Everolimus (certican) in heart transplantation: optimizing renal function through minimizing cyclosporine exposure

The proliferation signal inhibitor everolimus is efficacious for reducing the incidence of acute rejection and cardiac allograft vasculopathy (CAV) in heart transplantation; and it has the potential to facilitate cyclosporine (CsA) minimization in this setting. Reducing CsA dose in heart transplantation is dependent on everolimus trough blood levels of 3 to 8 ng/mL being achieved. Physicians experienced in the use of everolimus aim for CsA trough blood levels of 175 to 200 ng/mL in everolimus-treated patients during the initial 3 months following heart transplantation. Modeling data from the heart pivotal study suggest that CsA trough blood levels of 100 ng/mL at 6 months posttransplant could be targeted without loss of efficacy, and antibody induction therapy may assist with this approach. Target CsA trough blood levels for maintenance patients could possibly be reduced from the current 80 to 100 ng/mL to 50 to 80 ng/mL. Maintenance patients with renal dysfunction or CAV may benefit from conversion to everolimus and subsequent reduction in CsA trough blood levels (eg, by 50%). Initial experience of everolimus with reduced CsA trough blood levels in heart transplantation is favorable, but there is scope for further study.