title: Improved adherence to tacrolimus once-daily formulation in renal recipients:  a randomized controlled trial using electronic monitoring.
abstract: BACKGROUND
  With effective agents available to prevent posttransplantation acute organ rejection, medication adherence becomes a key factor for successful treatment outcomes after renal transplantation. A once-daily, modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence.
  
  
  METHODS
  Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a randomized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake. After enrolment, all patients continued the twice-daily regimen for 3 months and then were randomized 2:1 between the two formulations and followed for 6 months. Adherence was decomposed into patients' persistence and implementation of each regimen.
  
  
  RESULTS
  Two hundred nineteen patients (45% male; 3±2 years after transplantation) were analyzed (145 once daily and 74 twice daily). At 6 months after randomization, 81.5% of the once-daily group and 71.9% of the twice-daily group remained persistent with the treatment (P=0.0824). Among patients who remained engaged with the regimen, 88.2% of the once-daily group and 78.8% of the twice-daily group (P=0.0009) took the prescribed number of daily doses. When the patients took the twice-daily regimen, the average percentage of missed doses was 11.7% in the morning and 14.2% in the evening (P=0.0035).
  
  
  CONCLUSIONS
  Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen. There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification. Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management.
authors.affiliation: Department of Nephrology and Renal Transplantation, University Hospital Leuven, Gasthuisberg, Belgium. dirk.kuypers@uz.kuleuven.ac.be
authors.forename: Dirk R J
authors.initials: DR
authors.lastname: Kuypers
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Peeters
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Sennesael
authors.forename: Mireille N
authors.initials: MN
authors.lastname: Kianda
authors.forename: Bernard
authors.initials: B
authors.lastname: Vrijens
authors.forename: Paulus
authors.initials: P
authors.lastname: Kristanto
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dobbels
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: Nada
authors.initials: N
authors.lastname: Kanaan
mesh_terms: D000284:Administration, Oral; D001530:Belgium; D002626:Chemistry, Pharmaceutical; D004334:Drug Administration Schedule; D055615:Electrical Equipment and Supplies; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D016347:Medical Records Systems, Computerized; D055118:Medication Adherence; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus