Table 1.

Key pharmacological properties of NOACs and VKAs (eg, warfarin)

	Dabigatran	Rivaroxaban	Apixaban	Edoxaban	Warfarin
Drug class/mechanism of action	Direct thrombin inhibitor	Direct factor Xa inhibitor	Direct factor Xa inhibitor	Direct factor Xa inhibitor	VKA
Time to maximum plasma concentration (hours)	0.5–2	2–4	3–4	1–2	∼90 minutes but requiring 5–6 days to achieve effective anticoagulation
Half-life (hours)	12–14	5–13	8–13	10–14	∼40 hours for warfarin
Proportion of unchanged drug excreted renally (%)	∼80	∼33	∼25	50	Minor only
Predictable anticoagulant effect	Yes	Yes	Yes	Yes	No
Fixed dosing regimen	Yes	Yes	Yes	Yes	No
Routine coagulation monitoring required	No	No	No	No	Yes
Food effect	No interaction; taken with or without food	No interaction but 15 mg and 20 mg doses should be taken with food for optimal bioavailability	No interaction; taken with or without food	No interaction; taken with or without food	Affected by many common foods containing high levels of vitamin K
Relevant drug interactions	Strong P-gp inhibitors: ketoconazole, cyclosporin, itraconazole, and dronedarone are contraindicated. P-gp inducer rifampicin should be avoided	Strong inhibitors of both CYP3A4 and P-gp: azole antimycotics (eg, ketoconazole) and HIV protease inhibitors (eg, ritonavir) are not recommended	Strong inhibitors of CYP3A4 and P-gp: azole antimycotics (eg, ketoconazole) and HIV protease inhibitors (eg, ritonavir) are not recommended	Concomitant use of P-gp inhibitors cyclosporin, dronedarone, erythromycin, or ketoconazole requires edoxaban dose reduction to 30 mg oda	Interaction with numerous drugs

Notes:

^aConcomitant use of edoxaban with quinidine, verapamil, or amiodarone does not require dose reduction based on clinical data. The use of edoxaban with other P-gp inhibitors, including HIV protease inhibitors, has not been studied.⁹ Data from studies.²,⁸–¹¹,¹⁵

Abbreviations: CYP3A4, cytochrome P450 3A4; HIV, human immunodeficiency virus; NOAC, non-vitamin K antagonist oral anticoagulant; od, once daily; P-gp: P-glycoprotein; VKA, vitamin K antagonist.