Increase in tacrolimus trough levels after steroid withdrawal

Although there are experimental reports of cytochrome P450 3A4 iso-enzyme (CYP3A4) induction by glucocorticoids, there are no clinical reports about an interaction between tacrolimus and steroids. Therefore, tacrolimus trough level and dose were compared after dose-normalization before and after withdrawal of prednisolone. After withdrawal of 5 mg prednisolone, the median tacrolimus dose-normalized level increased by 14% in the retrospective (n = 54), and by 11% in the prospective (n = 8) part of the study. After withdrawal of 10 mg, this increase was 33% (n = 30) and 36% (n = 14), respectively. An additional pharmacokinetic part of the study (n=8) revealed an 18% increase in AUC (P = 0.05) after withdrawal of 5 mg prednisolone, which is compatible with a reduced metabolism after steroid withdrawal. The significant increase in tacrolimus exposure after steroid withdrawal may on the one hand counteract the reduction in immunosuppression intended by steroid withdrawal, and, on the other hand, may result in an increase of serum creatinine which could be misinterpreted as rejection.