Mifepristone and misoprostol sequential regimen side effects, complications and safety

Exhibiting a strong affinity to the progesterone and the glucocorticoid receptors, mifepristone exert competitive antagonism to these hormones both in in vitro and in animal experiments. Due to its antiprogesterone activity, it was proposed that mifepristone be used for the termination of early human pregnancy. Mifepristone, at a dose of 600 mg initially used alone, was then used with a subsequent low dose of prostaglandin that led to a success rate of 95% as a medical method for early termination of pregnancy (TOP), and the occurrence of continuing pregnancy was reduced to <= 1%. Its use was extended to other indications, such as cervical dilatation prior to surgical TOP in the first trimester, therapeutic TOP for medical reasons beyond the first trimester and for labor induction in case of fetal death in utero. The efficacy and safety of this treatment have been confirmed based on its use for over 15 years since its first approval in France and with close adherence to the approved recommendations. This article describes the toxicology studies conducted in animals as well as the safety follow-up and side effects reported with use of the compound when used with misoprostol in the main indication that is currently approved in 31 countries. Special emphasis is given to the rare but relevant safety issues, that is, heavy uterine bleeding, pelvic infections and continuing pregnancies. The rationale for warnings and contraindications for use of the product are also explained. (c) 2006 Elsevier Inc. All rights reserved.