Eltrombopag

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

Eltrombopag
Clinical data
Trade namesPromacta, Revolade, others
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
E number{{#property:P628}}
CompTox Dashboard (EPA)
  • {{#property:P3117}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value).
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value).
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.[6] 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.[6][7][8]

Eltrombopag was approved for medical use in the US in November 2008,[9] and authorized in the European Union in March 2010.[4]

Medical uses

[edit | edit source]

Eltrombopag is indicated for the treatment of thrombocytopenia in people with persistent or chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy;[3] for the treatment of thrombocytopenia in people with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy;[3] in combination with standard immunosuppressive therapy for the first-line treatment of people with severe aplastic anemia;[3] and for the treatment of people with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.[3][10]

Development

[edit | edit source]

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.[11]

Clinical trials

[edit | edit source]

Eltrombopag has been shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura (ITP)[12] and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).[13]

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).[14]

History

[edit | edit source]

Eltrombopag received breakthrough therapy designation from the US Food and Drug Administration (FDA) in February 2014, for people with aplastic anemia for which immunosuppression has not been successful.[15] In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.[16]

Society and culture

[edit | edit source]
[edit | edit source]

In October 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Eltrombopag Viatris, intended for the treatment of people with primary immune thrombocytopenia (ITP) and thrombocytopenia associated with chronic hepatitis C.[17] The applicant for this medicinal product is Viatris Limited.[17] Eltrombopag Viatris was authorized in December 2024.[18]

Research

[edit | edit source]

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.[19] Eltrombopag has been shown to target ELAVL1/HuR-RNA interactions affecting gene expression, iron metabolism, and glycoprotein hormones, alpha polypeptide (CGA) levels.[20] The transcription factor EB (TFEB) has been detected as an Eltrombopag target in starvation-induced conditions. [21]

References

[edit | edit source]
  1. ^ a b Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  2. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  3. ^ a b c d e f g h i Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  4. ^ a b c d Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  5. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  6. ^ a b Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  7. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  8. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  9. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  10. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  11. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  12. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  13. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  14. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  15. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  16. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  17. ^ a b Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  18. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  19. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  20. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  21. ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
[edit | edit source]
  • 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

Lua error in mw.title.lua at line 392: bad argument #2 to 'title.new' (unrecognized namespace name 'Portal'). Lua error in Module:Authority_control at line 153: attempt to index field 'wikibase' (a nil value).

Retrieved from "http://70.231.62.181/index.php?title=Eltrombopag&oldid=18229114"