Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

Table 2 Pharmacological characteristics of direct oral anticoagulant[71,87]

	Dabigatran	Apixaban	Edoxaban	Rivaroxaban
Target factor	Thrombin (Factor IIa)	Factor Xa	Factor Xa	Factor Xa
Half-time (h)	10.7-11.8	6.12-8.11	6.21-6.70	5.7-12.6
Time to peak effect (h)	4	3.0-3.5	1-1.5	1.4-3.3
Distribution volume (L)	50-70	21	107	50
Renal excretion (%)	85	27	35.4-50	50
Fecal excretion (%)	6	25	62.2	50
Hepatic metabolism	No	CYP3A4/5	CYP3A4	CYP3A4 and CYP2J2
Transporter	P-gP	P-gP/BCRP	P-gP	P-gP/BCRP
Protein binding (%)	28.2-31.5	87	40.0-58.9	92-95
Dialyzable	Yes	No	No	No
Prodrug	Yes	No	No	No
Bioavailability (%)	6.5	50	61.8	66-112
Dose for AF (in Japan)	150 mg	5 mg	60 mg	15 mg
Dosing time	Twice daily	Twice daily	Once daily	Once daily
Reversal agent	Idarucizumab	Andexanet alfa	Andexanet alfa	Andexanet alfa
FDA-approved indications	Nonvalvular AF, VTE (T, SP, P)	Nonvalvular AF, VTE (T, SP, P)	Nonvalvular AF, VTE (T)	Nonvalvular AF, VTE (T, SP, P)
Japanese insurance system-approved indications	Nonvalvular AF (P)	Nonvalvular AF (P), VTE (T, SP)	Nonvalvular AF (P), VTE (T, SP)	Nonvalvular AF (P), VTE (T, SP)
Non-pharmacologic interactions	Age, reduced GFR	Age, reduced body weight, reduced GFR, probable severe liver damage	Reduced GFR, probable severe liver damage	Age, reduced GFR, probable severe liver damage
Drug interactions	Dose reduction: Concomitant P-gp inhibitor, gastric acid inhibitory drug	Avoid: Concomitant P-gp and CYP3A4 inhibitors	Avoid: Concomitant rifampin	Avoid: Rivaroxaban with concomitant dual P-gp and CYP3A4 inhibitors
Contraindications	Ccr: < 30mL/min	Nonvalvular AF: Ccr: < 15mL/min, VTE:	Nonvalvular AF: Ccr: < 15mL/min, VTE:	Nonvalvular AF: Ccr: < 15mL/min, VTE:
		Ccr: < 30mL/min	Ccr: < 30mL/min	Ccr: < 30mL/min

AF: Atrial fibrillation; P: Prophylaxis; SP: Secondary prevention; T: Treatment; VTE: Venous thromboembolism; FDA: Food and Drug Administration; Ccr: Creatinine clearance.