Mechanism proposed for link between RU-486 and fatal infections

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

Contact: Stanley J. Lloyd, Pharm.D.
Annals of Pharmacotherapy

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