The mifepristone (or RU-486) is a synthetic compound steroid used as medicine with antiprogestágenas and antiglucocorticoid properties. It is a receptor antagonist progesterone used as an abortifacient in the early months of pregnancy , and lower doses as an emergency contraceptive in the days after intercourse . 1 2 During the first tests, it was known as RU-38486 or simply RU-486 , its designation in the company Roussel-Uclaf , who designed the pharmacist. . 3 4
Mifepristone is used as an abortifacient in voluntary abortion along with a prostaglandin analog (usually misoprostol ) between the first 7 to 9 weeks of pregnancy (49 to 63 days). 56 Mifepristone is also used to treat brain tumors , endometriosis , fibroids and to induce labor in women pregnant . 7 The drug was initially available in France , and subsequently other countries followed, often in the midst of controversy. It is marketed under the trade names Mefaprix , Zacafemyl , Mifeprex and Mifegyne . It is on the List of Essential Drugs of the World Health Organization . Referring to Fig.
In the presence of progesterone , mifepristone acts as a competitive progesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial antagonist ). Mifepristone is a steroid 10-nor with substituent p – (dimethylamino) phenyl bulky above the plane of the molecule at position 11β responsible for inducing or stabilizing aconformation of receptor inactive, and a substituent propynyl hydrophobic below the plane of the molecule At position 17α which increases its affinity with the progesterone receptor. 9 10 11
In addition to being an antiprogestin, mifepristone is also an antiglucocorticoid and a weak antiandrogen . The relative affinity of mifepristone at the progesterone receptor is more than double that of progesterone, its relative affinity of mifepristone at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of Cortisol ; Its relative affinity at the androgen receptor is less than one-third that of testosterone . It does not bind to either the estrogen receptor or the mineral corticoid receptor . 12
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 for 3 to 4 days and is as effective as an emergency contraceptive as a single 1.5 mg dose of the progestogen levonorgestrel 13
In women, mifepristone at doses greater than or equal to 1 mg / kg antagonizes the endometrial and myometrial effects of progesterone. In humans, an antiglucocorticoid effect is manifested at doses greater than 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. 14 15
In abortive regimens, blocking mifepristone in progesterone receptors directly causes degeneration of the decidua , cervical softening and dilatation , release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins. Decidual induced decomposition mifepristone indirectly leads to a detachment of the trophoblast , resulting in reduced production of hCG by the syncytiotrophoblast , which in turn causes a decrease in progesterone production by the corpus luteum (the pregnancy is dependent on the production Of progesterone by the corpus luteum during the first 9 weeks of gestation – until placental production has increased enough to take the place of progesterone production of the corpus luteum). When mifepristone is followed sequentially by a prostaglandin, 200 mg of mifepristone is (100 mg could be, but 50 mg is not) as effective as 600 mg in the production of a medical abortion. 9 11
In April 1980, as part of a formal research project at Roussel-Uclaf for the development of an antagonist of the glucocorticoid receptor , the chemist Georges Teutsch synthesized mifepristone (RU-38486, the compound number 38,486 by Roussel-Uclaf since 1949 To 1980, shortened to RU-486); Which was also discovered to be a progesterone receptor antagonist . 16 17 In October 1981, the endocrinologist Etienne-Emile Baulieu , a consultant to Roussel-Uclaf, organized tests for use in medical abortions in eleven women in Switzerland by the gynecologist Walter Herrmann at the Cantonal Hospital of the University of Geneva , with Successful results announced on April 19, 1982. 16 18 On October 9, 1987, following a worldwide clinical trial of 20,000 women using mifepristone with a prostaglandin analogue (initially sulprostone or gemeprost , subsequently misoprostol ) for medical abortion, Roussel -Uclaf sought approval in France for use in medical abortions, with the approval announced on September 23, 1988. 16 19
On October 21, 1988, Roussel-Uclaf executives and board of directors voted in favor of pro-abortion protests and the concerns of the majority owner (54.5%) Hoechst AG of Germany, voting 16 to 4 to stop the distribution of mifepristone, which announced on 26 October 1988. 16 20 Two days later, the French government ordered Roussel-Uclaf distribute mifepristone in the interest of public health. 16 21 French Minister of Health Claude Évin explained that: “I could not allow the abortion debate to deprive women of a product that represents a medical breakthrough.” From the moment the Government approved the drug, the RU- Became the moral property of women, not just the property of a pharmaceutical company. ” 16 Followed by the use of 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 Government of France) of $ 48 USD the 600 mg dose. 16
The mifegyne was subsequently approved in Great Britain on 1 July 1991, 22 and in Sweden in September 1992, 23 but until his retirement in late April 1994, the president of Hoechst AG, Wolfgang Hilger, a Catholic devotee , blocked Any further expansion in the availability of mifepristone. 16 24
On May 16, 1994, Roussel-Uclaf announced that it would donate unpaid all medical rights to mifepristone in the United States. To the Population Council , 25 which later licensed mifepristone to Danco Laboratories , a new single-product company immune to pro-boycott boycotts, which gained FDA approval as Mifeprex on September 28, 2000. 26
On April 8, 1997, after buying the remaining 43.5% of the shares of Roussel-Uclaf in early 1997, 27 Hoechst AG ($ 30 USD billion annual revenue) announced the end of its manufacture and sale of Mifegyne ($ 3.44 USD billion annual revenues) and the transfer of all rights for medical use outside the United States to Exelgyn SA, a new company from a single product immune to antiabortion boycotts, whose CEO was the former CEO Roussel-Uclaf, Édouard Sakiz. 28 In 1999, Exelgyn won Mifegyne’s approval in 11 additional countries, and in 28 more countries over the next decade. 29
In Mexico since 2011 it is available under the name of Zacafemyl. 30
The molecule was protected in French patent 2,497,807 ( 9 as January as 1981 ) and European Patent 0,057.115 B1 was obtained on 20 as March as 1985 . In the United States , patent 4,386,085 was obtained on May 31, 1983.
Mifepristone is sold outside the United States by Exelgyn Laboratories as Mifegyne , made in France, and is approved for:
- Medical termination of intrauterine pregnancies up to 49 days ‘ gestation (up to 63 days’ gestation in Great Britain and Sweden)
- Softening and dilation of the cervix prior to mechanical cervical dilation for termination of pregnancy
- Used in combination with gemeprost for termination of pregnancies between 13 and 24 weeks of gestation
- Induction of labor in fetal death in utero. 14
Mifepristone is sold within the United States by Danco Laboratories as Mifeprex , made in China, 31 and is approved by the FDA for termination of intrauterine pregnancies up to 49 days of gestation. Under the FDA-approved regimen, a 600 mg dose is administered by a physician followed by a counseling session. Two days later, one doctor administers 400 μg of another medicine, misoprostol , to induce contractions. In European studies, this method terminated 96 to 99% of pregnancies up to 49 days of gestation, but in a large multicenter trial in the United States conducted from September 1994 to September 1995, efficacy was lower (92%). , Which the study authors suggested may have been due to lack of experience with this method in the United States and / or study design. 32 In Europe and China, an observation period of several hours is required after administration of misoprostol. If the expulsion of fetal tissue does not occur during the observation period, a surgical abortion is offered. The observation period is not required in the United States, but is highly recommended. 33
According to the current evidence-based medical guide of the Royal College of Obstetricians and Gynecologists UK: 34
- All first-trimester abortion methods carry a small risk of failure to terminate pregnancy, which requires an additional procedure. The risk of a surgical abortion is about 0.23% and that of a medical abortion between 0.1% and 1.4% (depending on the regimen used and the experience of the medical center).
- Medical abortion using mifepristone plus prostaglandin is the most effective abortion method in gestations of less than 7 weeks.
- Conventional vacuolation should be avoided in gestations of less than 7 weeks.
- Vacuum extraction using a rigorous protocol (including magnification of the extracted matter and indications for follow-up of βhCG ) could be used in pregnancies less than 7 weeks, although the data suggest that the failure rate is higher than that of an abortion doctor.
- Medical abortion using mifepristone plus prostaglandin continues to be an appropriate method for women in the 7-9 week gestational age group.
Mifepristone may also be used at lower doses as an emergency contraceptive ; if is taken after intercourse but before ovulation , mifepristone can prevent ovulation and thus the pregnancy . In this role, a dose of 10 mg is not as effective as a 600 mg dose, but has fewer side effects. 35 The use of mifepristone in a dose of 25 mg to 50 mg (considered a mean dose) as emergency contraception is supported by clinical studies of 2008 36 who consider mifepristone along with levonorgestrel and the IUD , but ahead of These, as emergency contraceptive methods more effective than the Yuzpe method , danazol and anordrin, being associated with fewer side effects. 37 38 1 4 The Mifeprex and Mifegyne are only available in tablets of 200 mg 39
The ulipristal acetate and levonorgestrel are postcoital hormonal contraceptives reference in America and Western Europe . In China and Russia the most commonly used emergency contraceptive is mifepristone. 3 4
A review of human studies found that the contraceptive effects of a 10 mg dose were probably due mainly to their effects on ovulation, not inhibition of implantation, but “knowledge of the mechanism of action remains incomplete. ” Treatments with 200 mg of mifepristone change the expression of steroid receptors in the fallopian tubes , inhibiting endometrial development , and effectively preventing implantation. 40
Other medical applications of mifepristone that have been studied in Phase II clinical trials include regular and long-term use as an oral contraceptive, and treatment of: fibroids , endometriosis , depression with psychotic features , glaucoma , meningiomas , breast cancer , Ovarian cancer , and prostate cancer . Mifepristone has been used to treat Cushing’s syndrome with treatments lasting up to 10 years without notable adverse effects. 41
Mifepristone has been studied as an antiretroviral for its in vivo interference with the HIV vpr regulatory protein . It did not show detectable anti-HIV activity in clinical trials. 42 10 13 43 It is currently being studied as a treatment for Gulf Syndrome . 44 Mifepristone has not been approved by the FDA for any of these uses.
Mifepristone has shown significant efficacy 45 in greater psychotic depression , a form of resistant depression normal treatment. The effect was rapid and the study was double blind but limited by a small study group and limited treatment time.
It has also been described as a cervical ripening agent. 46
In clinical trials , almost all women using mifepristone experienced abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9-16 days. 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 . 47 The pelvic inflammatory disease (PID) is a rare but serious complication. 48 Excessive bleeding and incomplete termination of pregnancy requires additional intervention by a doctor (such as a vacuum aspiration). Between 4.5 and 7.9% of women required surgical intervention in clinical trials. 47 Mifepristone is contraindicated in the presence of an intrauterine device (IUD), as in ectopic pregnancy , failure adrenal disorders bleeding , porphyria inherited, and therapies anticoagulants or corticosteroids long term. 47
The information prescribed by the FDA indicates that there are no data on the safety and efficacy of mifepristone in women with chronic medical conditions, and that “women who are over 35 years of age and who also smoke more than 10 cigarettes per day should Treated with caution because such patients were generally excluded from clinical trials of mifepristone. ” 47
No long-term studies have been performed to evaluate the carcinogenic potential of mifepristone. Results from in vitro and animal studies revealed no genotoxic potential of mifepristone.
Neonatal exposure to a single high dose of mifepristone in rats was not associated with any reproductive problems, although chronic exposure to low doses of mifepristone in newborn rats was associated with structural and functional reproductive abnormalities. 47
Teratological studies in mice, rats and rabbits showed teratogenicity for rabbits, but not in rats or mice. 47 The rate of birth defects in human infants exposed in utero to mifepristone and misoprostol is very low, 49 and may be due only to misoprostol. fifty
A post-marketing summary found that of the approximately 1.52 million women who have received mifepristone by April 2011 in the United States, fourteen would have died after the application. Eight of these cases were associated with sepsis ; The other six had several cases such as drug abuse and suspected murder. Other incidents reported to the FDA included 612 non-lethal hospitalizations, 339 blood transfusions, 48 severe infections, and altogether 2,207 (0.15%) adverse events. 51
- ↑ Jump to:a b Mittal S. Interventions for emergency contraception: RHL commentary (last revised: November 1, 2008). The WHO Reproductive Health Library; Geneva: World Health Organization
- Back to top↑ Prospectus of Misive 200 Micrograms-vaginal tablets of Misoprostol, sinaem, Ministry of Health, Spain
- ↑ Jump to:a b Dr. Horacio Croxatto confirms that the acetate of Ulipristal is the most effective non-hormonal contraceptive for women, in Noticiasmedicas.es, 03/26/2010
- ↑ Jump to:a b c Emergency Contraception: A Last Chance to Prevent Unintended Pregnancy, James Trussell, PhD1, Elizabeth G. Raymond, MD, MPH2, September 2010
- Return to top↑ See general aspects of Mifepristone / Misoprostol Scheme
- Back to top↑ Spain, to the European tail in pharmacological abortion, Only 4% of the interruptions are done by this method, while in the EU they approach the half, 11/23/2010
- Back to top↑ Mifepristone in MedlinePlus
- Back to top↑ «WHO Model List of EssentialMedicines» . World Health Organization . October 2013 . Retrieved on April 22, 2014 .
- ↑ Jump to:a b Loose, Davis S .; Stancel, George M. (2006). Estrogens and Progestins. In Brunton, Laurence L .; Lazo, John S .; Parker, Keith L. (eds.). Goodman & Gilman’s The Pharmacological Basis of Therapeutics (11th edition). New York: McGraw-Hill. Pp. 1541-1571. ISBN 0-07-142280-3 .
- ↑ Jump to:a b Schimmer, Bernard P .; Parker, Keith L. (2006). «Adrenocorticotropic Hormone; Adrenocortical Steroids and Their Synthetic Analogs; Inhibitors of the Synthesis and Actions of Adrenocortical Hormones. In Brunton, Laurence L .; Lazo, John S .; Parker, Keith L. (eds.). Goodman & Gilman’s The Pharmacological Basis of Therapeutics (11th edition). New York: McGraw-Hill. Pp. 1587-1612. ISBN 0-07-142280-3 .
- ↑ Jump to:a b Fiala C, Gemzel-Danielsson K (2006). ‘Review of medical abortion using mifepristone in combination with a prostaglandin analogue’. Contraception 74 (1): 66-86. doi : 10.1016 / j.contraception.2006.03.018 . PMID 16781264 .
- Back to top↑ Heikinheimo O, Kekkonen R, Lahteenmaki P (2003). ‘The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action’. Contraception 68 (6): 421-6. doi : 10.1016 / S0010-7824 (03) 00077-5. PMID 14698071 .
- ↑ Jump to:a b 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. doi :10.1093 / humupd / dmi002 . PMID 15790602 .
- ↑ Jump to:a b Exelgyn Laboratories (February 2006). ‘Mifegyne UK Summary of Product Characteristics (SPC)’ . Accessed March 9, 2007 .
- Back to top↑ Danco Laboratories (July 19, 2005). «Mifeprex US prescribing information» (PDF) . Archived from the originalon January 7, 2007 . Accessed March 9, 2007 .
- ↑ Jump to:a b c d e f g h Baulieu, Étienne-Émile; Rosenblum, Mort (1991). The “abortion pill”: RU-486, a woman’s choice . New York: Simon & Schuster. ISBN 067173816X . Lader, Lawrence (1991). RU 486: the pill that could end the abortion wars and why American women do not have it . Reading: Addison-Wesley. ISBN 0201570696 . Villaran, Gilda (1998). «RU 486». In Schlegelmilch, Bodo B. (ed.). Marketing ethics: an international perspective . London: Thomson Learing. Pp. 155-190. ISBN 186152191X . Ulmann, André (2000). «The development of mifepristone: a pharmaceutical drama in three acts». J Am Med Womens Assoc 55 (3 Suppl): 117-20. PMID 10846319 .
- Back to top↑ Teutsch, Georges (November 24, 1989). «RU 486 development». Science 246 (4933): 985. doi : 10.1126 / science.2587990 . PMID 2587990 . Cherfas, J (November 24, 1989). ‘Dispute surfaces over paternity of RU 486’. Science 246 (4933): 994 doi : 10.1126 / science.2587988 . PMID 2587988 . Philibert, D; Teutsch, G (9 February 1990). «RU 486 development». Science 246 (4943): 622. doi : 10.1126 / science.2300819 . PMID 2300819 . Ulmann, A; Teutsch, G; Philibert, D (June 1990). «RU 486». Scientific American 262 (6): 42-8. doi : 10.1038 / scientificamerican0690-42 . PMID 2343294 . And redundant ( help ) Teutsch, G .; Deraedt, R .; Philibert, D. (1993). Mifepristone. In Lednicer, Daniel (ed.). Chronicles of drug discovery, Vol. 3 . Washington, DC: American Chemical Society. Pp. 1-43. ISBN 0841225230 . Teutsch, G; Philibert, D (June 1994). ‘History and perspectives of antiprogestins from the chemist’s point of view’. Human Reprod 9 (Suppl 1): 12-31. PMID 7962457 . Sittig, Marshall (ed.), Ed. (2007). Mifepristone. Pharmaceutical manufacturing encyclopedia (3rd edition). Norwich, NY: William Andrew Publishing. Pp. 2307-2310. ISBN 1601193394 . Template: US patent reference assigned to Roussel Uclaf
- Back to top↑ Eder, Richard (April 20, 1982). “Birth control: 4-day pill is promising in early test .” The New York Times . P. C1. Herrmann, Walter; Wyss, Rolf; Riondel, Anne; Philibert, Daniel; Teutsch, Georges; Sakiz, Edouard; Baulieu, Étienne-Émile (17 May 1982). “The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and early pregnancy”. CR Seances Acad Sci III 294 (18): 933-8. PMID 6814714 .
- Back to top↑ Kolata, Gina (September 24, 1988). «France and China allow sale of a drug for early abortion» . The New York Times . P. A1.
- Back to top^ Greenhouse, Steven (October 27, 1988). ‘Drug maker stops all distribution of abortion pill’ . The New York Times . P. A1.
- Back to top↑ Greenhouse, Steven (October 29, 1988). «France ordering company to sell its abortion drug» . The New York Times . P. A1.
- Back to top↑ Smith, W. (September 1991). ‘Great Britain second country to allow use of RU-486’. Parent Plan Eur 20 (2): 20. PMID 12284548 .
- Back to top↑ . (December 1992). ‘RU 486 licensed in Sweden’. IPPF Med Bull 26 (6): 6. PMID 12346922 .
- Back to top^ Newman, Barry (February 22, 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 US. The Wall Street Journal . P. A1. The Associated Press (April 16, 1993). «FDA says company delays abortion pill» . The New York Times . P. A14. Jouzaitis, Carol (October 17, 1994). ‘Abortion pill battle surprises French firm’ . Chicago Tribune . P. 1 (Business).
- Back to top↑ Seelye, Katharine Q. (17 May 1994). «Accord opens way for abortion pill in US in 2 years» . The New York Times . P. A1.
- Back to top↑ Kolata, Gina (September 29, 2000). ‘US approves abortion pill; Drug offers more privacy and could reshape debate » . The New York Times . P. A1.
- Back to top↑ Moore, Stephen D .; Kamm, Thomas; Fleming, Charles (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 . P. A3. Marshall, Matt (11 December 1996). «Hoechst offers to pay $ 3.6 billion for Roussel». The Wall Street Journal . P. A8. Bloomberg Business News (December 11, 1996). ‘Hoechst to buy rest of Roussel’ . The New York Times . P. D4.
- Back to top↑ Bloomberg News (April 9, 1997). Pill for abortion ends production . The New York Times . P. D2. Jouzaitis, Carol (April 9, 1997). «Abortion pill maker bows to boycott heat; German firm gives up RU-486 patent; Little impact likely in US ” . Chicago Tribune . P. 4. Lavin, Douglas (April 9, 1997). ‘Hoechst will stop making abortion pill’. The Wall Street Journal . P. A3. . (18 April 1997). ‘Roussel-Uclaf to transfer RU 486 rights’. Reprod Freedom News 6 (7): 8. PMID 12292550 . Dorozynski, Alexander (April 19, 1997). ‘Boycott threat forces French company to abandon RU486’. BMJ 314 (7088): 1150. PMC 2126515 . PMID 9146386 .
- Back to top↑ . (November 4, 2009). List of mifepristone approval . New York: Gynuity Health Projects. . (November 4, 2009). ‘Map of mifepristone approval’ . New York: Gynuity Health Projects . Retrieved on June 11, 2010 .
- Back to top↑ Zacafemyl, Information for prescription, at intelpharma.com.mx
- Back to top↑ Bread, Philip P. (October 12, 2000). «Chinese to Make RU-486 for US» . Washingtonpost.com . Archived from the original on June 30, 2012 . Accessed August 22, 2006 .
- Back to top↑ Spitz IM, Bardin CW, Benton L, Robbins A (1998). «Early pregnancy termination with mifepristone and misoprostol in the United States». N Engl J Med 338 (18): 1241-7. doi : 10.1056 / NEJM199804303381801 . PMID 9562577 .
- Back to top↑ Suzanne Daley (October 5, 2000). «Europe Finds Abortion Pill is No Magic Cure-All» . The New York Times . Consulted the 16 of September of 2006 .
- Back to top↑ RCOG (2004). The Care of Women Requesting Induced Abortion: Evidence-based clinical guideline number 7(PDF) . London: RCOG Press. ISBN 1-904752-06-3 . Archived from the original on February 27, 2008.
- Back to top↑ Piaggio G et al. (2003). ‘Meta-analysis of randomized trials comparing different doses of mifepristone in emergency contraception’. Contraception 68 (6): 447-52. doi : 10.1016 / S0010-7824 (03) 00142-2 . PMID 14698075 .
- Back to top↑ Virtual Health Library – Cochrane BVS – WHO – Bireme – OPS-
- Back to top↑ Interventions for emergency contraception. WHO
- Back to top↑ Cheng L, Gülmezoglu AM, Piaggio G, Ezcurra E, Van Look PFA. Interventions for emergency contraception.Systematic Reviews Database; 2008, number 2. Article no .: CD001324. DOI: 10.1002 / 14651858.CD001324.pub3.
- Back to top↑ Wertheimer, Randy E. (November 15, 2000). ‘Emergency Postcoital Contraception’ . American Family Physician (American Academy of Family Physicians) . Retrieved on July 23, 2006 .
- Back to top↑ Gemzell-Danielsson, K .; Marions, L. (June 10, 2004). Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception. Human Reproduction Update (Oxford University Press) 10 (4): 341-348. doi : 10.1093 / humupd / dmh027 . PMID 15192056 .
- Back to top↑ Healy, David (2009). “Mifepristone: an overview for Australian practice”. Australian Prescriber , 32: 152-154. Available at http://www.australianprescriber.com/magazine/32/6/152/4/
- Back to top↑ Flexner, Charles. “HIV drug development: the next 25 years”. Nat Rev Drug Discov. 2007 Dec; 6 (12): 959-66.
- Back to top↑ Tang OS, Ho PC (2006). Clinical applications of mifepristone. Gynecol Endocrinol 22 (12): 655-9. doi : 10.1080 / 09513590601005946 . PMID 17162706 .
- Back to top↑ «A Controlled Trial of Mifepristone in Gulf War Veterans with Chronic Multisymptom Illness» . ClinicalTrials.gov . US National Institutes of Health . June 2008. Retrieved on November 7, 2008.
- Back to top↑ Belanoff JK, Flowers BH, Kalezhan M, Sund B, Schatzberg AF (October 2001). Rapid reversal of psychotic depression using mifepristone . J Clin Psychopharmacol 21 (5): 516-21. doi : 10.1097 / 00004714-200110000-00009 . PMID 11593077 .
- Back to top↑ Clark K, Ji H, Feltovich H, Janowski J, Carroll C, Chien EK (May 2006). ‘Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events’. Am. J. Obstet. Gynecol. 194 (5): 1391-8. doi : 10.1016 / j.ajog.2005.11.026 . PMID 16647925 .
- ↑ Jump to:a b c d e f «Mifeprex label» (PDF) . FDA. July 19, 2005. Archived from the original on June 28, 2006 . Accessed August 22, 2006 .
- Back to top↑ Lawton, BA et al. (2006). ‘Atypical presentation of serious pelvic inflammatory disease following mifepristone-induced abortion’. Contraception 73 (4): 431-2. doi : 10.1016 / j.contraception.2005.09.003 . PMID 16531180 .
- Back to top↑ Margaret M. Gary and Donna J. Harrison (December 2005). ‘Analysis of Severe Adverse Events Related to the Use of Mifepristone as an Abortifacient’ . The Annals of Pharmacology . Consulted the 14 of September of 2006 .
- Back to top↑ Orioli, IM and Castilla, EE (2000). Epidemiological assessment of misoprostol teratogenicity. BJOG 107 (4): 519-23. doi : 10.1111 / j.1471-0528.2000.tb13272.x . PMID 10759272 .
- Back to top↑ Mifepristone US Postmarketing Adverse Events Summary through 04/30/2011