title: Four-year experience with tacrolimus once-daily prolonged release in patients from phase II conversion and de novo kidney, liver, and heart studies.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, The Netherlands. johannes.van.hooff@mumc.nl
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van Hooff
authors.forename: Rita R
authors.initials: RR
authors.lastname: Alloway
authors.forename: Pavel
authors.initials: P
authors.lastname: Trunečka
authors.forename: Michel
authors.initials: M
authors.lastname: Mourad
mesh_terms: D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D012449:Safety; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus