New oral pharmacotherapeutic agents for venous thromboprophylaxis after total hip arthroplasty

Table 2 Effects on target specific oral anticoagulants plasma concentrations from drug-drug interactions and dosing recommendations

	Drug interaction via	Dabigatran	Rivaroxaban	Apixaban	Edoxaban
Verapamil	P-gp inhibition and weak CYP3A4 inhibition	+ 12%-180% (take simultaneously and reduce dose)	Minor effect (use caution with CrCl 15-50 mL/min	No data yet	+ 53% (SR verapamil) (reduce dose by 50%)
Diltiazem	P-gp inhibition	No effect	Minor effect (use caution with CrCl 15-50 mL/min	+ 40%	No data yet
Quinidine	P-gp inhibition	+ 50%	+ 50%	No data yet	+ 80% (reduce dose by 50%)
Amiodarone	P-gp inhibition	+ 12%-60%	Minor effect (use caution with CrCl 15-50 mL/min	No data yet	No effect
Dronedarone	P-gp and CYP3A4 inhibition	+ 70%-100% (75 mg BID)	No data yet	No data yet	+ 85% (reduce dose by 50%)
Azole antifungals (1) Voriconazole (2) Ketoconazole (3) Itraconazole (4) Posaconazole	Strong P-gp and CYP3A4 inhibition	+ 140%-150% (75 mg BID)	Up to + 160%	+ 100%	No data yet
Fluconazole	Moderate CYP3A4 inhibition	No data yet	+ 42%	No data yet	No data yet
Clarithromycin Erythromycin	Strong P-gp and CYP3A4 inhibition	-0.05	+ 30%-54%	No data yet	No data yet
HIV Protease Inhibitors	Strong P-gp and CYP3A4 inhibition	No data yet	Up to + 153%	Strong increase	No data yet
Rifampin St. John’s Wort Carbamazepine Phenytoin Phenobarbital	Strong P-gp and CYP3A4 induction	- 66%	Up to - 50%	- 54%	- 35%

Table adapted from EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation[46]. Grey boxes indicate drug contraindicated or not recommended. AUC: Area under the curve; TSOA: Target specific oral anticoagulant; P-gp: Permeability glycoprotein; BID: Twice daily.