Details of the Drug Combination

General Information of Drug Combination (ID: DCWW9VB)

• Drug Combination Name: Brilinta + Rivaroxaban
• Indication: Acute Coronary Syndrome; Status: Phase 2 [1]
• Component Drugs:
  Brilinta (DMBR01X): Small molecular drug
  Rivaroxaban (DMQMBZ1): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Brilinta

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[2]
Thrombosis	DB61-GB90	Approved	[3]
Arterial thrombosis	DB61-DD30	Phase 3	[4]
Myocardial infarction	BA41-BA43	Phase 3	[4]
Peripheral vascular disease	BD4Z	Investigative	[5]

Brilinta Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
P2Y purinoceptor 12 (P2RY12)	TTZ1DT0	P2Y12_HUMAN	Antagonist	[10]

Brilinta Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Brilinta Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Brilinta Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Terminal nucleotidyltransferase 4A (TENT4A)	OT0G3KR0	PAPD7_HUMAN	Increases ADR	[13]
CD9 antigen (CD9)	OT2184XU	CD9_HUMAN	Increases ADR	[13]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases ADR	[13]
Aryl-hydrocarbon-interacting protein-like 1 (AIPL1)	OT4VBD78	AIPL1_HUMAN	Increases ADR	[14]
Actin-related protein 2/3 complex subunit 1A (ARPC1A)	OTAEEXGQ	ARC1A_HUMAN	Increases ADR	[9]
Putative protein CASTOR3P (GATS)	OTDYE3XK	CAST3_HUMAN	Increases ADR	[9]
LIM domain kinase 2 (LIMK2)	OTRJD7VZ	LIMK2_HUMAN	Increases ADR	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases ADR	[9]

Indication(s) of Rivaroxaban

Disease Entry	ICD 11	Status	REF
Deep vein thrombosis	BD71	Approved	[6]
Heparin-induced thrombocytopenia	3B64.12	Approved	[7]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[8]

Rivaroxaban Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Modulator	[15]

Rivaroxaban Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]

Rivaroxaban Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Metabolism	[18]

Rivaroxaban Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Hydroxylation	[20]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Hydroxylation	[20]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Atrial Fibrillation	DC5WOHZ	N. A.	Phase 3	[21]

References

• [1] ClinicalTrials.gov (NCT02293395) A Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome
• [2] Ticagrelor-Induced Syncope/Bradyarrhythmia. Cureus. 2021 Jan 23;13(1):e12874.
• [3] 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: 1765).
• [4] ClinicalTrials.gov (NCT01732822) A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease. U.S. National Institutes of Health.
• [5] Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis. Drugs. 2022 Aug;82(12):1287-1302.
• [6] 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: 6388).
• [7] Rivaroxaban FDA Label
• [8] Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19 (COVID-PREVENT)
• [9] Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015 Aug 1;36(29):1901-12.
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [11] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [12] Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010 Sep;38(9):1514-21.
• [13] Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. J Med Genet. 2013 Sep;50(9):599-605. doi: 10.1136/jmedgenet-2012-101466. Epub 2013 Jun 17.
• [14] Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy. Clin Cancer Res. 2015 Oct 1;21(19):4337-46. doi: 10.1158/1078-0432.CCR-15-0133. Epub 2015 May 26.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] Downregulation of ABCB1 gene in patients with total hip or knee arthroplasty influences pharmacokinetics of rivaroxaban: a population pharmacokinetic-pharmacodynamic study. Eur J Clin Pharmacol. 2019 Feb 6.
• [17] Absence of both MDR1 (ABCB1) and breast cancer resistance protein (ABCG2) transporters significantly alters rivaroxaban disposition and central nervous system entry. Basic Clin Pharmacol Toxicol. 2013 Mar;112(3):164-70.
• [18] Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85.
• [19] Pharmacology of the new target-specific oral anticoagulants. J Thromb Thrombolysis. 2013 Aug;36(2):133-40.
• [20] Mechanism-Based Inactivation of Cytochrome P450 3A4 and 3A5 by the Fibroblast Growth Factor Receptor Inhibitor Erdafitinib. Chem Res Toxicol. 2021 Jul 19;34(7):1800-1813. doi: 10.1021/acs.chemrestox.1c00178. Epub 2021 Jun 30.
• [21] ClinicalTrials.gov (NCT03331484) The Safety and Efficacy Of Rivaroxaban and Ticagrelor for Patients With Atrial Fibrillation After Percutaneous Coronary Intervention