Information about Mifepristone
Mifepristone, also known as RU-486, is a potent synthetic steroidal antiprogesterone which is used as a single dose in combination with misoprostol, a prostaglandin analogue, to induce medical abortion.
Liver safety of Mifepristone
Mifepristone with misoprostol have not been associated with serum enzyme elevations or with clinically apparent liver injury. Mifepristone alone, without misoprostol, is also approved as therapy of Cushing syndrome where it is given in a higher dose and for extended periods. Long term higher doses of mifepristone have been linked to a low rate of serum enzyme elevations during therapy and rare instances of clinically apparent liver injury. == Liver safety of Mifepristone ==
Mechanism of action of Mifepristone
Mifepristone (mif" e pris' tone) is a synthetic antiprogesterone which antagonizes the action of progesterone by competing with its binding to its receptor. The sudden loss of progesterone activity during pregnancy causes a series of intrauterine and cervical changes that result in termination of pregnancy. Misoprostol (mye" soe pros' tol) is a prostaglandin analogue that causes uterine contraction which completes the medical abortion. In multiple large prospective studies, the administration of a single dose of mifepristone followed within 24 to 48 hours by a prostaglandin agonist safely terminated early pregnancy in more than 90% of women.
FDA approval information for Mifepristone
Mifepristone was first approved for use in France in 1988, in Great Britain in 1991, Sweden in 1992, and the United States in 2000. The current indications for this combination is for medical termination of intrauterine pregnancy through 70 days of gestation. Mifepristone is available in tablets of 200 mg under the brand name Mifeprex. The currently recommended dose of mifepristone for inducing a medical abortion is as a single 200 mg tablet followed 24 to 48 hours later by buccal administration of 800 mcg of misoprostol (a prostaglandin agonist). Mifepristone has been used off-label as a means of emergency contraception, but is not approved for that use. Side effects are common, but generally mild-to-moderate in severity and can include uterine bleeding, nausea, vomiting, abdominal cramps, weakness, fever, headache, diarrhea, and dizziness. Rare, but potentially severe adverse events include serious uterine bleeding and serious bacterial infections, failed abortion and need for hospitalization. Contraindications to use of mifepristone/misoprostol include pregnancy beyond 70 days (10 weeks), ectopic pregnancy, presence of an intrauterine device, adrenal failure, porphyria and use of anticoagulants.
Because of the serious nature of these side effects, mifepristone/misoprostol is available only through a Risk Evaluation and Mitigation Strategy (REMS) program to certified prescribers. Mifepristone (without misoprostol) is also approved for use in Cushing syndrome caused by excessive production of glucocorticoids. Mifepristone also has antiglucocorticoid receptor activity and has been found to alleviate hyperglycemia in adults with hypercortisolism and glucose intolerance or diabetes who have failed to respond or are not candidates for surgical therapy.
Brand name for Mifepristone
Mifepristone was approved for this indication in 2012 and is available in 300 mg tablets under the brand name Korlym.
Dosage and administration for Mifepristone
The recommended dose is 300 mg once daily initially with subsequent increases based upon efficacy and tolerance to a maximum of 1200 mg daily.
Side effects of Mifepristone
Adverse events are not uncommon but generally mild and manageable, including nausea, vomiting, anorexia, fatigue, headache, arthralgia, peripheral edema, hypertension, dizziness, and hypokalemia. Severe adverse reactions include termination of pregnancy, adrenal insufficiency, vaginal bleeding, endometrial changes and QTc interval prolongation. Mifepristone is metabolized by CYP 3A4 and 2C8/2C9 and has many drug-drug interactions.
Obstetrical and Gynecological Agents