Details of the Drug Combination

General Information of Drug Combination (ID: DCYXVLP)

• Drug Combination Name: Tranexamic Acid + Rivaroxaban
• Indication: Osteoarthritis, Knee; Status: Phase 4 [1]
• Component Drugs:
  Tranexamic Acid (DMFI8A7): Small molecular drug
  Rivaroxaban (DMQMBZ1): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tranexamic Acid

Disease Entry	ICD 11	Status	REF
Excessive bleeding	GA30.02	Approved	[2]
Menorrhagia	GA20.50	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Endometriosis	GA10	Investigative	[3]

Tranexamic Acid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasminogen (PLG)	TTP86E2	PLMN_HUMAN	Inhibitor	[8]

Indication(s) of Rivaroxaban

Disease Entry	ICD 11	Status	REF
Deep vein thrombosis	BD71	Approved	[5]
Heparin-induced thrombocytopenia	3B64.12	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]

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	[9]

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	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]

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	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Metabolism	[12]

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	[14]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Hydroxylation	[14]

References

• [1] ClinicalTrials.gov (NCT03328832) Combined Topical Tranexamic Acid With Floseal in Total Knee Arthroplasty
• [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: 6573).
• [3] Tranexamic acid FDA Label
• [4] Tranexamic Acid (TXA) and Corona Virus 2019 (COVID19) in Inpatients (TCInpatient)
• [5] 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).
• [6] Rivaroxaban FDA Label
• [7] Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19 (COVID-PREVENT)
• [8] Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007 Oct;5(10):2113-8.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Pharmacology of the new target-specific oral anticoagulants. J Thromb Thrombolysis. 2013 Aug;36(2):133-40.
• [14] 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.