Everolimus: a classical mammalian target of rapamycin inhibitor?

Abstract

Purpose of review Everolimus administration after cardiac transplantation has been shown to reduce the incidence of cardiac allograft vasculopathy, acute cellular rejection, and cytomegalovirus infection. This immunosuppressive agent, which inhibits the mammalian target of rapamycin, has also been associated with impaired renal function when used with full-dose calcineurin inhibitors. Recent experience has provided strategies for using everolimus without the diminution in renal function. This review evaluates the most recent clinical experience with everolimus. Recent findings Everolimus was first shown in cardiac transplant recipients to reduce cardiac allograft vasculopathy, cardiac allograft rejection, and cytomegalovirus infection while diminishing renal function and exacerbating hypertriglyceridemia. Recent studies have evaluated new approaches for using everolimus while minimizing the adverse events noted in previous clinical trials. Recent clinical observations from European countries where everolimus is approved for clinical use have shown that everolimus dosed at an optimal trough blood level of 6-8 ng/ml can be used with reduced-dose cyclosporine with trough levels of 150-175 ng/ml in the first 3 months, with further reductions later, without the deterioration in renal function seen in the pivotal clinical trial in which full-dose cyclosporine was used. Steroids could also be discontinued in some patients. Summary Everolimus is a novel mammalian target of rapamycin or proliferation signal inhibitor that has been shown to reduce the incidence of cardiac allograft rejection and vasculopathy in clinical trials. In clinical practice with reduced-dose cyclosporine, renal function was preserved in cardiac allograft recipients.