Three deaths prompt new warnings for mifepristone; FDA: no causation proved in any events.(News)

In the wake of three deaths in women who had taken mifepristone to terminate an early pregnancy, the Food and Drug Administration has called on the manufacturer to strengthen the warnings in the drug's labeling, including the black box warning.

The warnings about missed ectopic pregnancy, bleeding, and sepsis have been in the product literature already, but are going to be given more prominence, said Steven Galson, M.D., acting director for the Center for Drug Evaluation and Research at FDA, in a teleconference announcing the changes.

The new, revised black box section of the prescribing information will take note of the fact that postmarketing surveillance has noted cases of infection and sepsis. The warnings section will now remind physicians that mifepristone (Mifeprex) is contraindicated in patients with confirmed or suspected ectopic pregnancy, and that ectopic pregnancy can be missed by ultrasound examination.

The company that makes the drug, Danco Laboratories, will also be revising the medication guide handed out to patients with the medicine. The new guide will advise women to seek medical attention immediately if they have prolonged heavy bleeding (soaking through two thick, full-size sanitary pads per hour for 2 consecutive hours), or if they have severe abdominal pain or pelvic tenderness, or if they have a fever of 100.4[degrees]F lasting at least 4 hours. Since mifepristone was approved in 2000, the FDA has recorded 676 reports of adverse events in women who had taken the drug, including 7 cases of serious bacterial infection or sepsis, 17 ectopic pregnancies, and 72 cases of severe blood loss requiring transfusions.

Two of the deaths were cases of sepsis and one was a ruptured ectopic pregnancy. The most recent death is a well-publicized case, because the family of the deceased California woman has begun pleading to have the drug taken off the market. The woman, who had just turned 18, died of sepsis in January 2004.

FDA officials have said they did not learn about this death until August because the medical record mistakenly said the woman had take methotrexate--not mifepristone--to terminate her pregnancy.

In announcing the ...