Effect of corticosteroid withdrawal on tacrolimus and mycophenolate mofetil exposure in a randomized multicenter study.

Publication Type
Journal Article
Year of Publication
Shihab, F S; Lee, S T; Smith, L D; Woodle, E S; Pirsch, J D; Gaber, A O; Henning, A K; Reisfield, R; Fitzsimmons, W; Holman, J; M. R. First for the Astellas Corticosteroid Withdrawal Group
Am J Transplant
Date Published
2013 Feb
Adrenal Cortex Hormones; Adult; African Americans; body mass index; Double-Blind Method; Female; Humans; Hyperkalemia; kidney transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Renal Insufficiency; Tacrolimus

As corticosteroid-sparing protocols are increasingly utilized in kidney transplant recipients, it is crucial to understand potential drug interactions between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting. This prospective, multicenter, randomized, double-blind study included 397 patients who were randomized on posttransplant day 8 to receive either placebo (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two posttransplant were significantly greater in the CSWD group whereas TAC doses were comparable to the CCS group. This interaction was not observed in the African American subgroup. Higher serum creatinine and potassium levels were also observed in the CSWD group. MMF dose was significantly reduced in the CSWD group by the investigators because of decreased WBC counts, mostly outside of study protocol criteria, despite similar incidence of neutropenia and reported cytomegalovirus infection. Understanding TAC and MMF exposure in the context of corticosteroid-sparing protocols should allow for improved dosing of immunosuppressants and better management of posttransplant patients.