For Health Professionals - Information Regarding Baraclude (entecavir)

Starting date:

February 21, 2007

Posting date:

February 21, 2007

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170001550

This is duplicated text of a letter from Bristol-Myers Squibb Canada.

Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Information Regarding Baraclude (entecavir)

February 21, 2007

Subject: Important Information Regarding BARACLUDE^{Footnote *} (entecavir) in Patients Co-infected with HIV and HBV

Dear Health Care Provider,

Bristol-Myers Squibb Canada is writing to advise you that the company has received a case report in which the selection of a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during BARACLUDE^{Footnote *} (entecavir) treatment for chronic hepatitis B virus (HBV) infection in an HIV/HBVV co-infected patient who was not simultaneously receiving highly active anti-retroviral therapy (HAART). Current treatment guidelines^{Footnote 1}-^{Footnote 2} recommend BARACLUDE^{Footnote *} 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 provided below, BMS advises caution if BARACLUDE^{Footnote *} is used in this setting.

• BARACLUDE^{Footnote *} has not been evaluated in HIV/HBV co-infected patients not simultaneously receiving effective HIV treatment.

• When considering therapy with BARACLUDE^{Footnote *} 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^{Footnote *} is used in this setting

Details of the newly reported case history are provided below:

• A 31 year old HIV/HBV co-infected male received combination zidovudine, lamivudine and nevirapine for less than 1 year in 2000. HAART was discontinued and the patient remained clinically stable with respect to his HIV. In early 2006, with a CD4+ of >500 cells/mm³ and an HIV-1 RNA of approximately 35,000 copies/mL, BARACLUDE^{Footnote *} monotherapy was initiated for the treatment of HBV. Within 2 months, the HBV DNA decreased by approximately 5.5 log₁₀ IU/mL, and the HIV RNA decreased to approximately 2,000 copies/mL, subsequently remaining below baseline levels. HIV resistance testing at the start of BARACLUDE^{Footnote *} therapy did not show resistance, but the M184V substitution was detected following 6 months of therapy with BARACLUDE^{Footnote *}.

This patient is one of three HIV/HBV co-infected patients not receiving HAART in whom a 1-log₁₀ reduction in HIV RNA has been noted while receiving BARACLUDE^{Footnote *} as treatment for chronic HBV infection.

Bristol-Myers Squibb has assessed the activity of BARACLUDE^{Footnote *} against HIV-1 in vitro: the EC₅₀ for laboratory strains NL4-3, BRU and LAI was >1 μM in cell culture assays.^{Footnote 3}

In addition, BMS has evaluated the use of BARACLUDE^{Footnote *} 1 mg in the HIV/HBV co-infected population that was receiving simultaneous HAART. These data were from a single randomized, double-blind, placebo-controlled evaluation of the activity of BARACLUDE^{Footnote *} in 68 HIV/HBV co-infected patients who entered the study with stable HIV-1 RNA 400 511 copies mL (mean CD4+ count of cells mm^{3). Patients continued their lamivudine-containing HAART regimen (lamivudine dose 300 mg/day) and were assigned to add either BARACLUDEFootnote * 1 mg once daily (51 patients) or placebo (17 patients) for 24 weeks followed by an open-label phase for an additional 24 weeks where all patients received BARACLUDEFootnote *. At Week 24, BARACLUDEFootnote *-treated patients had a mean reduction in HBV DNA of -3.65 log₁₀ copies/mL compared with an increase of 0.11 log₁₀ copies/mL in the placebo arm. In this setting no difference in HIV RNA or CD4 was noted between the BARACLUDEFootnote * and placebo treatment groups.Footnote 4, Footnote 5}

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious or unexpected adverse reactions, in patients receiving BARACLUDE^{Footnote *} should be reported to Bristol Myers Squibb or Health Canada at the following addresses:

Bristol Myers Squibb Canada

2365 Cote-de-Liesse

Saint-Laurent (Quebec) - H4N 2M7

Tel. 866-463-6267

Any suspected adverse reaction can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0701C

OTTAWA, Ontario, K1A 0K9

Tel: (613) 957-0337 or Fax: (613) 957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

If you have any questions, please contact the Medical Information Department at Bristol Myers Squibb Canada at Telephone number 866-463-6267 and Fax number 1-888-267-6211.

Sincerely,

original signed by

Dan Chiche, MD

Vice-President, Scientific Affairs

Bristol Myers Squibb Canada