BMS issue Dear Doctor letter about risk of entecavir in HIV/HBV coinfection

3 September 2007. Related: Hepatitis coinfection.

On 16 August 2007, U.S. health regulators on Thursday warned doctors of the potential for Bristol-Myers Squibb Co.’s (BMY.N: Quote, Profile, Research) hepatitis B treatment to lead to resistance to the HIV virus in patients with both diseases.

The U.S. Food and Drug Administration also added a black boxed warning, the strongest caution wielded by regulators, to the labeling of the treatment, known as Baraclude, or generically as entecavir.

In a letter to doctors, Bristol warned that patients co-infected with both the hepatitis B and the human immunodeficiency virus (HIV) should not take Baraclude unless they are also being treated with the standard anti-retroviral therapy. Resistance to the HIV virus can develop if a patient is not being treated for HIV, the warning said.

HIV antibody testing should be offered to any potential patient to get entecavir, BMS said. The most advanced stage of HIV infection is AIDS, or acquired immunodeficiency virus.

IMPORTANT DRUG WARNING – August 2007

Dear Healthcare Professional:

Bristol-Myers Squibb would like to inform you that therapy with entecavir is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) due to the potential for the development of HIV (human immunodeficiency virus) resistance.

Accordingly, the entecavir Full Prescribing Information has been updated to include the following information in the boxed WARNINGS1:

“Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if entecavir is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therapy with entecavir is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). See WARNINGS: Co-infection with HIV.”

In addition, the MICROBIOLOGY section of the entecavir Full Prescribing Information has been revised to include the following additional information:

Antiviral Activity against HIV

“A comprehensive analysis of the inhibitory activity of entecavir against a panel of laboratory and clinical human immunodeficiency virus type 1 (HIV-1) isolates using a variety of cells and assay conditions yielded EC50 values ranging from 0.026 to >10uM; the lower EC50 values were observed when decreased levels of virus were used in the assay. In cell culture, entecavir selected for an M184I substitution in HIV reverse transcriptase at micromolar concentrations, confirming inhibitory pressure at high entecavir concentrations. HIV variants containing the M184V substitution showed loss of susceptibility to entecavir.”

Consistent with clinical practice guidelines for chronic hepatitis B management, the WARNINGS section of the entecavir Full Prescribing Information has been updated with the following information:

“Before initiating entecavir therapy, HIV antibody testing should be offered to all patients. entecavir has not been studied as a treatment for HIV infection and is not recommended for this use.”

Other changes in the WARNINGS and PRECAUTIONS sections and PATIENT INFORMATION have been made consistent with the information described above. Please refer to the enclosed entecavir Full Prescribing Information, including boxed WARNINGS, for more information.

Bristol-Myers Squibb remains committed to providing you the most current and accurate information available for our products.

Please refer to the entecavir Full Prescribing Information, including boxed WARNINGS.

Source: FDA list serve