Details of the Drug

General Information of Drug (ID: DMA16BR)

• Drug Name: Vorapaxar
• Synonyms: Vorapaxar; 618385-01-6; Zontivity; SCH-530348; SCH530348; UNII-ZCE93644N2; CHEMBL493982; CHEBI:82702; ZCE93644N2; MK-5348; ethyl ((1R,3aR,4aR,6R,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)carbamate; Ethyl [(1r,3ar,4ar,6r,8ar,9s,9as)-9-{(E)-2-[5-(3-Fluorophenyl)pyridin-2-Yl]ethenyl}-1-Methyl-3-Oxododecahydronaphtho[2,3-C]furan-6-Yl]carbamate; Vorapaxar [USAN:INN]; Carbamic acid, [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)-2- pyridinyl]etheny

Indication

Disease Entry	ICD 11	Status	REF
Myocardial infarction	BA41-BA43	Approved	[1]
Stroke	8B20	Investigative	[2]

• ATC Code:
  B01AC26: Vorapaxar
  B01AC: Platelet aggregation inhibitors excl. heparin
  B01A: ANTITHROMBOTIC AGENTS
  B01: ANTITHROMBOTIC AGENTS
  B: BLOOD AND BLOOD FORMING ORGANS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 492.6
  Logarithm of the Partition Coefficient (xlogp); 5.3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1 h []
  Bioavailability: The bioavailability of drug is 100% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.34 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3 - 4 days [3]
  Metabolism: The drug is metabolized via the CYP3A4 and CYP 2J2 []
  Unbound Fraction: The unbound fraction of drug in plasma is 0.01% [3]
  Vd: The volume of distribution (Vd) of drug is 424 L []
• Chemical Identifiers:
  Formula: C29H33FN2O4
  IUPAC Name: ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1-methyl-3-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate
  Canonical SMILES: CCOC(=O)N[C@@H]1CC[C@@H]2[C@@H](C1)C[C@@H]3[C@H]([C@H]2/C=C/C4=NC=C(C=C4)C5=CC(=CC=C5)F)[C@H](OC3=O)C
  InChI: 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
  InChIKey: ZBGXUVOIWDMMJE-QHNZEKIYSA-N
• Cross-matching ID:
  PubChem CID: 10077130
  ChEBI ID: CHEMBL493982
  CAS Number: 618385-01-6
  UNII: ZCE93644N2
  DrugBank ID: DB09030
  TTD ID: D0VA0I
  INTEDE ID: DR1708
  ACDINA ID: D00732
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug Pharmacogenomic Perturbation (DPP)NEW: Click to Jump to the Detailed DPP Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proteinase activated receptor 1 (F2R)	TTL935N	PAR1_HUMAN	Antagonist	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2J2 (CYP2J2) Main DME	DERSX5P	CP2J2_HUMAN	Substrate	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Myocardial infarction
• ICD Disease Classification: BA41-BA43

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Proteinase activated receptor 1 (F2R)	DTT	F2R	4.89E-02	-0.32	-0.77
Cytochrome P450 2J2 (CYP2J2)	DME	CYP2J2	2.00E-01	-1.92E-02	-9.96E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	5.08E-01	-8.08E-02	-5.30E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Vorapaxar (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Major	Increased metabolism of Vorapaxar caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Vorapaxar caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[7]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Vorapaxar caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[8]
Tucatinib	DMBESUA	Major	Decreased metabolism of Vorapaxar caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[7]
Intedanib	DMSTA36	Moderate	Increased risk of bleeding by the combination of Vorapaxar and Intedanib.	Colorectal cancer [2B91]	[9]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Vorapaxar caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[10]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Vorapaxar and Vortioxetine.	Depression [6A70-6A7Z]	[11]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Vorapaxar and Apigenin.	Discovery agent [N.A.]	[12]
Tazemetostat	DMWP1BH	Major	Increased risk of bleeding by the combination of Vorapaxar and Tazemetostat.	Follicular lymphoma [2A80]	[6]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Vorapaxar and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[13]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Vorapaxar caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[7]
Ceritinib	DMB920Z	Major	Decreased metabolism of Vorapaxar caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[7]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Vorapaxar caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[14]
Idelalisib	DM602WT	Major	Decreased metabolism of Vorapaxar caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[7]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Vorapaxar and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[15]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Vorapaxar and Ibrutinib.	Mature B-cell lymphoma [2A85]	[16]
Fedratinib	DM4ZBK6	Major	Increased risk of bleeding by the combination of Vorapaxar and Fedratinib.	Myeloproliferative neoplasm [2A20]	[6]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Vorapaxar and MK-4827.	Ovarian cancer [2C73]	[13]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Vorapaxar caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[17]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Vorapaxar caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[18]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Vorapaxar caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[13]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Vorapaxar caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[7]
Curcumin	DMQPH29	Minor	Increased risk of bleeding by the combination of Vorapaxar and Curcumin.	Solid tumour/cancer [2A00-2F9Z]	[19]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Vorapaxar caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[20]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Vorapaxar and Betrixaban.	Venous thromboembolism [BD72]	[6]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Vorapaxar Sulfate eq 2.08mg base tablet	eq 2.08mg base	Tablet	Oral
Vorapaxar 2.08 mg tablet	2.08 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4047).
• [2] Vorapaxar FDA Label
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] In Process Citation. Pharm Unserer Zeit. 2009;38(4):320-8.
• [5] Vorapaxar: the missing link in antiplatelet therapy! J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):269-270.
• [6] Product Information. Zontivity (vorapaxar). Merck & Company Inc, Whitehouse Station, NJ.
• [7] Cerner Multum, Inc. "Australian Product Information.".
• [8] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [9] Product Information. Ofev (nintedanib). Boehringer Ingelheim, Ridgefield, CT.
• [10] Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
• [11] Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
• [12] Heck AM, DeWitt BA, Lukes AL "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm 57 (2000): 1221-7 quiz 1228-30. [PMID: 10902065]
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [14] Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [15] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [16] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [17] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [18] Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
• [19] Abebe W "Herbal medication: potential for adverse interactions with analgesic drugs." J Clin Pharm Ther 27 (2002): 391-401. [PMID: 12472978]
• [20] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.