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U.S. Department of Health and Human Services

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Questions and Answers on Mifeprex (mifepristone), 7/19/2005

   

For current information on Mifeprex, see
Mifeprex (mifepristone) Information.

November 4, 2005 update of questions 1, 3, and 9: 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.

1. What is FDA announcing?

FDA is announcing that the Prescribing Information, Medication Guide, and Patient Agreement for Mifeprex (mifepristone) have been updated to convey information concerning infection with Clostridium sordelli.

FDA is also issuing a Public Health Advisory to inform the public that it is aware of four women in California who died from sepsis following medical abortion with mifepristone and misoprostol. The bacteria that caused the sepsis in two of the cases has been identified as Clostridium sordelli. The other two cases are under investigation by FDA and we are collaborating with the Centers for Disease Control and Prevention, State and local health departments, and the manufacturer of Mifeprex to determine the cause of the sepsis.

(See November 4, 2005 update at the top of the page) 

Danco Laboratories has issued a new Dear Health Care Provider letter to communicate this safety information.

2. What sections of the Mifeprex label have been updated?

Information concerning the bacteria that has been identified in two of the sepsis cases, Clostridium sordelli, as well as information regarding the clinical circumstances and symptoms of the four women who died are now included in the BOXED WARNING and WARNINGS sections of the Prescribing Information. The Medication Guide and Patient Agreement have also been updated to inform patients to immediately contact their health care provider if they develop abdominal pain or discomfort, or are “feeling sick,” including weakness, nausea, vomiting, or diarrhea, with or without fever, more than 24 hours after taking misoprostol.

3. What is Clostridium sordelli and why is it included in the WARNINGS section of the Mifeprex label?

  • Clostridium sordelli is a bacteria that is anaerobic (it can live without oxygen) and in very rare cases produces toxins that are rapidly fatal. Rare infections with Clostridium sordelli can occur following childbirth (vaginal delivery and caesarian section), as well as following medical abortions. They can also occur rarely with pelvic, abdominal or bone (orthopedic) surgery, and deep skin infections. 
  • The bacteria may also be present in women’s intestinal and rectal areas and cause no symptoms whatsoever, not producing any toxins. This is called “colonization” and is not known to be a health problem. 
  • It is unclear exactly what factors cause the bacteria to produce the toxins in women. 
  • From September 2000 when Mifeprex was approved until June 2005, with over 460,000 estimated uses of Mifeprex in the United States, there have been four reported deaths in the U.S. that were associated with a serious bacterial infection. In two of the cases it was shown that the infection was due to Clostridium sordelli. These patients had no fever but had a rapid pulse, low blood pressure, and very high red and white blood cell counts. They also had symptoms that included weakness, nausea, vomiting or diarrhea with or without abdominal pain. The label changes were made to alert physicians and patients to the possibility of this rare infection.
(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.)

4. Why are women using misoprostol vaginally?

The FDA approved regimen for medical abortion consists of taking 600 mg (three- 200 mg tablets) of oral mifepristone on Day 1 and 400 mcg (two- 200 mcg tablets) of oral misoprostol on Day 3. FDA is aware that many medical practitioners use modified regimens, which may include prescribing different doses of mifepristone and misoprostol, dosing misoprostol on a different day, and advising the patient that the oral misoprostol tablets be inserted into the vagina. While some of the modified regimens have been well described in the literature, the safety and effectiveness of Mifeprex dosing regimens, other than the one approved by FDA, including use of oral misoprostol tablets intravaginally, has not been established by the FDA.

5. Does the vaginal use of oral misoprostol tablets in medical abortion cause infection?

FDA has no evidence that vaginal use of misoprostol causes infection. The companies making misoprostol tablets have performed and met the usual quality control tests for marketing misoprostol oral tablets.

6. Has any causal relationship between these events and the use of Mifeprex and misoprostol been established?

No. The FDA will continue to evaluate all case reports and other information to determine if there is any causal relationship.

7. Should women undergoing medical abortion be getting antibiotics to prevent fatal infections?

At this time FDA does not have sufficient information to recommend the use of preventive antibiotics for all women undergoing medical abortion. Reports of fatal sepsis in women undergoing medical abortion are very rare (1 in 100,000). Preventive antibiotic use carries its own risk of serious adverse events such as severe or fatal allergic reactions. Also, preventive use of antibiotics can stimulate the growth of “superbugs,” bacteria resistant to everyday antibiotics. While FDA cannot recommend preventive antibiotics, we advise physicians to be vigilant so that patients suspected of having an infection are immediately given antibiotics that would kill bacteria such as Clostridium sordelli.

8. Why are these fatal infections being reported from only one state, California?

  • Serious infections, sepsis, and death associated with medical abortion may occur anywhere. All providers of medical abortion and all medical abortion patients must be aware of the risks of sepsis. 
  • FDA is aware of another case of fatal Clostridium sordelli infection during medical abortion in a clinical trial in Canada in 2001. 
  • FDA does not know why the four U.S. cases of fatal infections are reported from only one State. The Centers for Disease Control and Prevention, the State and local health departments, and the manufacturer of Mifeprex are helping the FDA to investigate these cases.

9. What steps are being taken to investigate these cases and inform the public about risks?

FDA is working with the Centers for Disease Control and Prevention, the State and local health departments, and the manufacturer of Mifeprex to investigate these cases. FDA is also working with the manufacturers of Mifeprex and misoprostol tablets to conduct special tests to ensure there was no contamination of either product with Clostridium sordelli. The investigations are still ongoing, but in the interim, FDA felt it was important to update the public. In November 2004, FDA announced the addition of information concerning rare cases of serious and sometimes fatal infections to the WARNINGS section of the Mifeprex label. In January 2005, the manufacturer of Mifeprex provided additional information, including a book chapter, about the medical complications of abortion to all emergency room physicians and providers of medical abortions.

(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.)