Enzalutamide

Enzalutamide
Clinical data
Trade namesXtandi
Other namesMDV-3100; ASP-9785
AHFS/Drugs.comMonograph
MedlinePlusa612033
License data
Pregnancy
category
  • AU: X (High risk)[1]
Routes of
administration		By mouth[2][3]
Drug classNonsteroidal antiandrogen
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityRats: 89.7%[7]
Humans: unknown (but at least 84.6% based on recovery from excretion)[8][3]
Protein bindingEnzalutamide: 97–98% (primarily to albumin)[2]
NDME: 95%[2]
MetabolismLiver (primarily CYP2C8 and CYP3A4)[2]
Metabolites• NDMETooltip N-Desmethylenzalutamide (active)[2][3]
• Carboxylic acid derivative metabolite (inactive)[3]
Elimination half-lifeEnzalutamide: 5.8 days (range 2.8–10.2 days)[2]
NDME: 7.8–8.6 days[2]
ExcretionUrine: 71.0%[3]
Bile: 13.6%[3]
Feces: 0.39%[3]
Identifiers
  • 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.231.722 Edit this at Wikidata
Chemical and physical data
FormulaC21H16F4N4O2S
Molar mass464.44 g·mol−1
3D model (JSmol)
  • CNC(=O)c1ccc(N2C(=S)N(c3ccc(C#N)c(C(F)(F)F)c3)C(=O)C2(C)C)cc1F
  • InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)
  • Key:WXCXUHSOUPDCQV-UHFFFAOYSA-N

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer.[2][9] It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC),[2] nonmetastatic castration-resistant prostate cancer,[2] and metastatic castration-sensitive prostate cancer (mCSPC).[10] It is taken by mouth.[2]

Side effects of enzalutamide when added to castration include asthenia, back pain, diarrhea, arthralgia, and hot flashes.[2] Rarely, it can cause seizures.[2] It has a high potential for drug interactions.[2] Enzalutamide is an antiandrogen, and acts as an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[2] In doing so, it prevents the effects of these hormones in the prostate gland and elsewhere in the body.[2]

Enzalutamide was first described in 2006, and was introduced for the treatment of prostate cancer in 2012.[11][12][13] It was the first second-generation NSAA to be introduced.[14] It is on the World Health Organization's List of Essential Medicines.[15]

  1. ^ "Enzalutamide (Xtandi) Use During Pregnancy". Drugs.com. 4 September 2018. Archived from the original on 22 December 2019. Retrieved 21 December 2019.
  2. ^ a b c d e f g h i j k l m n o p q "Xtandi- enzalutamide capsule; Xtandi- enzalutamide tablet". DailyMed. 20 November 2023. Retrieved 9 March 2024.
  3. ^ a b c d e f g Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, et al. (2015). "Clinical Pharmacokinetic Studies of Enzalutamide". Clin Pharmacokinet. 54 (10): 1043–55. doi:10.1007/s40262-015-0271-5. PMC 4580721. PMID 25917876.
  4. ^ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  5. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  6. ^ "Xtandi EPAR". European Medicines Agency (EMA). 21 June 2013. Retrieved 4 June 2024.
  7. ^ Kim TH, Jeong JW, Song JH, Lee KR, Ahn S, Ahn SH, et al. (November 2015). "Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats". Archives of Pharmacal Research. 38 (11): 2076–82. doi:10.1007/s12272-015-0592-9. PMID 25956695. S2CID 26903608.
  8. ^ Benoist GE, Hendriks RJ, Mulders PF, Gerritsen WR, Somford DM, Schalken JA, et al. (2016). "Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide". Clin Pharmacokinet. 55 (11): 1369–1380. doi:10.1007/s40262-016-0403-6. PMC 5069300. PMID 27106175.
  9. ^ "Medivation's MDV3100 Shown to Be Effective in a Preclinical Model of Hormone-Refractory Prostate Cancer" (Press release). Medivation, Inc. 26 February 2007. Archived from the original on 16 September 2007. Retrieved 10 May 2009.
  10. ^ "FDA approves enzalutamide for metastatic castration-sensitive prostate cancer". U.S. Food and Drug Administration (FDA). 17 December 2019. Archived from the original on 22 December 2019. Retrieved 21 December 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ Cite error: The named reference US20070004753 was invoked but never defined (see the help page).
  12. ^ "FDA approves new treatment for a type of late stage prostate cancer" (Press release). U.S. Food and Drug Administration (FDA). 31 August 2012. Archived from the original on 2 October 2013. Retrieved 16 December 2019.
  13. ^ Anna Azvolinsky (4 September 2012). "FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer". CancerNetwork. Archived from the original on 13 September 2012. Retrieved 6 September 2012.
  14. ^ Cite error: The named reference SaadHeinrich2013 was invoked but never defined (see the help page).
  15. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.