Review articleMifepristone and misoprostol sequential regimen side effects, complications and safety☆
Introduction
Mifepristone is an orally active synthetic steroid with antiprogesterone and antiglucocorticoid activities. To date, mifepristone is approved in several countries for use in four indications: early termination of pregnancy (TOP), cervical dilatation prior to surgical TOP, preparation for prostaglandin-induced TOP during the second trimester and expulsion of a dead fetus during the third trimester. When used in a sequential regimen with prostaglandins, it shows a high efficacy inducing TOP at an early stage. The combined regimen has now been used by millions of women all over the world, and provided the contraindications and warnings are respected, the method proved to be safe. Infection, hemorrhage and retained tissue are among the more relevant complications.
Section snippets
Safety studies in animals
Roussel Uclaf conducted a comprehensive toxicology program in the mid-1980s demonstrating the safety of the molecule and allowing for mifepristone's use in humans. Most of the program focused on the development of indications using single-dose administration of the compound. Therefore, toxicology studies were conducted with durations of animal exposure not exceeding 6 months [1]. The compound was shown to have no mutagenic potential and no toxic effect up to 1000 mg/kg in acute administration
Antiglucocorticoid effects
Mifepristone has antiglucocorticoid properties and has antagonized the effects of dexamethasone in a number of models: mifepristone totally inhibited the effects of dexamethasone, such as inhibition of ACTH secretion, as well as its thymolytic action and diuretic effects [3]. In humans, mifepristone also exerts antiglucocorticoid activity. The antiglucocorticoid effect of mifepristone is exerted both on the central actions of cortisol (inhibition of feedback control of cortisol over its own
Discussion of the key issues
Although the conclusions of large studies indicate good tolerability of mifepristone, some issues have been identified that require special attention.
Conclusion
Mifepristone exhibits a strong affinity to the progesterone and the glucocorticoid receptors. Consequently, it exerted competitive antagonism to these hormones both in in vitro and in animal experiments. The identification of antiprogesterone activity led to the proposition of mifepristone use 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
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