FDA Issues Health Advisory for Mifepristone; Label To Be Updated

FDA on Tuesday issued a public health advisory warning physicians to watch for any signs of sepsis or other infection among women who have taken Danco Laboratories' Mifeprex -- known generically as mifepristone -- which when taken with misoprostol can cause a medical abortion, the AP/Seattle Post-Intelligencer reports. The agency is investigating four sepsis-related deaths among women who took the drug, including two cases reported to FDA in April and June (Neergaard, AP/Seattle Post-Intelligencer, 7/20).

Physicians have identified the bacterium Clostridium sordelli -- a common germ not usually associated with illness -- as the cause of two of the four deaths and suspect it as the cause of the other two deaths, the San Francisco Chronicle reports. Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, said it is not clear why the bacteria became fatal in the women (Barnum, San Francisco Chronicle, 7/20). Galson said the four deaths all occurred in women who did not follow FDA-approved instructions for using the drug. According to the directions, women should take both mifepristone and misoprostol orally, but some clinics instruct patients to insert misoprostol vaginally. Galson said it is unclear if such off-label use of the drug led to the deaths (AP/Seattle Post-Intelligencer, 7/20).

FDA has advised doctors to prescribe antibiotics immediately to women who have taken mifepristone and who have symptoms of Clostridium sordelli infection, including nausea, vomiting, diarrhea and weakness, Galson said. However, the agency advises against prescribing antibiotics to all patients who use mifepristone because the risk associated with antibiotic use outweighs the very low risk of bacterial infection, according to Galson (Harris, New York Times, 7/20).

Galson said there has been less than one infection per 100,000 users of mifepristone, adding, "There are no alarm bells going off because of this rate. But we are watching very closely" (San Francisco Chronicle, 7/20).

Eight months after FDA ruled that the labeling of Mifeprex should be revised to warn users of the possibility of bacterial infection and other complications, Danco on Monday announced it will modify the drug's label to reflect updated safety information, the Contra Costa Times reports (Brewer, Contra Costa Times, 7/19). The Mifeprex packaging already includes a warning stating that women who use the drug could experience serious and possibly fatal infections.

The updated information will give physicians more information so they can identify problems earlier, according to Danco spokesperson Cynthia Summers. Danco also plans to send a letter to physicians and emergency department directors to inform them of the updated warning and five known deaths -- four of which were sepsis-related -- among users of Mifeprex (Reuters AlertNet, 7/18). FDA approved Mifeprex in 2000 for the termination of early pregnancy, defined as 49 or fewer days gestation (California Healthline, 11/16/04).