First Clinical Experience With the New Once-Daily Formulation of Tacrolimus

Abstract

Once-daily tacrolimus is a new oral formulation of the established immunosuppressive agent tacrolimus (Prograf, Astellas Pharma US, Inc., Deerfield, IL), which is administered twice daily. It has been approved in the European Union for prophylaxis of rejection in liver and kidney transplant recipients, where it is registered as Advagraf, and in Canada for the prophylaxis of rejection in kidney transplant recipients, and is currently under review in the United States and Japan. Studies with once-daily tacrolimus have been performed in de novo kidney and liver transplant recipients, and conversion studies have been performed in stable adult kidney and liver transplant recipients and stable pediatric liver transplant recipients, who were converted on an mg:mg basis from twice-daily tacrolimus to a single morning dose of the new formulation. Results of these studies have established the safety and efficacy of this once-daily dosing alternative. Therapeutic regimens for transplant recipients are often complex, contributing to a high incidence of medication noncompliance and its consequences of increased mortality and morbidity. The tacrolimus once-daily regimen may improve compliance while enabling the use of the same patient care strategies, total daily dose, target trough concentrations, and therapeutic monitoring techniques as currently used with the twice-a-day formulation of tacrolimus.