Mifepristone Explained

Watchedfields:changed
Verifiedrevid:443306800
Width:200
Width2:200
Pronounce:[1]
Tradename:Mifegyne, Mifeprex, Korlym, others
Dailymedid:Mifepristone
Pregnancy Category:Not recommended
Routes Of Administration:By mouth
Class:Antiprogestogen
Antiglucocorticoid
Atc Prefix:G03
Atc Suffix:XB01
Legal Us:Rx-only
Legal Us Comment:[2]
Legal Status:Rx-only
Bioavailability:69%
Protein Bound:98%
Metabolism:Liver
Excretion:Feces

83%
urine: 9%

Cas Number:84371-65-3
Pubchem:55245
Iuphar Ligand:2805
Drugbank:DB00834
Chemspiderid:49889
Unii:320T6RNW1F
Kegg:D00585
Chebi:50692
Chembl:157
Synonyms:RU-486; RU-38486; ZK-98296; 11β-[''p''-(Dimethylamino)phenyl]-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one
Iupac Name:(8S,11R,13S,14S,17S)-11-[4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[''a'']phenanthren-3-one
C:29
H:35
N:1
O:2
Smiles:O=C5\C=C4/C(=C3/[C@@H](c1ccc(N(C)C)cc1)C[C@]2([C@@H](CC[C@]2(C#CC)O)[C@@H]3CC4)C)CC5
Stdinchi:1S/C29H35NO2/c1-5-15-29(32)16-14-26-24-12-8-20-17-22(31)11-13-23(20)27(24)25(18-28(26,29)2)19-6-9-21(10-7-19)30(3)4/h6-7,9-10,17,24-26,32H,8,11-14,16,18H2,1-4H3/t24-,25+,26-,28-,29-/m0/s1
Stdinchikey:VKHAHZOOUSRJNA-GCNJZUOMSA-N
Density:1.189
Melting Point:194
Boiling Point:629

Mifepristone, also known by its developmental code name RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage.[3] This combination is 97% effective during the first 63 days (9 weeks) of pregnancy.[4] It is also effective in the second trimester of pregnancy.[5] It is taken by mouth.[3]

The more common adverse effects include abdominal pain, feeling tired, and vaginal bleeding.[3] Serious side effects may include heavy vaginal bleeding, bacterial infection, and birth defects if the pregnancy does not end.[3] If used, appropriate follow-up care needs to be available.[3] [6] Mifepristone is an antiprogestogen.[3] It works by blocking the effects of progesterone, making both the cervix and uterine vessels dilate and causing uterine contraction.[3]

Mifepristone was developed in 1980 and came into use in France in 1987.[7] It became available in the United States in 2000.[8] [9] It is on the World Health Organization's List of Essential Medicines.[10] [11] Mifepristone was approved in Canada in January 2017.[12] [13]

Medical uses

Abortion

Mifepristone followed by a prostaglandin analog (misoprostol or gemeprost) is used for medical abortion.[14] [15] 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.[16] The World Health Organization and the American College of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion.[17] [18] [19] [20] 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.[21] [22] In a Phase III trial, it improved glycemic control, increased insulin sensitivity, and reduced body weight regardless of the cause of CS.[23]

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.[24]

Other uses

Mifepristone at low doses has been used for emergency contraception.[25] [26] [27] Mifepristone has also been used to treat symptomatic leiomyoma (uterine fibroids) and endometriosis.[28] As elevated cortisol levels have been implicated in psychotic depression, mifepristone has been used as a treatment.[29]

Side effects

Serious complications with mifepristone are rare with about 0.04%–0.09% requiring hospitalization and 0.05% requiring blood transfusion.[30]

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.[31] 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.[32] Pelvic inflammatory disease is a very rare but serious complication.[33] 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.

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.[34]

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.[35]

Pregnancy

Mifepristone alone results in abortion within 1–2 weeks in 54% to 92% of pregnancies.[36] [37] The effectiveness increases to greater than 90% if misoprostol is given after the mifepristone.[38] There is no evidence that the effects of mifepristone can be reversed,[36] [39] although some anti-abortion groups claim that it can be reversed by giving progesterone.[40] [41] Researchers in the United States initiated a trial of the so-called "reversal" regimen in 2019, but stopped prematurely due to serious safety concerns about using mifepristone without follow-up misoprostol.[42] [43] Giving progesterone has not been shown to halt medication abortion, and not completing the combination regimen of mifepristone and misoprostol may cause serious bleeding.

In those who continue pregnancy after use of mifepristone together with misoprostol for termination, birth defects may occur.[6] Exposure to a single large dose of mifepristone in newborn rats was not associated with any reproductive problems, although chronic low-dose exposure of newborn rats to mifepristone was associated with structural and functional reproductive abnormalities.[32] Studies in mice, rats, and rabbits revealed developmental abnormalities for rabbits, but not rats or mice.[32]

Pharmacology

Pharmacodynamics

Mifepristone is a steroidal antiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid (IC50 = 2.2 nM for the GR) and antiandrogen (IC50 = 10 nM for the AR) to a much lesser extent.[44] It antagonizes cortisol action competitively at the receptor level.[45]

In the presence of progesterone, mifepristone acts as a competitive progesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial agonist). Mifepristone is a 19-nor steroid with a bulky p-(dimethylamino) phenyl substituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptor conformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptor binding affinity.[46] [47] [48]

In addition to being an antiprogestogen, mifepristone is also an antiglucocorticoid and a weak antiandrogen. Mifepristone's relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of cortisol.[49] Its relative binding affinity at the androgen receptor is less than one-third that of testosterone, and it does not bind to the estrogen receptor or the mineralocorticoid receptor.[50]

Mifepristone as a regular contraceptive at 2 mg daily prevents ovulation (1 mg daily does not). A single preovulatory 10-mg dose of mifepristone delays ovulation by three to four days and is as effective an emergency contraceptive as a single 1.5-mg dose of the progestin levonorgestrel.[51]

In women, mifepristone at doses greater or equal to 1 mg/kg antagonizes the endometrial and myometrial effects of progesterone. In humans, an antiglucocorticoid effect of mifepristone is manifested at doses greater or equal to 4.5 mg/kg by a compensatory increase in ACTH and cortisol. In animals, a weak antiandrogenic effect is seen with prolonged administration of very high doses of 10 to 100 mg/kg.[52] [53]

In medication abortion regimens, mifepristone blockade of progesterone receptors directly causes endometrial decidual degeneration, cervical softening and dilatation, release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins. Mifepristone-induced decidual breakdown indirectly leads to trophoblast detachment, resulting in decreased syncytiotrophoblast production of hCG, which in turn causes decreased production of progesterone by the corpus luteum (pregnancy is dependent on progesterone production by the corpus luteum through the first nine weeks of gestation—until placental progesterone production has increased enough to take the place of corpus luteum progesterone production). When followed sequentially by a prostaglandin, mifepristone 200 mg is (100 mg may be, but 50 mg is not) as effective as 600 mg in producing a medical abortion.[46] [48]

'Contragestion' is a term promoted by Étienne-Émile Baulieu in the context of his advocacy of mifepristone, defining it as inclusive of some hypothesized mechanisms of action of some contraceptives and those of mifepristone to induce abortion.[54] Baulieu's definition of a 'contragestive' included any birth control method that could possibly act after fertilization and before nine-weeks gestational age.[54]

Pharmacokinetics

The elimination half-life is complex; according to the label: "After a distribution phase, elimination is at first slow, the concentration decreasing by a half between about 12 and 72 hours, and then more rapid, giving an elimination half-life of 18 hours. With radio receptor assay techniques, the terminal half-life is of up to 90 hours, including all metabolites of mifepristone able to bind to progesterone receptors."[14] Metapristone is the major metabolite of mifepristone.[55] [49] [56]

Chemistry

Mifepristone, also known as 11β-(4-(dimethylamino)phenyl)-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one, is a synthetic estrane steroid and a derivative of steroid hormones like progesterone, cortisol, and testosterone.[45] It has substitutions at the C11β and C17α positions and double bonds at the C4(5) and C9(10) positions.

History

1980–1987

In April 1980, as part of a formal research project at the French pharmaceutical company Roussel-Uclaf for the development of glucocorticoid receptor antagonists, endocrinologist Étienne-Émile Baulieu[57] [58] and chemist Georges Teutsch synthesized mifepristone (RU-38486, the 38,486th compound synthesized by Roussel-Uclaf from 1949 to 1980; shortened to RU-486), which was discovered to also be a progesterone receptor antagonist.[59] [60] In October 1981, Étienne-Émile Baulieu, a consultant to Roussel-Uclaf, arranged tests of its use for medical abortion in 11 women in Switzerland by gynecologist Walter Herrmann at the University of Geneva's Cantonal Hospital, with successful results announced on 19 April 1982.[61] On 9 October 1987, following worldwide clinical trials in 20,000 women of mifepristone with a prostaglandin analogue (initially sulprostone or gemeprost, later misoprostol) for medical abortion, Roussel-Uclaf sought approval in France for their use for medical abortion, with approval announced on 23 September 1988.[62]

1988–1990

On 21 October 1988, in response to antiabortion protests and concerns of majority (54.5%) owner Hoechst AG of Germany, Roussel-Uclaf's executives and board of directors voted 16 to 4 to stop distribution of mifepristone, which they announced on 26 October 1988.[63] Two days later, the French government ordered Roussel-Uclaf to distribute mifepristone in the interests of public health.[64] French Health Minister Claude Évin explained: "I could not permit the abortion debate to deprive women of a product that represents medical progress. From the moment Government approval for the drug was granted, RU-486 became the moral property of women, not just the property of a drug company." Following use by 34,000 women in France from April 1988 to February 1990 of mifepristone distributed free of charge, Roussel-Uclaf began selling Mifegyne (mifepristone) to hospitals in France in February 1990 at a price (negotiated with the French government) of per 600-mg dose.

1991–1996

Mifegyne was subsequently approved in Great Britain in July 1991,[65] and in Sweden in September 1992,[66] but until his retirement in April 1994, Hoechst AG chairman Wolfgang Hilger, a devout Roman Catholic,[67] blocked any further expansion in availability.[68] Soon after becoming U.S. President in 1993, Bill Clinton ordered the U.S. Health and Human Services Department to investigate mifepristone's potential as an abortion medication, and also pressured Hoeschst to make the RU-486 medication available in the United States.[69] [70] On 16 May 1994, Roussel-Uclaf announced it was donating without remuneration all rights for medical uses of mifepristone in the United States to the Population Council,[71] which would then sponsor clinical trials for mifepristone between September 1994 and September 1995.[72] In September 1995, The Population Council licensed mifpristone to Danco Laboratories and entered into a manufacturing agreement with Hungarian drug manufacturer Gedeon Richter.[73] In 1996, the US Food and Drug Administration (FDA) conditionally licensed RU-486 for early trimester abortion, pending a resolution on some remaining technical and manufacturing issues.

1997–1999

On 8 April 1997, after buying the remaining 43.5% of Roussel-Uclaf stock in early 1997,[74] Hoechst AG (billion annual revenue) announced the end of its manufacture and sale of Mifegyne (million annual revenue) and the transfer of all rights for medical uses of mifepristone outside of the United States to Exelgyn, a new single-product company immune to antiabortion boycotts, whose CEO was former Roussel-Uclaf CEO Édouard Sakiz.[75] In 1997, Gideon Richter would withdraw from efforts to manufacture mifepristone in the United States following opposition from pro-life groups, which led to Danco filing a breach of contract lawsuit.[76] In 1999, Exelgyn won approval of Mifegyne in 11 additional countries, and in 28 more countries over the following decade.[77]

2000–present

On September 28, 2000 Danco Laboratories, a sub-licencee of the Population Council, received approval from the US Food and Drug Administration (FDA) to sell mifepristone under the brand name Mifeprex. Danco Laboratories was a new, single-product company that was intended to be resistant to antiabortion boycotts.[78]

In 2019, the first generic form of mifepristone in the United States became available, manufactured by GenBioPro.[79]

Society and culture

Mifepristone is on the World Health Organization's List of Essential Medicines. Since 2019, it has been included on the core list, with misoprostol, with a special note "where permitted under national law and where culturally acceptable".

Economics

Cost and availability limit access in many parts of the world.[80] [81]

Frequency of use

United States

Medication abortions voluntarily reported by 33 U.S. states[82] to the Centers for Disease Control and Prevention (CDC) have increased as a percentage of total abortions every year since the approval of mifepristone: 1.0% in 2000, 2.9% in 2001, 5.2% in 2002, 7.9% in 2003, 9.3% in 2004, 9.9% in 2005, 10.6% in 2006, and 13.1% in 2007 (20.3% of those at less than 9 weeks gestation).[83]

A Guttmacher Institute survey of abortion providers estimated that medication abortions accounted for 17% of all abortions and slightly over 25% of abortions before 9 weeks gestation in the United States in 2008 (94% of nonhospital medication abortions used mifepristone and misoprostol, 6% used methotrexate and misoprostol).[84] Medication abortions accounted for 32% of first trimester abortions at Planned Parenthood clinics in the United States in 2008.[85] Considering abortions performed in non-hospital facilities, medication abortions accounted for 24% in 2011 and 31% in 2014. In 2014, facilities that provided a relatively small number of abortions (fewer than 400 procedures per year) were more likely to perform them with medication.[86] Medication abortions accounted for 39% of all U.S. abortions in 2017,[87] and 54% in 2020.[88]

Europe

In France, the percentage of medication abortions of all abortions continues to increase: 38% in 2003, 42% in 2004, 44% in 2005, 46% in 2006, 49% in 2007 (vs. 18% in 1996).[89] In England and Wales, 52% of early abortions (less than 9 weeks gestation) in 2009 were medication-based; the percentage of all abortions that are medication-based has increased every year for the past 14 years (from 5% in 1995 to 40% in 2009) and has more than doubled in the last five years.[90] In Scotland, 81.2% of early abortions in 2009 were medication-based (up from 55.8% in 1992 when medication abortion was introduced); the percentage of all abortions that are medication-based has increased every year for the past 17 years (from 16.4% in 1992 to 69.9% in 2009).[91] In Sweden, 85.6% of early abortions and 73.2% of abortions before the end of the 12th week of gestation in 2009 were medication-based; 68.2% of all abortions in 2009 were medication-based.[92] In Great Britain and Sweden, mifepristone is licensed for use with vaginal gemeprost or oral misoprostol. As of 2000, more than 620,000 women in Europe had had medication abortions using a mifepristone regimen.[93] In Denmark, mifepristone was used in between 3,000 and 4,000 of just over 15,000 abortions in 2005.[94]

Legal status

In the United States

Mifepristone was approved for abortion in the United States by the FDA in September 2000.[95], it was legal and available in all 50 states, Washington, D.C., Guam, and Puerto Rico.[96] It is a prescription drug, but was not initially available to the public through pharmacies; its distribution is primarily restricted to specially qualified licensed physicians, sold by Danco Laboratories under the brand name Mifeprex. As of September 2021, in 32 states, the drug could only be provided by a licensed physician, and in 19 states, the prescribing clinician was required to be physically in the room with the patient while they are taking the drug.

Roussel Uclaf did not seek U.S. approval, so in the United States legal availability was not initially possible.[97] The United States banned importation of mifepristone for personal use in 1989,[98] a decision supported by Roussel Uclaf. In 1994, Roussel Uclaf gave the U.S. drug rights to the Population Council in exchange for immunity from any product liability claims.[71] [99] The Population Council sponsored clinical trials in the United States.[100] The drug went on approvable status from 1996. Production was intended to begin through the Danco Group in 1996, but they withdrew briefly in 1997 due to a corrupt business partner, delaying availability again.[101] [102]

In 2016, the US Food and Drug Administration (FDA) approved mifepristone, to end a pregnancy through 70 days gestation (70 days or less since the first day of a woman's last menstrual period). The approved dosing regimen is 200 mg of mifepristone taken by mouth (swallowed).  24 to 48 hours after taking mifepristone, 800 mcg (micrograms) of misoprostol is taken buccally (in the cheek pouch), at a location appropriate for the patient.[15] [103] [104] [105]

Mifepristone tablets have a marketing authorization in the United States for the treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.[21]

Due to the COVID-19 pandemic, safe access to mifepristone was a concern, and the American College of Obstetricians and Gynecologists among other groups filed a lawsuit to relax the FDA's rule as to allow mifepristone to be acquired from mail-order and retail pharmacies. While the Fourth Circuit had granted a preliminary injunction to allow this distribution, the Supreme Court of the United States issued a stay order in January 2021 to retain the FDA's rule pending the results of the ongoing litigation.[106]

On 16 December 2021, the FDA voluntarily adopted a new rule permanently relaxing the requirement that the pill be obtained in person, allowing it to be sent through the mail. A prescription is still required, so that a doctor can screen for risk factors that would make taking the pill unsafe for the mother.[107] In January 2023, the FDA further relaxed rules, allowing any retail pharmacy to become certified to fill mifepristone prescriptions.[108] [109]

After regulations on abortion early in pregnancy were ruled constitutional by the 2022 decision Dobbs v. Jackson Women's Health Organization, some states enacted restrictions on abortions and abortion pills. In January 2023, the United States Department of Justice issued an interpretation of the Comstock Act[110] that it was legal for United States Postal Service employees to deliver the pills in any state, because they could not know whether the pills would be used for an abortion or other purposes.

In January 2023, GenBioPro filed suit to overturn state laws that prohibit sale of mifepristone, claiming that such laws are invalid because it is a federally approved drug.[111]

The argument that state laws seeking to ban or restrict the use of mifepristone are preempted by the FDA's decision to make the drug available is supported by a number of Supreme Court decisions, including opinions by the traditionally more conservative Justices.[112]

In March 2023, Wyoming became the first US state to ban the pill.[113] [114]

In April 2023, in a lawsuit brought by 17 U.S. states and the District of Columbia, federal district judge Thomas O. Rice issued a temporary injunction that the FDA should not reduce access to mifepristone in these states and the district.[115] [116]

In May 2024, the state of Louisiana classified mifepristone and misoprostol as controlled substances, with penalties for possession without a prescription. The move follows concerns over coerced abortion and has drawn criticism from over 240 doctors in the state.[117] [118]

FDA v. Alliance for Hippocratic Medicine

See main article: FDA v. Alliance for Hippocratic Medicine. In April 2023, in the FDA v. Alliance for Hippocratic Medicine lawsuit, federal district judge Matthew J. Kacsmaryk issued a preliminary injunction suspending the 2000 approval of mifepristone, which would take effect a week later.[119] The Fifth Circuit reversed parts of Kacsmaryk's injunction, but placed a temporary injunction on the 2016 REMS change to mifepristone. On appeal to the Supreme Court, the Court stayed both injunctions on 21 April 2023, with only Justices Samuel Alito and Clarence Thomas stating their dissent. The stay allowed mifepristone to remain legally available while the lower courts consider the merits of the case.

In June 2024, the U.S. Supreme Court unanimously overturned judge Kacsmaryk's Fifth Circuit decision on the grounds that the Alliance for Hippocratic Medicine had no standing to challenge the FDA's regulations of mifepristone.[120] [121] The Supreme Court ruled that Alliance for Hippocratic Medicine did not demonstrate that they would suffer harm to warrant standing. The Court did not rule on the substance of mifepristone, abortion, or the FDA's procedures.[122]

Subsection H

Some drugs are approved by the FDA under subsection H, which has two subparts. The first sets forth ways to rush experimental drugs, such as aggressive HIV and cancer treatments, to market when speedy approval is deemed vital to the health of potential patients. The second part of subsection H applies to drugs that not only must meet restrictions for use due to safety requirements, but also are required to meet postmarketing surveillance to establish that the safety results shown in clinical trials are seconded by use in a much wider population. Until December 2021, Mifepristone was approved under the second part of subsection H. The result is that women could not pick the drug up at a pharmacy, but were required to receive it directly from a doctor. Due to the possibility of adverse reactions such as excessive bleeding, which may require a blood transfusion, and incomplete abortion, which may require surgical intervention, the drug was only considered safe if a physician who is capable of administering a blood transfusion or a surgical abortion is available to the patient in the event of such emergencies.[123] The approval of mifepristone under subsection H included a black box warning.

European Union

Outside the United States, mifepristone is marketed and distributed by Exelgyn Laboratories under the brand name Mifegyne. It was approved for use in France in 1988 (initial marketing in 1989), the United Kingdom in 1991, Sweden in 1992, then Austria, Belgium, Denmark, Finland, Germany, Greece, Luxembourg, the Netherlands, Spain, and Switzerland in 1999.[124] In 2000, it was approved in Norway, Russia and Ukraine. Serbia and Montenegro approved it in 2001,[125] Belarus and Latvia in 2002, Estonia in 2003, Moldova in 2004, Albania and Hungary in 2005, Portugal in 2007, Romania in 2008,[77] Bulgaria, Czech Republic and Slovenia in 2013.[126] In Italy, clinical trials have been constrained by protocols requiring women be hospitalized for three days, but the drug was finally approved on 30 July 2009 (officialized later in the year), despite strong opposition from the Vatican. In Italy, the pill must be prescribed and used in a clinical structure and is not sold at chemists.[127] It was approved in Hungary in 2005, but as of 2005 had not been released on the market yet, and was the target of protests.[128] Mifepristone is licensed in Ireland for use of abortions up to 12 weeks since it was legalised in 2018.[129] Mifepristone is not available in Poland, where abortion is highly restricted.[130]

Mifepristone 200 mg tablets (Mifegyne, Mifepristone Linepharma, Medabon) have marketing authorizations in the European Economic Area from the European Medicines Agency (EMA) for:[14] [131] [132]

Other countries

Mifepristone was banned in Australia in 1996. In 2005, a private member's bill was introduced to the Australian Senate to lift the ban and transfer the power of approval to the Therapeutic Goods Administration (TGA). The move caused much debate in the Australian media and among politicians. The bill passed the Senate in February 2006, and mifepristone is legal in Australia. It is provided regularly at several specialized abortion clinics per state.[133] [134] Mifepristone 200 mg tablets have marketing authorizations in Australia from the TGA for early first trimester medication abortion when followed by the prostaglandin analog misoprostol through 63 days gestational age[135] and second trimester medication abortion when followed by a prostaglandin analog.[136]

In New Zealand, pro-abortion rights doctors established an import company, Istar, and submitted a request for approval to Medsafe, the New Zealand pharmaceutical regulatory agency. After a court case brought by Right to Life New Zealand failed, use of mifepristone was permitted.[137]

Mifepristone was approved in Israel in 1999.[138]

Clinical trials of mifepristone in China began in 1985. In October 1988, China became the first country in the world to approve mifepristone. Chinese organizations tried to purchase mifepristone from Roussel Uclaf, which refused to sell it to them, so in 1992 China began its own domestic production of mifepristone. In 2000, the cost of medication abortion with mifepristone was higher than surgical abortion and the percentage of medication abortions varied greatly, ranging from 30% to 70% in cities to being almost nonexistent in rural areas.[139] [140] A report from the United States Embassy in Beijing in 2000 said mifepristone had been widely used in Chinese cities for about two years, and that according to press reports, a black market had developed with many women starting to buy it illegally (without a prescription) from private clinics and drugstores for about, causing Chinese authorities to worry about medical complications from use without physician supervision.[141]

In 2001, mifepristone was approved in Taiwan.[142] Vietnam included mifepristone in the National Reproductive Health program in 2002.[143]

Mifepristone is approved in only one sub-Saharan African country—South Africa, where it was approved in 2001.[144] It is also approved in one north African country—Tunisia, also in 2001.[145]

Mifepristone was approved for use in India in 2002, where medication abortion is referred to as "medical termination of pregnancy". It is only available under medical supervision, not by prescription, due to adverse reactions such as excessive bleeding, and criminal penalties are given for buying or selling it on the black market or over-the-counter at pharmacies.[146]

Medication induced abortion used to be available in Canada but on a limited basis using methotrexate and misoprostol. Clinical trials were done in 2000 in various Canadian cities comparing methotrexate to mifepristone, after approbation by the federal government. While both drugs had overall similar results, mifepristone was found to act faster.[147] Health Canada gave approval to mifepristone in July 2015.[148] Initially, its use was limited to seven weeks into a pregnancy, but this was changed to nine weeks in 2017. The previous requirement of written consent from the woman was also ended at the same time. It can be dispensed directly to a patient by a pharmacist or a prescribing health professional. Women are required to have an ultrasound to ensure the pregnancy is not ectopic.[149]

Mifepristone was registered for use in Azerbaijan, Georgia, and Uzbekistan in 2002, in Guyana and Moldova in 2004, in Mongolia in 2005, and in Armenia in 2007.[77] [150]

Low dose mifepristone tablets for emergency contraception are available directly from a pharmacist without a prescription and with a prescription in China.[151] [152] [153]

Low dose mifepristone tablets for emergency contraception are available by prescription in Armenia (Gynepriston), Russia (Agesta, Gynepriston, Mifepristone 72, Negele), Ukraine (Gynepriston), and Vietnam (Mifestad 10, Ciel EC).[151] [152] [153]

Controversy

Many anti-abortion groups in the United States actively campaigned against the approval of mifepristone[154] [155] [156] and continue to actively campaign for its withdrawal.[157] They cite either ethical issues with abortion or safety concerns regarding the drug and the adverse reactions associated with it.[158]

Religious and anti-abortion groups outside the United States have also protested mifepristone, especially in Germany[159] and Australia.[160] [161]

A court case that originated in Texas in 2023 argued that mifepristone was unsafe and women should no longer be able to order it by mail. This case was won in Texas but was appealed, and on June 13, 2024, the U.S. Supreme Court ruled unanimously on that case to keep mifepristone available.[162]

Research

The original target for the research group was the discovery and development of compounds with antiglucocorticoid properties.[163]

Use of mifepristone as a cervical ripening agent has been described.[164] The medication has been studied as an antiandrogen in the treatment of prostate cancer.[165] [166] Mifepristone showed no detectable anti-HIV activity in clinical trials.[47] [51] [167] [168]

Mifepristone showed initial promise in psychotic major depression, a difficult-to-treat form of depression,[169] [170] but a phase-III clinical trial was terminated early due to lack of efficacy.[171] It has been studied in bipolar disorder,[172] post traumatic stress disorder, and anorexia nervosa.[173]

External links

Notes and References

  1. Encyclopedia: mifepristone. https://www.merriam-webster.com/dictionary/mifepristone. Merriam-Webster.com Dictionary. Merriam-Webster. 3 March 2023. 3 March 2023. https://web.archive.org/web/20230303213038/https://www.merriam-webster.com/dictionary/mifepristone. live. Mifepristone Definition & Meaning - Merriam-Webster .
  2. Web site: Mifepristone tablet . DailyMed . 30 March 2023 . 24 April 2023 . 10 April 2023 . https://web.archive.org/web/20230410145605/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b63fad9b-7f12-4400-9019-b0586054e534 . live .
  3. Web site: Mifepristone . live . https://web.archive.org/web/20151222083002/http://www.drugs.com/monograph/mifepristone.html . 22 December 2015 . 25 February 2023 . . Drugs.com.
  4. Chen MJ, Creinin MD . July 2015 . Mifepristone With Buccal Misoprostol for Medical Abortion: A Systematic Review . live . . 126 . 1 . 12–21 . 10.1097/AOG.0000000000000897 . 26241251 . 20800109 . https://web.archive.org/web/20200726105924/https://escholarship.org/uc/item/2pw521h5 . 26 July 2020 . 27 July 2019 . eScholarship.
  5. Wildschut H, Both MI, Medema S, Thomee E, Wildhagen MF, Kapp N . Medical methods for mid-trimester termination of pregnancy . The Cochrane Database of Systematic Reviews . 1 . CD005216 . January 2011 . 2011 . 21249669 . 10.1002/14651858.CD005216.pub2 . 8557267 .
  6. Web site: 20 January 2023 . Mifepristone Use During Pregnancy . live . https://web.archive.org/web/20230423000420/https://www.drugs.com/pregnancy/mifepristone.html . 23 April 2023 . 22 April 2023 . Drugs.com.
  7. Book: Molecules and Medicine . Corey EJ, Czakó B, Kürti L . 2012 . John Wiley & Sons . 978-1-118-36173-3 . Mifepristone . https://books.google.com/books?id=jz2GN6DYoOoC&pg=RA1-PT108 . https://web.archive.org/web/20170908184336/https://books.google.com/books?id=jz2GN6DYoOoC&pg=RA1-PT108 . 8 September 2017 . live . Google Books.
  8. Web site: Drug Approval Package: Mifeprex (Mifepristone) NDA #20687 . U.S. Food and Drug Administration (FDA) . 18 June 2001 . 24 April 2023 . 21 April 2023 . https://web.archive.org/web/20230421173537/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20687_mifepristone.cfm . live .
  9. Book: Women and Health . 2012 . Academic Press . 978-0-12-384979-3 . Goldman MB, Troisi R, Rexrode KM . 2nd . Oxford . 236 . 5 September 2017 . https://web.archive.org/web/20170908184336/https://books.google.com/books?id=mavb4v8w8bsC&pg=PA236 . 8 September 2017 . live . Google Books.
  10. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  11. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
  12. Web site: Mifepristone Product information . . 22 October 2009 . 24 April 2023 . 24 April 2023 . https://web.archive.org/web/20230424143549/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=92881 . live .
  13. News: 5 February 2017 . How the arrival of the abortion pill reveals a double standard . . live . 21 February 2017 . https://web.archive.org/web/20170221055406/http://www.macleans.ca/society/new-pill-old-headaches/ . 21 February 2017 . Kingston A.
  14. Web site: 21 November 2022 . Mifegyne 200 Mg Tablets Summary of Product Characteristics (SPC) . 22 April 2023 . Medicines and Healthcare products Regulatory Agency (MHRA) . 23 April 2023 . https://web.archive.org/web/20230423003527/https://mhraproducts4853.blob.core.windows.net/docs/da0a3830e2ed46fc9835502a30ab00a2be19f8fc . live .
  15. Web site: 23 March 2023 . Information about Mifepristone for Medical Termination of Pregnancy Through Ten Weeks Gestation . live . https://web.archive.org/web/20230421235002/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-mifepristone-medical-termination-pregnancy-through-ten-weeks-gestation . 21 April 2023 . 22 April 2023 . Drugs . U.S. Food and Drug Administration (FDA) .
  16. Book: The Care of Women Requesting Induced Abortion . November 2011 . RCOG Press . 3rd . Evidence-based Clinical Guideline No. 7 . London . 68–75 . 25 April 2023 . https://web.archive.org/web/20220526233950/https://www.rcog.org.uk/media/nwcjrf0o/abortion-guideline_web_1.pdf . 26 May 2022 . live.
  17. Book: World Health Organization . Safe abortion: technical and policy guidance for health systems . 21 June 2012 . WHO . 978-92-4-154843-4 . 2nd . Geneva . 113–116 . en . Annex 5 . 10665/70914 . free . 26 April 2023 . 10 February 2023 . https://web.archive.org/web/20230210092721/http://apps.who.int/iris/bitstream/handle/10665/70914/9789241548434_eng.pdf . live .
  18. Book: Clinical practice handbook for safe abortion . 10 January 2014 . . 978-92-4-154871-7 . Geneva . en . 10665/97415 . free . 26 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408070843/https://apps.who.int/iris/bitstream/handle/10665/97415/9789241548717_eng.pdf . live .
  19. Web site: Committee on Practice Bulletins—Gynecology and the Society of Family Planning . October 2020 . Medication Abortion Up to 70 Days of Gestation . 25 April 2023 . Practice Bulletin 225 . . 25 April 2023 . https://web.archive.org/web/20230425173524/https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/medication-abortion-up-to-70-days-of-gestation . live .
  20. Committee on Practice Bulletins—Gynecology . June 2013 . Practice Bulletin No. 135: Second-Trimester Abortion . . 121 . 6 . 1394–1406 . 10.1097/01.AOG.0000431056.79334.cc . 23812485 . 205384119 . . 26 April 2023 . 6 April 2023 . https://web.archive.org/web/20230406064221/https://blog.utp.edu.co/maternoinfantil/files/2012/04/135-Aborto-2-trimestre.pdf . live .
  21. Web site: 20 December 2022 . Korlym- mifepristone tablet . live . 6 October 2022 . 19 March 2023 . . https://web.archive.org/web/20221006220203/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=542f3fae-8bc8-4f00-9228-e4b66c9ad6a9 .
  22. Ciato D, Mumbach AG, Paez-Pereda M, Stalla GK . January 2017 . Currently used and investigational drugs for Cushing´s disease . . 26 . 1 . 75–84 . 10.1080/13543784.2017.1266338 . 27894193 . free . doi.
  23. Varlamov EV, Purnell JQ, Fleseriu M . Glucocorticoid Receptor Antagonism as a New "Remedy" for Insulin Resistance-Not There Yet! . The Journal of Clinical Endocrinology and Metabolism . 106 . 6 . e2447–e2449 . May 2021 . 33659987 . 10.1210/clinem/dgab127 . 8118574 . free .
  24. Web site: Early Pregnancy Loss . 2024-03-28 . www.acog.org . en.
  25. Web site: 13 February 2013 . Dedicated emergency contraceptive pills worldwide . dead . https://web.archive.org/web/20160304190311/http://ec.princeton.edu/pills/Dedicated_ECPs.pdf . 4 March 2016 . 4 April 2016 . Office of Population Research, Princeton University . Trussell J, Cleland K . Princeton.
  26. Web site: 2016 . EC pill types and countries of availability, by brand . dead . https://web.archive.org/web/20160405095026/http://www.cecinfo.org/country-by-country-information/status-availability-database/ec-pill-types-and-countries-of-availability-by-brand/ . 5 April 2016 . 4 April 2016 . International Consortium for Emergency Contraception . New York.
  27. Web site: March 2016 . Emergency Contraception: A Last Chance to Prevent Unintended Pregnancy . live . https://web.archive.org/web/20100923040101/http://ec.princeton.edu/questions/ec-review.pdf . 23 September 2010 . 7 April 2016 . Office of Population Research, Princeton University . Trussell J, Raymond E . Princeton.
  28. Murji A, Whitaker L, Chow TL, Sobel ML . April 2017 . Selective progesterone receptor modulators (SPRMs) for uterine fibroids . The Cochrane Database of Systematic Reviews . 2017 . 4 . CD010770 . 10.1002/14651858.CD010770.pub2 . 6478099 . 28444736 . Cochrane Gynaecology and Fertility Group.
  29. Block TS, Kushner H, Kalin N, Nelson C, Belanoff J, Schatzberg A . July 2018 . Combined Analysis of Mifepristone for Psychotic Depression: Plasma Levels Associated With Clinical Response . Biological Psychiatry . 84 . 1 . 46–54 . 10.1016/j.biopsych.2018.01.008 . 29523415 . free.
  30. Cleland K, Creinin MD, Nucatola D, Nshom M, Trussell J . Significant adverse events and outcomes after medical abortion . Obstetrics and Gynecology . 121 . 1 . 166–71 . January 2013 . 23262942 . 3711556 . 10.1097/AOG.0b013e3182755763 .
  31. Friedlander EB, Soon R, Salcedo J, Davis J, Tschann M, Kaneshiro B . Prophylactic Pregabalin to Decrease Pain During Medication Abortion: A Randomized Controlled Trial . Obstetrics and Gynecology . 132 . 3 . 612–618 . September 2018 . 30095762 . 6105469 . 10.1097/AOG.0000000000002787 .
  32. Web site: Mifeprex label . FDA . 19 July 2005 . 22 August 2006 . https://web.archive.org/web/20060628212659/https://www.fda.gov/cder/foi/label/2005/020687s013lbl.pdf . 28 June 2006.
  33. Lawton BA, Rose SB, Shepherd J . Atypical presentation of serious pelvic inflammatory disease following mifepristone-induced medical abortion . Contraception . 73 . 4 . 431–2 . April 2006 . 16531180 . 10.1016/j.contraception.2005.09.003 .
  34. Web site: Mifepristone U.S. Postmarketing Adverse Events Summary through 04/30/2011 . 14 November 2011 . live . https://web.archive.org/web/20120118020524/http://downloads.frc.org/EF/EF11G29.pdf . 18 January 2012 .
  35. Guideline IH. Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals S1A. . International Conference on Harmonization . 1996 . live . https://web.archive.org/web/20131228140714/http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S1A/Step4/S1A_Guideline.pdf. 28 December 2013.
  36. . September 2015 . Continuing pregnancy after mifepristone and "reversal" of first-trimester medical abortion: a systematic review . . Review article . 92 . 3 . 206–11 . 10.1016/j.contraception.2015.06.001 . 26057457 . subscription . 26 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408185711/https://www.contraceptionjournal.org/article/S0010-7824(15)00226-7/fulltext . live .
  37. Book: Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care. Paul M, Lichtenberg S, Borgatta L, Grimes DA, Stubblefield PG, Creinin MD . 24 August 2011. John Wiley & Sons. 978-1-4443-5847-6. live. https://web.archive.org/web/20170908135429/https://books.google.com/books?id=iK7xrRr2p9sC. 8 September 2017.
  38. Book: CADTH Canadian Drug Expert Committee Final Recommendation Mifepristone and Misoprostol . 18 April 2017 . 30512906 . Canadian Agency for Drugs and Technologies in Health . CADTH Common Drug Reviews . 19 April 2019 . 28 August 2021 . https://web.archive.org/web/20210828172922/https://www.ncbi.nlm.nih.gov/books/NBK534607/ . live .
  39. Bhatti KZ, Nguyen AT, Stuart GS . Medical abortion reversal: science and politics meet . American Journal of Obstetrics and Gynecology . 218 . 3 . 315.e1–315.e6 . March 2018 . 29141197 . 10.1016/j.ajog.2017.11.555 . 205373684 .
  40. News: As controversial 'abortion reversal' laws increase, researcher says new data shows protocol can work . . subscription . 23 April 2018. 4 May 2018. https://web.archive.org/web/20180504011657/https://www.washingtonpost.com/news/to-your-health/wp/2018/04/03/as-controversial-abortion-reversal-laws-multiply-researcher-says-new-data-shows-it-can-work-critics-are-still-skeptical/. live.
  41. News: California Board of Nursing Sanctions Unproven Abortion 'Reversal' (Updated) - Rewire. 23 November 2017. Rewire. 1 December 2017. https://web.archive.org/web/20171201034343/https://rewire.news/article/2017/08/17/california-board-nursing-sanctions-unproven-abortion-reversal/. live.
  42. News: Controversial 'Abortion Reversal' Regimen Is Put To The Test . NPR . 22 March 2019 . 19 April 2019 . Gordon M . 18 April 2019 . https://web.archive.org/web/20190418231735/https://www.npr.org/sections/health-shots/2019/03/22/688783130/controversial-abortion-reversal-regimen-is-put-to-the-test . live .
  43. News: Gordon M. 5 December 2019. Safety Problems Lead To Early End For Study Of 'Abortion Pill Reversal'. NPR. 12 December 2019. 6 December 2019. https://web.archive.org/web/20191206191742/https://www.npr.org/sections/health-shots/2019/12/05/785262221/safety-problems-lead-to-early-end-for-study-of-abortion-pill-reversal. live.
  44. Book: Nuclear Receptors as Drug Targets: Design and Biological Evaluation of Small Molecule Modulators of Nuclear Receptor Action. 2006. 978-0-549-70288-7. 46–.
  45. Gallagher P, Young AH . Mifepristone (RU-486) treatment for depression and psychosis: a review of the therapeutic implications . Neuropsychiatr Dis Treat . 2 . 1 . 33–42 . March 2006 . 19412444 . 2671735 .
  46. Book: Loose DS, Stancel GM . 2006 . Estrogens and Progestins . Brunton LL, Lazo JS, Parker KL . Goodman & Gilman's The Pharmacological Basis of Therapeutics . 11th . 1541–1571 . New York . McGraw-Hill . 978-0-07-142280-2.
  47. Book: Schimmer BP, Parker KL . 2006 . Adrenocorticotropic Hormone; Adrenocortical Steroids and Their Synthetic Analogs; Inhibitors of the Synthesis and Actions of Adrenocortical Hormones . Brunton LL, Lazo JS, Parker KL . Goodman & Gilman's The Pharmacological Basis of Therapeutics . 11th . 1587–1612 . New York . McGraw-Hill . 978-0-07-142280-2.
  48. Fiala C, Gemzel-Danielsson K . Review of medical abortion using mifepristone in combination with a prostaglandin analogue . Contraception . 74 . 1 . 66–86 . July 2006 . 16781264 . 10.1016/j.contraception.2006.03.018 .
  49. Heikinheimo O, Kekkonen R, Lähteenmäki P . The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action . Contraception . 68 . 6 . 421–6 . December 2003 . 14698071 . 10.1016/S0010-7824(03)00077-5 .
  50. Brogden RN, Goa KL, Faulds D . Mifepristone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential . Drugs . 45 . 3 . 384–409 . March 1993 . 7682909 . 10.2165/00003495-199345030-00007 . 195691895 .
  51. Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM . 2005 . Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications . Hum Reprod Update . 11 . 3 . 293–307 . 15790602 . 10.1093/humupd/dmi002. free . doi .
  52. Web site: Exelgyn Laboratories . February 2006 . Mifegyne UK Summary of Product Characteristics (SPC) . 9 March 2007 . dead . https://web.archive.org/web/20070928060430/http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=617 . 28 September 2007 .
  53. Web site: Danco Laboratories . 19 July 2005 . Mifeprex U.S. prescribing information . 9 March 2007 . https://web.archive.org/web/20051211142330/http://www.earlyoptionpill.com/pdfs/prescribing071905.pdf. dead . 11 December 2005.
  54. Book: Baulieu ÉÉ . 1985. RU 486: An antiprogestin steroid with contragestive activity in women. Baulieu ÉÉ, Segal SJ . The antiprogesin steroid RU 486 and human fertility control (Proceedings of a conference on the antiprogestational compound RU 486, held October 23–25, 1984, in Bellagio, Italy). New York. Plenum Press. 1–25. 978-0-306-42103-7.
    Book: Baulieu ÉÉ . 1985. Contragestion by antiprogestin: a new approach to human fertility control. Abortion: medical progress and social implications (Symposium held at the Ciba Foundation, London, 27–29 November 1984). Ciba Foundation Symposium. 115. London. Pitman. 192–210. 978-0-272-79815-7. 3849413. 10.1002/9780470720967.ch15.
    Baulieu EE . Contragestion with RU 486: a new approach to postovulatory fertility control . Acta Obstetricia et Gynecologica Scandinavica Supplement . 149 . S149 . 5–8 . January 1989 . 2694738 . 10.1111/j.1600-0412.1989.tb08041.x . 723825 .
    News: Greenhouse S. 12 February 1989. A new pill, a fierce battle. The New York Times Magazine. SM22. subscription . live. https://web.archive.org/web/20170901111424/http://www.nytimes.com/1989/02/12/magazine/a-new-pill-a-fierce-battle.html. 1 September 2017.
    Palca J . The pill of choice? . Science . 245 . 4924 . 1319–23 . September 1989 . 2781280 . 10.1126/science.2781280 . 1989Sci...245.1319P . 1704254 .
    Baulieu EE . Contragestion and other clinical applications of RU 486, an antiprogesterone at the receptor . Science . 245 . 4924 . 1351–7 . September 1989 . 2781282 . 10.1126/science.2781282 . 1989Sci...245.1351B . 1704267 .
    Baulieu EE . RU-486 as an antiprogesterone steroid. From receptor to contragestion and beyond . JAMA . 262 . 13 . 1808–14 . October 1989 . 2674487 . 10.1001/jama.262.13.1808 .
    Bonner S. July 1991. Drug of choice. SPIN. 7. 4. 55–56, 88. 0886-3032. live. https://web.archive.org/web/20160512194531/https://books.google.com/books?id=wbkGT02oWs4C&pg=PA55. 12 May 2016.
    Book: Baulieu EE, Rosenblum M. 15 November 1991. The "abortion pill": RU-486: a woman's choice (translation of: 'Génération pilule). New York. Simon & Schuster. 978-0-671-73816-7. 18, 26–28. live. https://web.archive.org/web/20160527195325/https://books.google.com/books?ei=0BRFUP-YE5SC8ASL3IEQ&id=pC1pZDcibsUC&pg=PA27&vq=contragestion. 27 May 2016.
    News: Beck J. 2 January 1992. RU-486 pill adds a new dimension to the abortion debate. Chicago Tribune. 25. live. https://web.archive.org/web/20130218151716/http://articles.chicagotribune.com/1992-01-02/news/9201010286_1_ru-486-so-called-abortion-pill-abortion-debate. 18 February 2013.
    News: Chesler E. 31 July 1992. RU-486: we need prudence, not politics. The New York Times. A27. subscription . live. https://web.archive.org/web/20160304063117/http://www.nytimes.com/1992/07/31/opinion/ru-486-we-need-prudence-not-politics.html. 4 March 2016.
    Book: Baulieu ÉÉ. 13 April 1993. 1993: RU 486—a decade on today and tomorrow. Benet LZ, Brown SS, Dorflinger L, Donaldson MS. Clinical applications of mifepristone (RU 486) and other antiprogestins; assessing the science and recommending a research agenda; (Committee on Anti-progestins: Assessing the Science; Division of Health Promotion and Disease Prevention; Institute of Medicine). Washington, D.C.. National Academy Press. 71–119. 978-0-309-04949-8. http://www.nap.edu/openbook.php?record_id=2203&page=98. live. https://web.archive.org/web/20130327101237/http://www.nap.edu/catalog.php?record_id=2203. 27 March 2013. 10.17226/2203. 25144090.
    Baulieu ÉÉ . RU486: a compound that gets itself talked about . Hum. Reprod. . 9 . Suppl 1 . 1–6 . June 1994 . 7962455 . 10.1093/humrep/9.suppl_1.1 .
    Book: Baulieu ÉÉ. 1997. Innovative procedures in family planning. Johannisson E, Kovács L, Resch BA, Bruyniks NP. Assessment of research and service needs in reproductive health in Eastern Europe — concerns and commitments. Proceedings of a workshop organized by the ICRR and the WHO Collaborating Centre on Research in Human Reproduction in Szeged, Hungary, 25–27 October 1993. New York. Parthenon Publishing. 51–60. 978-1-85070-696-0. https://books.google.com/books?id=fPS5Kx6YkeQC&pg=PA53. live. https://web.archive.org/web/20160503110848/https://books.google.com/books?id=fPS5Kx6YkeQC&pg=PA53. 3 May 2016.
    Book: 2008. contragestive. The American Heritage medical dictionary. Boston. Houghton Mifflin. 978-0-618-94725-6. 124. https://books.google.com/books?id=kT7ykAhh3fsC&q=contragestive&pg=PA124. 9 October 2020. 29 June 2022. https://web.archive.org/web/20220629032702/https://books.google.com/books?id=kT7ykAhh3fsC&q=contragestive&pg=PA124. live.
    adj. Capable of preventing gestation, either by preventing implantation or by causing the uterine lining to shed after implantation. —n. A contragestive drug or agent.
    Book: Ammer C. 2009. contragestive. The encyclopedia of women's health. 6th. New York. Facts On File. 978-0-8160-7407-5. 124–125. https://books.google.com/books?id=_MRDimrELCIC&q=contragestive&pg=PA124. 9 October 2020. 29 June 2022. https://web.archive.org/web/20220629032703/https://books.google.com/books?id=_MRDimrELCIC&q=contragestive&pg=PA124. live.
    Also contragestant, abortion pill. A substance called mifepristone, or RU-486, which was developed by Dr. Etienne Baulieu and the Roussel-Uclaf company. The contragestive blocks progesterone receptors in the endometrium (uterine lining), preventing its buildup by progesterone; hence the uterus cannot sustain a pregnancy. It does not prevent fertilization or implantation, so technically it is an ABORTIFACIENT rather than a contraceptive.
  55. Heikinheimo O . Clinical pharmacokinetics of mifepristone . Clin Pharmacokinet . 33 . 1 . 7–17 . July 1997 . 9250420 . 10.2165/00003088-199733010-00002 . 25101911 .
  56. Wang J, Chen J, Wan L, Shao J, Lu Y, Zhu Y, Ou M, Yu S, Chen H, Jia L . Synthesis, spectral characterization, and in vitro cellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486) . AAPS J . 16 . 2 . 289–98 . March 2014 . 24442753 . 3933578 . 10.1208/s12248-013-9559-2 .
  57. Book: The "abortion Pill": RU-486, a Woman's Choice. 978-0-671-73816-7. Baulieu EE, Rosenblum M. 1991. Simon & Schuster . 20 February 2022. 29 June 2022. https://web.archive.org/web/20220629032703/https://books.google.com/books?id=pC1pZDcibsUC&q=%C3%89tienne-%C3%89mile+Baulieu+mifepristone. live.
  58. Book: Reproductive Medicine for Clinical Practice: Medical and Surgical Aspects. 978-3-319-78009-2. Schenker JG, Sciarra JJ, Mettler L, Genazzani AR, Birkhaeuser M. 29 September 2018. Springer . 4 March 2022. 29 June 2022. https://web.archive.org/web/20220629032703/https://books.google.com/books?id=RuJwDwAAQBAJ&dq=%C3%89tienne-%C3%89mile+Baulieu+mifepristone&pg=PA148. live.
  59. Book: Baulieu ÉÉ, Rosenblum M . 1991 . The "abortion pill": RU-486, a woman's choice . New York . Simon & Schuster . 978-0-671-73816-7 .
    Book: Lader L . 1991 . RU 486: the pill that could end the abortion wars and why American women don't have it . Reading . Addison-Wesley . 978-0-201-57069-4 .
    Book: Villaran G . RU 486 . 155–190 . Schlegelmilch, Bodo B . 1998 . Marketing ethics: an international perspective . London . Thomson Learning . 978-1-86152-191-0.
    Ulmann A . The development of mifepristone: a pharmaceutical drama in three acts . Journal of the American Medical Women's Association . 55 . 3 Suppl . 117–20 . 2000 . 10846319 .
  60. Teutsch G . RU 486 development . Science . 246 . 4933 . 985 . November 1989 . 2587990 . 10.1126/science.2587990 . 41144964 .
    Cherfas J . Dispute surfaces over paternity of RU 486 . Science . 246 . 4933 . 994 . November 1989 . 2587988 . 10.1126/science.2587988 . 1989Sci...246..994C .
    Philibert D, Teutsch G . RU 486 development . Science . 247 . 4943 . 622 . February 1990 . 2300819 . 10.1126/science.2300819 . 1990Sci...247..622P .
    10.1038/scientificamerican0690-42 . Ulmann A, Teutsch G, Philibert D . June 1990 . RU 486 . Scientific American. 262 . 6 . 42–8 . 2343294.
    Book: Teutsch G, Deraedt R, Philibert D . 1993 . Mifepristone . 1–43 . Lednicer D . Chronicles of drug discovery, Vol. 3 . Washington, DC . American Chemical Society . 978-0-8412-2523-7 . https://archive.org/details/chroniclesofdrug0000unse/page/1 .
    Teutsch G, Philibert D . History and perspectives of antiprogestins from the chemist's point of view . Human Reproduction . 9 . Suppl 1 . 12–31 . June 1994 . 7962457 . 10.1093/humrep/9.suppl_1.12 .
    Book: 2007 . Mifepristone . 2307–2310 . Sittig M . Pharmaceutical manufacturing encyclopedia . 3rd . Norwich, NY . William Andrew Publishing . 978-1-60119-339-1.
    US . 4386085 . 31 May 1983 . Teutsch JG, Costerousse G, Philibert D Deraedt R . Novel steroids . Roussel Uclaf . . .
  61. News: Eder R . 20 April 1982 . Birth control: 4-day pill is promising in early test . The New York Times . C1 . live . https://web.archive.org/web/20160625131822/http://www.nytimes.com/1982/04/20/science/birth-control-4-day-pill-is-promising-in-early-test.html?&pagewanted=all . 25 June 2016 .
    Herrmann W, Wyss R, Riondel A, Philibert D, Teutsch G, Sakiz E, Baulieu EE . [The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy] . Comptes Rendus de l'Académie des Sciences, Série III . 294 . 18 . 933–8 . May 1982 . 6814714 .
  62. News: Kolata G . 24 September 1988 . France and China allow sale of a drug for early abortion . The New York Times . A1 . subscription . live . https://web.archive.org/web/20170901111410/http://www.nytimes.com/1988/09/24/us/france-and-china-allow-sale-of-a-drug-for-early-abortion.html . 1 September 2017 .
  63. News: . A1 . Greenhouse S . 27 October 1988 . Drug maker stops all distribution of abortion pill . live . https://web.archive.org/web/20160305014315/http://www.nytimes.com/1988/10/27/us/drug-maker-stops-all-distribution-of-abortion-pill.html . 5 March 2016 .
  64. News: Greenhouse S . 29 October 1988 . France ordering company to sell its abortion drug . The New York Times . A1 . live . https://web.archive.org/web/20160304235250/http://www.nytimes.com/1988/10/29/world/france-ordering-company-to-sell-its-abortion-drug.html . 4 March 2016 .
  65. Smith W . September 1991 . Great Britain second country to allow use of RU-486 . Plan Parent Eur . 20. 2 . 20 . 12284548.
  66. December 1992 . RU 486 licensed in Sweden . IPPF Med Bull . 26 . 6 . 6 . 12346922.
  67. News: . Nazi link may keep RU-486 out . Peyser A . 2 July 1992 . 5, 18.
  68. News: Newman B . 22 February 1993 . Drug dilemma: among those wary of abortion pill is maker's parent firm; Germany's Hoechst is facing pressure from Clinton to sell RU-486 in U.S. . The Wall Street Journal . A1.
    News: Associated Press . 16 April 1993 . F.D.A. says company delays abortion pill . The New York Times . A14 . live . https://web.archive.org/web/20160803201914/http://www.nytimes.com/1993/04/16/us/fda-says-company-delays-abortion-pill.html . 3 August 2016 .
    News: Jouzaitis C . 17 October 1994 . Abortion pill battle surprises French firm . Chicago Tribune . 1 (Business) . dead . https://web.archive.org/web/20130218193337/http://pqasb.pqarchiver.com/chicagotribune/access/24140469.html?dids=24140469%3A24140469&FMT=ABS&FMTS=ABS%3AFT . 18 February 2013 .
  69. News: The History of Mifepristone. Reproductive Health Access Project. April 18, 2023. June 13, 2024.
  70. News: Persistence Brought Abortion Pill to U.S.. Bernstein S . Los Angeles. November 5, 2000. June 13, 2024.
  71. News: Seelye KQ . 17 May 1994 . Accord opens way for abortion pill in U.S. in 2 years . The New York Times . A1 . live . https://web.archive.org/web/20160803200331/http://www.nytimes.com/1994/05/17/us/accord-opens-way-for-abortion-pill-in-us-in-2-years.html?&pagewanted=all . 3 August 2016 .
  72. Simonds W, Ellertson C, Springer K, Winikoff B . Abortion, revised: participants in the U.S. clinical trials evaluate mifepristone . Social Science & Medicine . 46 . 10 . 1313–1323 . May 1998 . 9665563 . 10.1016/S0277-9536(97)10063-6 .
  73. Web site: DANCO LABORATORIES LIMITED v. The Washington Post Company, Intervenor-Appellant. (2000). Supreme Court, Appellate Division, First Department, New York. . July 27, 2000 . June 13, 2024 . caselaw.findlaw.com.
  74. News: Moore SD, Kamm T, Fleming C . 11 December 1996 . Hoechst to seek rest of Roussel-Uclaf; expected $3.04 billion offer would add to the wave of drug-sector linkups . The Wall Street Journal . A3.
    News: Marshall M . 11 December 1996 . Hoechst offers to pay $3.6 billion for rest of Roussel. The Wall Street Journal . A8.
    News: . 11 December 1996 . Hoechst to buy rest of Roussel . . D4 . subscription . live . https://web.archive.org/web/20160625124549/http://www.nytimes.com/1996/12/11/business/hoechst-to-buy-rest-of-roussel.html . 25 June 2016 .
  75. News: Bloomberg News. 9 April 1997. Pill for abortion ends production. The New York Times. D2. live . subscription . https://web.archive.org/web/20160625134359/http://www.nytimes.com/1997/04/09/business/pill-for-abortion-ends-production.html. 25 June 2016.
    News: Jouzaitis C . 9 April 1997 . Abortion pill maker bows to boycott heat; German firm gives up RU-486 patent; little impact likely in U.S. . Chicago Tribune . 4 . dead . https://web.archive.org/web/20130218193350/http://pqasb.pqarchiver.com/chicagotribune/access/11401570.html?dids=11401570%3A11401570&FMT=ABS&FMTS=ABS%3AFT . 18 February 2013 .
    News: Lavin D . 9 April 1997 . Hoechst will stop making abortion pill . The Wall Street Journal . A3.
    18 April 1997 . Roussel-Uclaf to transfer RU 486 rights . Reprod Freedom News . 6 . 7 . 8 . 12292550.
    Dorozynski A . 19 April 1997 . Boycott threat forces French company to abandon RU486 . BMJ . 314. 7088 . 1150 . 9146386 . 2126515 . 10.1136/bmj.314.7088.1145m.
  76. News: ABORTION PILL'S U.S. SPONSOR SUING HUNGARIAN DRUG FIRM. 1997-06-12. . subscription . 2024-06-13. en-US. 0190-8286.
  77. Web site: 4 November 2009. List of mifepristone approval. New York. Gynuity Health Projects. dead. https://web.archive.org/web/20110726135110/http://gynuity.org/downloads/mife_approval_2009_list.pdf. 26 July 2011. 4 May 2018.
    Web site: 4 November 2009. Map of mifepristone approval. New York. Gynuity Health Projects. 11 June 2010. dead. https://web.archive.org/web/20110726135136/http://gynuity.org/downloads/Mife_approval_2009_map.pdf. 26 July 2011.
  78. News: Kolata G . 29 September 2000 . U.S. approves abortion pill; drug offers more privacy and could reshape debate . The New York Times . A1 . live . https://web.archive.org/web/20170804114939/http://www.nytimes.com/2000/09/29/us/us-approves-abortion-pill-drug-offers-more-privacy-and-could-reshape-debate.html . 4 August 2017 .
  79. Web site: North A . 20 August 2019. The first generic abortion pill just hit the US market. Here's what that means.. 14 July 2020. Vox. 13 July 2020. https://web.archive.org/web/20200713184519/https://www.vox.com/identities/2019/8/20/20750226/abortion-pill-mifepristone-pregnancy-genbiopro-mifeprex-generic. live.
  80. Book: Hussein J, McCaw-Binns A, Webber R . Maternal and perinatal health in developing countries . 2012 . CABI . Wallingford, Oxfordshire . 978-1-84593-746-1 . 104. live. https://web.archive.org/web/20170908184336/https://books.google.com/books?id=BlRMxAOSeNIC&pg=PA104. 8 September 2017.
  81. Winikoff B, Sheldon W . Use of medicines changing the face of abortion . International Perspectives on Sexual and Reproductive Health . 38 . 3 . 164–6 . September 2012 . 23018138 . 10.1363/3816412 . free . doi .
  82. excluding Alabama, California, Connecticut, Washington, D.C., Florida, Georgia, Hawaii, Illinois, Kentucky, Louisiana, Massachusetts, Maryland, Nebraska, Nevada, New Hampshire, Rhode Island, Tennessee, and Wisconsin
  83. Berg C, Cook DA, Gamble SB, Hall LR, Hamdan S, Parker WY, Pazol K, Zane SB . Division of Reproductive Health . 25 February 2011 . [<!-- Official URL --> https://www.cdc.gov/mmwr/pdf/ss/ss6001.pdf Abortion surveillance — United States, 2007 ]. MMWR Surveill Summ . 60 . 1 . 1–44 . 21346710 . live . https://web.archive.org/web/20110406111142/http://www.cdc.gov/mmwr/pdf/ss/ss6001.pdf . 6 April 2011 .
  84. Jones RK, Kooistra K . March 2011 . Abortion incidence and access to services in the United States, 2008 . Perspect Sex Reprod Health . 43 . 1 . 41–50 . 10.1363/4304111 . 21388504 . 2045184 . live . https://web.archive.org/web/20110927030139/http://www.guttmacher.org/pubs/journals/4304111.pdf . 27 September 2011 .
    News: Stein R . 11 January 2011 . Decline in U.S. abortion rate stalls . . A3 . subscription . live . https://web.archive.org/web/20160304091118/http://www.washingtonpost.com/wp-dyn/content/article/2011/01/11/AR2011011107331.html . 4 March 2016 .
  85. Fjerstad M, Trussell J, Sivin I, Lichtenberg ES, Cullins V . Rates of serious infection after changes in regimens for medical abortion . The New England Journal of Medicine . 361 . 2 . 145–51 . July 2009 . 19587339 . 3568698 . 10.1056/NEJMoa0809146 .
    News: Allday E . 9 July 2009 . Change cuts infections linked to abortion pill . San Francisco Chronicle . A1 . 29 June 2022 . 14 April 2020 . https://web.archive.org/web/20200414180754/http://www.sfgate.com/cgi-bin/article.cgi?file=%2Fc%2Fa%2F2009%2F07%2F09%2FMNJE18L6TR.DTL . live .
  86. Jones RK, Jerman J. March 2017. Abortion Incidence and Service Availability In the United States 2014. Perspectives on Sexual and Reproductive Health. 49-1. 1. 17–27. 10.1363/psrh.12015. 28094905. 5487028. 16 October 2017. 17 October 2017. https://web.archive.org/web/20171017044955/https://www.guttmacher.org/journals/psrh/2017/01/abortion-incidence-and-service-availability-united-states-2014. live.
  87. Web site: 26 April 2017. Medication Abortion. 22 September 2021. Guttmacher Institute. 21 September 2021. https://web.archive.org/web/20210921114046/https://www.guttmacher.org/evidence-you-can-use/medication-abortion. live.
  88. Web site: Medication Abortion Now Accounts for More Than Half of All US Abortions . Jones RK . . 24 February 2022 . 10 May 2022 . 10 May 2022 . https://web.archive.org/web/20220510232112/https://www.guttmacher.org/article/2022/02/medication-abortion-now-accounts-more-half-all-us-abortions . live .
  89. Web site: Vilain A . December 2009 . Voluntary terminations of pregnancies in 2007 . DREES, Ministry of Health . 9 June 2010 . dead . https://web.archive.org/web/20100331210210/http://www.sante.gouv.fr/drees/etude-resultat/er-pdf/er713.pdf . 31 March 2010 .
  90. Web site: Department of Health . 25 May 2010 . Abortion statistics, England and Wales: 2009 . Department of Health (United Kingdom) . 9 June 2010 . live . https://web.archive.org/web/20101115103350/http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsStatistics/DH_116039 . 15 November 2010 .
  91. Web site: ISD Scotland . 25 May 2010 . Abortion Statistics, year ending December 2009 . Information Services Division (ISD), NHS National Services Scotland . 9 June 2010 . 21 April 2010 . https://web.archive.org/web/20100421091655/http://www.isdscotland.org/isd/1918.html . live .
  92. Web site: National Board of Health and Welfare, Sweden . 12 May 2010 . Induced Abortions 2010 . National Board of Health and Welfare, Sweden . 9 June 2010 . dead . https://web.archive.org/web/20110727140340/http://www.socialstyrelsen.se/Lists/Artikelkatalog/Attachments/18031/2010-5-12.pdf . 27 July 2011 .
  93. Web site: FDA Approves Mifepristone for the Termination of Early Pregnancy. FDA . 2000 . 27 April 2009. http://webarchive.loc.gov/all/20060910174529/http%3A//www%2Efda%2Egov/bbs/topics/news/NEW00737%2Ehtml . 10 September 2006 .
  94. Web site: The abortion pill Mifegyne tested for adverse reactions . Danish Medicines Agency . 27 July 2005 . 20 September 2006 .
  95. Web site: FDA approval letter for Mifepristone. FDA . 28 September 2000. 16 September 2006. http://webarchive.loc.gov/all/20011116012552/http%3A//www%2Efda%2Egov/cder/foi/appletter/2000/20687appltr%2Ehtm . 16 November 2001 .
  96. Web site: Medication Abortion in the United States: Mifepristone Fact Sheet . 2005 . Gynuity Health Projects . dead . https://web.archive.org/web/20070924010831/http://www.gynuity.org/documents/mife_fact_sheet.pdf . 24 September 2007 .
  97. Klitsch M . Antiprogestins and the abortion controversy: a progress report. Fam Plann Perspect. NovemberDecember 1991. 23. 6. 1786809. 275–82. 10.2307/2135779. 2135779.
  98. News: . U.S. Grabs Banned Abort Pill From an Activist here . Garcilazo M . 2 July 1992 . 5.
  99. News: Gibbs N . The Pill Arrives. Cnn.com. 2 October 2000. 20 September 2006. live. https://web.archive.org/web/20061006031705/http://www.cnn.com/ALLPOLITICS/time/2000/10/09/pill.html. 6 October 2006.
  100. News: Lewin T . Clinical Trials Giving Glimpse of Abortion Pill. The New York Times. 30 January 1995. 20 September 2006. live. https://web.archive.org/web/20071128093915/http://query.nytimes.com/gst/fullpage.html?res=990CE6D9173DF933A05752C0A963958260. 28 November 2007.
  101. News: Lewin T . Lawsuits' Settlement Brings New Hope for Abortion Pill. The New York Times. 13 November 1997. 16 September 2006. live. https://web.archive.org/web/20070210071338/http://query.nytimes.com/gst/fullpage.html?sec=health. 10 February 2007.
  102. Web site: Lerner S . RU Pissed Off Yet?. The Village Voice. August 2000. 16 September 2006. dead. https://web.archive.org/web/20061107151729/http://www.villagevoice.com/news/0035%2Clerner%2C17757%2C1.html. 7 November 2006.
  103. Web site: Danco Laboratories. 29 March 2016. Mifeprex prescribing information. U.S. Food and Drug Administration (FDA). live. https://web.archive.org/web/20160330220744/http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf. 30 March 2016.
  104. Web site: American Congress of Obstetricians and Gynecologists. 30 March 2016. ACOG Statement on Medication Abortion. Washington, D.C.. ACOG. 7 April 2016. live. https://web.archive.org/web/20160403194210/http://www.acog.org/About-ACOG/News-Room/Statements/2016/ACOG-Statement-on-Medication-Abortion. 3 April 2016.
  105. Web site: Postmarket Drug Safety Information for Patients and Providers. 30 March 2016. US Food & Drug Administration. 16 October 2017. 3 April 2016. https://web.archive.org/web/20160403194206/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111323.htm. live.
  106. Web site: The Supreme Court hands down its first anti-abortion decision of the Amy Coney Barrett era . Millhauser I . 13 January 2021 . 13 January 2021 . . 13 January 2021 . https://web.archive.org/web/20210113003935/https://www.vox.com/22227912/supreme-court-anti-abortion-amy-coney-barrett-era-fda-american-college-sonia-sotomayor-john-roberts . live .
  107. Web site: FDA relaxes restrictions on abortion pill . NPR.org . 17 December 2021 . 17 December 2021 . https://web.archive.org/web/20211217001550/https://www.npr.org/2021/12/16/1064951611/today-is-the-fda-s-deadline-to-complete-a-review-of-its-rules-for-abortion-pill . live .
  108. News: Justice Dept.: Postal Service may deliver abortion pills in any state . . subscription . 5 January 2023 . 4 January 2023 . https://web.archive.org/web/20230104235818/https://www.washingtonpost.com/national-security/2023/01/04/abortion-pills-mailed-legal/ . live .
  109. News: Abortion Pills to Be Available More Widely Under New FDA Rules - Patients will be able to get the drug, called mifepristone, from bricks-and-mortar pharmacies . Whyte LE . . 3 January 2023 . 7 January 2023 . 7 January 2023 . https://web.archive.org/web/20230107011153/https://www.wsj.com/articles/abortion-pills-to-be-available-more-widely-under-new-fda-rules-11672789765 . live .
  110. News: Smith T . Tina Smith . I Hope to Repeal an Arcane Law That Could Be Misused to Ban Abortion Nationwide . April 2, 2024 . . live . https://archive.today/20240402124934/https://www.nytimes.com/2024/04/02/opinion/comstock-act-abortion-repeal.html . April 2, 2024 . April 2, 2024 .
  111. Web site: Belluck P . New Lawsuit Challenges State Bans on Abortion Pills . The New York Times . 25 January 2023 . 19 March 2023 . 25 January 2023 . https://web.archive.org/web/20230125191039/https://www.nytimes.com/2023/01/25/health/abortion-pills-ban-genbiopro.html . live .
  112. Grossi P, O'Connor D . FDA preemption of conflicting state drug regulation and the looming battle over abortion medications . The Journal of Law and the Biosciences . 2023 . 10 . 1 . lsad005 . 10.1093/jlb/lsad005 . 36938304 . 10017072 .
  113. News: Horti S . Abortion pills banned in Wyoming as Texas judge considers nationwide decision . . 18 March 2023 . 1 April 2023 . 27 March 2023 . https://web.archive.org/web/20230327173353/https://www.bbc.com/news/world-us-canada-64998920 . live .
  114. News: Wyoming Becomes First State to Outlaw the Use of Pills for Abortion . . 18 March 2023 . 2 April 2023 . 2 April 2023 . https://web.archive.org/web/20230402023506/https://www.nytimes.com/2023/03/17/us/wyoming-abortion-pills-ban.html . live .
  115. News: Judge in Washington orders feds to keep abortion pill access . 8 April 2023 . . 7 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408000944/https://apnews.com/article/washington-abortion-pills-lawsuit-fda-1857d1a4fd356c61ad76e00621e93b44 . live .
  116. News: Ables K, Rosenzweig-Ziff D . Who is Thomas Rice, the Washington judge who ruled mifepristone is safe? . subscription . 8 April 2023 . . 8 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408083946/https://www.washingtonpost.com/politics/2023/04/08/washington-judge-abortion-thomas-rice/ . live .
  117. News: Wax-Thibodeaux E . 2024-05-13 . Louisiana moves to make abortion pills 'controlled dangerous substances' . subscription . 2024-05-13 . The Washington Post.
  118. "Louisiana governor signs bill making two abortion drugs controlled dangerous substances" Kevin McGill May 24, 2024 AP News https://apnews.com/article/abortion-pills-louisiana-controlled-dangerous-substances-0984bfed536a5110997dd9c8264bf9e3
  119. News: https://archive.today/20230408075712/https://www.nytimes.com/2023/04/07/health/abortion-pills-ruling-texas.html . Belluck P . 8 April 2023. Texas Judge Invalidates FDA Approval of the Abortion Pill Mifepristone . The New York Times . 7 April 2023 . 7 April 2023.
  120. News: Unanimous Supreme Court preserves access to widely used abortion medication. Sherman M . Associated Press. June 13, 2024. June 13, 2024.
  121. News: Supreme Court rejects bid to restrict access to abortion pill. Hurley L . NBC News. June 13, 2024. June 13, 2024.
  122. Food and Drug Administration et al. v. Alliance for Hippocratic Medicine et al. . 602. U.S. . 23-235 . United States Supreme Court. 13 June 2004 . https://www.supremecourt.gov/opinions/23pdf/23-235_n7ip.pdf .
  123. Web site: Woodcock J . Testimony on RU-486 . Committee on Government Reform, House of Representatives . FDA . 12 May 2006 . 19 August 2006 . https://web.archive.org/web/20060927090806/https://www.fda.gov/ola/2006/mifepristone0517.html . 27 September 2006.
  124. Christin-Maitre S, Bouchard P, Spitz IM . Medical termination of pregnancy . The New England Journal of Medicine . 342 . 13 . 946–56 . March 2000 . 10738054 . 10.1056/NEJM200003303421307 .
  125. Stojnić J, Ljubić A, Jeremić K, Radunović N, Tulić I, Bosković V, Dukanac J . [Medicamentous abortion with mifepristone and misoprostol in Serbia and Montenegro] . Vojnosanitetski Pregled . 63 . 6 . 558–63 . June 2006 . 16796021 . 10.2298/VSP0606558S . free . doi .
  126. Web site: List of Mifepristone Approvals . Gynuity Health Projects . March 2017 . 28 September 2017 . https://web.archive.org/web/20170926164348/http://gynuity.org/resources/read/llist-of-mifepristone-approval-en . 26 September 2017 . dead .
  127. News: 31 July 2009 . Abortion pill approved in Italy . BBC News . 31 July 2009 . 8 September 2017 . https://web.archive.org/web/20170908184336/http://news.bbc.co.uk/1/hi/world/europe/8178152.stm . live .
  128. News: Abortion pill sparks bitter protest. The Budapest Times. 19 September 2005. 16 September 2006. live. https://web.archive.org/web/20070111100214/http://www.budapesttimes.hu/index.php?art=1077. 11 January 2007.
  129. Web site: Medicines for Termination of Pregnancy Services . Hoey AM . Health Service Executive. Primary Care Reimbursement Service . Dublin, Ireland . 20 December 2018 . 28 June 2022 . 2 April 2022 . https://web.archive.org/web/20220402045614/https://www.hse.ie/eng/staff/pcrs/circulars/pharmacy/pharmacy-circular-040-2018.pdf . live .
  130. News: Green PS . A Rocky Landfall for a Dutch Abortion Boat. The New York Times. 24 June 2003. 16 September 2006. live. https://web.archive.org/web/20070210071338/http://query.nytimes.com/gst/fullpage.html?sec=health. 10 February 2007.
  131. Web site: Linepharma. 7 November 2014. Mifepristone Linepharma Summary of Product Characteristics (SPC). London. Medicines and Healthcare Products Regulatory Agency (MHRA). 14 April 2016. dead. https://web.archive.org/web/20160602234626/http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1452842392219.pdf. 2 June 2016.
  132. Web site: Sun Pharmaceuticals. 4 March 2015. Medabon Summary of Product Characteristics (SPC). London. Medicines and Healthcare Products Regulatory Agency (MHRA). 4 April 2016. dead. https://web.archive.org/web/20160603014327/http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1454653236118.pdf. 3 June 2016.
  133. Web site: Marie Stopes International Australia – Medical Abortion . 2010 . 15 December 2010 . dead . https://web.archive.org/web/20101122164158/http://www.mariestopes.org.au/our-services/women/abortion/medical-abortion . 22 November 2010 .
  134. Web site: Abortion pill – RU486 (mifepristone) . Better Health Channel Victoria . July 2010 . 15 December 2010 . dead . https://web.archive.org/web/20100814183721/http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Abortion_pill_RU486_%28mifepristone%29?open . 14 August 2010 .
  135. Web site: MS Health. 24 December 2014. Mifepristone Linepharma (MS-2 Step) 200 mg tablet product information. Symonston, Australian Capital Territory, Australia. Therapeutic Goods Administration. 4 April 2016. live. https://web.archive.org/web/20170908184336/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2014-PI-01965-1. 8 September 2017.
  136. Web site: MS Health. 12 May 2015. Mifepristone Linepharma 200 mg tablet product information. Symonston, Australian Capital Territory, Australia. Therapeutic Goods Administration. 4 April 2016. 9 September 2017. https://web.archive.org/web/20170909005923/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-02513-1. live.
  137. Sparrow MJ . A woman's choice . The Australian & New Zealand Journal of Obstetrics & Gynaecology . 44 . 2 . 88–92 . April 2004 . 15089829 . 10.1111/j.1479-828X.2004.00190.x . 27365359 .
  138. Baulieu EE, Seidman DS, Hajri S . Mifepristone (RU486) and voluntary termination of pregnancy: enigmatic variations or anecdotal religion-based attitudes? . Human Reproduction . 16 . 10 . 2243–4 . October 2001 . 11574524 . 10.1093/humrep/16.10.2243 . free . doi .
  139. Ulmann A . 2000 . The development of mifepristone: a pharmaceutical drama in three acts . J Am Med Women's Assoc . 55 . 3 Suppl . 117–20 . 10846319.
  140. Wu S . 2000 . Medical abortion in China . J Am Med Women's Assoc . 55 . 3 Suppl . 197–9, 204 . 10846339.
  141. Web site: Family planning in China: RU-486, abortion, and population trends . U.S. Embassy Beijing . 2000 . 14 September 2006 . https://web.archive.org/web/20020311164554/http://www.usembassy-china.org.cn/sandt/ru486.html . dead . 11 March 2002 .
  142. Tsai EM, Yang CH, Lee JN . Medical abortion with mifepristone and misoprostol: a clinical trial in Taiwanese women. J Formos Med Assoc. 2002. 101. 4. 12101864. 277–82.
  143. Ganatra B, Bygdeman M, Nguyen DV, Vu ML, Phan BT . From research to reality: the challenges of introducing medical abortion into service delivery in Vietnam. Reprod Health Matters. 2004. 12. 24. 105–13. 15938163. 10.1016/S0968-8080(04)24022-8. 23303852.
  144. Web site: Medical Abortion-Implications for Africa. Ipas. 2003. 16 September 2006. dead. https://web.archive.org/web/20070928082424/http://www.ipas.org/publications/en/Medical_Abortion/med_ab_africa_web_only_en.pdf.. 28 September 2007.
  145. Hajri S. Medication abortion: the Tunisian experience. Afr J Reprod Health. 2004. 8. 1. 15487615. 63–9. 10.2307/3583307. 3583307. 1807/3883. free.
  146. Web site: Mifepristone can be sold only to approved MTP Centres: Rajasthan State HRC. Indian Express Health Care Management. 2000. dead. https://web.archive.org/web/20120124021131/http://www.expresshealthcaremgmt.com/20040515/oped01.shtml. 24 January 2012.
  147. Web site: Results of the Canadian trials of RU486, the 'Abortion Pill . https://web.archive.org/web/20060621162826/http://www.cbctrust.com/ru486_trials_canada.php . 21 June 2006 . 8 December 2006 .
  148. Web site: RU-486 abortion pill approved by Health Canada. 30 July 2015. live . https://web.archive.org/web/20150731021931/http://www.cbc.ca/news/health/ru-486-abortion-pill-approved-by-health-canada-1.3173515?cmp=rss . 31 July 2015 .
  149. News: Health Canada eases restrictions on abortion pill Mifegymiso . CBC News . 28 April 2018 . 8 May 2018 . https://web.archive.org/web/20180508043809/http://www.cbc.ca/news/health/mifegymiso-abortion-pill-health-canada-1.4391267 . live .
  150. Web site: Medication Abortion. Ibis. 2002. 19 September 2006. live. https://web.archive.org/web/20061104040928/http://www.medicationabortion.com/mifepristone/index.html. 4 November 2006.
  151. Web site: 13 February 2013 . Dedicated emergency contraceptive pills worldwide . dead . https://web.archive.org/web/20160304190311/http://ec.princeton.edu/pills/Dedicated_ECPs.pdf . 4 March 2016 . 4 April 2016 . Office of Population Research, Princeton University . Trussell J, Cleland K . Princeton.
  152. Web site: 2016 . EC pill types and countries of availability, by brand . dead . https://web.archive.org/web/20160405095026/http://www.cecinfo.org/country-by-country-information/status-availability-database/ec-pill-types-and-countries-of-availability-by-brand/ . 5 April 2016 . 4 April 2016 . International Consortium for Emergency Contraception . New York.
  153. Web site: March 2016 . Emergency Contraception: A Last Chance to Prevent Unintended Pregnancy . live . https://web.archive.org/web/20100923040101/http://ec.princeton.edu/questions/ec-review.pdf . 23 September 2010 . 7 April 2016 . Office of Population Research, Princeton University . Trussell J, Raymond E . Princeton.
  154. Web site: Cunningham PC, McCoy L, Ferguson CD . Citizen Petition to the U.S. Food and Drug Administration . Americans United for Life . 28 February 1995 . 20 September 2006 . dead . https://web.archive.org/web/20061003131224/http://www.fnsa.org/v1n3/americans1.html . 3 October 2006 .
  155. News: Talbot M . The Little White Bombshell . The New York Times . 11 July 1999 . 20 September 2006 . subscription . 28 August 2021 . https://web.archive.org/web/20210828172922/https://www.nytimes.com/1999/07/11/magazine/the-little-white-bombshell.html . live .
  156. Web site: Abortion Foes to Boycott Drugs (Altace) Made By RU-486 Manufacturer . The Virginia Pilot . 8 July 1994 . 15 September 2006 . https://archive.today/20080220223236/http://scholar.lib.vt.edu/VA-news/VA-Pilot/issues/1994/vp940708/07080818.htm . dead . 20 February 2008 .
  157. Web site: Guthrie S . Counteroffensive Launched on RU-486 . Christianity Today . 11 June 2001 . 20 September 2006 . live . https://web.archive.org/web/20060920105409/http://www.christianitytoday.com/ct/2001/008/13.58.html . 20 September 2006 .
  158. News: Kolata G . Death at 18 Spurs Debate Over a Pill For Abortion . The New York Times . 24 September 2003 . 20 September 2006 . 28 August 2021 . https://web.archive.org/web/20210828172952/https://www.nytimes.com/2003/09/24/us/death-at-18-spurs-debate-over-a-pill-for-abortion.html . live .
  159. Web site: Allen JL . Abortion debates rock Germany: introduction of abortion pill exacerbates controversy . National Catholic Reporter . 12 February 1999 . 14 September 2006 . https://web.archive.org/web/20050528125020/http://www.findarticles.com/p/articles/mi_m1141/is_15_35/ai_53924378 . dead . 28 May 2005 .
  160. Web site: Catholic and Evangelical students join Muslims in RU-486 fight . Catholic News . 9 February 2006 . 18 September 2006 . dead . https://web.archive.org/web/20061027200522/http://www.cathnews.com/news/602/54.php . 27 October 2006 .
  161. Web site: Death Toll Rises to 11 Women . Australians Against RU-486 . 2006 . 20 September 2006 . dead . https://web.archive.org/web/20060820140044/http://www.aaru486.com.au/index.php?option=com_content&task=view&id=29&Itemid=26 . 20 August 2006 .
  162. https://www.wsj.com/us-news/law/supreme-court-rejects-abortion-pill-challenge-preserving-wide-access-to-drug-f78f3320?st=4qzabwgst2uclm2&reflink=desktopwebshare_permalink Supreme Court Rejects Abortion Pill Challenge, Preserving Wide Access to Drug
  163. Hazra BG, Pore VS . Mifepristone (RU-486), the recently developed antiprogesterone drug and its analogues . J Indian Inst Sci . 2001 . 81 . 287–298 .
  164. Clark K, Ji H, Feltovich H, Janowski J, Carroll C, Chien EK . Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events . Am. J. Obstet. Gynecol. . 194 . 5 . 1391–8 . May 2006 . 16647925 . 10.1016/j.ajog.2005.11.026 .
  165. Taplin ME, Manola J, Oh WK, Kantoff PW, Bubley GJ, Smith M, Barb D, Mantzoros C, Gelmann EP, Balk SP . A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones . BJU Int. . 101 . 9 . 1084–9 . 2008 . 18399827 . 10.1111/j.1464-410X.2008.07509.x . 205538600 .
  166. Web site: Mifepristone - Corcept Therapeutics - AdisInsight . 27 December 2017 . 27 December 2017 . https://web.archive.org/web/20171227235346/http://adisinsight.springer.com/drugs/800001657 . live .
  167. Flexner C . HIV drug development: the next 25 years . Nat Rev Drug Discov . 6 . 12 . 959–66 . December 2007 . 17932493 . 10.1038/nrd2336 . 31261997 .
  168. Tang OS, Ho PC . 2006 . Clinical applications of mifepristone . Gynecol Endocrinol . 22 . 12 . 655–9 . 17162706 . 10.1080/09513590601005946. 23295715 .
  169. Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF . Rapid reversal of psychotic depression using mifepristone . Journal of Clinical Psychopharmacology . 21 . 5 . 516–21 . October 2001 . 11593077 . 10.1097/00004714-200110000-00009 . 3067889 .
  170. Howland RH . Mifepristone as a therapeutic agent in psychiatry . Journal of Psychosocial Nursing and Mental Health Services . 51 . 6 . 11–4 . June 2013 . 23814820 . 10.3928/02793695-20130513-01 .
  171. News: Gard D . Fierce Biotech . 7 May 2014 . Corcept tanks as depression drug comes up short in Phase III . https://web.archive.org/web/20160302191829/http://www.fiercebiotech.com/story/corcept-tanks-depression-drug-comes-short-phase-iii/2014-05-07 . 2 March 2016 .
  172. Soria V, González-Rodríguez A, Huerta-Ramos E, Usall J, Cobo J, Bioque M, Barbero JD, García-Rizo C, Tost M, Monreal JA, Labad J . Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis . Psychoneuroendocrinology . 93 . 8–19 . July 2018 . 29680774 . 10.1016/j.psyneuen.2018.04.012 . 5041081 .
  173. Bou Khalil R, Souaiby L, Farès N . The importance of the hypothalamo-pituitary-adrenal axis as a therapeutic target in anorexia nervosa . Physiology & Behavior . 171 . 13–20 . March 2017 . 28043861 . 10.1016/j.physbeh.2016.12.035 . 6329552 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Mifepristone".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.