Details of the Drug Combination

General Information of Drug Combination (ID: DCFC0H9)

• Drug Combination Name: Apixaban + Rivaroxaban
• Indication: Renal Insufficiency; Status: Phase 3 [1]
• Component Drugs:
  Apixaban (DM89JLN): Small molecular drug
  Rivaroxaban (DMQMBZ1): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Apixaban

Disease Entry	ICD 11	Status	REF
Thrombosis	DB61-GB90	Approved	[2]

Apixaban Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[6]

Apixaban Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

Apixaban Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[10]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[10]

Indication(s) of Rivaroxaban

Disease Entry	ICD 11	Status	REF
Deep vein thrombosis	BD71	Approved	[3]
Heparin-induced thrombocytopenia	3B64.12	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[5]

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	[12]

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	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]

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	[15]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[16]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Metabolism	[15]

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	[17]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Hydroxylation	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Cancer-associated Thrombosis	DCMI6XF	N. A.	Phase 2	[18]

References

• [1] ClinicalTrials.gov (NCT02664155) Venous Thromboembolism in Renally Impaired Patients and Direct Oral Anticoagulants
• [2] 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: 6390).
• [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: 6388).
• [4] Rivaroxaban FDA Label
• [5] Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19 (COVID-PREVENT)
• [6] Pfizer. Product Development Pipeline. March 31 2009.
• [7] Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa. Am J Cardiovasc Drugs. 2016 Apr;16(2):119-27.
• [8] Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013 Apr;41(4):827-35.
• [9] In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010 Mar;38(3):448-58.
• [10] Apixaban. Hosp Pharm. 2013 Jun;48(6):494-509.
• [11] Apixaban. After hip or knee replacement: LMWH remains the standard treatment. Prescrire Int. 2012 Sep;21(130):201-2, 204.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Pharmacology of the new target-specific oral anticoagulants. J Thromb Thrombolysis. 2013 Aug;36(2):133-40.
• [17] 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.
• [18] ClinicalTrials.gov (NCT03139487) A Randomized Phase II Open Label Study to Compare the Safety and Efficacy of Subcutaneous Dalteparin Versus Direct Oral Anticoagulants for Cancer-associated Venous Thromboembolism