoside-naïve, Black/African American (n=40) and Hispanic (n=6) subjects with chronic HBV infection. In this trial, 76% of subjects were male, the mean age was 42 years, 57% were HBeAg-positive, the mean baseline HBV DNA was 7.0 log10 IU/mL, and Reference ID: 3202104 14 the mean baseline ALT was 162 U/L. At Week 48 of treatment, 32 of 46 (70%) subjects had HBV DNA <50 IU/mL (approximately 300 copies/mL), 31 of 46 (67%) subjects had ALT normalization (≤1 X ULN), and 12 of 26 (46%) HBeAg-positive subjects had HBe seroconversion. Safety data were similar to those observed in the larger controlled clinical trials. Because of low enrollment, safety and efficacy have not been established in the US Hispanic population.
8.8 Liver Transplant Recipients The safety and efficacy of BARACLUDE were assessed in a single-arm, open-label trial in 65 subjects who received a liver transplant for complications of chronic HBV infection. Eligible subjects who had HBV DNA less than 172 IU/mL (approximately 1000 copies/mL) at the time of transplant were treated with BARACLUDE 1 mg once daily in addition to usual posttransplantation management, including hepatitis B immune globulin. The trial population was 82% male, 39% Caucasian, and 37% Asian, with a mean age of 49 years; 89% of subjects had HBeAg-negative disease at the time of transplant.
Four of the 65 subjects received 4 weeks or less of BARACLUDE (2 deaths, 1 retransplantation, and 1 protocol violation) and were not considered evaluable. Of the 61 subjects who received more than 4 weeks of BARACLUDE, 60 received hepatitis B immune globulin post-transplant. Fifty-three subjects (82% of all 65 subjects treated) completed the trial and had HBV DNA measurements at or after 72 weeks treatment post-transplant. All 53 subjects had HBV DNA <50 IU/mL (approximately 300 copies/mL). Eight evaluable subjects did not have HBV DNA data available at 72 weeks, including 3 subjects who died prior to study completion. No subjects had HBV DNA values ≥50 IU/mL while receiving BARACLUDE (plus hepatitis B immune globulin). All 61 evaluable subjects lost HBsAg post-transplant; 2 of these subjects experienced recurrence of measurable HBsAg without recurrence of HBV viremia. This trial was not designed to determine whether addition of BARACLUDE to hepatitis B immune globulin decreased the proportion of subjects with measurable HBV DNA post-transplant compared to hepatitis B immune globulin alone.
If BARACLUDE treatment is determined to be necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus, renal function must be carefully monitored both before and during treatment with BARACLUDE [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
The complete revised label is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021797s013s014,021798s014s016lbl.pdf
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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