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Why can Mifepristone cause fatal infections
Aug 3, 2005, 21:39, Reviewed by: Dr.
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The antiprogesterone effects of mifepristone also cause changes in the cervix that allow C. sordellii, a common vaginal bacteria, to enter the cervical canal. C. sordellii thrives in this low-oxygen environment and derives nutrition from the decaying fetal tissue.
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By The Annals of Pharmacotherapy,
The abortion drug mifepristone (Mifeprex,TM RU-486) has been linked to rare cases of fatal bacterial infections, but until now the connection has not been clearly understood. In "Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii," author and Brown University professor Ralph P. Miech, MD, PhD, proposes two models of how this devastating reaction may occur. The article appears in The Annals of Pharmacotherapy Online and in the journal's upcoming September print issue.
During an abortion, mifepristone works by blocking the effects of progesterone, shutting off nutrition to the placenta and fetus. However, Miech points out, the antiprogesterone effects of mifepristone also cause changes in the cervix that allow C. sordellii, a common vaginal bacteria, to enter the cervical canal. C. sordellii thrives in this low-oxygen environment and derives nutrition from the decaying fetal tissue.
Meanwhile, other hormonal effects of mifepristone, known as antiglucocorticoid actions, are taking place throughout the body. Through two models proposed by Miech, these antiglucocorticoid effects may interfere with chemical regulators known as cytokines, offsetting the delicate balance between over- and under-activation of the immune system.
This disruption impairs the body's ability to fight off C. sordellii and may help spread the bacteria's toxic by-products, a combination that sometimes results in widespread septic shock.
At least 5 women in the US and Canada have died from septic shock after taking mifepristone. C. sordellii has been linked to 3 of those cases, while the bacteria remains unidentified in the others. C. sordellii infections are rare outside of mifepristone use and have proven particularly dangerous because they often lack the usual warning signs, such as fever and tenderness on examination.
In 2004, the labeling of mifepristone was amended to include a black box warning about bacterial infections, sepsis, and death that may occur after use. A citizen petition for withdrawal of mifepristone from the US market has been submitted to the FDA. It cites numerous safety concerns as well as procedural violations that occurred during the drug's approval process. 
- The article appears in The Annals of Pharmacotherapy Online and in the journal's upcoming September print issue.
www.theannals.com
The Annals of Pharmacotherapy is a leading peer-reviewed, international pharmacotherapy journal for physicians, pharmacists, and other healthcare professionals. Published by Harvey Whitney Books Company, for over 39 years The Annals has featured articles directly related to the safe, effective, and economical use of medications and related devices in patient care. The journal's editorial office is headquartered at 8044 Montgomery Road, Suite 415, Cincinnati, Ohio 45236-2919, USA.
The journal is available in print and online in full text at http://www.theannals.com.
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