Ulipristal acetate

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Ulipristal acetate
File:Ulipristal acetate skeletal.svg
Systematic (IUPAC) name
(8S,11S,13S,14R,17R)-17-Acetoxy-11-[4-(dimethylamino)phenyl]-19-norpregna-4,9-diene-3,20-dione
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]
Pregnancy
category
  • contraindicated
Routes of
administration		 oral
Legal status
Legal status
Pharmacokinetic data
Bioavailability nearly 100%
Protein binding 96.7–99.5%
Metabolism likely CYP3A4
Biological half-life 32 hours
Excretion ca. 90% with faeces
Identifiers
CAS Number 126784-99-4
ATC code none
PubChem CID 130904
Chemical data
Formula C30H37NO4
Molar mass 475.62 g/mol[[Script error: No such module "String".]]
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Ulipristal acetate (trade name ellaOne in the European Union, ella in the U.S.,[1] HRA Pharma) is a selective progesterone receptor modulator (SPRM) for emergency contraception[2] within 120 hours (5 days) after an unprotected intercourse or contraceptive failure. It has shown to prevent about 60% of expected pregnancies,[3] which is comparable to the emergency contraception scheme with levonorgestrel. It was granted marketing authorisation by the European Medicines Agency (EMEA) in March 2009.[4] The FDA advisory committee has recommended that it be approved in the United States.[5][6] The FDA approved the drug on August 13, 2010.[7]

Pharmacokinetics

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.[8]

Ulipristal acetate is metabolised 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.[9]

Pharmacodynamics

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.[10] Phase II clinical trials suggest that the mechanism might consist of blocking or delaying ovulation and of delaying the maturation of the endometrium.[11]

Contraindications

Ulipristal acetate should not be taken by women with severe liver diseases[12] because of its CYP mediated metabolism. It has not been studied in women under the age of 18.[13]

Pregnancy

Unlike levonorgestrel, and like mifepristone, ulipristal acetate is embryotoxic in animal studies.[14] Before taking the drug, a pregnancy must be excluded.[12] The EMEA proposed to avoid any allusion to a possible use as an abortifacient in the package insert to avert off-label use.[15] It is unlikely that Ellaone 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.[16] 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".[17]

Lactation

It is not recommended to breast feed within 36 hours of taking the drug since it is not known whether ulipristal acetate or its metabolites are excreted into the breast milk.[12][18]

Adverse effects

Common side effects include abdominal pain and menstrual disorder.[12]

Interactions

No interaction studies have been conducted. Ulipristal acetate is likely to interact with substrates of CYP3A4, like St John's wort or carbamazepine, but this might not be clinically relevant because only a single dose of the drug is taken.[19] It might also interact with levonorgestrel and other substrates of the progesterone receptor, as well as with glucocorticoids.

References

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Estrogens and progestogens (G03C-D, L02)
Progestogens/
progestins
(progesterone)
Agonist
Other/
ungrouped
antagonist: Mifepristone Asoprisnil · CDB-4124  · Ulipristal acetate
Estrogens
Agonist
Comparison
Behavioral
Avoiding vaginal intercourse: Abstinence · Anal sex · Masturbation · Non-penetrative sex · Oral sex
Including vaginal intercourse: Breastfeeding infertility (LAM) · Calendar-based methods (rhythm, etc.) · Fertility awareness · Withdrawal ·
Barrier or
spermicidal
Hormonal
(formulations)
Anti-estrogen
Ormeloxifene (Centchroman)
Post-intercourse
Emergency contraception (pills or copper IUD) (Yuzpe regimen, Ulipristal acetate)
Intrauterine device
Abortion
Surgical · Medical (RU-486/abortion pill)
Sterilization
Female: Tubal ligation · Essure
Male: Vasectomy
es:Acetato de ulipristal

it:Ulipristal acetato

pt:Acetato de ulipristal
  1. ↑ "FDA grants approval of ella® for emergency contraception" (Press release). HRA Pharma. August 13, 2010. http://www.hra-pharma.com/downloads/HRA%20FDA%20Approval%20FINAL.pdf. Retrieved 2010-08-15. 
  2. ↑ Creinin, MD; Schlaff, W; Archer, DF; Wan, L; Frezieres, R; Thomas, M; Rosenberg, M; Higgins, J (2006). "Progesterone receptor modulator for emergency contraception: a randomized controlled trial". Obstetrics and gynecology. 108 (5): 1089–97. doi:10.1097/01.AOG.0000239440.02284.45. PMC 2853373 Freely accessible. PMID 17077229. 
  3. ↑ "European Public Assessment Report for Ellaone. Summary for the public" (PDF). EMEA. 2009. p. 2. Retrieved 22 November 2009. 
  4. ↑ CHMP (2009). "Assessment Report for Ellaone" (PDF). EMEA. Retrieved 22 November 2009. 
  5. ↑ Emma Hitt (18 June 2010). "FDA Panel Gives Ulipristal Acetate Unanimous Positive Vote for Emergency Contraception Indication". Retrieved 06-22-2010.  Check date values in: |access-date= (help)
  6. ↑ Harris, Gardiner (August 14, 2010). "F.D.A. Approves 5-Day Emergency Contraceptive". The New York Times. Retrieved August 14, 2010. 
  7. ↑ "FDA grants approval of ella® for emergency contraception" (Press release). HRA Pharma. August 13, 2010. http://www.hra-pharma.com/downloads/HRA%20FDA%20Approval%20FINAL.pdf. Retrieved 2010-08-15. 
  8. ↑ CHMP (2009:12, 20)
  9. ↑ CHMP (2009:13–14, 21)
  10. ↑ 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.  edit
  11. ↑ CHMP (2009:22–23)
  12. ↑ 12.0 12.1 12.2 12.3 "Package leaflet: Ellaone 30 mg tablet" (PDF). Retrieved 22 November 2009. 
  13. ↑ CHMP (2009:33, 43)
  14. ↑ CHMP (2009:16)
  15. ↑ CHMP (2009:41)
  16. ↑ RCOG (2004). The Care of Women Requesting Induced Abortion : Evidence-based clinical guideline number 7 (PDF). London: RCOG Press. ISBN 1-904752-06-3. 
  17. ↑ CHMP (2009:37)
  18. ↑ CHMP (2009:43)
  19. ↑ CHMP (2009:12, 14)
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