Extended-Release Tacrolimus: A Review of Its Use in De Novo Kidney Transplantation

Extended-release tacrolimus (tacrolimus ER) [Advagraf®; Astagraf XL®; Graceptor®; Prograf XL®] is a once-daily formulation of the immunosuppressive calcineurin inhibitor, which is approved in many countries worldwide for the prophylaxis of transplant rejection in adult de novo kidney transplant recipients. It is absorbed more slowly than the conventional, twice-daily, immediate-release formulation, initially producing lower exposure when administered at the same daily dosage, but providing equivalent exposure upon repeat administration with therapeutic drug monitoring. In randomized, controlled, phase III/IV trials, with extended follow-up to 4 years, the efficacy of tacrolimus ER was similar to that of twice-daily tacrolimus with regard to the prevention of acute rejection or graft dysfunction in adult de novo kidney transplant recipients. Renal function was significantly better with tacrolimus ER, but not tacrolimus, than with ciclosporin. The tolerability profile of tacrolimus ER was descriptively similar to that of the original twice-daily formulation, with no notable differences. Therefore, tacrolimus ER retains the immunosuppressive activity of the original formulation in the prophylaxis of transplant rejection in adult de novo kidney transplant recipients and offers the benefits of once-daily administration.