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Details

Stereochemistry ACHIRAL
Molecular Formula C25H21N4O4.C5H14NO
Molecular Weight 545.6294
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ELTROMBOPAG CHOLINE

SMILES

C[N+](C)(C)CCO.CC1=NN(C(=O)\C1=N/NC2=C(O)C(=CC=C2)C3=CC(=CC=C3)C([O-])=O)C4=CC=C(C)C(C)=C4

InChI

InChIKey=XSHFVAAXJHNDKZ-OUFJFOJPSA-M
InChI=1S/C25H22N4O4.C5H14NO/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;1-6(2,3)4-5-7/h4-13,26,30H,1-3H3,(H,32,33);7H,4-5H2,1-3H3/q;+1/p-1/b27-22-;

HIDE SMILES / InChI

Molecular Formula C25H21N4O4
Molecular Weight 441.4586
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C5H14NO
Molecular Weight 104.1708
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Eltrombopag is a thrombopoietin (TPO) nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. Eltrombopag under brand name promacta is approved for the treatment of the 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 approved 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 and to treat patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

CNS Activity

Curator's Comment: Known to be CNS penetrant in mouse; bovine. Human data not available

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PROMACTA

Approved Use

PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Limitations of Use: PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. PROMACTA is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. Limitations of Use: PROMACTA should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection. Treatment of Severe Aplastic Anemia PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

Launch Date

1.22713919E12
Primary
PROMACTA

Approved Use

PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Limitations of Use: PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. PROMACTA is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. Limitations of Use: PROMACTA should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection. Treatment of Severe Aplastic Anemia PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

Launch Date

1.22713919E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.03 μg/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ELTROMBOPAG plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
101 μg × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ELTROMBOPAG plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21 h
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ELTROMBOPAG plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ELTROMBOPAG plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources: Page: p.1747
unhealthy, 52
n = 9
Health Status: unhealthy
Condition: Thrombocytopenia
Age Group: 52
Sex: M+F
Population Size: 9
Sources: Page: p.1747
75 mg 1 times / day multiple, oral (max)
Recommended
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocytopenia|Aplastic anemia
Sources: Page: p.1
Disc. AE: Hepatic decompensation, Hepatotoxicity...
AEs leading to
discontinuation/dose reduction:
Hepatic decompensation
Hepatotoxicity
Portal vein thrombosis
Sources: Page: p.1
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Other AEs: Hemorrhage, Ataxia...
Other AEs:
Hemorrhage (serious, 3 patients)
Ataxia (serious, 1 patient)
Dyspnea (serious, 3 patients)
Colitis (serious, 1 patient)
Diarrhea (serious, 1 patient)
Graft versus host disease (serious, 1 patient)
Rash (serious, 1 patient)
Seizure (serious, 1 patient)
Cellulitis (serious, 1 patient)
Hypoxia (serious, 1 patient)
Infection (serious, 5 patients)
Nausea (below serious, 12 patients)
Abdominal pain (below serious, 1 patient)
Ascites (below serious, 1 patient)
Headache (below serious, 2 patients)
Bilirubin increased (below serious, 10 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hepatic decompensation Disc. AE
75 mg 1 times / day multiple, oral (max)
Recommended
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocytopenia|Aplastic anemia
Sources: Page: p.1
Hepatotoxicity Disc. AE
75 mg 1 times / day multiple, oral (max)
Recommended
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocytopenia|Aplastic anemia
Sources: Page: p.1
Portal vein thrombosis Disc. AE
75 mg 1 times / day multiple, oral (max)
Recommended
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Thrombocytopenia|Aplastic anemia
Sources: Page: p.1
Abdominal pain below serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Ascites below serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Bilirubin increased below serious, 10 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Nausea below serious, 12 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Headache below serious, 2 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Ataxia serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Cellulitis serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Colitis serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Diarrhea serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Graft versus host disease serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Hypoxia serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Rash serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Seizure serious, 1 patient
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Dyspnea serious, 3 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Hemorrhage serious, 3 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
Infection serious, 5 patients
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: Thrombocytopenia
Population Size: 39
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
weak
yes [IC50 2.7 uM]
yes (co-administration study)
Comment: concurrent eltrombopag and rosuvastatin treatment resulted in increased rosuvastatin Cmax by 2.03-fold and AUC by 55%
Page: 30, 76
yes [IC50 24.8 uM]
yes [IC50 3.5 uM]
yes [IC50 9.3 uM]
yes
yes
yes
yes
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Eltrombopag: Is this "24 karat gold platelet" treatment for thrombocytopenia in cirrhosis associated with hepatitis C?
2008 Apr
Eltrombopag: an effective remedy for thrombocytopaenia?
2008 Jun
Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects.
2011 Sep
The biology of thrombopoietin and thrombopoietin receptor agonists.
2013 Jul
Patents

Sample Use Guides

Chronic Immune (Idiopathic) Thrombocytopenia: use the lowest dose of PROMACTA (eltrombopag) to achieve and maintain a platelet count greater than or equal to 50 x 109 /L as necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Initial Dose Regimen: Adult and Pediatric Patients 6 Years and Older with ITP: Initiate PROMACTA at a dose of 50 mg once daily, except in patients who are of East Asian ancestry (such as Chinese, Japanese, Taiwanese, or Korean) or who have mild to severe hepatic impairment (Child-Pugh Class A, B, C). For patients of East Asian ancestry with ITP, initiate PROMACTA at a reduced dose of 25 mg once daily. For patients with ITP and mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiate PROMACTA at a reduced d ose of 25 mg once daily. For patients of East Asian ancestry with ITP and hepatic impairment (Child-Pugh Class A, B, C), consider initiating PROMACTA at a reduced dose of 12.5 mg once daily. Pediatric Patients with ITP Aged 1 to 5 Years: Initiate PROMACTA at a dose of 25 mg once daily. Monitoring and Dose Adjustment: After initiating PROMACTA, adjust the dose to achieve and maintain a platelet count greater than or equal to 50 x 109 /L as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with PROMACTA and modify the dosage regimen of PROMACTA based on platelet counts as outlined in Table 1. During therapy with PROMACTA, assess CBCs with differentials, including platelet counts, weekly until a stable platelet count has been achieved. Obtain CBCs with differentials, including platelet counts, monthly thereafter. When switching between Chronic Hepatitis C-associated Thrombocytopenia Use the lowest dose of PROMACTA to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Dose adjustments are based upon the platelet count response. Do not use PROMACTA to normalize platelet counts. In clinical trials, platelet counts generally began to rise within the first week of treatment with PROMACTA. Initial Dose Regimen: Initiate PROMACTA at a dose of 25 mg once daily. Monitoring and Dose Adjustment: Adjust the dose of PROMACTA in 25-mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy. Monitor platelet counts every week prior to starting antiviral therapy. During antiviral therapy, adjust the dose of PROMACTA to avoid dose reductions of peginterferon. Monitor CBCs with differentials, including platelet counts, weekly during antiviral therapy until a stable platelet count is achieved. Monitor platelet counts monthly thereafter. Do not exceed a dose of 100 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with PROMACTA.
Route of Administration: Oral
It was investigated eltrombopag's effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, and CD41+ cells in bone marrow compartment without effects on mouse bone marrow cells in the NOD/SCID mice xenotrans plant model. Eltrombopag increased peripheral human platelets and white blood cells. Both eltrombopag and recombinant human TPO (rhTPO) induced phosphorylation of STAT5 of CD34+ CD41-, CD34- CD41+, and CD34- CD41- cells. For this purpose the cells were treated with 100ng/ml rhTPO or 3μg/ml eltrombopag for 10 to 60 minutes at 37°C. rhTPO preferentially induced pSTAT3, pAKT, and more pSTAT5 in CD34- C41+ cells, while eltrombopag had no effects on pSTAT3. Eltrombopag differed somewhat from rhTPO in the signal transduction pathways by favoring earlier HSC/HPC populations.
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:40:10 UTC 2023
Edited
by admin
on Sat Dec 16 15:40:10 UTC 2023
Record UNII
F9G8XE24IB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ELTROMBOPAG CHOLINE
Common Name English
ETHANAMINIUM, 2-HYDROXY-N,N,N-TRIMETHYL-, 3'-((2Z)-2-(1-(3,4-DIMETHYLPHENYL)-1,5-DIHYDRO-3-METHYL-5-OXO-4H-PYRAZOL-4-YLIDENE)HYDRAZINYL)-2'-HYDROXY(1,1'-BIPHENYL)-3-CARBOXYLATE (1:1)
Systematic Name English
ALVAIZ
Brand Name English
Code System Code Type Description
SMS_ID
300000039932
Created by admin on Sat Dec 16 15:40:10 UTC 2023 , Edited by admin on Sat Dec 16 15:40:10 UTC 2023
PRIMARY
FDA UNII
F9G8XE24IB
Created by admin on Sat Dec 16 15:40:10 UTC 2023 , Edited by admin on Sat Dec 16 15:40:10 UTC 2023
PRIMARY
CAS
2336813-25-1
Created by admin on Sat Dec 16 15:40:10 UTC 2023 , Edited by admin on Sat Dec 16 15:40:10 UTC 2023
PRIMARY
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