Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C29H33FN2O4 |
Molecular Weight | 492.5817 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12C[C@]3([H])C[C@@]([H])(CC[C@@]3([H])[C@]([H])(\C=C\C4=CC=C(C=N4)C5=CC(F)=CC=C5)[C@]1([H])[C@@H](C)OC2=O)NC(=O)OCC
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
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/26022529
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P25116 Gene ID: 2149.0 Gene Symbol: F2R Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=23222541 |
13.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | ZONTIVITY Approved UseIndicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). Launch Date2014 |
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Preventing | ZONTIVITY Approved UseIndicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). Launch Date2014 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
262 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27121783 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18400 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27121783 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
240 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27121783 |
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
Dose | Population | Adverse events |
---|---|---|
40 mg single, oral (starting) Highest studied dose |
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%) Other AEs: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%) 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... Other AEs: Bleeding Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000ClinPharmR.pdf#page=63 Page: 63.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000ClinPharmR.pdf#page=100 Page: 100.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000ClinPharmR.pdf#page=100 Page: 100.0 |
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%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000ClinPharmR.pdf#page=100 Page: 100.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000PharmR.pdf#page=37 Page: 37.0 |
Sample Use Guides
One tablet of ZONTIVITY orally once daily (Tablets: 2.08 mg vorapaxar)
Route of Administration:
Oral
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C78274
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NCI_THESAURUS |
C1327
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WHO-ATC |
B01AC26
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NDF-RT |
N0000190996
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4870
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N0000190995
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PRIMARY | Protease-activated Receptor-1 Antagonists [MoA] | ||
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ZCE93644N2
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82702
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CHEMBL493982
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618385-01-6
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1537034
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C152912
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m11500
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100000139516
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8852
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DB09030
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C530299
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DTXSID201009336
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VORAPAXAR
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SUB88191
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ZCE93644N2
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ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)