Eltrombopag Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:461093150
Width:270
Tradename:Promacta, Revolade, Alvaiz
Licence Eu:yes
Inn Ema:eltrombopag olamine
Dailymedid:Eltrombopag_olamine
Licence Us:Eltrombopag
Pregnancy Au:B3
Routes Of Administration:By mouth
Atc Prefix:B02
Atc Suffix:BX05
Legal Au:S4
Legal Au Comment:[1]
Legal Uk:POM
Legal Uk Comment:[2]
Legal Us:Rx-only
Legal Us Comment:[3]
Legal Eu:Rx-only
Legal Eu Comment:[4]
Bioavailability:~52%
Protein Bound:>99%
Metabolism:extensive liver (through CYP1A2 and CYP2C8)
Elimination Half-Life:21–35 hours
Excretion:feces (59%), urine (31%)
Index2 Label:as olamine
Cas Number:496775-61-2
Cas Number2:496775-62-3
Pubchem:9846180
Pubchem2:135449331
Drugbank:DB06210
Drugbank2:DBSALT000063
Chemspiderid:21106301
Chemspiderid2:28475107
Unii:S56D65XJ9G
Unii2:4U07F515LG
Kegg:D03978
Chebi:85010
Chembl:461101
Chembl2:3989691
Synonyms:SB-497115-GR
Iupac Name:3'--2'-hydroxy-3-biphenylcarboxylic acid
C:25
H:22
N:4
O:4
Smiles:CC1=NN(c2ccc(C)c(C)c2)C(=O)/C1=N\Nc1cccc(-c2cccc(C(=O)O)c2)c1O
Stdinchi:1S/C25H22N4O4/c1-14-10-11-19(12-15(14)2)29-24(31)22(16(3)28-29)27-26-21-9-5-8-20(23(21)30)17-6-4-7-18(13-17)25(32)33/h4-13,26,30H,1-3H3,(H,32,33)/b27-22-
Stdinchikey:XDXWLKQMMKQXPV-QYQHSDTDSA-N

Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia (abnormally low platelet counts) and severe aplastic anemia. Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis.[5] It is a thrombopoietin receptor agonist. It is taken by mouth.

Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals and is transferred to Novartis Pharmaceuticals.[6] [7]

Medical uses

Eltrombopag was initially approved by the U.S. Food and Drug Administration (FDA) on 20 November 2008, for the treatment of thrombocytopenia in people with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulin therapy, or splenectomy.[8] [9] [10]

On 24 August 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in children one year and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.[11]

Development

In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.[12]

Clinical trials

Eltrombopag has been shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura (ITP)[13] and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).[14]

After six weeks of therapy in a phase III trial, eltrombopag 50 mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic idiopathic thrombocytopenic purpura (ITP).[15]

History

Eltrombopag received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) in February 2014, for people with aplastic anemia for which immunosuppression has not been successful.[16] In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.[17]

Research

It has been shown to produce a trilineage hematopoiesis in some people with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts.[18]

External links

Notes and References

  1. Web site: Revolade Product Information . Therapeutic Goods Administration (TGA) . 23 May 2021 . 23 May 2021 . https://web.archive.org/web/20210523204750/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-01377-3 . live .
  2. Web site: Revolade 25 mg film-coated tablets - Summary of Product Characteristics (SmPC) . (emc) . 17 August 2020 . 22 May 2021 . 23 May 2021 . https://web.archive.org/web/20210523051334/https://www.medicines.org.uk/emc/product/7819/smpc . live .
  3. Web site: Promacta- eltrombopag olamine tablet, film coated Promacta- eltrombopag olamine powder, for suspension . DailyMed . 22 May 2021 . 23 May 2021 . https://web.archive.org/web/20210523051335/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2 . live .
  4. Web site: Revolade EPAR . European Medicines Agency (EMA) . 17 September 2018 . 22 May 2021 . 23 May 2021 . https://web.archive.org/web/20210523051333/https://www.ema.europa.eu/en/medicines/human/EPAR/revolade . live .
  5. 5 March 2019. Ligand Sells Promacta Assets and Royalty for $827 Million. 17 June 2021. Ligand Pharmaceuticals. Business Wire. 24 June 2021. https://web.archive.org/web/20210624200825/https://www.businesswire.com/news/home/20190305005956/en/Ligand-Sells-Promacta-Assets-and-Royalty-for-827-Million. live.
  6. Web site: Revolade . 17 June 2021 . GSK Canada . 28 June 2021 . https://web.archive.org/web/20210628033247/https://ca.gsk.com/en-ca/products/revolade/ . dead .
  7. Novartis announces completion of transactions with GSK. 17 June 2021. Sandoz. 24 June 2021. https://web.archive.org/web/20210624201927/https://www.sandoz.com/news/media-releases/novartis-announces-completion-transactions-gsk. live.
  8. Web site: Approval Letter. U.S. Food and Drug Administration (FDA). 18 March 2016. 28 February 2017. https://web.archive.org/web/20170228134225/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf. live.
  9. Web site: Drug Approval Package: Promacta (Eltrombopag) NDA #022291 . U.S. Food and Drug Administration (FDA) . 14 January 2009 . 22 May 2021 . 3 April 2021 . https://web.archive.org/web/20210403054745/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm . live .
  10. Web site: Summary Review . U.S. Food and Drug Administration (FDA) . 19 January 2008 . 22 May 2021 . 23 May 2021 . https://web.archive.org/web/20210523051334/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf . live .
  11. FDA extends use of Promacta in young children with rare blood disorder. U.S. Food and Drug Administration (FDA). 18 March 2016. 26 January 2018. https://web.archive.org/web/20180126103132/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm. dead.
  12. Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL . Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist . Blood . 109 . 11 . 4739–4741 . June 2007 . 17327409 . 10.1182/blood-2006-11-057968 . doi . free .
  13. Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM . 6 . Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura . The New England Journal of Medicine . 357 . 22 . 2237–2247 . November 2007 . 18046028 . 10.1056/NEJMoa073275 . free .
  14. McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH . 6 . Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C . The New England Journal of Medicine . 357 . 22 . 2227–2236 . November 2007 . 18046027 . 10.1056/NEJMoa073255 . 12 December 2019 . live . free . https://web.archive.org/web/20211017000257/https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs . 17 October 2021 .
  15. Garnock-Jones KP, Keam SJ . Eltrombopag . Drugs . 69 . 5 . 567–576 . 2009 . 19368418 . 10.2165/00003495-200969050-00005 . 265943270 .
  16. Web site: Eltrombopag / Promacta. U.S. Food and Drug Administration (FDA). 18 March 2016. 6 December 2016. https://web.archive.org/web/20161206124948/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm. live.
  17. Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS . 6 . Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia . The New England Journal of Medicine . 376 . 16 . 1540–1550 . April 2017 . 28423296 . 5548296 . 10.1056/NEJMoa1613878 . doi . free .
  18. Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE . 6 . Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug . Blood . 123 . 12 . 1818–1825 . March 2014 . 24345753 . 3962161 . 10.1182/blood-2013-10-534743 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Eltrombopag".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.