FDA warns again of abortion pill risk

FDA Advisory
FDA has advised doctors to prescribe antibiotics immediately to women who have taken mifepristone and who have symptoms of Clostridium sordelli infection, including nausea, vomiting, diarrhea and weakness, Galson said. However, the agency advises against prescribing antibiotics to all patients who use mifepristone because the risk associated with antibiotic use outweighs the very low risk of bacterial infection, according to Galson (Harris, New York Times, 7/20). Galson said there has been less than one infection per 100,000 users of mifepristone, adding, "There are no alarm bells going off because of this rate. But we are watching very closely" (San Francisco Chronicle, 7/20).

Danco To Change Mifeprex Label
Eight months after FDA ruled that the labeling of Mifeprex should be revised to warn users of the possibility of bacterial infection and other complications, Danco on Monday announced it will modify the drug's label to reflect updated safety information, the Contra Costa Times reports (Brewer, Contra Costa Times, 7/19). The Mifeprex packaging already includes a warning stating that women who use the drug could experience serious and possibly fatal infections. The updated information will give physicians more information so they can identify problems earlier, according to Danco spokesperson Cynthia Summers. Danco also plans to send a letter to physicians and emergency department directors to inform them of the updated warning and five known deaths -- four of which were sepsis-related -- among users of Mifeprex (Reuters AlertNet, 7/18). FDA approved Mifeprex in 2000 for the termination of early pregnancy, defined as 49 or fewer days gestation (Kaiser Daily Reproductive Health Report, 11/18/04).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . Â© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

FDA Public Health Advisory
Sepsis and Medical Abortion

The Food and Drug Administration (FDA) is aware of four cases of septic deaths in the United States, from September 2003 to June 2005 in women 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 Mifeprex. All cases involve the off-label dosing regimen consisting of 200 mg of oral Mifeprex followed by 800 mcg of intra-vaginally placed misoprostol. The two confirmed cases of Clostridium sordellii did not have the usual signs and symptoms of an infection. Although these deaths are reported from California, all providers of medical abortion and their patients need to be aware of the risks of sepsis. As more information becomes available, FDA will alert the public.

In the meantime, FDA recommends that healthcare professionals and patients 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. 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 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 is also working with the manufacturers of Mifeprex and misoprostol tablets to conduct special tests to ensure that there was no contamination of either product with Clostridium sordellii.

Information pertaining to Mifeprex can be found at http://www.fda.gov/cder/drug/infopage/mifepristone/default.htm

FDA will update this advisory as more definitive information becomes available.

My NCBI

[Sign In] [Register]

Search for

About Entrez

Text Version

Entrez PubMed
Overview
Help | FAQ
Tutorial
New/Noteworthy
E-Utilities

PubMed Services
Journals Database
MeSH Database
Single Citation Matcher
Batch Citation Matcher
Clinical Queries
Special Queries
LinkOut
My NCBI (Cubby)

Related Resources
Order Documents
NLM Catalog
NLM Gateway
TOXNET
Consumer Health
Clinical Alerts
ClinicalTrials.gov
PubMed Central

Display Show


	All: 1

1: J Trauma. 1975 Jun;15(6):515-8. Related Articles,

Clostridium sordelli infection.

Browdie DA, Davis JH, Koplewitz MJ, Corday L, Leadbetter AW.

A case of human Clostridium sordelli soft tissue infection is presented. Analysis of this patient's course led to the use of a mouse experimental model for examination of this organism's potential for toxin production. Data thus obtained correlated with that seen in this instance of human infection, indicates that the lethal effects of this organism may be related to the ability to Clostridium sordelli to produce a widespread "toxin-mediated" edema with subsequent marked "third-space" sequestration of fluid.

Publication Types:

Case Reports

PMID: 1127784 [PubMed - indexed for MEDLINE]

Display Show

Write to the Help Desk
NCBI | NLM | NIH
Department of Health & Human Services
Privacy Statement | Freedom of Information Act | Disclaimer

Jul 18 2005 15:16:48

Med Microbiol Immunol (Berl). 1975 Jul 2;161(3):145-54.
Extracellular proteins in five clostridial species from human infections.

Nord CE, Wadstrom T, Dornbusch K, Wretlind B.

347 strains from human infections were identified by gas-liquid chromatography of metabolic products and by conventional tests. Simple agar-plate assays were used to analyze the ability to form extracellular proteins. More than 90% of all strains were hemolytic on agar containing rabbit erythrocytes and all were gelatinase producers. All strains of C. bifermantans, C. sordelli, and C. sporogenes were also caseinolytic on skimmed-milk agar, but strains of C. perfringens, C. novyi types A and B were not. Less than 10% of C. perfringens strains were producers of elastase and staphylolytic enzyme and all other species were non-producers. All C. perfringens, C. novyii, C. bifermentans, and C. sordelli were lecithinase producers, but C. sporogenes was not. All strains of C. sporogenes formed deoxyribonuclease, while a varying number of the other species showed a positive reaction.

PMID: 170498 [PubMed - indexed for MEDLINE]

Am J Clin Pathol. 1989 Jan;91(1):104-6.
Erratum in: Am J Clin Pathol 1989 Jul;92(1):128.
Fatal acute spontaneous endometritis resulting from Clostridium sordelli.
Hogan SF, Ireland K.

Department of Pathology, Good Samaritan Hospital, Corvallis, Oregon 97339.

Intrauterine clostridial infections have historically been associated with puerperal sepsis, often subsequent to instrumented abortions. Isolated reports have been associated with a malignant neoplasm or degenerating leiomyoma, most often after instrumentation, radiation therapy, or chemotherapy. In these cases, well-known risk factors or obvious niduses for growth and causation of disease were identified. The authors report a case of fatal spontaneous endometritis resulting from Clostridum sordellii, which, to their knowledge, has not been previously reported in the literature. Characteristics of this rare virulent human pathogen are discussed.

Publication Types: Case Reports

PMID: 2910010 [PubMed - indexed for MEDLINE]

J Vet Intern Med. 1997 Nov-Dec;11(6):319-22.
Prevalence and identity of translocating bacteria in healthy dogs.
Dahlinger J, Marks SL, Hirsh DC.

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.

Bacterial translocation is characterized by the passage of intestinally derived bacteria across the intestinal mucosa to local or regional tissues. This phenomenon is believed to be important in the pathogenesis of gram-negative bacteremia and septicemia; however, the pathway or route of translocation remains unclear. To define the route of translocation better, mesenteric lymph nodes from 50 apparently healthy dogs undergoing elective ovariohysterectomies were cultured aerobically and anaerobically. The aims of this study were to determine the prevalence of bacterial translocation and to quantify and identify types of organisms found in mesenteric lymph nodes. Peripheral blood and portal blood samples were similarly cultured to rule out hematogenous organisms as a source of lymph node contamination. Bacteria were isolated from mesenteric lymph nodes of 26 dogs (52%). The number of bacteria varied from 50 to > 10(5) organisms/g of tissue. Bacteria isolated included Staphylococcus intermedius (n = 3), coagulase-negative Staphylococcus (n = 2), nonhemolytic Streptococcus (n = 4), Bacillus species (n = 5), Escherichia coli (n = 6), Salmonella species (n = 3), Pseudomonas species (n = 2), Enterococcus species (n = 2), Clostridium sordelli (n = 1), Micrococcus species (n = 1), Lactobacillus species (n = 1), and Propionibacterium acnes (n = 1). One of 50 peripheral blood samples yielded an unidentified gram-positive coccus and a coagulase-negative Staphylococcus. No bacteria were isolated from portal blood samples of any dog. Further studies of this type on sick dogs are warranted before clinical recommendations can be made to culture mesenteric lymph nodes routinely.

PMID: 9470154 [PubMed - indexed for MEDLINE]

Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.

FDA Issues Health Advisory for Mifepristone Citing Four Sepsis-Related Deaths Among Users; Drug Labeling To Be Updated