title: Impact of Mycophenolate Mofetil Dose Reduction on Allograft Outcomes in Kidney Transplant Recipients on Tacrolimus-Based Regimens: A Systematic Review.
abstract: OBJECTIVE
  To systematically evaluate the clinical consequences of mycophenolate dose reduction in renal transplant recipients on tacrolimus-based regimens.
  
  
  METHODS
  PubMed (1949-July 2010), EMBASE (1980-July 2010), Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Web of Science were searched using the terms mycophenolate mofetil, tacrolimus, dose reduction, and kidney and/or renal transplant. References from publications identified were reviewed.
  
  
  METHODS
  Studies reporting on rejection rate, allograft survival, or renal function were included and ranked according to the US Preventive Services Task Force classification; excluded were studies that were dose-finding or used cyclosporine only, involved patients on enteric-coated mycophenolate sodium or those with multiorgan transplant, or provided no information on concomitant immunosuppressants. Data extracted were study design, sample size, immunosuppression regimen, type of transplant, and allograft outcomes.
  
  
  RESULTS
  Of 13 studies included, 1 was level I evidence, 3 were level II-2, 6 were level II-3, and 3 were level III evidence. Three focused on tacrolimus-based regimens, whereas 7 included either cyclosporine or tacrolimus. The only prospective, randomized, multicenter trial demonstrated that early taper of mycophenolate dosage to 1 g/day can be utilized without increased risk of rejection, compared with late tapering, but the rejection rate was high (30-40%). Overall, we found conflicting evidence regarding the impact of mycophenolate dose reduction on rejection rate and allograft loss and that discontinuing mycophenolate led to an increased risk of graft loss as high as 8 fold. Allograft survival was lowest in patients with gastrointestinal complications and those in whom mycophenolate was discontinued, compared with patients with neither gastrointestinal complications nor mycophenolate discontinuation.
  
  
  CONCLUSIONS
  Weak evidence suggests that mycophenolate dose modifications, either reduction or discontinuation, may increase rejection rate and graft loss; however, this is more apparent in cyclosporine-based regimens. Prospective, well-designed trials are necessary to definitively determine the impact of dose reduction in renal transplant recipients on tacrolimus-based regimens.
authors.affiliation: Victoria CH Su BSc (Pharm) ACPR, PharmD student, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Victoria Ch
authors.initials: VCh
authors.lastname: Su
authors.affiliation: Erica D Greanya BSc (Pharm) ACPR PharmD, Pharmacy Specialist-Solid Organ Transplantation, Vancouver General Hospital, Vancouver; Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia.
authors.forename: Erica D
authors.initials: ED
authors.lastname: Greanya
authors.affiliation: Mary HH Ensom BSc (Pharm) PharmD FASHP FCCP FCSHP FCAHS, Professor and Director, Doctor of Pharmacy Program, Faculty of Pharmaceutical Sciences, and Distinguished University Scholar, The University of British Columbia; Clinical Pharmacy Specialist, Children's and Women's Health Centre of British Columbia, Vancouver ensom@interchange.ubc.ca.
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
mesh_terms: D064591:Allografts; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus