Reconsideration of Interactions Between Direct Oral Anticoagulants and Calcineurin Inhibitors

From the first published guidelines on the use of direct oral anti-coagulants (DOACs) in non-valvular atrial fibrillation in 2013 up to the latest updates in 2018 (1), DOAC interactions with other drugs have been one of the important challenges in their prescribing. Given the rapid increase in the number of solid organ transplant recipients, the need for anticoagulant therapy among transplant patients is on the rise. Based on in vivo studies (2, 3) and clinical reviews (4, 5) on concomitant administration of calcineurin inhibitors (CNIs) and DOACs, reassessing the color coding indicating the severity of interactions in the guidelines (1) seems to be necessary. The use of midazolam as a human Cytochrome P450 3A (CYP3A) probe has shown that cyclosporine inhibits CYP3A more strongly than tacrolimus, while there was no significant difference in CYP3A inhibition between tacrolimus and the control group (2). The same pattern of inhibition is seen with the P-glycoprotein (P-gp) pathway (3). Hence, cyclosporine may be considered as a moderate to strong P-gp inhibitor and moderate CYP3A inhibitor while tacrolimus could be regarded as a mild to moderate P-gp and mild CYP 3A inhibitor. Based on current data, higher rivaroxaban exposure and risk of bleeding has been reported when concomitantly used with cyclosporine. However, coadministration of cyclosporine with apixaban J Pharm Care 2020; 8(2): 88-89.