Archived - Important Drug Warning - Videx-Zerit - Bristol-Myers Squibb

Important Drug Warning - Videx-Zerit - Bristol-Myers Squibb

Bristol-Myers Squibb Canada Inc.

January 18, 2001

Important Drug Safety Information

Dear Healthcare Professional(s):

Fatal lactic acidosis has recently been reported in three pregnant women treated throughout gestation with the combination of stavudine and didanosine. Based on these cases, the combination of stavudine (Zerit™) and didanosine (Videx™) should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk, such as when there are few remaining treatment options.

This recommendation is based on three cases of fatal lactic acidosis, two with and one without pancreatitis, that occurred in women who were either pregnant or postpartum and whose antiretroviral therapy during pregnancy included stavudine and didanosine in combination with other antiretroviral agents. Two of the infants of these women died, one in utero at 32 weeks gestation and one after emergency caesarian section at 36 weeks gestation. Two of the fatal cases occurred in patients enrolled in BMS study AI424-007, an open-label, multinational, randomized, two-arm comparison of stavudine plus didanosine plus nelfinavir (Viracept®) versus stavudine plus didanosine plus BMS-232632 (an investigational protease inhibitor). A third pregnancy-related death attributed to lactic acidosis was reported through worldwide postmarketing surveillance. This patient had received long-term therapy with stavudine and didanosine together with the non-nucleoside reverse transcriptase inhibitor nevirapine (Viramune®). In addition, postmarketing surveillance identified several nonfatal cases of pancreatitis, with and without lactic acidosis or hepatic failure, in pregnant women receiving stavudine plus didanosine.

Patient Management

Stavudine and didanosine are nucleoside reverse transcriptase inhibitors indicated for use in the treatment of HIV infection. The nucleoside analogue class of antiretroviral drugs has been implicated in idiopathic lactic acidosis and severe hepatomegaly with steatosis, and all members of this class carry a warning in the label to this effect. Data have suggested that women may be at higher risk for these toxicities and it is unclear whether pregnancy potentiates these known side effects. However, the temporal occurrence of the three deaths should serve as a reminder that potential risks may be associated with use of these agents in pregnancy. Decisions regarding antiretroviral therapy for pregnant women are complex and should be made by healthcare providers experienced in the treatment of HIV infection. Although the Videx (didanosine) and Zerit (stavudine) Product Monographs have advised of the risks of lactic acidosis, Bristol-Myers Squibb is currently revising the Warnings and Precautions sections to advise that the combination of stavudine and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk.

If you have any further questions, please contact the Medical Information Department at Bristol-Myers Squibb Canada Inc. at 1-800-267-1088, ext. 2274.

Sincerely,

original signed by

Nacia Faure, M.D.

Medical Director

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Reaction Monitoring Program (CADRMP)

Bureau of Licensed Product Assessment

Therapeutic Products Directorate

Health Canada

Address Locator: 0201C2

Ottawa, Ontario, K1A 1B9

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

cadrmp@hc-sc.gc.ca

The ADR Reporting Form can be found in The Canadian Compendium of Pharmaceutical and Specialties, or on the TPD website, along with the ADR Guidelines.