Identification

Name
Eltrombopag
Accession Number
DB06210
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Eltrombopag
  • Eltrombopagum
External IDs
SB 497115 / SB497115
Product Ingredients
IngredientUNIICASInChI Key
Eltrombopag Olamine4U07F515LG496775-62-3TYYXAUPVEKKAFG-HTQZHWFGSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PromactaTablet, film coated12.5 mg/1OralGlaxosmithkline Inc2012-01-022019-04-30Us
PromactaTablet, film coated100 mg/1OralGlaxosmithkline Inc2014-03-102016-12-01Us
PromactaTablet, film coated25 mg/1OralNovartis2016-05-24Not applicableUs
PromactaTablet, film coated12.5 mg/1OralNovartis2016-08-22Not applicableUs
PromactaTablet, film coated50 mg/1OralGlaxosmithkline Inc2008-11-242019-04-30Us00007 4641 13 nlmimage10 fd18fea7
PromactaTablet, film coated75 mg/1OralNovartis2016-04-01Not applicableUs
PromactaTablet, film coated75 mg/1OralGlaxosmithkline Inc2009-01-052019-03-31Us00007 4642 13 nlmimage10 8c18c666
PromactaTablet, film coated50 mg/1OralNovartis2016-04-07Not applicableUs
PromactaTablet, film coated25 mg/1OralGlaxosmithkline Inc2008-11-242019-04-30Us00007 4640 13 nlmimage10 ed18f697
RevoladeTablet75 mgOralNovartisNot applicableNot applicableCanada
International/Other Brands
Promacta
Categories
UNII
S56D65XJ9G
CAS number
496775-61-2
Weight
Average: 442.4666
Monoisotopic: 442.164105212
Chemical Formula
C25H22N4O4
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-(3-{2-[(4Z)-1-(3,4-dimethylphenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1-yl}-2-hydroxyphenyl)benzoic acid
SMILES
CC1=NN(C(=O)\C1=N/NC1=C(O)C(=CC=C1)C1=CC=CC(=C1)C(O)=O)C1=CC=C(C)C(C)=C1

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.

Structured Indications
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.

TargetActionsOrganism
UThrombopoietin receptor
agonist
Human
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
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/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Coagulation factor VFactor V Leiden(A;A) / (A;G)A alleleADR Directly StudiedPatients who carry this polymorphism in F5 are associated with an increased risk of thromboembolism when treated with eltrombopag.Details
Antithrombin-III---(T;T)C > TADR Directly StudiedPatients 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
DrugInteractionDrug group
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Eltrombopag.Approved
AbirateroneThe serum concentration of Eltrombopag can be increased when it is combined with Abiraterone.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Eltrombopag.Approved
Aluminum hydroxideThe serum concentration of Eltrombopag can be decreased when it is combined with Aluminum hydroxide.Approved
AlvocidibThe serum concentration of Alvocidib can be increased when it is combined with Eltrombopag.Experimental, Investigational
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Eltrombopag.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Eltrombopag.Approved, Investigational
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Eltrombopag.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Eltrombopag.Approved
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Eltrombopag.Approved, Investigational
AzithromycinThe metabolism of Eltrombopag can be decreased when combined with Azithromycin.Approved
BenzylpenicillinThe serum concentration of Benzylpenicillin can be increased when it is combined with Eltrombopag.Approved, Vet Approved
BortezomibThe metabolism of Eltrombopag can be decreased when combined with Bortezomib.Approved, Investigational
CaffeineThe metabolism of Eltrombopag can be decreased when combined with Caffeine.Approved
Calcium AcetateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Acetate.Approved
Calcium CarbonateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Carbonate.Approved
Calcium ChlorideThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Chloride.Approved
Calcium CitrateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Citrate.Approved
Calcium glubionateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium lactate gluconate.Experimental
Calcium laevulateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium laevulate.Experimental
Calcium pangamateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium pangamate.Experimental
Calcium PhosphateThe serum concentration of Eltrombopag can be decreased when it is combined with Calcium Phosphate.Approved
CamptothecinThe serum concentration of Camptothecin can be increased when it is combined with Eltrombopag.Experimental
CarbamazepineThe metabolism of Eltrombopag can be increased when combined with Carbamazepine.Approved, Investigational
CarboplatinThe serum concentration of Carboplatin can be increased when it is combined with Eltrombopag.Approved
CaseinThe serum concentration of Eltrombopag can be decreased when it is combined with Casein.Approved
CelecoxibThe metabolism of Eltrombopag can be decreased when combined with Celecoxib.Approved, Investigational
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Eltrombopag.Withdrawn
CholesterolThe serum concentration of Cholesterol can be increased when it is combined with Eltrombopag.Experimental, Investigational
Cholic AcidThe serum concentration of Cholic Acid can be increased when it is combined with Eltrombopag.Approved
CisplatinThe serum concentration of Cisplatin can be increased when it is combined with Eltrombopag.Approved
CitalopramThe metabolism of Eltrombopag can be decreased when combined with Citalopram.Approved
CladribineThe serum concentration of Cladribine can be increased when it is combined with Eltrombopag.Approved, Investigational
ClofarabineThe serum concentration of Clofarabine can be increased when it is combined with Eltrombopag.Approved, Investigational
ClotrimazoleThe metabolism of Eltrombopag can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobimetinibThe serum concentration of Cobimetinib can be increased when it is combined with Eltrombopag.Approved
Conjugated estrogensThe serum concentration of Conjugated estrogens can be increased when it is combined with Eltrombopag.Approved
CopanlisibThe serum concentration of Copanlisib can be increased when it is combined with Eltrombopag.Approved
CrisaboroleThe metabolism of Eltrombopag can be decreased when combined with Crisaborole.Approved
Cyproterone acetateThe serum concentration of Eltrombopag can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Eltrombopag can be decreased when it is combined with Dabrafenib.Approved
DactinomycinThe serum concentration of Dactinomycin can be increased when it is combined with Eltrombopag.Approved
DasatinibThe serum concentration of Dasatinib can be increased when it is combined with Eltrombopag.Approved, Investigational
DaunorubicinThe serum concentration of Daunorubicin can be increased when it is combined with Eltrombopag.Approved
DeferasiroxThe serum concentration of Eltrombopag can be increased when it is combined with Deferasirox.Approved, Investigational
DelafloxacinThe serum concentration of Delafloxacin can be increased when it is combined with Eltrombopag.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Eltrombopag.Approved
DinoprostoneThe serum concentration of Dinoprostone can be increased when it is combined with Eltrombopag.Approved
DocetaxelThe serum concentration of Docetaxel can be increased when it is combined with Eltrombopag.Approved, Investigational
DosulepinThe metabolism of Eltrombopag can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Eltrombopag.Approved, Investigational
EfavirenzThe metabolism of Eltrombopag can be decreased when combined with Efavirenz.Approved, Investigational
EluxadolineThe serum concentration of Eluxadoline can be increased when it is combined with Eltrombopag.Approved
EnasidenibThe serum concentration of Enasidenib can be increased when it is combined with Eltrombopag.Approved
ErythromycinThe serum concentration of Erythromycin can be increased when it is combined with Eltrombopag.Approved, Vet Approved
EtoposideThe serum concentration of Etoposide can be increased when it is combined with Eltrombopag.Approved
EzetimibeThe serum concentration of Ezetimibe can be increased when it is combined with Eltrombopag.Approved
FelodipineThe metabolism of Eltrombopag can be decreased when combined with Felodipine.Approved, Investigational
Ferric CarboxymaltoseThe serum concentration of Eltrombopag can be decreased when it is combined with Ferric Carboxymaltose.Approved
Ferric CitrateThe serum concentration of Eltrombopag can be decreased when it is combined with Ferric Citrate.Approved, Investigational
Ferric pyrophosphateThe serum concentration of Eltrombopag can be decreased when it is combined with Ferric pyrophosphate.Approved
FluorouracilThe serum concentration of Fluorouracil can be increased when it is combined with Eltrombopag.Approved
FluvoxamineThe metabolism of Eltrombopag can be decreased when combined with Fluvoxamine.Approved, Investigational
Folic AcidThe serum concentration of Folic Acid can be increased when it is combined with Eltrombopag.Approved, Nutraceutical, Vet Approved
FosphenytoinThe metabolism of Eltrombopag can be increased when combined with Fosphenytoin.Approved
Gadoxetic acidThe serum concentration of Gadoxetic acid can be increased when it is combined with Eltrombopag.Approved
GefitinibThe serum concentration of Gefitinib can be increased when it is combined with Eltrombopag.Approved, Investigational
GimatecanThe serum concentration of Gimatecan can be increased when it is combined with Eltrombopag.Investigational
GlecaprevirThe serum concentration of Glecaprevir can be increased when it is combined with Eltrombopag.Approved
GlyburideThe serum concentration of Glyburide can be increased when it is combined with Eltrombopag.Approved
GrazoprevirThe serum concentration of Grazoprevir can be increased when it is combined with Eltrombopag.Approved
IdelalisibThe serum concentration of Idelalisib can be increased when it is combined with Eltrombopag.Approved
ImatinibThe serum concentration of Imatinib can be increased when it is combined with Eltrombopag.Approved
IrbesartanThe metabolism of Eltrombopag can be decreased when combined with Irbesartan.Approved, Investigational
IrinotecanThe serum concentration of Irinotecan can be increased when it is combined with Eltrombopag.Approved, Investigational
IronThe serum concentration of Eltrombopag can be decreased when it is combined with Iron.Approved
Iron DextranThe serum concentration of Eltrombopag can be decreased when it is combined with Iron Dextran.Approved, Vet Approved
Iron saccharateThe serum concentration of Eltrombopag can be decreased when it is combined with Iron saccharate.Approved
IvermectinThe serum concentration of Ivermectin can be increased when it is combined with Eltrombopag.Approved, Vet Approved
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Eltrombopag.Approved, Investigational
LapatinibThe metabolism of Eltrombopag can be decreased when combined with Lapatinib.Approved, Investigational
LeflunomideThe serum concentration of Leflunomide can be increased when it is combined with Eltrombopag.Approved, Investigational
LenvatinibThe serum concentration of Lenvatinib can be increased when it is combined with Eltrombopag.Approved
LetermovirThe serum concentration of Letermovir can be increased when it is combined with Eltrombopag.Approved
LevomenolThe serum concentration of Levomenol can be increased when it is combined with Eltrombopag.Approved, Experimental
LevosalbutamolThe serum concentration of Levosalbutamol can be increased when it is combined with Eltrombopag.Approved
LidocaineThe metabolism of Eltrombopag can be decreased when combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Liothyronine can be increased when it is combined with Eltrombopag.Approved, Vet Approved
LiotrixThe serum concentration of Liotrix can be increased when it is combined with Eltrombopag.Approved
LobeglitazoneThe metabolism of Eltrombopag can be decreased when combined with Lobeglitazone.Approved, Investigational
LosartanThe metabolism of Eltrombopag can be decreased when combined with Losartan.Approved
LumacaftorThe serum concentration of Eltrombopag can be increased when it is combined with Lumacaftor.Approved
Magnesium HydroxideThe serum concentration of Eltrombopag can be decreased when it is combined with Magnesium Hydroxide.Approved
Magnesium oxideThe serum concentration of Eltrombopag can be decreased when it is combined with Magnesium oxide.Approved
Magnesium salicylateThe serum concentration of Eltrombopag can be decreased when it is combined with Magnesium salicylate.Approved
Magnesium SulfateThe serum concentration of Eltrombopag can be decreased when it is combined with Magnesium Sulfate.Approved, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Eltrombopag.Approved
MexiletineThe metabolism of Eltrombopag can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Eltrombopag can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Eltrombopag can be increased when it is combined with Mifepristone.Approved, Investigational
MitoxantroneThe serum concentration of Mitoxantrone can be increased when it is combined with Eltrombopag.Approved, Investigational
Mycophenolate mofetilThe serum concentration of Mycophenolate mofetil can be increased when it is combined with Eltrombopag.Approved, Investigational
NevirapineThe metabolism of Eltrombopag can be decreased when combined with Nevirapine.Approved
NilotinibThe serum concentration of Nilotinib can be increased when it is combined with Eltrombopag.Approved, Investigational
NitrofurantoinThe serum concentration of Nitrofurantoin can be increased when it is combined with Eltrombopag.Approved, Vet Approved
OlmesartanThe serum concentration of Olmesartan can be increased when it is combined with Eltrombopag.Approved, Investigational
OmbitasvirThe serum concentration of Ombitasvir can be increased when it is combined with Eltrombopag.Approved
OsimertinibThe serum concentration of Eltrombopag can be decreased when it is combined with Osimertinib.Approved
OuabainThe serum concentration of Ouabain can be increased when it is combined with Eltrombopag.Approved
OxaliplatinThe serum concentration of Oxaliplatin can be increased when it is combined with Eltrombopag.Approved, Investigational
PaclitaxelThe serum concentration of Paclitaxel can be increased when it is combined with Eltrombopag.Approved, Vet Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Eltrombopag.Approved
Peginterferon alfa-2bThe serum concentration of Eltrombopag can be increased when it is combined with Peginterferon alfa-2b.Approved
PenicillamineThe serum concentration of Penicillamine can be increased when it is combined with Eltrombopag.Approved
PhenobarbitalThe metabolism of Eltrombopag can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Eltrombopag can be increased when combined with Phenytoin.Approved, Vet Approved
PibrentasvirThe serum concentration of Pibrentasvir can be increased when it is combined with Eltrombopag.Approved
PioglitazoneThe metabolism of Eltrombopag can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Eltrombopag.Approved
PonatinibThe serum concentration of Ponatinib can be increased when it is combined with Eltrombopag.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Eltrombopag.Approved
PrazosinThe serum concentration of Prazosin can be increased when it is combined with Eltrombopag.Approved
PrimidoneThe metabolism of Eltrombopag can be increased when combined with Primidone.Approved, Vet Approved
QuinineThe metabolism of Eltrombopag can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Eltrombopag can be decreased when combined with Rabeprazole.Approved, Investigational
RepaglinideThe serum concentration of Repaglinide can be increased when it is combined with Eltrombopag.Approved, Investigational
RifampicinThe metabolism of Eltrombopag can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Eltrombopag can be increased when combined with Rifapentine.Approved
RiluzoleThe serum concentration of Riluzole can be increased when it is combined with Eltrombopag.Approved, Investigational
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Eltrombopag.Approved
RopiniroleThe metabolism of Eltrombopag can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Eltrombopag can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Eltrombopag.Approved
SafinamideThe serum concentration of Safinamide can be increased when it is combined with Eltrombopag.Approved
SecobarbitalThe metabolism of Eltrombopag can be increased when combined with Secobarbital.Approved, Vet Approved
SeleniumThe serum concentration of Eltrombopag can be decreased when it is combined with Selenium.Approved, Vet Approved
SelexipagThe serum concentration of Selexipag can be increased when it is combined with Eltrombopag.Approved
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Eltrombopag.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Eltrombopag.Approved
SofosbuvirThe serum concentration of Sofosbuvir can be increased when it is combined with Eltrombopag.Approved
SorafenibThe serum concentration of Sorafenib can be increased when it is combined with Eltrombopag.Approved, Investigational
SucralfateThe serum concentration of Eltrombopag can be decreased when it is combined with Sucralfate.Approved
SulfamethoxazoleThe metabolism of Eltrombopag can be decreased when combined with Sulfamethoxazole.Approved
SulfasalazineThe serum concentration of Sulfasalazine can be increased when it is combined with Eltrombopag.Approved
SumatriptanThe serum concentration of Sumatriptan can be increased when it is combined with Eltrombopag.Approved, Investigational
TamoxifenThe serum concentration of Tamoxifen can be increased when it is combined with Eltrombopag.Approved
Taurocholic AcidThe serum concentration of Taurocholic Acid can be increased when it is combined with Eltrombopag.Experimental
Technetium Tc-99m mebrofeninThe serum concentration of Technetium Tc-99m mebrofenin can be increased when it is combined with Eltrombopag.Approved
TeniposideThe serum concentration of Teniposide can be increased when it is combined with Eltrombopag.Approved
Tenofovir disoproxilThe metabolism of Eltrombopag can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Eltrombopag can be decreased when it is combined with Teriflunomide.Approved
TestosteroneThe serum concentration of Testosterone can be increased when it is combined with Eltrombopag.Approved, Investigational
TheophyllineThe metabolism of Eltrombopag can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Eltrombopag can be decreased when combined with Ticlopidine.Approved
TopiroxostatThe metabolism of Eltrombopag can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Eltrombopag.Approved, Investigational
TrimethoprimThe metabolism of Eltrombopag can be decreased when combined with Trimethoprim.Approved, Vet Approved
ValsartanThe serum concentration of Valsartan can be increased when it is combined with Eltrombopag.Approved, Investigational
VelpatasvirThe serum concentration of Velpatasvir can be increased when it is combined with Eltrombopag.Approved
VenetoclaxThe serum concentration of Venetoclax can be increased when it is combined with Eltrombopag.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Eltrombopag.Approved, Investigational
VoxilaprevirThe serum concentration of Voxilaprevir can be increased when it is combined with Eltrombopag.Approved
ZidovudineThe serum concentration of Zidovudine can be increased when it is combined with Eltrombopag.Approved
ZucapsaicinThe metabolism of Eltrombopag can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

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]
External Links
KEGG Drug
D03978
PubChem Compound
9846180
PubChem Substance
175427059
ChemSpider
19879943
ChEBI
85010
ChEMBL
CHEMBL461101
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Eltrombopag
ATC Codes
B02BX05 — Eltrombopag
AHFS Codes
  • 20:16.00 — Hematopoietic Agents
FDA label
Download (197 KB)
MSDS
Download (33.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherLiver Cirrhosis1
1CompletedOtherPurpura, Thrombocytopaenic, Idiopathic / Purpura, Thrombocytopenic, Idiopathic1
1CompletedOtherPurpura, Thrombocytopenic, Idiopathic1
1CompletedOtherThrombocytopenias1
1CompletedSupportive CareSarcomas / Thrombocytopenias / Thrombopoiesis1
1CompletedTreatmentChronic Hepatitis C Infection / Thrombocytopenias1
1CompletedTreatmentHealthy Volunteers / Purpura, Thrombocytopaenic, Idiopathic / Purpura, Thrombocytopenic, Idiopathic1
1CompletedTreatmentHealthy Volunteers / Purpura, Thrombocytopenic, Idiopathic1
1CompletedTreatmentHematopoietic Subsyndrome of Acute Radiation Syndrome / Thrombocytopenias1
1CompletedTreatmentHepatic Impairment / Purpura, Thrombocytopaenic, Idiopathic / Purpura, Thrombocytopenic, Idiopathic1
1CompletedTreatmentImpaired Renal Function / Purpura, Thrombocytopaenic, Idiopathic / Purpura, Thrombocytopenic, Idiopathic1
1CompletedTreatmentMyelodysplastic Syndrome1
1CompletedTreatmentMyelodysplastic Syndrome / Thrombocytopenias1
1TerminatedPreventionNeoplasms, Connective and Soft Tissue / Sarcoma, Osteogenic / Soft Tissue Sarcoma (STS)1
1TerminatedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
1, 2Active Not RecruitingTreatmentMale and Female Subjects, Greater Than 60 Years of Age With Non-M3 AML1
1, 2Active Not RecruitingTreatmentMyelodysplastic Syndromes (MDS) / Thrombocytopenias1
1, 2RecruitingTreatmentAnemias / Aplastic Anaemia (AA) / Neutropenias / Pancytopenia / Thrombocytopenias1
1, 2RecruitingTreatmentCMML / Thrombocytopenias1
1, 2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Thrombocytopenias1
1, 2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia / Chronic Myeloid Leukemia (CML) / Leukemias1
2Active Not RecruitingTreatmentAplastic Anaemia (AA) / Aplastic Anemia Treatment / Eltrombopag / Moderate Aplastic Anemia / Moderate Aplastic Anemia Treatment / Unilineage Bone Marrow Failure Disorders1
2Active Not RecruitingTreatmentAplastic Anaemia (AA) / Congenital Hypoplastic Anemia / Thrombocytopenias1
2Active Not RecruitingTreatmentCLL / Leukemias1
2Active Not RecruitingTreatmentHaemorrhage / Thrombocytopenias / Wiskott-Aldrich Syndrome (WAS)1
2Active Not RecruitingTreatmentInherited Platelet Disorders1
2Active Not RecruitingTreatmentLeukemias2
2Active Not RecruitingTreatmentMyelodysplastic Syndromes / Thrombocytopenias1
2Active Not RecruitingTreatmentSevere Aplastic Anemia (SAA)1
2Active Not RecruitingTreatmentThrombocytopenias1
2CompletedSupportive CareThrombocytopenias2
2CompletedTreatmentBlood Platelet Disorders1
2CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C, Chronic / Thrombocytopenias1
2CompletedTreatmentCytopaenia2
2CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)1
2CompletedTreatmentImmune Thrombocytopenic Purpura ( ITP )1
2CompletedTreatmentLeukaemia, Acute1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS)1
2CompletedTreatmentLiver Diseases1
2CompletedTreatmentModerate Aplastic Anemia / Severe Aplastic Anemia (SAA) / Very Severe Aplastic Anemia1
2CompletedTreatmentMultiple Myeloma (MM) / Thrombocytopenias1
2CompletedTreatmentPurpura, Thrombocytopaenic, Idiopathic3
2CompletedTreatmentThrombocytopenias1
2Not Yet RecruitingTreatmentCongenital Hypoplastic Anemia1
2Not Yet RecruitingTreatmentSevere Aplastic Anemia (SAA)1
2RecruitingSupportive CareAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Secondary Acute Myeloid Leukemia1
2RecruitingTreatmentAdult Myelodysplastic Syndrome / Anemias / Chronic Myelomonocytic Leukemia1
2RecruitingTreatmentAplastic Anaemia (AA)1
2RecruitingTreatmentBlood And Marrow Transplantation1
2RecruitingTreatmentImmune Thrombocytopenia1
2RecruitingTreatmentImmune Thrombocytopenia / Platelet disorders1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentMyelodysplastic Syndromes1
2RecruitingTreatmentMyelodysplastic Syndromes / Thrombocytopenias1
2RecruitingTreatmentPediatric Patients Undergoing Allogeneic Cord Blood Transplantation1
2RecruitingTreatmentPrimacy Immune Thrombocytopenia1
2RecruitingTreatmentThrombocytopenias1
2TerminatedTreatmentFollicular Lymphoma (FL) / Mantle Cell Lymphoma (MCL) / Marginal Zone Lymphoma1
2Unknown StatusTreatmentAutoimmune Thrombocytopenia / Autoimmune Thrombocytopenic Purpura / Chronic Lymphocytic Leukaemia (CLL) / Non Hodgkin Lymphoma (NHL) / Purpura, Thrombocytopenic, Idiopathic1
2Unknown StatusTreatmentBone Marrow Failure Syndromes / Haematological Malignancies1
2WithdrawnTreatmentThrombocytopenias1
2, 3RecruitingTreatmentAplastic Anaemia (AA)1
2, 3Unknown StatusTreatmentChronic Hepatitis C Infection / Thrombocytopenias1
3Active Not RecruitingTreatmentPurpura, Thrombocytopenic, Idiopathic and Hepatitis C1
3CompletedTreatmentChronic Hepatitis C Infection1
3CompletedTreatmentHepatitis C, Chronic2
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Purpura, Thrombocytopenic, Idiopathic1
3CompletedTreatmentPurpura, Thrombocytopaenic, Idiopathic1
3CompletedTreatmentPurpura, Thrombocytopenic, Idiopathic2
3CompletedTreatmentThrombocytopenias1
3Enrolling by InvitationTreatmentGynecologic Cancers / Tumors, Solid1
3RecruitingSupportive CareImmune Thrombocytopenic Purpura ( ITP )1
3RecruitingTreatmentImmune Thrombocytopenic Purpura ( ITP )1
3RecruitingTreatmentSevere Aplastic Anemia (SAA)1
3TerminatedTreatmentChronic Liver Diseases (CLD) / HBV / HCV / Hepatitis B Virus (HBV) / Hepatitis C Virus (HCV) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Liver Diseases / Nash / Non-Alcoholic Steatohepatitis / Thrombocytopenias1
3TerminatedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)1
4CompletedDiagnosticIdiopathic Thrombocytopenic Purpura (ITP)1
4CompletedTreatmentPurpura, Thrombocytopaenic, Idiopathic1
4WithdrawnNot AvailableThrombocytopenias1
Not AvailableActive Not RecruitingNot AvailablePurpura, Thrombocytopaenic, Idiopathic1
Not AvailableCompletedNot AvailableChronic Hepatitis C Infection2
Not AvailableCompletedNot AvailableImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableImmune Thrombocytopenic Purpura ( ITP )1
Not AvailableCompletedNot AvailablePurpura, Thrombocytopaenic, Idiopathic2
Not AvailableCompletedNot AvailableThrombocytopenias2
Not AvailableRecruitingNot AvailableImmune Thrombocytopenia1
Not AvailableRecruitingNot AvailableImmune Thrombocytopenia / Purpura, Thrombocytopenic, Idiopathic1
Not AvailableRecruitingSupportive CareMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral12.5 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral75 mg/1
TabletOral12.5 mg
TabletOral25 mg
TabletOral50 mg
TabletOral75 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8052995Yes2008-02-012028-02-01Us
US6280959Yes1999-04-302019-04-30Us
US7790704Yes2001-11-242021-11-24Us
US7452874Yes2001-11-242021-11-24Us
US7473686Yes2001-11-242021-11-24Us
US7160870Yes2003-05-202023-05-20Us
US7795293Yes2003-11-212023-11-21Us
US7547719Yes2006-01-132026-01-13Us
US7332481Yes2001-11-242021-11-24Us
US8062665Yes2008-02-012028-02-01Us
US8052994Yes2008-02-012028-02-01Us
US8071129Yes2008-02-012028-02-01Us
US8052993Yes2008-02-012028-02-01Us
US8828430Yes2008-02-012028-02-01Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityEltrombopag 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
PropertyValueSource
Water Solubility0.0103 mg/mLALOGPS
logP4.02ALOGPS
logP6.03ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)3.99ChemAxon
pKa (Strongest Basic)0.17ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area114.59 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.48 m3·mol-1ChemAxon
Polarizability47.64 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6946
Blood Brain Barrier-0.6616
Caco-2 permeable-0.5811
P-glycoprotein substrateNon-substrate0.6578
P-glycoprotein inhibitor INon-inhibitor0.8297
P-glycoprotein inhibitor IINon-inhibitor0.9187
Renal organic cation transporterNon-inhibitor0.944
CYP450 2C9 substrateNon-substrate0.5991
CYP450 2D6 substrateNon-substrate0.8495
CYP450 3A4 substrateSubstrate0.5424
CYP450 1A2 substrateNon-inhibitor0.8173
CYP450 2C9 inhibitorInhibitor0.6357
CYP450 2D6 inhibitorNon-inhibitor0.8982
CYP450 2C19 inhibitorNon-inhibitor0.7625
CYP450 3A4 inhibitorNon-inhibitor0.7595
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6304
Ames testNon AMES toxic0.5993
CarcinogenicityNon-carcinogens0.5481
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.1796 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9862
hERG inhibition (predictor II)Non-inhibitor0.6936
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (91.2 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
show 4 more
Substituents
Biphenyl / Benzoic acid or derivatives / Benzoic acid / Benzoyl / Phenylhydrazine / Xylene / O-xylene / 1-hydroxy-4-unsubstituted benzenoid / Phenol / Pyrazolinone
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrazoles, hydrazines, benzoic acids (CHEBI:85010)

Targets

Details
1. Thrombopoietin receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.
Gene Name
MPL
Uniprot ID
P40238
Uniprot Name
Thrombopoietin receptor
Molecular Weight
71244.08 Da
References
  1. Kuter DJ: Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med. 2009;60:193-206. [PubMed:19642221]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. 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]

Drug created on March 19, 2008 10:17 / Updated on November 22, 2017 12:36