Chemistry:Eltrombopag

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Short description: Chemical compound
Eltrombopag
Eltrombopag.svg
Clinical data
Trade namesPromacta, Revolade, Alvaiz
Other namesSB-497115-GR
AHFS/Drugs.comMonograph
MedlinePlusa609011
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~52%[3]
Protein binding>99%
Metabolismextensive liver (through CYP1A2 and CYP2C8)
Elimination half-life21–35 hours
Excretionfeces (59%), urine (31%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC25H22N4O4
Molar mass442.475 g·mol−1
3D model (JSmol)
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Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia (abnormally low platelet counts) and severe aplastic anemia.[3][4] Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis.[5] It is a thrombopoietin receptor agonist.[3] It is taken by mouth.[3][4]

Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals and is transferred to Novartis Pharmaceuticals.[5][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]

References

  1. ↑ 1.0 1.1 "Revolade Product Information". https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-01377-3. 
  2. ↑ "Revolade 25 mg film-coated tablets - Summary of Product Characteristics (SmPC)". 17 August 2020. https://www.medicines.org.uk/emc/product/7819/smpc. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Promacta- eltrombopag olamine tablet, film coated Promacta- eltrombopag olamine powder, for suspension". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2. 
  4. ↑ 4.0 4.1 4.2 "Revolade EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/revolade. 
  5. ↑ 5.0 5.1 "Ligand Sells Promacta Assets and Royalty for $827 Million" (Press release). Ligand Pharmaceuticals. 5 March 2019. Archived from the original on 24 June 2021. Retrieved 17 June 2021 – via Business Wire.
  6. ↑ "Revolade". http://ca.gsk.com/en-ca/products/revolade/. 
  7. ↑ "Novartis announces completion of transactions with GSK". Sandoz (Press release). Archived from the original on 24 June 2021. Retrieved 17 June 2021.
  8. ↑ "Approval Letter". U.S. Food and Drug Administration (FDA). http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf. 
  9. ↑ "Drug Approval Package: Promacta (Eltrombopag) NDA #022291". U.S. Food and Drug Administration (FDA). 14 January 2009. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm. 
  10. ↑ "Summary Review". U.S. Food and Drug Administration (FDA). 19 January 2008. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf. 
  11. ↑ "FDA extends use of Promacta in young children with rare blood disorder" (Press release). U.S. Food and Drug Administration (FDA). Archived from the original on 26 January 2018. Retrieved 18 March 2016.
  12. ↑ "Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist". Blood 109 (11): 4739–4741. June 2007. doi:10.1182/blood-2006-11-057968. PMID 17327409. 
  13. ↑ "Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura". The New England Journal of Medicine 357 (22): 2237–2247. November 2007. doi:10.1056/NEJMoa073275. PMID 18046028. 
  14. ↑ "Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C". The New England Journal of Medicine 357 (22): 2227–2236. November 2007. doi:10.1056/NEJMoa073255. PMID 18046027. https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs. Retrieved 12 December 2019. 
  15. ↑ "Eltrombopag". Drugs 69 (5): 567–576. 2009. doi:10.2165/00003495-200969050-00005. PMID 19368418. 
  16. ↑ "Eltrombopag / Promacta". U.S. Food and Drug Administration (FDA). https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm. 
  17. ↑ "Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia". The New England Journal of Medicine 376 (16): 1540–1550. April 2017. doi:10.1056/NEJMoa1613878. PMID 28423296. 
  18. ↑ "Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug". Blood 123 (12): 1818–1825. March 2014. doi:10.1182/blood-2013-10-534743. PMID 24345753. 

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