Eltrombopag

Identification

Name

Eltrombopag

Accession Number

DB06210

Description

Eltrombopag is used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood. Eltrombopag has also been recently approved (late 2012) for the treatment of thrombocytopenia (low blood platelet counts) in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy.

Type

Small Molecule

Groups

Approved

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Eltrombopag (DB06210)

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Weight

Average: 442.4666
Monoisotopic: 442.164105212

Chemical Formula

C₂₅H₂₂N₄O₄

Synonyms

• Eltrombopag
• Eltrombopagum

External IDs

• SB 497115
• SB-497115
• SB497115

Pharmacology

Indication

Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction.

Associated Conditions

• Severe Aplastic Anemia (SAA)
• Thrombocytopenia
• Refractory Aplastic anemia
• Refractory immune thrombocytopenia

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Not Available

Mechanism of action

Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor. Eltrombopag is a stimulator of STAT and JAK phosphorylation. Unlike recombinant TPO or romiplostim, Eltrombopag does not activate the AKT pathway in any way. It should be noted that when given to patients with aplastic anemia, other lineages besides platelet count were increased, suggesting that either eltrombopag enhanced the effect of TPO in vivo; or there is a yet uncovered mechanism of action at work.

Target	Actions	Organism
UThrombopoietin receptor	agonist	Humans

Absorption

Peak absorption of Eltrombopag occurs around 2-6 hours following oral administration, and the total oral absorption of drug-related material following a 75 mg dose was estimated to be at least 52%.

Volume of distribution

Based on a radiolabel study, the concentration of eltrombopag in blood cells is approximately 50% to 79% of plasma concentrations.

Protein binding

Eltrombopag is highly protein bound (>99%).

Metabolism

Eltrombopag is predominantly through pathways including cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism of eltrombopag. UGT1A1 and UGT1A3 are responsible for the glucuronidation of eltrombopag.

Route of elimination

Eltrombopag is eliminated primarily via the feces (59%), along with 31% being renally excreted.

Half-life

About 21-32 hours in healthy patients. About 26-35 hours in patients with idiopathic thrombocytopenic purpura.

Clearance

Not Available

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

Eltrombopag may cause hepatotoxicity, especially if administered in combination with interferon and ribavirin in patients with chronic hepatitis C (may increase the risk of hepatic decompensation).

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Coagulation factor V	Factor V Leiden	(A;A) / (A;G)	A allele	ADR Directly Studied	Patients who carry this polymorphism in F5 are associated with an increased risk of thromboembolism when treated with eltrombopag.	Details
Antithrombin-III	---	(T;T)	C > T	ADR Directly Studied	Patients who carry this polymorphism in SERPINC1 are associated with antithrombin III deficiency and an increased risk of thromboembolism when treated with eltrombopag.	Details

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	The metabolism of Abacavir can be decreased when combined with Eltrombopag.
Abametapir	The serum concentration of Eltrombopag can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Eltrombopag can be increased when combined with Abatacept.
Abemaciclib	Eltrombopag may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abiraterone	The serum concentration of Eltrombopag can be increased when it is combined with Abiraterone.
Acemetacin	The metabolism of Acemetacin can be decreased when combined with Eltrombopag.
Acenocoumarol	The metabolism of Eltrombopag can be decreased when combined with Acenocoumarol.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Eltrombopag.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be decreased when combined with Eltrombopag.
Acyclovir	The metabolism of Eltrombopag can be decreased when combined with Acyclovir.

Additional Data Available

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Extended Description
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Severity
Severity
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Evidence Level
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Food Interactions

• Avoid multivalent ions. Polyvalent cations in food or supplements will be chelated by eltrombopag; therefore, they should be separated by 4 hours before or 2 hours after taking eltrombopag.
• Take on an empty stomach. Separate the administration of eltrombopag from food by at least 1 hour before and 2 hours after eating.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Eltrombopag olamine	4U07F515LG	496775-62-3	PLILLUUXAVKBPY-SBIAVEDLSA-N

Product Images

International/Other Brands

Promacta / Revolade

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Promacta	Tablet, film coated	12.5 mg/1	Oral	Novartis Pharmaceuticals Corporation	2016-08-22	Not applicable
Promacta	Powder, for suspension	12.5 mg/1	Oral	Novartis Pharmaceuticals Corporation	2018-09-27	Not applicable
Promacta	Tablet, film coated	100 mg/1	Oral	Glaxosmithkline Inc	2014-03-10	2016-11-28
Promacta	Tablet, film coated	50 mg/1	Oral	Glaxosmithkline Inc	2008-11-24	2019-04-30
Promacta	Tablet, film coated	25 mg/1	Oral	Novartis Pharmaceuticals Corporation	2016-05-24	Not applicable
Promacta	Tablet, film coated	100 mg/1	Oral	GlaxoSmithKline LLC	2012-11-16	2012-11-16
Promacta	Tablet, film coated	12.5 mg/1	Oral	Glaxosmithkline Inc	2012-01-02	2019-04-30
Promacta	Tablet, film coated	75 mg/1	Oral	Novartis Pharmaceuticals Corporation	2016-04-01	Not applicable
Promacta	Tablet, film coated	25 mg/1	Oral	Glaxosmithkline Inc	2008-11-24	2019-04-30
Promacta	Powder, for suspension	25 mg/1	Oral	Glaxosmithkline Inc	2016-11-27	2016-11-28

Additional Data Available

Application Number
Application Number
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A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
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A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

B02BX05 — Eltrombopag

• B02BX — Other systemic hemostatics
• B02B — VITAMIN K AND OTHER HEMOSTATICS
• B02 — ANTIHEMORRHAGICS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Acids, Carbocyclic
• BCRP/ABCG2 Inhibitors
• Benzene Derivatives
• Blood and Blood Forming Organs
• Breast Cancer Resistance Protein Inhibitors
• Cytochrome P-450 CYP1A2 Substrates
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2C8 Inhibitors (moderate)
• Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Hematinics
• Hemostatics
• Increased Megakaryocyte Maturation
• Increased Platelet Production
• OATP1B1/SLCO1B1 Inhibitors
• Organic Anion Transporting Polypeptide 1B1 Inhibitors
• Thrombopoietin Receptor Agonist
• Thrombopoietin Receptor Agonists
• UGT1A1 Inhibitors
• UGT1A1 Substrates
• UGT1A3 Inhibitors
• UGT1A3 substrates
• UGT1A4 Inhibitors
• UGT1A6 Inhibitors
• UGT1A9 Inhibitors
• UGT2B15 Inhibitors
• UGT2B7 Inhibitors

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Biphenyls and derivatives

Direct Parent

Biphenyls and derivatives

Alternative Parents

Benzoic acids / o-Xylenes / Phenylhydrazines / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / Pyrazolones / Monocarboxylic acids and derivatives / Hydrazones / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds

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Substituents

1-hydroxy-4-unsubstituted benzenoid / Aromatic heteromonocyclic compound / Azacycle / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Biphenyl / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Hydrazone / Hydrocarbon derivative / Monocarboxylic acid or derivatives / O-xylene / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenol / Phenylhydrazine / Pyrazoline / Pyrazolinone / Xylene

show 16 more

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pyrazoles, hydrazines, benzoic acids (CHEBI:85010)

Chemical Identifiers

UNII

S56D65XJ9G

CAS number

496775-61-2

InChI Key

XDXWLKQMMKQXPV-QYQHSDTDSA-N

InChI

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-

IUPAC Name

3'-{2-[(4Z)-1-(3,4-dimethylphenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1-yl}-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid

SMILES

CC1=NN(C(=O)\C1=N/NC1=CC=CC(C2=CC=CC(=C2)C(O)=O)=C1O)C1=CC=C(C)C(C)=C1

References

Synthesis Reference

http://doc.sciencenet.cn/upload/file/2011531154034454.pdf

General References

1. Zekry A, Freiman J: Eltrombopag: Is this "24 karat gold platelet" treatment for thrombocytopenia in cirrhosis associated with hepatitis C? Hepatology. 2008 Apr;47(4):1418-21. doi: 10.1002/hep.22300. [PubMed:18366111]
2. Mondelli MU: Eltrombopag: an effective remedy for thrombocytopaenia? J Hepatol. 2008 Jun;48(6):1030-2. doi: 10.1016/j.jhep.2008.03.008. Epub 2008 Mar 31. [PubMed:18433923]
3. Tarantino MD, Fogarty P, Mayer B, Vasey SY, Brainsky A: Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia. Blood Coagul Fibrinolysis. 2013 Apr;24(3):284-96. doi: 10.1097/MBC.0b013e32835fac99. [PubMed:23492914]
4. Kiang TK, Ensom MH, Chang TK: UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther. 2005 Apr;106(1):97-132. Epub 2005 Jan 12. [PubMed:15781124]
5. Deng Y, Madatian A, Wire MB, Bowen C, Park JW, Williams D, Peng B, Schubert E, Gorycki F, Levy M, Gorycki PD: Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects. Drug Metab Dispos. 2011 Sep;39(9):1734-46. doi: 10.1124/dmd.111.040170. Epub 2011 Jun 6. [PubMed:21646437]
6. Kuter DJ: The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3. [PubMed:23821332]
7. Eltrombopag [File]

External Links

KEGG Drug

D03978

PubChem Compound

9846180

PubChem Substance

175427059

ChemSpider

19879943

RxNav

711942

ChEBI

85010

ChEMBL

CHEMBL461101

ZINC

ZINC000011679756

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Eltrombopag

AHFS Codes

• 20:16.00 — Hematopoietic Agents

FDA label

Download (197 KB)

MSDS

Download (33.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Diagnostic	Idiopathic Thrombocytopenic Purpura	1
4	Completed	Treatment	Purpura, Thrombocytopaenic, Idiopathic	1
4	Not Yet Recruiting	Treatment	Immune Thrombocytopenia	1
4	Recruiting	Treatment	Aplastic Anemia	1
4	Recruiting	Treatment	Eltrombopag	1
4	Recruiting	Treatment	Hematological Neoplasms	1
4	Recruiting	Treatment	Primary Immune Thrombocytopenia	1
4	Recruiting	Treatment	Primary Immune Thrombocytopenia (ITP)	1
4	Withdrawn	Not Available	Thrombocytopenia	1
3	Completed	Supportive Care	Immune Thrombocytopenic Purpura ( ITP )	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Powder, for suspension	Oral	12.5 mg/1
Powder, for suspension	Oral	25 mg/1
Tablet, film coated	Oral	100 mg/1
Tablet, film coated	Oral	12.5 mg/1
Tablet, film coated	Oral	25 mg/1
Tablet, film coated	Oral	50 mg/1
Tablet, film coated	Oral	75 mg/1
Powder, for suspension	Oral	25 MG
Tablet	Oral
Tablet, coated	Oral	25 mg
Tablet, coated	Oral	50 mg
Tablet, film coated	Oral	75 MG
Tablet, film coated	Oral	12.5 mg
Tablet, film coated	Oral	25 mg
Tablet, film coated	Oral	50 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US8052995	Yes	2011-11-08	2028-02-01
US6280959	Yes	2001-08-28	2019-04-30
US7790704	Yes	2010-09-07	2021-11-24
US7452874	Yes	2008-11-18	2021-11-24
US7473686	Yes	2009-01-06	2021-11-24
US7160870	Yes	2007-01-09	2023-05-20
US7795293	Yes	2010-09-14	2023-11-21
US7547719	Yes	2009-06-16	2026-01-13
US7332481	Yes	2008-02-19	2021-11-24
US8062665	Yes	2011-11-22	2028-02-01
US8052994	Yes	2011-11-08	2028-02-01
US8071129	Yes	2011-12-06	2028-02-01
US8052993	Yes	2011-11-08	2028-02-01
US8828430	Yes	2014-09-09	2028-02-01

Additional Data Available

Filed On
Filed On
Available for Purchase
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Eltrombopag olamine is practically insoluble in aqueous buffer across a pH range of 1 to 7.4, and is sparingly soluble in water.	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.0103 mg/mL	ALOGPS
logP	4.02	ALOGPS
logP	6.03	ChemAxon
logS	-4.6	ALOGPS
pKa (Strongest Acidic)	3.97	ChemAxon
pKa (Strongest Basic)	-0.12	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	7	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	114.59 Å2	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	126.48 m3·mol-1	ChemAxon
Polarizability	47.7 Å3	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.6946
Blood Brain Barrier	-	0.6616
Caco-2 permeable	-	0.5811
P-glycoprotein substrate	Non-substrate	0.6578
P-glycoprotein inhibitor I	Non-inhibitor	0.8297
P-glycoprotein inhibitor II	Non-inhibitor	0.9187
Renal organic cation transporter	Non-inhibitor	0.944
CYP450 2C9 substrate	Non-substrate	0.5991
CYP450 2D6 substrate	Non-substrate	0.8495
CYP450 3A4 substrate	Substrate	0.5424
CYP450 1A2 substrate	Non-inhibitor	0.8173
CYP450 2C9 inhibitor	Inhibitor	0.6357
CYP450 2D6 inhibitor	Non-inhibitor	0.8982
CYP450 2C19 inhibitor	Non-inhibitor	0.7625
CYP450 3A4 inhibitor	Non-inhibitor	0.7595
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6304
Ames test	Non AMES toxic	0.5993
Carcinogenicity	Non-carcinogens	0.5481
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.1796 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9862
hERG inhibition (predictor II)	Non-inhibitor	0.6936

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (91.2 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on March 19, 2008 10:17 / Updated on January 23, 2021 21:03