Risk factors for toxicity
Although apixaban and rivaroxaban have dose-dependent effects on coagulation, patient-associated factors are the primary drivers of increased bleeding risk (see Patient-associated factors that increase bleeding risk with anticoagulant therapy for patient-associated factors that increase bleeding risk with anticoagulant therapy).
Renal clearance contributes significantly to apixaban and rivaroxaban elimination, so kidney impairment delays drug clearance and prolongs anticoagulant effects. In addition, apixaban and rivaroxaban are both substrates of the cytochrome P450 enzyme CYP3A4 and of the P-glycoprotein drug transporter. People taking drugs that inhibit CYP3A4 and P-glycoprotein are more susceptible to overanticoagulation because CYP3A4 and P-glycoprotein inhibition can raise serum apixaban and rivaroxaban concentrations and prolong their half-lives1.