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Questions and Answers on
Mifeprex (mifepristone)
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.)
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Date created: July 19, 2005, updated November 4, 2005 |
