Possible interaction between mycophenolatemofetil and tacrolimus in kidney transplant patients

Abstract

Aims: Tacrolimus is the mainstay of transplant immunosuppression in kidney graft recipients. It is most commonly used in combinationwith mycophenolate mofetil. Literature data on the existence and significance of drug-drug interaction of these twodrugs is contradictory and inconclusive for kidney transplant patients. The aim of the study was to confirm and quantify theinteraction in kidney transplant patients.Methods: A total of 4,220 tacrolimus level measurements spanning 5 years in 181 renal graft recipients in a single transplant centerwere analyzed. Change in dose needed to achieve a unit concentration was used as a surrogate for drug clearance variability. A regressionmultivariate model was constructed to identify significant predictors of tacrolimus dose required to reach a unit concentration.Results: The model identified significant predictors of tacrolimus dose, including hematocrit, liver function, body weight, prednisonedose, and age. The coefficient for mycophenolate mofetil dose was -8.76e-04 (standard error 1.35e-04, p < 0.001), i.e. each 1000 mg increaseof mycophenolate dose lead on average to a 15.1 % reduction in the dose of tacrolimus required to reach the same concentration.Conclusions: Based on our analysis, the interaction between mycophenolate mofetil and tacrolimus reported previously in livertransplant patients is present in kidney transplant patients as well. After prospective validation, a pharmacokinetic model couldbe used to predict tacrolimus level changes following adjustment of mycophenolate mofetil doses.