Optimal dose of everolimus administered with tacrolimus in living donor kidney transplantation

Abstract

Everolimus (EVR) is often administered with cyclosporine A (CsA), according to an established protocol. Although the administration protocol of EVR with tacrolimus (TAC) has not been established, it has been clinically demonstrated that a higher dose of EVR is necessary when used in combination with TAC than with CsA. In this study, we aimed to determine the optimal dose of EVR administered with TAC to maintain a similar EVR level in the blood to that observed when EVR is administered with CsA. Between June 2009 and January 2016, 22 patients who underwent living donor kidney transplantation were enrolled in this study. Among them, 12 patients were administered steroids, basiliximab, CsA, and EVR (CsA + EVR group) and 10 were administered steroids, basiliximab, TAC, and EVR (TAC + EVR group). Blood samples were collected at different time points from patients in both CsA + EVR and TAC + EVR groups, after drug administration. The trough EVR level in both groups was maintained within 3–8 ng/mL during the perioperative period. The optimal EVR doses for both groups were estimated by using a population pharmacokinetic analysis. Overall, the optimal dose of EVR for the TAC + EVR group was 3.59-fold higher than that for the CsA + EVR group to maintain a similar trough level to that of the latter group. Thus, administration of a higher EVR dose is recommended when provided in combination with TAC than with CsA to prevent adverse events caused by under immunosuppression, that could lead to acute kidney rejection.