The most frequently used immunosuppressive treatment in kidney transplant recipients is the combination therapy of a calcineurin inhibitor and mycophenolate mofetil (MMF), with or without corticosteroids. Cyclosporin and tacrolimus are the two calcineurin inhibitors registered for this indication. Also in the treatment of glomerular diseases calcineurin inhibitors and mycophenolic acid are being used on a worldwide scale, either alone or as combined treatment. In January 2021 the U.S. Food and Drug Administration (FDA) has approved voclosporin, a novel calcineurin inhibitor for the treatment of adult patients with active lupus nephritis. There is a clinically relevant drug-drug interaction between cyclosporin and mycophenolate. As a result of cyclosporin-induced inhibition of the enterohepatic recirculation of mycophenolate, the mycophenolic acid-AUC is significantly lower (40%) in case of cyclosporin co-administration as compared to cotreatment with either tacrolimus or voclosporin (or no CNI co-treatment). The aim of this mini review is to summarize this potential drug-drug interaction and explain how cyclosporin affects the pharmacokinetics of mycophenolate. The optimal dose of MMF is likely to depend on the calcineurin inhibitor with which it is co-administered. Furthermore clinical implications are discussed, including the potential emergence of mycophenolic acid (MPA)-related side effects after discontinuation of cyclosporin co-treatment.
Copyright © 2021. Published by Elsevier Inc.