The Food and Drug Administration said it has been informed of two additional deaths following medical abortion with mifepristone, the medical abortion pill also known as RU-486.
The agency said it received verbal notification of the deaths in the United States from the manufacturer, Danco Laboratories.
"At this time we are investigating all circumstances associated with these cases and are not able to confirm the causes of death," the FDA said in a statement.
"However, all providers of medical abortion and their patients need to be aware of the specific circumstances and directions for use of this drug and all risks including sepsis when considering treatment. In particular, physicians and their patients should fully discuss early potential signs and symptoms that may warrant immediate medical evaluation."
The FDA said it is aware of four previous confirmed deaths from sepsis in the United States, from September 2003 to June 2005, in women following medical abortion with mifepristone (Mifeprex) and misoprostol.
All four cases of fatal infection tested positive for Clostridium sordellii. All four cases involved the off-label dosing regimen consisting of 200 mg of oral Mifeprex followed by 800 mcg of intra-vaginally placed misoprostol.
In addition, FDA tested drug from manufacturing lots of mifepristone and misoprostol and found no contamination with Clostridium sordellii.
"We do not know whether these new deaths were caused by sepsis or, if they were, if they were caused by infection with Clostridium sordellii," the FDA said.
Although sometimes called a "morning after" contraceptive, RU-486 is more correctly referred to as a medical abortion treatment.
"Morning after" pills, also known as "emergency contraception," prevent pregnancy. Medical abortion terminates pregnancy. By helping women to prevent unplanned pregnancies after unprotected intercourse, emergency contraception helps decrease the rate of abortion.
More information is available on the Planned Parenthood Web site.
FDA Guidance
The FDA said 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 also emphasizes that healthcare professionals and patients should 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.
• FDA does not have sufficient information to recommend the use of prophylactic antibiotics. Reports of fatal sepsis in women undergoing medical abortion are 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.