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Mifepristone, commonly known as RU-486, is a potent synthetic antiprogesterone that is primarily used for the medical termination of intrauterine pregnancies, in combination with a prostaglandin analogue, misoprostol. Mifepristone is also approved for the treatment of Cushing syndrome due to its antiglucocorticoid receptor activity.<ref>[[Schaff EA]], [[Fielding SL]], [[Westhoff C]], [[Ellertson C]], [[Eisinger SH]], [[Stadalius LS]], [[Fuller L]]. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. Journal of Family Practice, 2001.</ref>
== Mifepristone ==
== Pharmacology and Mechanism of Action ==
[[File:Mifepristone_structure.svg|Structure of Mifepristone|thumb|right]]
Mifepristone acts as a competitive inhibitor of progesterone at the progesterone receptor sites. The subsequent lack of progesterone activity during pregnancy initiates a series of intrauterine and cervical changes that culminate in the termination of pregnancy. The process is completed by the administration of misoprostol, a prostaglandin analogue, which induces uterine contractions.<ref>[[Norman JE]], [[Thong KJ]], [[Baird DT]]. Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone. Lancet, 1991.</ref>
'''Mifepristone''', also known as RU-486, is a medication typically used in combination with [[misoprostol]] to bring about a medical [[abortion]]. This combination is effective in terminating a pregnancy up to 10 weeks of gestation. Mifepristone is also used in the management of [[Cushing's syndrome]], [[endometriosis]], and as an emergency contraceptive.
== Clinical Use and FDA Approval ==
== Mechanism of Action ==
Mifepristone, in conjunction with misoprostol, is approved for the medical termination of intrauterine pregnancies up to 70 days of gestation. Additionally, mifepristone alone is approved for the treatment of hyperglycemia in adults with Cushing syndrome who are not candidates for surgical therapy or have not responded to it. Off-label uses include emergency contraception, although it is not officially approved for this purpose.<ref>[[Winikoff B]], [[Dzuba IG]], [[Chong E]], [[Goldschmidt R]], [[de Moira EC]], [[Singh K]], [[Gallagher K]]. Extending outpatient medical abortion services through 70 days of gestational age. Obstetrics & Gynecology, 2012.</ref>
Mifepristone is a [[progesterone]] receptor antagonist. It works by blocking the action of progesterone, a hormone necessary for pregnancy to continue. By inhibiting progesterone, mifepristone causes the lining of the [[uterus]] to break down, leading to the detachment of the [[embryo]]. This process is followed by the administration of misoprostol, which induces uterine contractions to expel the embryo.
== Safety and Side Effects ==
== Medical Uses ==
Despite the common occurrence of mild-to-moderate side effects like uterine bleeding, nausea, vomiting, and abdominal cramps, mifepristone is generally considered safe. However, serious adverse events can occur, including severe uterine bleeding, serious bacterial infections, and the failure of abortion leading to the need for hospitalization. Mifepristone has been associated with a low rate of serum enzyme elevations and rare instances of clinically apparent liver injury, particularly when used in higher doses for the long-term treatment of Cushing syndrome.<ref>[[Grossman D]], [[White K]], [[Harris L]], [[Reeves M]], [[Blanco K]], [[Crowley M]], [[Espey E]]. Continuing pregnancy after mifepristone and "reversal" of first-trimester medical abortion: a systematic review. Contraception, 2015.</ref>
=== Abortion ===
== REMS Program and Contraindications ==
Mifepristone is primarily used for medical abortion. It is administered orally, followed by misoprostol 24 to 48 hours later. This regimen is effective in over 95% of cases when used within the first 10 weeks of pregnancy.
Due to the severity of potential side effects, the administration of mifepristone and misoprostol is regulated through a Risk Evaluation and Mitigation Strategy (REMS) program, which ensures that prescribers are certified. Contraindications for the use of mifepristone/misoprostol include pregnancy beyond 70 days, ectopic pregnancy, presence of an intrauterine device, adrenal failure, porphyria, and use of anticoagulants.<ref>[[Creinin MD]], [[Hou MY]], [[Chen MJ]], [[Lichtenberg ES]], [[Paul M]]. Mifepristone antagonization with progesterone to prevent medical abortion: a randomized controlled trial. Obstetrics & Gynecology, 2020.</ref>
=== Cushing's Syndrome ===
== Brands and Administration ==
In patients with [[Cushing's syndrome]], mifepristone is used to control hyperglycemia secondary to hypercortisolism. It acts by blocking the effects of cortisol at the glucocorticoid receptor.
Mifepristone is available in 200 mg tablets under the brand name Mifeprex for the termination of pregnancy, and in 300 mg tablets under the brand name Korlym for the treatment of Cushing syndrome. The recommended dose for inducing medical abortion is a single 200 mg tablet of mifepristone followed 24 to 48 hours later by the buccal administration of 800 mcg of misoprostol. For the treatment of Cushing syndrome, the recommended starting dose of mifepristone is 300 mg once daily, which can be increased based on efficacy and tolerance up to a maximum of 1200 mg daily.<ref>[[Fiala C]], [[Gemmell LA]], [[Tang OS]], [[von Hertzen H]]. Cervical priming with misoprostol prior to transcervical procedures. International Journal of Gynaecology and Obstetrics, 2007.</ref>
=== Other Uses ===
== Drug Interactions ==
Mifepristone has been investigated for use in [[endometriosis]], [[leiomyoma]]s, and as an emergency contraceptive. Its role in these conditions is due to its ability to modulate the effects of progesterone.
Mifepristone is metabolized by cytochrome P450 enzymes CYP 3A4 and 2C8/2C9, resulting in potential drug-drug interactions with medications that inhibit or induce these enzymes. Therefore, concomitant use with other medications metabolized by these enzymes should be approached with caution.<ref>[[Larrey D]], [[Pageaux GP]]. Drug-induced acute liver failure. European Journal of Gastroenterology & Hepatology, 2005.</ref>
== Side Effects ==
==Conclusion==
Common side effects of mifepristone include [[nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], and [[fatigue]]. Serious side effects can include heavy bleeding, infection, and incomplete abortion, which may require surgical intervention.
Mifepristone, in combination with misoprostol, is an effective option for medical termination of early intrauterine pregnancy. It is also used for the treatment of Cushing syndrome. Despite its common side effects, with proper management and administration, mifepristone is a critical component of reproductive health.
== Contraindications ==
==See also==
Mifepristone is contraindicated in individuals with chronic [[adrenal failure]], [[porphyria]], and those on long-term [[corticosteroid]] therapy. It should not be used in cases of suspected [[ectopic pregnancy]].
== Legal and Ethical Issues ==
The use of mifepristone for abortion has been subject to significant legal and ethical debate. Its availability varies widely around the world, with some countries having strict regulations or bans on its use.
== [[File:Mifepristona3D.png|3D model of Mifepristone|thumb|left]] Pharmacokinetics ==
Mifepristone is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It is highly protein-bound and metabolized primarily by the liver. The elimination half-life of mifepristone is approximately 18 to 25 hours.
Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion. This combination is effective in terminating a pregnancy up to 10 weeks of gestation. Mifepristone is also used in the management of Cushing's syndrome, endometriosis, and as an emergency contraceptive.
Mifepristone is a progesterone receptor antagonist. It works by blocking the action of progesterone, a hormone necessary for pregnancy to continue. By inhibiting progesterone, mifepristone causes the lining of the uterus to break down, leading to the detachment of the embryo. This process is followed by the administration of misoprostol, which induces uterine contractions to expel the embryo.
Mifepristone is primarily used for medical abortion. It is administered orally, followed by misoprostol 24 to 48 hours later. This regimen is effective in over 95% of cases when used within the first 10 weeks of pregnancy.
In patients with Cushing's syndrome, mifepristone is used to control hyperglycemia secondary to hypercortisolism. It acts by blocking the effects of cortisol at the glucocorticoid receptor.
Mifepristone has been investigated for use in endometriosis, leiomyomas, and as an emergency contraceptive. Its role in these conditions is due to its ability to modulate the effects of progesterone.
Common side effects of mifepristone include nausea, vomiting, diarrhea, abdominal pain, and fatigue. Serious side effects can include heavy bleeding, infection, and incomplete abortion, which may require surgical intervention.
The use of mifepristone for abortion has been subject to significant legal and ethical debate. Its availability varies widely around the world, with some countries having strict regulations or bans on its use.
Mifepristone is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It is highly protein-bound and metabolized primarily by the liver. The elimination half-life of mifepristone is approximately 18 to 25 hours.
