Antiretroviral Combination May Put Pregnant Women At Risk of Fatal Lactic Acidosis
Bristol-Myers Squibb Co. issued a "Dear Healthcare Provider" letter in response to three deaths from lactic acidosis, with or without pancreatitis, in women who took stavudine, didanosine, and other HIV drugs while pregnant. Two of the three infants died.
The company reported that two of the women were enrolled in a multinational clinical trial involving stavudine and didanosine plus either nelfinavir or an investigational HIV protease inhibitor, and that the other woman was identified through worldwide postmarketing surveillance. Separately, the Food and Drug Administration (FDA) acknowledged it had received reports that nonfatal lactic acidosis had developed in several pregnant women taking only stavudine and didanosine. The company and FDA stated that data collected on the use of the two drugs suggested a higher risk for lactic acidosis and pancreatitis among women than men.
Warnings about the occurrence of severe lactic acidosis and pancreatitis appear in a black box at the beginning of the product labeling for Zerit, or stavudine, and for Videx and Videx EC, containing didanosine. FDA and the company said they will upgrade these warnings to include a precaution specific for pregnant women.
Bristol-Myers Squibb now recommends that clinicians prescribe the two drugs for pregnant women only when the potential benefit clearly outweighs the potential risk of lactic acidosis and liver damage, as when other treatment options have been unsuccessful at abating the disease. Clinicians caring for pregnant women taking the drug combination should closely monitor them for clinical or laboratory signs of lactic acidosis and liver damage but remain aware that the metabolic disorder can develop abruptly, without warning.
Adverse events that occur during stavudine or didanosine therapy should be reported to Bristol-Myers Squibb (telephone 800-426-7644) or FDA (telephone 800-332-1088, fax 800-332-0178, or online).