Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation

ObjectivesFor revealing the peculiarities of the drug–drug interaction of rivaroxaban (substrate CYP3A4 and P-gp) and calcium channel blockers (CCBs) (verapamil – inhibitor CYP3A4 and P-gp and amlodipine – substrate CYP3A4) in patients 80 years and older with nonvalvular atrial fibrillation (NAF) we studied 128 patients.MethodsAll patients were divided into groups depending on the therapy taken: the 1st – rivaroxaban + amlodipine (n=51), the 2nd – rivaroxaban + verapamil (n=30), the control group – rivaroxaban without CCBs (n=47). A trough steady-state plasma concentration (Cmin,ss) of rivaroxaban, prothrombin time (PT) in the blood plasma and the event of clinically relevant non-major (CRNM) bleeding were assessed for each patient.ResultsPatient in group 2 had higher Cmin,ss of rivaroxaban, PT and CRNM than subjects in the control group (Me 73.8 [50.6–108.8] ng/mL vs. 40.5 [25.6–74.3] ng/mL; Me 14.8 [13.4–17.3] s vs. 13.8 [12.6–14.4] s; 34% vs. 13%, respectively, p<0.05 for all). When compared, the PT and complication rate in group 1 with the control group Cmin,ss of rivaroxaban were practically the same (p>0.05 for all).ConclusionsIn patients ≥80 years with NAF, the use of rivaroxaban in combination with verapamil may not be safe and can lead to CRNM bleeding.