Mifepristone, also known by its developmental code name RU-486, is a drug typically used in combination with misoprostol to bring about a medical abortion during pregnancy. This combination is 97% effective during the first 63 days (9 weeks) of pregnancy, and is effective in the second trimester as well. It is also used on its own to treat Cushing's syndrome or in low doses as an emergency contraceptive. The most common adverse effects include abdominal pain, feeling tired, and vaginal bleeding. Serious side effects may include heavy vaginal bleeding, bacterial infection, and, if pregnant, birth defects. When used, appropriate follow-up care needs to be available. Mifepristone is primarily an antiprogestogen. It works by blocking the effects of progesterone, making both the cervix and uterine vessels dilate and causing uterine contraction. Mifepristone also works, to a lesser extent, as an antiglucocorticoid and diminishes the effects of hypercortisolism. Mifepristone was developed in France in 1980 and came into use there in 1987. It became available in the United States in 2000, for medication abortion, and in 2010, for Cushing's syndrome. It is on the World Health Organization's List of Essential Medicines. Mifepristone was approved in China in 1988, India in 2002, and Canada in 2017.
Medical uses
Abortion Mifepristone followed by a prostaglandin analog (misoprostol or gemeprost) is used for medical abortion. Medical organizations have found this combination to be safe and effective. Guidelines from the Royal College of Obstetricians and Gynaecologists describe medication abortion using mifepristone and misoprostol as effective and appropriate at any gestational age. The World Health Organization and the American College of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion. Mifepristone alone is less effective, resulting in abortion within 1–2 weeks in anywhere from 54% to 92% of pregnancies, according to review of 13 studies.
Cushing's syndrome Mifepristone is used for the medical treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushing's syndrome who also have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery. In a Phase III trial, it improved glycemic control, increased insulin sensitivity, and reduced body weight regardless of the cause of CS.
Medical management of early pregnancy loss Mifepristone combined with misoprostol is the preferred medication regimen for management of early pregnancy loss. While misoprostol alone can be used, the addition of a dose of mifepristone twenty-four hours before misoprostol administration improves treatment efficacy.
Other uses Mifepristone at low doses has been used for emergency contraception. Mifepristone has also been used to treat symptomatic leiomyoma (uterine fibroids) and endometriosis. As elevated cortisol levels have been implicated in psychotic depression, mifepristone has been used as a treatment.
Side effects Serious complications with mifepristone are rare with about 0.04%–0.09% requiring hospitalization and 0.05% requiring blood transfusion. Nearly all women using the mifepristone/misoprostol regimen experienced abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9–16 days. For most women, the most severe cramps after use of misoprostol last for less than 6 hours and can generally be managed with ibuprofen. Up to 8% of women experienced some type of bleeding for 30 days or more. Other less common side effects included nausea, vomiting, diarrhea, dizziness, fatigue, and fever. Pelvic inflammatory disease is a very rare but serious complication. Excessive bleeding and incomplete termination of a pregnancy require further intervention by a doctor (such as a repeat dose of misoprostol or a vacuum aspiration). Mifepristone is contraindicated in the presence of adrenal failure, long-term oral corticosteroid therapy (although inhaled and topical steroids are not contraindications), hemorrhagic disorders, inherited porphyria, and hemophilia or anticoagulant use. Women with an intrauterine device in their uterus should remove the IUD prior to medication abortion to avoid unnecessary cramping. Mifepristone is not effective in treating ectopic pregnancy. Mifepristone has been found to have negative effects on sleep in small clinical studies. These have included worsened sleep quality, increased wakefulness, and reduced slow wave sleep (SWS) and rapid eye movement sleep (REM sleep). The adverse effects of mifepristone on sleep are thought to be related to its antiglucocorticoid activity. A postmarketing summary found, of about 1.52 million women who had received mifepristone until April 2011 in the United States, 14 were reported to have died after application. Eight of these cases were associated with sepsis; the other six had various causes such as drug abuse and suspected murder. Other incidents reported to the FDA included 612 nonlethal hospitalizations, 339 blood transfusions, 48 severe infections, and 2,207 (0.15%) adverse events altogether. No long-term studies to evaluate the carcinogenic potential of mifepristone have been performed. This is in accord with ICH guidelines, which do not require carcinogenicity testing in nongenotoxic drugs intended for administration for less than six months.
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