Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management

Table 2 Dosing of different novel oral anticoagulants according to indications and renal function

	Dabigatran	Rivaroxaban	Apixaban	Edoxaban
Non-valvular AF
United States	150mg b.i.d	20 mg daily	5 mg b.i.d	60 mg daily
	75 mg b.i.d if CrCl 15-30 mL/min	15 mg daily if CrCl 15-50 mL/min	2.5 mg b.i.d if Cr 15-29 mL/min OR two out of the following:	30 mg daily if CrCl 15-50 mL/min
			age ≥ 80 years, BW ≤ 60 kg, Cr ≥ 1.5 mg/dL
	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 25 mL/min or Cr > 2.5 mg/dL	Avoid if CrCl < 15 mL/min
Europe	150 mg b.i.d	20 mg daily	5 mg b.i.d	60 mg daily
	110 mg b.i.d if age ≥ 80 years	-	2.5 mg b.i.d if Cr 15-29 mL/min OR two out of the following:	30 mg daily if one out of the following: CrCl 15-50 mL/min, BW ≤ 60 kg, concomitant use of p-gp inhibitors
	(may consider 110 mg b.i.d also if increased risk of bleeding)		age ≥ 80 years, BW ≤ 60 kg, Cr ≥ 1.5 mg/dL
	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min
Postoperative DVT / PE thromboprophylaxis (hip or knee replacement)
United States	Initial dose of 110 mg 1-4 h after operation, then 220 mg daily	Initial dose of 10 mg 6-10 h after operation, then 10 mg daily	Initial dose of 2.5 mg 12-24 h after operation, then 2.5 mg b.i.d	-
	-	-	-	-
	Avoid if CrCl < 30	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 30 mL/min	-
Europe	Initial dose of 110 mg 1-4 h after operation, then 220 mg daily	Initial dose of 10 mg 6-10 h after operation, then 10 mg daily	Initial dose of 2.5 mg 12-24 h after operation, then 2.5 mg b.i.d	60 mg daily after 5 d of initial therapy with a parenteral anticoagulant
	Initial dose of 75 mg 1-4 h after operation, then 150 mg daily if CrCl 30-50 mL/min	-	-	30 mg daily after 5 d of initial therapy with a parenteral anticoagulant if one out of the following: CrCl 15-50 mL/min, BW ≤ 60 kg, concomitant use of p-gp inhibitors
	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min
Treatment and prevention of recurrent DVT/PE
United States	150 mg b.i.d after 5-10 d of initial therapy with a parenteral anticoagulant	15 mg b.i.d for 3 wk, then 20 mg daily	10 mg b.i.d for 1 wk, then 5 mg b.i.d	60 mg daily after 5-10 d of initial therapy with a parenteral anticoagulant
	-	-	-	30 mg daily after 5-10 d of initial therapy with a parenteral anticoagulant if one out of the following: CrCl 15-50 mL/min, BW ≤ 60 kg, concomitant use of p-gp inhibitors
	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 25 mL/min or Cr > 2.5 mg/dL	Avoid if CrCl < 15 mL/min
Europe	150 mg b.i.d after 5 d of initial therapy with a parenteral anticoagulant	15 mg b.i.d for 3 wk, then 20 mg daily	10 mg b.i.d for 1 wk, then 5 mg b.i.d	60 mg daily after 5 d of initial therapy with a parenteral anticoagulant
	110 mg b.i.d after 5 d of initial therapy with a parenteral anticoagulant if age ≥ 80 years	-	-	30 mg daily after 5 d of initial therapy with a parenteral anticoagulant if one out of the following: CrCl 15-50 mL/min, BW ≤ 60 kg, concomitant use of p-gp inhibitors
	(may consider 110 mg b.i.d also if increased risk of bleeding)
	Avoid if CrCl < 30 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min	Avoid if CrCl < 15 mL/min

NOACs: Novel oral anticoagulants; AF: Atrial fibrillation; CrCl: Creatinine clearance; BW: Body weight; Cr: Creatinine; DVT: Deep vein thrombosis; PE: Pulmonary embolism; p-gp inhibitors: p-glycoprotein inhibitors.