Public Health Advisory: Sepsis and Medical Abortion
November 4, 2005 Update: All four cases of fatal infection tested positive for Clostridium sordellii. In addition, FDA tested drug from manufacturing lots of mifepristone and misoprostol and found no contamination with Clostridium sordellii.
July 19, 2005: The Food and Drug Administration (FDA) is aware of four cases of septic deaths in the United States, from September 2003 to June 2005 in women following medical abortion with mifepristone (Mifeprex) and misoprostol. The bacteria causing sepsis has been identified in two of the cases as Clostridium sordellii. The other two cases are under ongoing investigation by FDA along with the Centers for Disease Control and Prevention, State and local health departments, and the manufacturer of Mifeprex. All cases involve the off-label dosing regimen consisting of 200 mg of oral Mifeprex followed by 800 mcg of intra-vaginally placed misoprostol. The two confirmed cases of Clostridium sordellii did not have the usual signs and symptoms of an infection. Although these deaths are reported from California, all providers of medical abortion and their patients need to be aware of the risks of sepsis. As more information becomes available, FDA will alert the public.
In the meantime, FDA recommends that healthcare professionals and patients be aware of the following:
All providers of medical abortion and emergency room health care providers should investigate the possibility of sepsis in patients who are undergoing medical abortion and present with nausea, vomiting, or diarrhea and weakness with or without abdominal pain, and without fever or other signs of infection more than 24 hours after taking misoprostol. To help identify those patients with hidden infection, strong consideration should be given to obtaining a complete blood count.
FDA recommends that physicians suspect infection in patients with this presentation and consider immediately initiating treatment with antibiotics that includes coverage of anaerobic bacteria such as Clostridium sordellii.
At this time FDA does not have sufficient information to recommend the use of prophylactic antibiotics. Reports of fatal sepsis in women undergoing medical abortion is very rare (approximately 1 in 100,000). Prophylactic antibiotic use carries its own risk of serious adverse events such as severe or fatal allergic reactions. Also, prophylactic use of antibiotics can stimulate the growth of “superbugs,” bacteria resistant to everyday antibiotics. Finally, it is not known which antibiotic and regimen (what dose and for how long) will be effective in cases such as the ones that have occurred.
The approved Mifeprex regimen for a medical abortion through 49 days’ pregnancy is:
Day One: Mifeprex Administration: 3 tablets of 200 mg of Mifeprex orally at once
Day Three: Misoprostol Administration: 2 tablets of 200 mcg of misoprostol orally at once.
Day 14: Post-Treatment: the patient must return to confirm that a complete termination has occurred. If not, surgical termination is recommended to manage medical abortion treatment failures.
The safety and effectiveness of other Mifeprex dosing regimens, including use of oral misoprostol tablets intravaginally has not been established by the FDA.
These recommendations are consistent with warnings in the Prescribing Information and information for the patient in the Medication Guide.
FDA is also working with the manufacturers of Mifeprex and misoprostol tablets to conduct special tests to ensure that there was no contamination of either product with Clostridium sordellii.
Information pertaining to Mifeprex can be found at Mifeprex (mifepristone) Information.
FDA will update this advisory as more definitive information becomes available.