Mifepristone

Mifepristone is a progesterone receptor blocker used to terminate pregnancy by medication. The active ingredient inhibits the effects of the pregnancy hormone progesterone. This causes the uterine lining to detach, and the subsequent intake of a prostaglandin (misoprostol) after 48 hours triggers an artificial miscarriage.

In tablet form under the trade name Mifegyne®, mifepristone has been approved in France since 1998, in the United Kingdom since 1991, in Germany and Sweden since 1992, and in most other European countries since 1999.
Das Arzneimittel ist während der gesamten Schwangerschaft wirksam, darf aber nur bis zum 49. Tag bzw. 7. Woche und 63. Tag bzw. 9. Woche (in Schweden und Großbritannien) nach Einsetzen der letzten Regelblutung auf Verschreibung und unter Aufsicht eines behandelnden Arztes eingenommen werden. In medizinischen Ausnahmefällen, wie zur Vorbereitung eines chirurgischen Schwangerschaftsabbruchs oder zur Weheneinleitung nach einem frühzeitigen fetalen Tod, ist Mifepriston auch zu späteren Zeitpunkten zugelassen. Aufgrund der Muttermund-öffnenden Eigenschaften wird das Medikament auch bei nicht schwangeren Frauen vor manchen gynäkologischen Eingriffen angewendet.

In addition to the progesterone receptor, mifepristone also inhibits the activity of the glucocorticoid receptor and is therefore also used to treat hypercortisolism (excess cortisol) or Cushing's syndrome (with secondary diseases such as type 2 diabetes mellitus or glucose intolerance).

Pharmacodynamics

Mifepristone-induced inhibition of the homon progesterone, which is important for the maintenance of pregnancy, prevents its contraction-inhibiting effects, allowing contraction of the uterus to occur through the administration of prostaglandins.

In the treatment of Cushing's syndrome, mifepristone inhibits the binding of cortisol to its receptor. This reduces the effects of excess cortisol (e.g., high blood glucose levels). The drug also exhibits mild inhibitory effects of the male sex hormone androgen, but these are negligible for the human organism.

Pharmacokinetics

When administered orally at low doses, the bioavailability of mifepristone is 69%. The highest concentration in the blood is reached after 1.5 hours and the drug binds to 98% of plasma proteins. In the liver, oxidative degradation involving the CYP3A4 enzyme removes a methyl group from mifepristone and introduces a hydroxyl group. The drug has a half-life of 18 hours and 90% percent is excreted in the feces, the remainder by the kidneys.

Contraindications

Mifepristone should not be taken in case of hypersensitivity to the active substance, chronic renal insufficiency, severe (uncontrollable) asthma, congenital metabolic disorders (porphyria).

Drug Interactions

Since mifepristone is a substrate of the enzyme CYP3A4, interactions with CYP3A4-stimulating or -inhibiting drugs (rifampicin, phenytoin, carbamazepine, St. John's wort or erythromycin, itraconazole, ketoconazole, grapefruit juice) are possible, as well as with other CYP3A4 substrates (atorvastatin, phenprocoumon). Furthermore, mifepristone may decrease the effects of glucocorticoids (e.g., dexamethasone).

Side effects

Common side effects of mifepristone therapy include:

• Vaginal bleeding
• contractions of the uterus
• Cramps
• Infections
• Diarrhea
• Nausea and vomiting