Elagolix

Elagolix
Clinical data
Pronunciation/ˌɛləˈɡoʊlɪks/
EL-ə-GOH-liks
Trade namesOrilissa, Oriahnn
Other namesNBI-56418, ABT-620
AHFS/Drugs.comMonograph
MedlinePlusa618044
License data
Pregnancy
category
  • Contraindicated
Routes of
administration		By mouth[1]
Drug classGnRH antagonist
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityLow (5.8% in rats, 11% in monkeys; no human data)[4]
Protein binding80%[1]
MetabolismLiver (CYP3A)[1]
Elimination half-lifeTypical: 4–6 hours[1]
Single dose: 2.4–6.3 hrs[5][6]
Continuous: 2.2–10.8 hours[5]
ExcretionUrine: <3%[1]
Feces: 90%[1]
Identifiers
  • 4-[[(1R)-2-[5-(2-Fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]amino]butanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.259.758 Edit this at Wikidata
Chemical and physical data
FormulaC32H30F5N3O5
Molar mass631.600 g·mol−1
3D model (JSmol)
  • COc1cccc(-c2c(C)n(Cc3c(F)cccc3C(F)(F)F)c(=O)n(C[C@H](NCCCC(=O)O)c3ccccc3)c2=O)c1F
  • InChI=1S/C32H30F5N3O5/c1-19-28(21-11-6-14-26(45-2)29(21)34)30(43)40(18-25(20-9-4-3-5-10-20)38-16-8-15-27(41)42)31(44)39(19)17-22-23(32(35,36)37)12-7-13-24(22)33/h3-7,9-14,25,38H,8,15-18H2,1-2H3,(H,41,42)/t25-/m0/s1
  • Key:HEAUOKZIVMZVQL-VWLOTQADSA-N

Elagolix, sold under the brand name Orilissa, is a gonadotropin-releasing hormone antagonist (GnRH antagonist) medication which is used in the treatment of pain associated with endometriosis in women.[1][2][3][7][6][4][8][9] It is also under development for the treatment of uterine fibroids and heavy menstrual bleeding in women.[9] The medication was under investigation for the treatment of prostate cancer and enlarged prostate in men as well, but development for these conditions was discontinued.[9] Elagolix is taken by mouth once or twice per day.[1][9] It can be taken for up to 6 to 24 months, depending on the dosage.[1]

Side effects of elagolix include menopausal-like symptoms such as hot flashes, night sweats, insomnia, amenorrhea, mood changes, anxiety, and decreased bone density, among others.[1] Elagolix is a GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor (GnRHR), the biological target of the hypothalamic hormone gonadotropin-releasing hormone (GnRH).[1] By blocking the GnRHR, it dose-dependently suppresses the gonadal production and hence circulating levels of sex hormones such as estradiol, progesterone, and testosterone.[1] Elagolix is a short-acting GnRH antagonist, and can be used to achieve either partial or more substantial suppression of sex hormone levels.[8] Reduced estrogen levels in the endometrium are responsible for the efficacy of elagolix in the treatment of endometriosis.[8]

Elagolix was first described in 2008 and was approved for medical use in July 2018.[10][9] It has been described as a "second-generation" GnRH modulator due to its non-peptide and small-molecule nature and its oral activity.[6][9] Unlike GnRH agonists and older GnRH antagonists, which are peptides and first-generation GnRH modulators, elagolix is not a GnRH analogue as it is not structurally related to GnRH.[6][9] Elagolix was the first second-generation and orally active GnRH modulator to be introduced for medical use.[9] The introduction of elagolix in the United States and Canada was followed by that of relugolix (brand name Relumina), the next second-generation GnRH antagonist, in Japan in January 2019.[11] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[12]

  1. ^ a b c d e f g h i j k l m "Orilissa- elagolix tablet, film coated". DailyMed. 5 May 2020. Archived from the original on 24 September 2020. Retrieved 30 May 2020.
  2. ^ a b "Orilissa Product information". Health Canada. 25 April 2012. Archived from the original on 1 June 2022. Retrieved 31 May 2022.
  3. ^ a b "Orilissa (elagolix) Health Canada Product Monograph" (PDF). 4 October 2018. Archived (PDF) from the original on 16 February 2019. Retrieved 15 February 2019.
  4. ^ a b Tukun FL, Olberg DE, Riss PJ, Haraldsen I, Kaass A, Klaveness J (December 2017). "Recent Development of Non-Peptide GnRH Antagonists". Molecules. 22 (12): 2188. doi:10.3390/molecules22122188. PMC 6149776. PMID 29232843.
  5. ^ a b Cite error: The named reference pmid19033369 was invoked but never defined (see the help page).
  6. ^ a b c d Ezzati M, Carr BR (January 2015). "Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain". Women's Health. 11 (1): 19–28. doi:10.2217/whe.14.68. PMID 25581052.
  7. ^ Lamb YN (September 2018). "Elagolix: First Global Approval". Drugs. 78 (14): 1501–1508. doi:10.1007/s40265-018-0977-4. PMC 6244606. PMID 30194661.
  8. ^ a b c Clemenza S, Sorbi F, Noci I, Capezzuoli T, Turrini I, Carriero C, Buffi N, Fambrini M, Petraglia F (February 2018). "From pathogenesis to clinical practice: Emerging medical treatments for endometriosis". Best Pract Res Clin Obstet Gynaecol. 51: 92–101. doi:10.1016/j.bpobgyn.2018.01.021. PMID 29559388. S2CID 3952054.
  9. ^ a b c d e f g h Cite error: The named reference AdisInsight was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference pmid19006286 was invoked but never defined (see the help page).
  11. ^ "Relugolix - Myovant/Takeda - AdisInsight". Archived from the original on 2018-09-20. Retrieved 2019-02-16.
  12. ^ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Archived from the original on 17 September 2020. Retrieved 16 September 2020.