Four-year experience with tacrolimus once-daily prolonged release in patients from phase II conversion and de novo kidney, liver, and heart studies

Introduction: This study assessed the long-term effects of prolonged-release tacrolimus (Advagraf (R) [Tacrolimus QD]), which has been developed to provide similar efficacy and safety to twice-daily tacrolimus (Prograf (R) [Tacrolimus BID]) with the added benefit of once-daily dosing. Methods: Adult participants from four phase II de novo (kidney, liver) or Tacrolimus BID to QD conversion (kidney, heart) studies were enrolled into the follow-up study. Patients remained on the immunosuppressive regimen they were receiving on entry, unless medical needs required otherwise. The primary endpoint was patient and graft survival, and secondary endpoints were biopsy-confirmed acute rejection (BPAR) and safety. Results: The full analysis set comprised 240 patients. Tacrolimus mean total daily dose and whole-blood trough levels decreased over time, particularly in de novo patients. At four yr, Kaplan-Meier estimates of patient and graft survival were over 90%. Freedom from BPAR was 90.9/92.6% and 100/87.0% in the de novo kidney/liver and conversion kidney/heart patients, respectively. There were 13 deaths, and 20% patients withdrew from the study, mainly because of adverse events. Conclusions: The efficacy and safety of Tacrolimus QD was maintained for four yr in kidney, liver, and heart transplant recipients. Therefore, this formulation offers a convenient alternative to Tacrolimus BID.