|Systematic (IUPAC) name|
|Trade names||Ellaone, Ella, Esmya|
|Licence data||EMA: , US FDA:|
|Excretion||ca. 90% with faeces|
|ATC code||G03 G03|
|Mol. mass||475.62 g/mol|
|(what is this?)|
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 60% 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.
Treatment of uterine fibroids
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. Treatment of uterine fibroids with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. Two intermittent 3-month 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%).
Common side effects include abdominal pain and temporary menstrual irregularity or disruption. Headache and nausea were observed under long-term administration (12 weeks), but not after a single dose.
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 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.
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- Glasier, A. F.; Cameron, S. T.; Fine, P. M.; Logan, S. J.; Casale, W.; Van Horn, J.; Sogor, L.; Blithe, D. L.; Scherrer, B.; Mathe, H.; Jaspart, A.; Ulmann, A.; Gainer, E. (2010). "Ulipristal acetate versus levonorgestrel for emergency contraception: A randomised non-inferiority trial and meta-analysis". The Lancet 375 (9714): 555–562. doi:10.1016/S0140-6736(10)60101-8. PMID 20116841.
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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". Retrieved 20 February 2014.
- Nieman, L. K.; Blocker, W.; Nansel, T.; Mahoney, S.; Reynolds, J.; Blithe, D.; Wesley, R.; Armstrong, A. (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): 767–772.e1–772. doi:10.1016/j.fertnstert.2010.09.059. PMID 21055739.
- Levens, E. D.; Potlog-Nahari, C.; Armstrong, A. Y.; Wesley, R.; Premkumar, A.; Blithe, D. L.; Blocker, W.; Nieman, L. K. (2008). "CDB-2914 for Uterine Leiomyomata Treatment". Obstetrics & Gynecology 111 (5): 1129–1136. doi:10.1097/AOG.0b013e3181705d0e. PMC 2742990. PMID 18448745.
- Jacques Donnez; Tetyana F. Tatarchuk, Philippe Bouchard, Lucian Puscasiu, Nataliya F. Zakharenko, Tatiana Ivanova, Gyula Ugocsai, Michal Mara, Manju P. Jilla, Elke Bestel, Paul Terrill, Ian Osterloh, and Ernest Loumaye, for the PEARL I Study Group. "Ulipristal Acetate versus Placebo for Fibroid Treatment before Surgery". New England Journal of Medicine. doi:10.1056/NEJMoa1103182. PMID 22296075.
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- Attardi, B.; Burgenson, J.; Hild, S.; Reel, J. (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): 277–288. doi:10.1016/j.jsbmb.2003.12.004. PMID 15120421.
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