Table 13.

OACs Pharmacokinetic Characteristics and Dosing

Class	VKA	Direct Thrombin Inhibitor		Factor Xa Inhibitor
Name	Warfarin	Dabigatran		Rivaroxaban		Apixaban		Edoxaban
Metabolism	S-isomer: CYP2C9 R-isomer: CYP1A2, CYP2C19, CYP3A4	Minimal		CYP3A4/5		CYP3A4		Minimal CYP3A4
P-glycoprotein substrate	No	Yes		Yes		Yes		Yes
Excretion	0% renal; very little warfarin excreted unchanged in urine	80% renal		66% renal, 28% feces		27% renal, 73% biliary and intestinal		50% renal, 50% liver and biliary/intestinal
Half-life	20–60 h	12–17 h		5–9 h		12 h		10–14 h
Renal dosing adjustment based on actual body weight	N/A	CrCl >30 mL/min	150 mg twice daily	CrCl >50 mL/min	20 mg daily with the biggest meal*		5 mg twice daily	CrCl >50–≤95 mL/min	60 mg once daily
		CrCl 15–30 mL/min	75 mg twice daily	CrCl 15–50 mL/min	15 mg daily with the biggest meal*	If any 2 of the following: age ≥80y, body weight ≤60 kg, SCr ≥1.5 mg/dL	2.5 mg twice daily	CrCl 15–50 mL/min	30 mg once daily
Drug interaction management based on concomitant therapy of CYP3A4 inhibitors/p-glycoprotein inhibitors	Adjust dose based on INR trends	CrCl 30–50 mL/min with concomitant use of dronedarone or systemic ketoconazole: 75 mg twice daily CrCl <30 mL/min: avoid dabigatran use concomitantly with dronedarone or systemic ketoconazole		Avoid rivaroxaban use with concomitant therapy of combined p-glycoprotein and strong CYP3A4 inhibitors (eg, systemic ketoconazole and ritonavir) No dose adjustment required with clarithromycin Avoid rivaroxaban use in patients with CrCl 15–<80 mL/min receiving combined p-glycoprotein and moderate CYP3A4 inhibitors (eg, erythromycin)		In patients receiving apixaban 5 mg twice daily, reduce dose to 2.5 mg twice daily when combined p-glycoprotein and strong CYP3A4 inhibitors (eg, itraconazole, systemic ketoconazole, ritonavir) are used concomitantly If patients already receiving apixaban 2.5 mg twice daily, avoid apixaban use if combined p-glycoprotein and strong CYP3A4 inhibitors are concomitantly used		No dose adjustment is required
Drug interaction management based on concomitant therapy of p-glycoprotein/CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort)	Adjust dose based on INR trends	Avoid use		Avoid use		Avoid use		Avoid use with rifampin. No study evaluated the effect of other p-glycoprotein/CYP3A4 inducers on edoxaban drug levels
Appropriate use based on liver function (Child-Pugh score)†  Child-Pugh A (mild)	Not mentioned in the labeling	No dose adjustment needed		No dose adjustment needed		No dose adjustment needed		No dose adjustment needed
Child-Pugh B (moderate)		Use with caution		Avoid use		Use with caution		Use with caution
Child-Pugh C (severe)		Avoid use		Avoid use		Avoid use		Avoid use

Information obtained from manufacturer package inserts.^{13,14,20–22} Adapted with permission from pgs. 28–31 of Kido et al.²³ Copyright 2021 American College of Clinical Pharmacy.

^*The effect of food (high-fat, high-calorie meal) on bioavailability for 10- and 20-mg tablet was evaluated in 24 subjects under fed and fasting conditions. After a single oral 20-mg dose, area under the curve was increased by 39%, and Cmax was increased by 76% under fed condition, but area under the cuive and Cmax were similar between fasting and fed conditions.¹⁹

^†Child-Pugh scoring: the severity of liver disease, primarily cirrhosis. Child-Pugh A (mild): 5 to 6 points; Child-Pugh B (moderate): 7 to 9 points; Child-Pugh C (severe): 10 to 15 points. The score is based on the 5 variables: encephalopathy (none=1 point, grade 1 and 2=2 points, grade 3 and 4=3 points); ascites (none=1 point, slight=2 points, moderate=3 points); total bilirubin (<2 mg/mL=1 point, 2–3 mg/mL=2 points, >3 mg/mL=3 points); albumin (>3.5 mg/mL=1 point, 2.8–3.5 mg/mL=2 points, <2.8 mg/mL=3 points); INR (<1.7=1 point, 1.7–2.2=2 points, >2.2=3 points).

CrCl indicates creatinine clearance; INR, international normalized ratio; OAC, oral anticoagulant; Scr, serum creatinine; and VKA, vitamin K antagonist.