Table 3

Dosing considerations for novel oral anticoagulants. Common P-gp inhibitors ketoconazole, verapamil, amiodarone, dronedarone, cyclosporine and erythromycin. Rifampin is a potent inducer of P-gp. Child-Pugh classification is a prognostic scoring system used to assess the severity of chronic liver disease, mainly cirrhosis, which incorporates clinical and laboratory variables (total bilirubin, serum albumin, severity of ascites, hepatic encephalopathy grade). Online calculator can be accessed at http://www.hepatitis.va.gov/provider/tools/child-pugh-calculator.asp.4 5 52 69

	Renal impairment	Hepatic dysfunction	Drug interactions
Dabigatran	Normal/mild/moderate impairment (CrCl >30 mL/min): 150 mg twice daily.	No restriction based on Child-Pugh score.	Increased activity with P-gp inhibitors
	Severe impairment (CrCl 15–30 mL/min): 75 mg twice daily	No restriction based on Child-Pugh score.	Increased activity with P-gp inhibitors
	Not recommended for ESRD (CrCl <15 mL/min)	Not recommended in patients with elevated liver enzymes >2× ULN	Decreased activity with P-gp inducer
Rivaroxaban	Normal/mild impairment (CrCl >50 mL/min): 20 mg once daily with the evening meal.	No restriction with Child-Pugh class A	Increased activity with cytochrome P450 inhibitors
	Moderate renal impairment (CrCl 30–50 mL/min): 15 mg once daily with the evening meal.	No restriction with Child-Pugh class A	Increased activity with cytochrome P450 inhibitors
	Severe renal impairment (CrCl 15–30 mL/min): 15 mg once daily with the evening meal.	Contraindicated in patients with Child-Pugh class B and class C	Decreased activity with cytochrome P450 inducers
	Not recommended for ESRD
Apixaban	Reduce dose to 2.5 mg twice daily if any two patient characteristics are present: Cr ≥1.5 mg/dL, ≥80 years of age, body weight ≤60 kg.	Use with caution with Child-Pugh scores A and B or elevated liver enzymes >2× ULN	Increased activity with cytochrome P450 inhibitors
Apixaban	Approved for use in ESRD on dialysis	Not recommended in Child-Pugh class C	Decreased activity with cytochrome P450 inducers
Edoxaban	Not recommended for CrCl >95 mL/min.	No restriction with Child-Pugh score A or B	No dose alterations required for P-gp inhibitors
	Moderate renal impairment (CrCl 15–50 mL/min) 30 mg daily.	No restriction with Child-Pugh score A or B	No dose alterations required for P-gp inhibitors
	Not recommended for ESRD (CrCl <15 mL/min)	Not recommended in patients with Child-Pugh C	Avoid with use of P-gp inducers

CrCl, creatinine clearance; P-gp, permeability glycoprotein; ESRD, end stage renal disease; ULN, upper-limit of normal