Table 14.

Permeability glycoprotein (p-gp) and Cytochrome 3A4 drug–drug Interactions with rivaroxaban and apixaban) [134–139] (list is not exhaustive)

P-gp and strong CYP3A4 inducers	Interacting drug’s effect on rivaroxaban/apixaban concentration	Suggested management
Barbiturate	↓, no specific studies	Avoid use of rivaroxaban or apixaban with p-gp and strong CYP3A4 inducers
Carbamazepine	↓, no specific studies
Phenytoin	↓, no specific studies
Rifampin	↓, rivaroxaban and apixaban exposure by 50 %
St John’s Wort	↓, no specific studies

P-gp and strong CYP3A4 inhibitors	Interacting drug’s effect on Factor Xa inhibitor concentration	Suggested management
Clarithromycin	↑, rivaroxaban exposure by 54 % ↑,no specific studies for apixaban	Rivaroxaban: Avoid use of rivaroxaban with p-gp and strong CYP3A4 inhibitors Apixaban: If taking 5 mg or 10 mg BID reduce dose by 50 % if combined with strong p-gp and CYP3A4 inhibitors If taking 2.5 mg BID avoid apixaban with strong p-gp and CYP3A4 inhibitors
Conivaptan	↑, no specific studies
Grapefruit	↑, no specific studies
Indinavir	↑, no specific studies
Itraconazole	↑, no specific studies
Ketoconazole	↑, rivaroxaban exposure by 160 %
	↑, apixaban exposure by 200 %
Nelfinavir	↑, no specific studies
Posaconazole	↑, no specific studies
Ritonavir	↑, rivaroxaban exposure by 160 % ↑, no specific studies for apixaban
Saquinavir	↑, no specific studies

P-gp and moderate CYP3A4 inhibitors	Interacting drug’s effect on rivaroxaban/apixaban concentration	Suggested management
Cyclosporine	↑, no specific studies	Rivaroxaban: Avoid use of rivaroxaban with p-gp and moderate CYP3A4 inhibitors if CrCl is < 80 mL/min Apixaban: No dose adjustment is recommended with p-gp and moderate CYP3A4 inhibitors. Use with caution
Diltiazem	↑, apixaban exposure by 30–40 % ↑, no specific studies with rivaroxaban
Dronedarone	↑, no specific studies
Tamoxifen	↑, no specific studies
Verapamil	↑, no specific studies

CrCl Creatinine clearance, CYP3A4 cytochrome 3A4, p-gp permeability lycoprotein