USA. The FDA has received four reports of septic deaths in women in the United States, from September 2003 to June 2005, 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 mifepristone (Mifeprex). All cases involve the off-label dosing regimen consisting of 200 mg of oral mifepristone (Mifeprex) followed by 800 mcg of intravaginally placed misoprostol. The FDA has issued a Public Health Advisory with the following recommendations:

• 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 mifepristone (Mifeprex) regimen for a medical abortion through 49 days’ pregnancy is:

• Day One: mifepristone (Mifeprex) Administration: 3 tablets of 200 mg of mifepristone (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 mifepristone (Mifeprex) dosing regimens, including use of oral misoprostol tablets intravaginally has not been established by the FDA.

Reference:

FDA Public Health Advisory. United States Food and Drug Administration, 19 July 2005 (http://www.fda.gov).