Medication Adverse Event Alert

February 27, 2007

ISSUE:	Revised labeling due to development of an HIV variant containing the M184V resistance substitution during Baraclude treatment for chronic hepatitis B virus in an HIV/HBV co-infected patient who was not receiving highly active antiretroviral therapy
MEDICATION:	Baraclude® (entecavir) tablets and oral solution, Bristol-Myers Squibb

The following was posted on FDA Med Watch alert website dated February 24, 2007:
"FDA and Bristol-Myers Squibb notified healthcare professionals of revisions to the MICROBIOLOGY/Antiviral Activity and INDICATIONS AND USAGE/Description of Clinical Studies/Special Populations sections of the prescribing information for Baraclude. The revised labeling is the result of a case report in which a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during Baraclude treatment for chronic hepatitis B virus (HBV) infection in an HIV/HBV co-infected patient who was not simultaneously receiving highly active antiretroviral therapy (HAART). Current treatment guidelines recommend Baraclude as an option for treatment of HBV in the HIV/HBV co-infected adult patient who does not qualify for HAART. Healthcare professionals are advised that when considering therapy with Baraclude in an HIV/HBV co-infected patient not receiving HAART, the risk of developing HIV resistance cannot be excluded based on current information."

An excerpt of Bristol-Myers Squibb "Dear Health Care Provider" letter is provided below:
"Current treatment guideline recommend BARACLUDE as an option for treatment of HBV in the HIV/HBV co-infected adult patient who does not qualify for HAART; however, in light of the newly-reported case history, BMS advises caution if BARACLUDE is used in this setting. Details of the newly-reported case history are provided below:

Xolair was approved in 2003 to treat adults and adolescents (12 years of age and above) with moderate to severe persistent asthma who have tested positive for a perennial aeroallergen (pollen, grass or dust) and whose symptoms are inadequately controlled with inhaled steroids. In clinical trials, Xolair decreased the rate of asthma exacerbations, which were defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of baseline inhaled corticosteroid dose.

BARACLUDE has not been evaluated in HIV/HBV co-infected patients not simultaneously receiving effective HIV treatment. When considering therapy with BARACLUDE in an HIV/HBV co-infected patient not receiving HAART, the risk of developing HIV resistance cannot be excluded based on current information. Caution is advised if BARACLUDE is used in this setting. The following changes to the package insert are in process of being made:

Under section MICROBIOLOGY/ Antiviral Activity:
"The EC50 value of entecavir against human immunodeficiency virus (HIV) type 1 laboratory strains NL4-3, BRU, and LAI was >1 µM in cell culture assays."

Under section INDICATIONS AND USAGE/ Description of Clinical Studies/ Special Populations:
"BARACLUDE has not been evaluated in HIV/HBV co-infected patients who were not simultaneously receiving effective HIV treatment."

The revised package insert will be available on www.baraclude.com. If you have any questions about this new information or require additional medical information, please contact Bristol-Myers Squibb at 1-800-321-1335."