INTRODUCTION: This study assessed the long-term effects of prolonged-release tacrolimus (Advagraf(®) [Tacrolimus QD]), which has been developed to provide similar efficacy and safety to twice-daily tacrolimus (Prograf(®) [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.
INTRODUCTION: This study assessed the long-term effects of prolonged-release tacrolimus (Advagraf(®) [Tacrolimus QD]), which has been developed to provide similar efficacy and safety to twice-daily tacrolimus (Prograf(®) [TacrolimusBID]) with the added benefit of once-daily dosing. METHODS: Adult participants from four phase II de novo (kidney, liver) or TacrolimusBID 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 TacrolimusBID.
Authors: Frank Stifft; Franciscus Vandermeer; Cees Neef; Sander van Kuijk; Maarten H L Christiaans Journal: Eur J Clin Pharmacol Date: 2020-02-04 Impact factor: 2.953
Authors: Katherine A Barraclough; Nicole M Isbel; David W Johnson; Scott B Campbell; Christine E Staatz Journal: Drugs Date: 2011-08-20 Impact factor: 9.546
Authors: Tiong Yeng Lim; Mark J McPhail; Amar Shah; Sara Mahgoub; Jeremy Nayagam; Matthew Cramp; William Bernal; Krish Menon; Wayel Jassem; Deepak Joshi; Michael A Heneghan; Kosh Agarwal; Nigel D Heaton; Abid Suddle; John G O'Grady; Varuna R Aluvihare Journal: Transplant Direct Date: 2020-01-17