title: Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review.
abstract: BACKGROUND
  A simplified dosing regimen may improve drug compliance in kidney transplant recipients and long-term graft outcomes. We aimed to identify, appraise, and synthesize the current evidence comparing the relative safety and efficacy of the recently introduced daily versus standard twice-daily tacrolimus administration.
  
  
  METHODS
  We systematically reviewed all randomized controlled trials and observational studies that compared the outcomes of daily versus twice-daily tacrolimus formulation in kidney transplant recipients. Medline (from 1948 to July week 4 2011), Embase (1980 to 2011 week 31), the Cochrane Library (1991 to June 2011), and conference proceedings were searched without language restriction.
  
  
  RESULTS
  Six randomized controlled trials (n=2499) and 15 observational studies (n=2886) were included in the review. There were no significant differences in biopsy-proven acute rejection (two trials, n=1093; risk ratio [RR; confidence interval (CI)], 1.24 [0.93-1.65]; P=0.15; I=0%), patient survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.55; I=32%), and graft survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.67; I=0%) between the two formulations at 12 months. Similar results for acute rejection (five studies, n=391; RR [CI], 0.99 [0.93-1.06]; P=0.84; I=0%) and overall patient survival (two studies, n=218; RR [CI], 1.02 [0.94-1.10]; P=0.62; I=0%) were observed in observational studies.
  
  
  CONCLUSIONS
  Once-daily tacrolimus appears to be as effective as twice-daily tacrolimus up to 12 months after kidney transplantation.
authors.affiliation: Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia 2145.
authors.forename: Elaine T L
authors.initials: ET
authors.lastname: Ho
authors.forename: Germaine
authors.initials: G
authors.lastname: Wong
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
mesh_terms: D001424:Bacterial Infections / Q000453:epidemiology; D004334:Drug Administration Schedule; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus