Mifepristone ruled out in one of two deaths
The Food and Drug Administration (FDA) has ruled out mifepristone (Mifeprex, Danco Laboratories, New York City) as the cause in one of two recent deaths of women who had taken the drug. The agency is continuing to investigate the other death.1
The FDA issued a March 17 public health advisory in light of the two reported deaths. The advisory comes after reports of four previous U.S. deaths from serious bacterial infection and sepsis following use of the medication abortion regimen. According to a 2005 report, the four earlier deaths were linked to toxic shock caused by the bacterium Clostridium sordellii.2 The FDA has tested batches of Mifeprex and misoprostol and has not found any contamination with the type of bacteria involved in the four cases.
Health officials are looking to results from a May 2006 public workshop on emerging clostridial disease sponsored by the FDA, National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention (CDC) to provide possible answers to the health issues surrounding the deaths.
The workshop is intended to develop a draft research agenda to better understand the virulence, pathogenesis, host factors, and nonantimicrobial risk factors contributing to reports of morbidity and mortality associated with Clostridium sordellii and Clostridium difficile, says Pam Long, Danco Laboratories spokeswoman. Representatives from Danco are scheduled to attend the meeting, she adds.
About 575,000 women in the United States have used Mifeprex since the FDA approved the drug in 2000. Reports of fatal sepsis in women undergoing medical abortion are very rare: about one in 100,000, according to the agency. Danco Laboratories is working closely with the FDA, CDC, health care providers, and other medical experts to understand the circumstances surrounding these events, says Long.
Changes in protocol?
In issuing the March 2006 advisory, the FDA reiterated the approved Mifeprex regimen for a medical abortion through 49 days' pregnancy:
- Day One: Mifeprex Administration: Three tablets of 200 mg Mifeprex orally at once.
- Day Three: Misoprostol Administration: Two tablets of 200 mcg 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 medication abortion treatment failures.3
Many medication abortion providers have used vaginal administration of misoprostol in "off-label" practice following research indicating effectiveness of the delivery method.4-7 Following the FDA public health advisory, the Planned Parenthood Federation of America (PPFA) said it would no longer offer vaginal administration of misoprostol in its medication abortion procedures.
"Patients will now receive misoprostol orally or buccally [where the pill is placed between the cheek and gum and dissolves]," says Vanessa Cullins, MD, MPH, PPFA vice president for medical affairs. "This change in protocol is effective immediately."
The National Abortion Federation has updated its protocol for use of mifepristone/misoprostol in early abortion.8 The organization continues to support a variety of regimens, including vaginal administration of misoprostol.9
Be alert for symptoms
All providers of medical abortion and emergency department health care providers should be alert for 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, according to the FDA. Strong consideration should be given to obtaining a complete blood count to help identify patients with hidden infections, the FDA advises.
If patients do present with the described symptoms, the FDA recommends that providers consider immediate initiation of antibiotic treatment that includes coverage of anaerobic bacteria such as Clostridium sordellii.
When it comes to use of prophylactic antibiotics, the FDA says it does not have sufficient information to recommend the use of drug treatment. Prophylactic antibiotic use can be dangerous: Some patients may have severe or fatal allergic drug reactions, and high use of antibiotics can lead to bacterial resistant to such drugs, notes the FDA.
- Bridges A. RU-486 Ruled Out in 1 of 2 Recent Deaths. Washington Post; April 10, 2006. Accessed at: www.washingtonpost.com/wp-dyn/content/article/2006/04/10/AR2006041000829.html.
- Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005; 353:2,352-2,360.
- Food and Drug Administration. FDA Public Health Advisory. Sepsis and Medical Abortion Update. Accessed at: www.fda.gov/cder/drug/advisory/mifeprex200603.htm.
- Schaff EA, Eisinger SH, Stadalius LS, et al. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Contraception 1999; 59:1-6.
- Schaff EA, Fielding SL, Eisenger SH, et al. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception 2000; 61:41-46.
- Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral vs. vaginal misoprostol at one day after mifepristone or early medical abortion. Contraception 2001; 64:81-85.
- Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial. JAMA 2000; 284:1,984-1,953.
- National Abortion Federation. NAF Protocol for Mifepristone/Misoprostol in Early Abortion. Revised March 2006. Accessed at: www.prochoice.org/pubs_research/publications/downloads/professional_education/medical_abortion/protocol_mife_miso.pdf.
- National Abortion Federation. Medical abortion update. Clinicians for Choice 2006; accessed at: www.prochoice.org/cfc/newsletter.html#5.