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{{Short description|Chemical compound}}
{{Drugbox
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=October 2022}}
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 461093150
| verifiedrevid = 461093150
| drug_name =
| IUPAC_name = 3'-{(2''Z'')-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4''H''-pyrazol-4-ylidene]hydrazino}-2'-hydroxy-3-biphenylcarboxylic acid
| INN =
| type = <!-- empty -->
| image = eltrombopag.svg
| image = eltrombopag.svg
| width = 270
| width = 270
| alt =
| caption =


<!--Clinical data-->
<!-- Clinical data -->
| tradename = Promacta, Revolade, Elbonix
| pronounce =
| tradename = Promacta, Revolade, Alvaiz
| synonyms = SB-497115-GR
| Drugs.com = {{drugs.com|monograph|eltrombopag}}
| Drugs.com = {{drugs.com|monograph|eltrombopag}}
| MedlinePlus = a609011
| MedlinePlus = a609011
| licence_EU = yes
| INN_EMA = eltrombopag olamine
| DailyMedID = Eltrombopag_olamine
| licence_US = Eltrombopag
| licence_US = Eltrombopag
| pregnancy_AU = B3
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Revolade TGA label" />
| pregnancy_US = C
| pregnancy_category =
| pregnancy_category =
| dependency_liability =
| licence_EU = yes
| routes_of_administration = [[Oral administration|By mouth]]
| INN_EMA = eltrombopag olamine
| class =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| ATC_prefix = B02
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_suffix = BX05
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| ATC_supplemental =
| legal_US = Rx Only <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| legal_status =
<!-- Legal status -->
| dependency_liability =
| legal_AU = S4
| routes_of_administration = By mouth
| legal_AU_comment = <ref name="Revolade TGA label">{{cite web | title=Revolade Product Information | website=[[Therapeutic Goods Administration]] (TGA) | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-01377-3 | access-date=23 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523204750/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-01377-3 | url-status=live }}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Revolade 25 mg film-coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=17 August 2020 | url=https://www.medicines.org.uk/emc/product/7819/smpc | access-date=22 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523051334/https://www.medicines.org.uk/emc/product/7819/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Promacta FDA label">{{cite web | title=Promacta- eltrombopag olamine tablet, film coated Promacta- eltrombopag olamine powder, for suspension | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2 | access-date=22 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523051335/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7714a0ed-34bb-46e6-a0a5-b363908b22c2 | url-status=live }}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Revolade EPAR">{{cite web | title=Revolade EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/revolade | access-date=22 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523051333/https://www.ema.europa.eu/en/medicines/human/EPAR/revolade | url-status=live }}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability = ~52%<ref name="Promacta FDA label" />
| bioavailability = ~52%<ref>{{cite web|title=Promacta<sup>®</sup> (eltrombopag) Tablets, for Oral Use and for Oral Suspension. Full Prescribing Information|url=http://www.pharma.us.novartis.com/product/pi/pdf/promacta.pdf|publisher=GlaxoSmithKline, Research Triangle Park, NC 27709|accessdate=13 September 2015}}</ref>
| protein_bound = >99%
| protein_bound = >99%
| metabolism = extensive [[Liver|hepatic]] (through [[CYP1A2]] and [[CYP2C8]]
| metabolism = extensive [[liver]] (through [[CYP1A2]] and [[CYP2C8]])
| metabolites =
| onset =
| elimination_half-life = 21–35 hours
| elimination_half-life = 21–35 hours
| duration_of_action =
| excretion = feces (59%), urine (31%)
| excretion = feces (59%), urine (31%)


<!--Identifiers-->
<!-- Identifiers -->
| index2_label = as olamine
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 496775-61-2
| CAS_number = 496775-61-2
| CAS_supplemental = <br />{{CAS|496775-62-3}} ([[olamine]])
| CAS_number2 = 496775-62-3
| ATC_prefix = B02
| CAS_supplemental =
| ATC_suffix = BX05
| ATC_supplemental =
| PubChem = 9846180
| PubChem = 9846180
| PubChem2 = 135449331
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| DrugBank = DB06210
| DrugBank2 = DBSALT000063
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21106301
| ChemSpiderID = 21106301
| ChemSpiderID2 = 28475107
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = S56D65XJ9G
| UNII = S56D65XJ9G
| UNII2 = 4U07F515LG
| KEGG_Ref =
| KEGG = D03978
| ChEBI_Ref =
| ChEBI = 85010
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 461101
| ChEMBL = 461101
| ChEMBL2 = 3989691
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = SB-497115-GR


<!--Chemical data-->
<!-- Chemical and physical data -->
| IUPAC_name = 3'-{(2''Z'')-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4''H''-pyrazol-4-ylidene]hydrazino}-2'-hydroxy-3-biphenylcarboxylic acid
| C=25 | H=22 | N=4 | O=4
| C=25 | H=22 | N=4 | O=4
| molecular_weight = 442.467 g/mol
| smiles = CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)NN=C3C=CC=C(C3=O)C4=CC(=CC=C4)C(=O)O)C
| SMILES = CC1=NN(c2ccc(C)c(C)c2)C(=O)/C1=N\Nc1cccc(-c2cccc(C(=O)O)c2)c1O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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+
| 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-
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XDXWLKQMMKQXPV-HPNDGRJYSA-N
| StdInChIKey = XDXWLKQMMKQXPV-QYQHSDTDSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}


'''Eltrombopag''', sold under the brand name '''Promacta''' among others, is a medication used to treat [[thrombocytopenia]] (abnormally low [[platelet]] counts) and severe aplastic anemia.<ref name="Promacta FDA label" /><ref name="Revolade EPAR" /> Eltrombopag is sold under the brand name '''Revolade''' outside the US and is marketed by [[Novartis]].<ref name=":0">{{Cite press release|date=5 March 2019|title=Ligand Sells Promacta Assets and Royalty for $827 Million|url=https://www.businesswire.com/news/home/20190305005956/en/Ligand-Sells-Promacta-Assets-and-Royalty-for-827-Million|access-date=17 June 2021|publisher=Ligand Pharmaceuticals|via=Business Wire|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624200825/https://www.businesswire.com/news/home/20190305005956/en/Ligand-Sells-Promacta-Assets-and-Royalty-for-827-Million|url-status=live}}</ref> It is a thrombopoietin receptor agonist.<ref name="Promacta FDA label" /> It is taken [[Oral administration|by mouth]].<ref name="Promacta FDA label" /><ref name="Revolade EPAR" />
'''Eltrombopag''' is a [[medication]] that has been developed for certain conditions that lead to [[thrombocytopenia]] (abnormally low [[platelet]] counts). It is a small molecule [[agonist]] of the [[c-mpl]] (TpoR) [[receptor (biochemistry)|receptor]], which is the physiological target of the [[hormone]] [[thrombopoietin]]. Eltrombopag was discovered as a result of research collaboration between [[GlaxoSmithKline]] and [[Ligand Pharmaceuticals]]. Designated an [[orphan drug]] in the United States and [[European Union]], it is being manufactured and marketed by [[Novartis]] under the trade name '''Promacta''' in the USA and is marketed as '''Revolade''' in the EU. Novartis acquired the drug as a part of its asset swap deal with GlaxoSmithKline.


Eltrombopag was discovered as a result of research collaboration between [[GlaxoSmithKline]] and [[Ligand Pharmaceuticals]] and is transferred to Novartis Pharmaceuticals.<ref name=":0" /><ref>{{Cite web |title=Revolade |url=http://ca.gsk.com/en-ca/products/revolade/ |access-date=17 June 2021 |website=GSK Canada |archive-date=28 June 2021 |archive-url=https://web.archive.org/web/20210628033247/https://ca.gsk.com/en-ca/products/revolade/ |url-status=dead }}</ref><ref>{{Cite press release|title=Novartis announces completion of transactions with GSK|url=https://www.sandoz.com/news/media-releases/novartis-announces-completion-transactions-gsk|access-date=17 June 2021|website=Sandoz|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624201927/https://www.sandoz.com/news/media-releases/novartis-announces-completion-transactions-gsk|url-status=live}}</ref>
Price for a single dose ranges from £27.50 (25 mg) to £55 (50 mg).<ref>{{Cite journal|last=National Institute for Health and Care Excellence|date=May 2013|title=Eltrombopag for treating chronic immune (idiopathic) thrombocytopenic purpura (review of technology appraisal 205)|url=https://www.nice.org.uk/guidance/ta293/documents/thrombocytopenic-purpura-eltrombopag-rev-ta205-final-appraisal-determination3|journal=Technology appraisal guidance [TA293]|volume=|pages=|via=National Institute for Health and Care Excellence}}</ref>


== Medical uses ==
==Approvals and indications==
Eltrombopag was initially approved by the [[U.S. Food and Drug Administration]] on November 20, 2008, for the treatment of thrombocytopenia in patients with chronic [[immune thrombocytopenic purpura|immune (idiopathic) thrombocytopenic purpura]] who have had an insufficient response to [[corticosteroids]], [[immunoglobulin therapy]], or [[splenectomy]].<ref>{{cite web|title=Approval Letter|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf|website=fda.gov|publisher=United States Food and Drug Administration|accessdate=18 March 2016}}</ref>
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 thrombocytopenic purpura|immune (idiopathic) thrombocytopenic purpura]] who have had an insufficient response to [[corticosteroids]], [[immunoglobulin therapy]], or [[splenectomy]].<ref>{{cite web|title=Approval Letter|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=18 March 2016|archive-date=28 February 2017|archive-url=https://web.archive.org/web/20170228134225/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf|url-status=live}}</ref><ref>{{cite web | title=Drug Approval Package: Promacta (Eltrombopag) NDA #022291 | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=14 January 2009 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm | access-date=22 May 2021 | archive-date=3 April 2021 | archive-url=https://web.archive.org/web/20210403054745/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm | url-status=live }}</ref><ref>{{cite web | title=Summary Review | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=19 January 2008 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf | access-date=22 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523051334/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf | url-status=live }}</ref>


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.<ref>{{cite press release|title=FDA extends use of Promacta in young children with rare blood disorder|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=18 March 2016|archive-date=26 January 2018|archive-url=https://web.archive.org/web/20180126103132/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm|url-status=dead}}</ref>
Eltrombopag received FDA [[breakthrough therapy|breakthrough treatment]] designation in February 2014 for patients with [[aplastic anemia]] for which immunosuppression has not been successful.<ref>{{cite web|title=Eltrombopag / Promacta|url=http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm|website=fda.gov|publisher=United States Food and Drug Administration|accessdate=18 March 2016}}</ref> In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.<ref>{{Cite journal|last=Townsley|first=Danielle M.|last2=Scheinberg|first2=Phillip|last3=Winkler|first3=Thomas|last4=Desmond|first4=Ronan|last5=Dumitriu|first5=Bogdan|last6=Rios|first6=Olga|last7=Weinstein|first7=Barbara|last8=Valdez|first8=Janet|last9=Lotter|first9=Jennifer|date=2017-04-20|title=Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia|journal=New England Journal of Medicine|volume=376|issue=16|pages=1540–1550|doi=10.1056/NEJMoa1613878|issn=0028-4793|pmid=28423296|pmc=5548296}}</ref> It has been shown to produce a trilineage hematopoesis in some patients with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts.<ref>{{cite journal|vauthors=Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE|title=Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug|journal=Blood|volume=123|issue=12|pages=1818–25|date=March 2014|pmid=24345753|pmc=3962161|doi=10.1182/blood-2013-10-534743}}</ref>

On August 24, 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in pediatric patients 1 year and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.<ref>{{cite web|title=FDA extends use of Promacta in young children with rare blood disorder|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm|website=fda.gov|publisher=United States Food and Drug Administration|accessdate=18 March 2016}}</ref>


==Development==
==Development==
In [[Phase III trials#Pre-clinical studies|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 [[megakaryocyte]]s. 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.<ref name=Jenkins>{{cite journal|vauthors = Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL|title=Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist|journal=Blood|volume=109|issue=11|pages=4739–41|date=June 2007|pmid=17327409|doi = 10.1182/blood-2006-11-057968}}</ref>
In [[Phase III trials#Pre-clinical studies|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 [[megakaryocyte]]s. 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.<ref name=Jenkins>{{cite journal | vauthors = Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL | title = Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist | journal = Blood | volume = 109 | issue = 11 | pages = 4739–4741 | date = June 2007 | pmid = 17327409 | doi = 10.1182/blood-2006-11-057968 | title-link = doi | doi-access = free }}</ref>


==Clinical trials==
==Clinical trials==
Eltrombopag has been shown to be effective in two major clinical syndromes: [[idiopathic thrombocytopenic purpura]]<ref>{{cite journal|vauthors=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|title=Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura|journal=The New England Journal of Medicine|volume=357|issue=22|pages=2237–2247|date=November 29, 2007|pmid=18046028|doi= 10.1056/NEJMoa073275}}</ref> and [[cirrhosis]] due to [[hepatitis C]] (in which low platelet counts may be a contraindication for [[interferon]] treatment).<ref>{{cite journal|vauthors=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|title=Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C|journal=The New England Journal of Medicine|volume=357|issue=22|pages=2227–2236|date=November 29, 2007|pmid=18046027|doi = 10.1056/NEJMoa073255 }}</ref>
Eltrombopag has been shown to be effective in two major clinical syndromes: [[idiopathic thrombocytopenic purpura]] (ITP)<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura | journal = The New England Journal of Medicine | volume = 357 | issue = 22 | pages = 2237–2247 | date = November 2007 | pmid = 18046028 | doi = 10.1056/NEJMoa073275 | doi-access = free }}</ref> and [[cirrhosis]] due to [[hepatitis C]] (in which low platelet counts may be a contraindication for [[interferon]] treatment).<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C | journal = The New England Journal of Medicine | volume = 357 | issue = 22 | pages = 2227–2236 | date = November 2007 | pmid = 18046027 | doi = 10.1056/NEJMoa073255 | url = https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs | access-date = 12 December 2019 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20211017000257/https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs | archive-date = 17 October 2021 }}</ref>


After 6 weeks of therapy in a [[Phase III trials#Phase III|phase III trial]], eltrombopag 50&nbsp;mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic ITP.<ref name="pmid19368418">{{cite journal|vauthors=Garnock-Jones KP, Keam SJ|title=Eltrombopag|journal=Drugs|volume=69|issue=5|pages=567–76|year=2009|pmid=19368418|doi=10.2165/00003495-200969050-00005 }}</ref>
After six weeks of therapy in a [[Phase III trials#Phase III|phase III trial]], eltrombopag 50&nbsp;mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic [[idiopathic thrombocytopenic purpura]] (ITP).<ref name="pmid19368418">{{cite journal | vauthors = Garnock-Jones KP, Keam SJ | title = Eltrombopag | journal = Drugs | volume = 69 | issue = 5 | pages = 567–576 | year = 2009 | pmid = 19368418 | doi = 10.2165/00003495-200969050-00005 | s2cid = 265943270 }}</ref>


==Brand names==
== 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.<ref>{{cite web|title=Eltrombopag / Promacta|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=18 March 2016|archive-date=6 December 2016|archive-url=https://web.archive.org/web/20161206124948/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm|url-status=live}}</ref> In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia | journal = The New England Journal of Medicine | volume = 376 | issue = 16 | pages = 1540–1550 | date = April 2017 | pmid = 28423296 | pmc = 5548296 | doi = 10.1056/NEJMoa1613878 | title-link = doi | doi-access = free }}</ref>
In [[Bangladesh]] a trade name is Elbonix.

== 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.<ref>{{cite journal | vauthors = Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE | display-authors = 6 | title = Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug | journal = Blood | volume = 123 | issue = 12 | pages = 1818–1825 | date = March 2014 | pmid = 24345753 | pmc = 3962161 | doi = 10.1182/blood-2013-10-534743 }}</ref>


== References ==
== References ==
{{reflist|33em}}
{{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/eltrombopag | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Eltrombopag }}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/eltrombopag%20olamine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Eltrombopag olamine}}
* {{ClinicalTrialsGov|NCT00102739|SB-497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adults With Refractory Immune Thrombocytopenic Purpura (ITP)}}
* {{ClinicalTrialsGov|NCT00370331|RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag (RAISE)}}
* {{ClinicalTrialsGov|NCT00351468|EXTEND (Eltrombopag Extended Dosing Study) (EXTEND)}}
* {{ClinicalTrialsGov|NCT01520909|Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body. (PETIT2)}}
* {{ClinicalTrialsGov|NCT00908037|Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP) (PETIT)}}
* {{ClinicalTrialsGov|NCT00516321|Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease}}
* {{ClinicalTrialsGov|NCT00529568|Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease}}
* {{ClinicalTrialsGov|NCT01623167|Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia}}
* {{ClinicalTrialsGov|NCT00922883|A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients}}


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[[Category:Drugs acting on the blood and blood forming organs]]
[[Category:Orphan drugs]]
[[Category:Biphenyls]]
[[Category:Biphenyls]]
[[Category:Hydrazines]]
[[Category:Breakthrough therapy]]
[[Category:Carboxylic acids]]
[[Category:Carboxylic acids]]
[[Category:Drugs acting on the blood and blood forming organs]]
[[Category:Drugs developed by GSK plc]]
[[Category:Hydrazines]]
[[Category:Drugs developed by Novartis]]
[[Category:Orphan drugs]]
[[Category:Thrombopoietin receptor agonists]]
[[Category:Thrombopoietin receptor agonists]]

Latest revision as of 12:50, 14 January 2024

Eltrombopag
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
  • 3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]hydrazino}-2'-hydroxy-3-biphenylcarboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.128.125 Edit this at Wikidata
Chemical and physical data
FormulaC25H22N4O4
Molar mass442.475 g·mol−1
3D model (JSmol)
  • CC1=NN(c2ccc(C)c(C)c2)C(=O)/C1=N\Nc1cccc(-c2cccc(C(=O)O)c2)c1O
  • InChI=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- checkY
  • Key:XDXWLKQMMKQXPV-QYQHSDTDSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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

[edit]

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

[edit]

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

[edit]

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

[edit]

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

[edit]

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

[edit]
  1. ^ a b "Revolade Product Information". Therapeutic Goods Administration (TGA). Archived from the original on 23 May 2021. Retrieved 23 May 2021.
  2. ^ "Revolade 25 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 17 August 2020. Archived from the original on 23 May 2021. Retrieved 22 May 2021.
  3. ^ a b c d e "Promacta- eltrombopag olamine tablet, film coated Promacta- eltrombopag olamine powder, for suspension". DailyMed. Archived from the original on 23 May 2021. Retrieved 22 May 2021.
  4. ^ a b c "Revolade EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 23 May 2021. Retrieved 22 May 2021.
  5. ^ a b "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". GSK Canada. Archived from the original on 28 June 2021. Retrieved 17 June 2021.
  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" (PDF). U.S. Food and Drug Administration (FDA). Archived (PDF) from the original on 28 February 2017. Retrieved 18 March 2016.
  9. ^ "Drug Approval Package: Promacta (Eltrombopag) NDA #022291". U.S. Food and Drug Administration (FDA). 14 January 2009. Archived from the original on 3 April 2021. Retrieved 22 May 2021.
  10. ^ "Summary Review" (PDF). U.S. Food and Drug Administration (FDA). 19 January 2008. Archived (PDF) from the original on 23 May 2021. Retrieved 22 May 2021.
  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. ^ Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL (June 2007). "Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist". Blood. 109 (11): 4739–4741. doi:10.1182/blood-2006-11-057968. PMID 17327409.
  13. ^ Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. (November 2007). "Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura". The New England Journal of Medicine. 357 (22): 2237–2247. doi:10.1056/NEJMoa073275. PMID 18046028.
  14. ^ McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, et al. (November 2007). "Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C". The New England Journal of Medicine. 357 (22): 2227–2236. doi:10.1056/NEJMoa073255. PMID 18046027. Archived from the original on 17 October 2021. Retrieved 12 December 2019.
  15. ^ Garnock-Jones KP, Keam SJ (2009). "Eltrombopag". Drugs. 69 (5): 567–576. doi:10.2165/00003495-200969050-00005. PMID 19368418. S2CID 265943270.
  16. ^ "Eltrombopag / Promacta". U.S. Food and Drug Administration (FDA). Archived from the original on 6 December 2016. Retrieved 18 March 2016.
  17. ^ Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, et al. (April 2017). "Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia". The New England Journal of Medicine. 376 (16): 1540–1550. doi:10.1056/NEJMoa1613878. PMC 5548296. PMID 28423296.
  18. ^ Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, et al. (March 2014). "Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug". Blood. 123 (12): 1818–1825. doi:10.1182/blood-2013-10-534743. PMC 3962161. PMID 24345753.
[edit]
  • "Eltrombopag". Drug Information Portal. U.S. National Library of Medicine.
  • "Eltrombopag olamine". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT00102739 for "SB-497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adults With Refractory Immune Thrombocytopenic Purpura (ITP)" at ClinicalTrials.gov
  • Clinical trial number NCT00370331 for "RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag (RAISE)" at ClinicalTrials.gov
  • Clinical trial number NCT00351468 for "EXTEND (Eltrombopag Extended Dosing Study) (EXTEND)" at ClinicalTrials.gov
  • Clinical trial number NCT01520909 for "Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body. (PETIT2)" at ClinicalTrials.gov
  • Clinical trial number NCT00908037 for "Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP) (PETIT)" at ClinicalTrials.gov
  • Clinical trial number NCT00516321 for "Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease" at ClinicalTrials.gov
  • Clinical trial number NCT00529568 for "Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease" at ClinicalTrials.gov
  • Clinical trial number NCT01623167 for "Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia" at ClinicalTrials.gov
  • Clinical trial number NCT00922883 for "A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients" at ClinicalTrials.gov
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