|Trade names||Ella, EllaOne, Esmya, others|
|Drug class||Selective progesterone receptor modulator|
|Elimination half-life||32 hours|
|Excretion||ca. 90% with feces|
|Chemical and physical data|
|Molar mass||475.62 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Ulipristal acetate, sold under the brand name Ella among others, is a medication used for emergency birth control and uterine fibroids. As emergency birth control it should be used within 120 hours of sex. For fibroids it may be taken for up to six months. It is taken by mouth.
Common side effects include headache, nausea, feeling tired, and abdominal pain. It should not be used in people who are already pregnant. It is in the selective progesterone receptor modulator (SPRM) class of medications. It works by preventing the effects of progesterone thus stopping ovulation.
Ulipristal acetate was approved for medical use in the United States in 2010. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. In the United Kingdom it costs the NHS about 17 pounds per course of emergency birth control of 2015. To improve access, some recommend all who can get pregnant be given a prescription for use if needed.
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.
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.
Volume reduction of uterine fibroid induced by ulipristal acetate 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 under the action of matrix metalloproteinases.
In February 2018, the European Medicines Agency released a report concerning reports of serious liver injury associated with long term ulipristal. The EMA have advised monthly liver tests and against further people being started on the medication for uterine fibroids until further review is completed.
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.
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.
As an 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.
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 feces.
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.
Society and culture
Ulipristal acetate is marketed in the United States under the brand name Ella and in Canada under the brand name Fibristal. It is also marketed under the brand names EllaOne and Esmya both in over 20 countries, of which include the United Kingdom and Ireland. A few less-widely used brand names also exist.
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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.
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- 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. doi:10.1016/j.fertnstert.2014.02.008. PMID 24630081.
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- Courtoy, Guillaume E.; Henriet, Patrick; Marbaix, Etienne; de Codt, Matthieu; Luyckx, Mathieu; Donnez, Jacques; Dolmans, Marie-Madeleine (2018-02-01). "Matrix metalloproteinase activity correlates with uterine myoma volume reduction after ulipristal acetate treatment". The Journal of Clinical Endocrinology and Metabolism. doi:10.1210/jc.2017-02295. ISSN 1945-7197. PMID 29408988.
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