U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H33FN2O4
Molecular Weight 492.5828
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of VORAPAXAR

SMILES

CCOC(=N[C@]1([H])CC[C@]2([H])[C@@]([H])(C1)C[C@]3([H])[C@@]([H])([C@@]([H])(C)OC3=O)[C@@]2([H])/C(/[H])=C(\[H])/c4ccc(cn4)-c5cccc(c5)F)O

InChI

InChIKey=ZBGXUVOIWDMMJE-QHNZEKIYSA-N
InChI=1S/C29H33FN2O4/c1-3-35-29(34)32-23-10-11-24-20(14-23)15-26-27(17(2)36-28(26)33)25(24)12-9-22-8-7-19(16-31-22)18-5-4-6-21(30)13-18/h4-9,12-13,16-17,20,23-27H,3,10-11,14-15H2,1-2H3,(H,32,34)/b12-9+/t17-,20+,23-,24-,25+,26-,27+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/26022529

Vorapaxar is a tricyclic himbacine-derived oral thrombin receptor antagonist that acts by reversible inhibition of the protease-activated receptor-1 (PAR-1). PAR-1 is expressed on platelets and its inhibition prevents platelets from aggregation. Vorapaxar is approved by FDA and is indicated for the reduction of recurring thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Vorapaxar at the same time may cause bleeding complications including intracranial haemorrhage (ICH), when compared to standard therapy alone. That is why Vorapaxar is contraindicated in patients with prior stroke, transient ischemic attack and ICH.

Originator

Curator's Comment:: The drug was discovered by Schering-Plough and developed by Merck.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P25116
Gene ID: 2149.0
Gene Symbol: F2R
Target Organism: Homo sapiens (Human)
13.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
ZONTIVITY

Approved Use

Indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD).

Launch Date

1.39950726E12
Preventing
ZONTIVITY

Approved Use

Indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD).

Launch Date

1.39950726E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
262 ng/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORAPAXAR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
18400 ng × h/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORAPAXAR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
240 h
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORAPAXAR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg single, oral (starting)
Highest studied dose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
unhealthy, 63.5 years
n = 173
Health Status: unhealthy
Condition: coronary artery disease
Age Group: 63.5 years
Sex: M+F
Population Size: 173
Sources:
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Disc. AE: Melaena, Rectal haemorrhage...
Other AEs: Venous thrombosis...
AEs leading to
discontinuation/dose reduction:
Melaena (0.2%)
Rectal haemorrhage (0.2%)
Haemorrhage intracranial (0.3%)
Haematuria (0.2%)
Epistaxis (0.4%)
Increased tendency to bruise (0.2%)
Anaemia (0.3%)
Visual acuity reduced (0.1%)
Hypertransaminasaemia (0.1%)
Transaminases abnormal (0.1%)
Initial insomnia (0.1%)
Depressive symptom (0.1%)
Varicose vein (0.1%)
Vein pain (0.1%)
Other AEs:
Venous thrombosis (0.1%)
Sources: Page: p. 142
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: intracranial hemorrhage | transient ischemic attack
Age Group: adult
Sources:
Other AEs: Bleeding...
AEs

AEs

AESignificanceDosePopulation
Venous thrombosis 0.1%
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Depressive symptom 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Hypertransaminasaemia 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Initial insomnia 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Transaminases abnormal 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Varicose vein 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Vein pain 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Visual acuity reduced 0.1%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Haematuria 0.2%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Increased tendency to bruise 0.2%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Melaena 0.2%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Rectal haemorrhage 0.2%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Anaemia 0.3%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Haemorrhage intracranial 0.3%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Epistaxis 0.4%
Disc. AE
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources: Page: p. 142
unhealthy, adult
n = 13186
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 13186
Sources: Page: p. 142
Bleeding
2.5 mg 1 times / day multiple, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: intracranial hemorrhage | transient ischemic attack
Age Group: adult
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 1.2 uM]
no (co-administration study)
Comment: Based on in vitro results, the DDI potential of vorapaxar (as a P-gp inhibitor) with digoxin (as a P-gp substrate), is not expected to be of clinical consequences 2.5 mg dose.
Page: 63.0
yes [IC50 1.5 uM]
no (co-administration study)
Comment: In vivo drug interaction studies with warfarin and rosiglitazone were performed as vorapaxar showed a very modest potential to inhibit CYP2C8 [IC50=1.5 µM]
Page: 73.0
yes [IC50 2.2 uM]
yes [IC50 2.5 uM]
yes [IC50 30 uM]
no (co-administration study)
Comment: Vorapaxar did not affect the pharmacokinetics or pharmacodynamics of warfarin.
Page: 70.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes
yes (co-administration study)
Comment: Upon repeat co-administration, ketoconazole, a strong CYP3A inhibitor, increases the systemic exposures to vorapaxar by 2-fold, while rifampin, a strong CYP3A inducer, decreases the systemic exposure to vorapaxar by 55%.
Page: 100.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist.
2011 Jan
Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.
2012 Jan 5
Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee meeting regarding cangrelor.
2015 Apr 15
Vorapaxar in atherosclerotic disease management.
2015 May
Patents

Sample Use Guides

One tablet of ZONTIVITY orally once daily (Tablets: 2.08 mg vorapaxar)
Route of Administration: Oral
In human platelet-rich plasma,vorapaxar inhibited thrombin and TRAP-induced platelet aggregation with an IC50 of 47 and 25nM, respectively, without affecting aggregation induced by other reagents, such as ADP, TXA2 mimetic U46619 or collagen.
Name Type Language
VORAPAXAR
DASH   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
VORAPAXAR [USAN]
Common Name English
VORAPAXAR [VANDF]
Common Name English
VORAPAXAR [MART.]
Common Name English
VORAPAXAR [WHO-DD]
Common Name English
VORAPAXAR [INN]
Common Name English
CARBAMIC ACID,((1R,3AR,4AR,6R,8AR,9S,9AS)-9-((1E)-2-(5-(3-FLUOROPHENYL)-2-PYRIDINYL)ETHENYL)DODECAHYDRO-1-METHYL-3-OXONAPHTHO(2,3-C)FURAN-6-YL)-,ETHYL ESTER
Common Name English
VORAPAXAR [MI]
Common Name English
ETHYL ((1R,3AR,4AR,6R,8AR,9S,9AS)-9-((1E)-2-(5-(3-FLUOROPHENYL)PYRIDINE-2-YL)ETHEN-1-YL)-1-METHYL-3-OXODODECAHYDRONAPHTHO(2,3-C)FURAN-6-YL)CARBAMATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C78274
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
NCI_THESAURUS C1327
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
WHO-ATC B01AC26
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
NDF-RT N0000190996
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
Code System Code Type Description
DRUG CENTRAL
4870
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
NDF-RT
N0000190995
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY Protease-activated Receptor-1 Antagonists [MoA]
ChEMBL
CHEMBL493982
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
CAS
618385-01-6
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
RXCUI
1537034
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C152912
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
MERCK INDEX
M11500
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY Merck Index
INN
8852
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
IUPHAR
4047
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
PUBCHEM
10077130
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
DRUG BANK
DB09030
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
MESH
C530299
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
WIKIPEDIA
VORAPAXAR
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
EVMPD
SUB88191
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY
FDA UNII
ZCE93644N2
Created by admin on Fri Jun 25 23:01:43 UTC 2021 , Edited by admin on Fri Jun 25 23:01:43 UTC 2021
PRIMARY