|Trade names||Ellaone, Ella, Esmya|
|AHFS/Drugs.com||Multum Consumer Information|
|Biological half-life||32 hours|
|Excretion||ca. 90% with faeces|
|Chemical and physical data|
|Molar mass||475.62 g/mol|
|3D model (JSmol)|
|(what is this?)|
It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.
For emergency contraception a 30 mg tablet is used within 120 hours (5 days) after an unprotected intercourse or contraceptive failure. It has been shown to prevent about 62–85% of expected pregnancies, and prevents more pregnancies than emergency contraception with levonorgestrel. Ulipristal acetate is available by prescription for emergency contraception in over 50 countries, with access through pharmacists without a prescription being tested in the United Kingdom. In November 2014 European Medicines Agency recommended availability of ellaOne emergency contraceptive without prescription in the European Union. In January 2015 the European Commission issued an implementing decision amending accordingly the marketing authorization of EllaOne in the EU . Since July 2016, it is available without prescription in Israel.
Ulipristal acetate is used for pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age in a daily dose of a 5 mg tablet.
Two intermittent 3-months treatment courses of ulipristal acetate 10 mg resulted in amenorrhea at the end of the first treatment course in 79.5%, at the end of the second course in 88.5% of subjects. Mean myoma volume reduction observed during the first treatment course (−41.9%) was maintained during the second one (−43.7%). After two to four 3-months courses of treatment, UPA-treated fibroids shown about -70% in volume reduction. This phenomenon was tentatively explained by the combination of multifactorial events involving control of proliferation of the tumor cells, induction of apoptosis and remodeling of the extracellular matrix.
Ulipristal acetate is metabolized by CYP3A4 in vitro. Ulipristal acetate is likely to interact with substrates of CYP3A4, like rifampicin, phenytoin, St John's wort, carbamazepine or ritonavir, therefore concomitant use with these agents is not recommended. It might also interact with hormonal contraceptives and progestogens such as levonorgestrel and other substrates of the progesterone receptor, as well as with glucocorticoids.
Unlike levonorgestrel, and like mifepristone, ulipristal acetate is embryotoxic in animal studies. Before taking the drug, a pregnancy must be excluded. The EMA proposed to avoid any allusion to a possible use as an abortifacient in the package insert to avert off-label use. It is unlikely that ulipristal acetate could effectively be used as an abortifacient, since it is used in much lower doses (30 mg) than the roughly equipotent mifepristone (600 mg), and since mifepristone has to be combined with a prostaglandin for the induction of abortion. However, data on embryotoxicity in humans are very limited, and it is not clear what the risk for an abortion or for teratogenicity (birth defects) is. Of the 29 women studied who became pregnant despite taking ulipristal acetate, 16 had induced abortions, six had spontaneous abortions, six continued the pregnancies, and one was lost to follow-up.
In animal studies, the drug was quickly and nearly completely absorbed from the gut. Intake of food delays absorption, but it is not known whether this is clinically relevant.
Ulipristal acetate is metabolized in the liver, most likely by CYP3A4, and to a small extent by CYP1A2 and CYP2D6. The two main metabolites have been shown to be pharmacologically active, but less than the original drug. The main excretion route is via the faeces.
As a SPRM, ulipristal acetate has partial agonistic as well as antagonistic effects on the progesterone receptor. It also binds to the glucocorticoid receptor, but is only a weak antiglucocorticoid relative to mifepristone, and has no relevant affinity to the estrogen, androgen and mineralocorticoid receptors. Phase II clinical trials suggest that the mechanism might consist of blocking or delaying ovulation and of delaying the maturation of the endometrium.
The U.S. Food and Drug Administration approved the drug for use in the United States on 13 August 2010, following the FDA advisory committee's recommendation. Watson Pharmaceuticals announced the availability of ulipristal acetate in the United States on 1 December 2010, in retail pharmacies, clinics, and one on-line pharmacy, KwikMed.
- "FDA approves ella tablets for prescription emergency contraception" (Press release). FDA. 13 August 2010. Retrieved 2013-06-12.
- "WHO Model List of Essential Medicines (20th List)" (PDF). World Health Organization. March 2017. Retrieved 29 June 2017.
- Creinin, Mitchell D.; Schlaff, William; Archer, David F.; Wan, Livia; Frezieres, Ron; Thomas, Michael; Rosenberg, Michael; Higgins, James (2006). "Progesterone Receptor Modulator for Emergency Contraception". Obstetrics & Gynecology. 108 (5): 1089–97. PMC . PMID 17077229. doi:10.1097/01.AOG.0000239440.02284.45.
- "Summary of Product Characteristics: ellaOne 30 mg tablet" (PDF). Retrieved 20 November 2010.
- Trussell, James; Raymond, Elizabeth G.; Cleland, Kelly (2014). "Emergency Contraception: A Last Chance to Prevent Unintended Pregnancy" (PDF). Contemporary Readings in Law and Social Justice. 6 (2): 7–38.
- Glasier, Anna F; Cameron, Sharon T; Fine, Paul M; Logan, Susan JS; Casale, William; Van Horn, Jennifer; Sogor, Laszlo; Blithe, Diana L; Scherrer, Bruno; Mathe, Henri; Jaspart, Amelie; Ulmann, Andre; Gainer, Erin (2010). "Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis". The Lancet. 375 (9714): 555–62. PMID 20116841. doi:10.1016/S0140-6736(10)60101-8.
- Trussell, James; Cleland, Kelly (February 13, 2013). "Dedicated emergency contraceptive pills worldwide" (PDF). Princeton: Office of Population Research at Princeton University, Association of Reproductive Health Professionals. Retrieved March 25, 2014.
- ICEC (2014). "EC pill types and countries of availability, by brand". New York: International Consortium for Emergency Contraception (ICEC). Retrieved March 25, 2014.
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Ulipristal acetate Emergency Contraception Pills (UPA ECPs), while available in most European countries since 2010, are not yet available in Albania, Estonia, Macedonia, Malta, Switzerland and Turkey. For now UPA ECPs are sold with a prescription in all countries, although provision without a prescription is currently being tested in the United Kingdom.
- "Summary of Product Characteristics: Esmya 5mg tablet" (PDF). Retrieved 20 February 2014.
- Nieman, Lynnette K.; Blocker, Wendy; Nansel, Tonja; Mahoney, Sheila; Reynolds, James; Blithe, Diana; Wesley, Robert; Armstrong, Alicia (2011). "Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study". Fertility and Sterility. 95 (2): 767–72.e1–2. PMC . PMID 21055739. doi:10.1016/j.fertnstert.2010.09.059.
- Levens, Eric D.; Potlog-Nahari, Clariss; Armstrong, Alicia Y.; Wesley, Robert; Premkumar, Ahalya; Blithe, Diana L.; Blocker, Wendy; Nieman, Lynnette K. (2008). "CDB-2914 for Uterine Leiomyomata Treatment". Obstetrics & Gynecology. 111 (5): 1129–36. PMC . PMID 18448745. doi:10.1097/AOG.0b013e3181705d0e.
- Donnez, Jacques; Tatarchuk, Tetyana F.; Bouchard, Philippe; Puscasiu, Lucian; Zakharenko, Nataliya F.; Ivanova, Tatiana; Ugocsai, Gyula; Mara, Michal; Jilla, Manju P.; Bestel, Elke; Terrill, Paul; Osterloh, Ian; Loumaye, Ernest (2012). "Ulipristal Acetate versus Placebo for Fibroid Treatment before Surgery". New England Journal of Medicine. 366 (5): 409–20. PMID 22296075. doi:10.1056/NEJMoa1103182.
- Donnez, Jacques; Vázquez, Francisco; Tomaszewski, Janusz; Nouri, Kazem; Bouchard, Philippe; Fauser, Bart C.J.M.; Barlow, David H.; Palacios, Santiago; Donnez, Olivier; Bestel, Elke; Osterloh, Ian; Loumaye, Ernest (2014). "Long-term treatment of uterine fibroids with ulipristal acetate". Fertility and Sterility. 101 (6): 1565–73.e1–18. PMID 24630081. doi:10.1016/j.fertnstert.2014.02.008.
- Courtoy, Guillaume E.; Donnez, Jacques; Marbaix, Etienne; Dolmans, Marie-Madeleine (2015). "In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment". Fertility and Sterility. 104 (2): 426–34.e1. PMID 26003270. doi:10.1016/j.fertnstert.2015.04.025.
- CHMP (2009:12, 14)
- CHMP (2009:33, 43)
- CHMP (2009:10, 44)
- CHMP (2009:16)
- CHMP (2009:41)
- 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 (PDF) on 27 February 2008.
- CHMP (2009:37)
- CHMP (2009:43)
- CHMP (2009:12, 20)
- CHMP (2009:13–14, 21)
- Hilal-Dandan, Randa; Brunton, Laurence L. (2013). Goodman and Gilman's Manual of Pharmacology and Therapeutics. McGraw Hill Professional. ISBN 978-0-07-176917-4.[page needed]
- Attardi, Barbara J.; Burgenson, Janet; Hild, Sheri A.; Reel, Jerry R. (2004). "In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone". The Journal of Steroid Biochemistry and Molecular Biology. 88 (3): 277–88. PMID 15120421. doi:10.1016/j.jsbmb.2003.12.004.
- CHMP (2009:22–23)
- CHMP (2009:[page needed])
- "FDA grants approval of ella for emergency contraception" (PDF) (Press release). HRA Pharma. 13 August 2010. Retrieved 2010-08-15.
- Emma Hitt (18 June 2010). "FDA Panel Gives Ulipristal Acetate Unanimous Positive Vote for Emergency Contraception Indication". Retrieved 2010-06-22.
- Harris, Gardiner (14 August 2010). "F.D.A. Approves 5-Day Emergency Contraceptive". The New York Times. Retrieved 14 August 2010.
- Watson PR (1 December 2010). "Watson Launches ella(R)(ulipristal acetate)". Retrieved 12 January 2010.