Flucloxacillin decreases tacrolimus blood trough levels: a single-center retrospective cohort study.

Veenhof, Herman; Schouw, Hugo M.; Besouw, Martine T. P.; Touw, Daan J.; Gracchi, Valentina

Purpose: Tacrolimus and everolimus are widely used to prevent allograft rejection. Both are metabolized by the hepatic cytochrome P450 (CYP) enzyme CYP3A4 and are substrate for P-glycoprotein (P-gp). Drugs influencing the activity or expression of CYP enzymes and P-gp can cause clinically relevant changes in the metabolism of immunosuppressants. Several case reports have reported that flucloxacillin appeared to decrease levels of drugs metabolized by CYP3A4 and P-gp. The magnitude of this decrease has not been reported yet. Methods: In this single-center retrospective cohort study, we compared the tacrolimus and everolimus blood trough levels (corrected for the dose) before, during, and after flucloxacillin treatment in eleven transplant patients (tacrolimus n = 11 patients, everolimus n = 1 patient, flucloxacillin n = 11 patients). Results: The median tacrolimus blood trough level decreased by 37.5% (interquartile range, IQR 26.4–49.7%) during flucloxacillin treatment. After discontinuation of flucloxacillin, the tacrolimus blood trough levels increased by a median of 33.7% (IQR 22.5–51.4%). A Wilcoxon signed-rank test showed statistically significantly lower tacrolimus trough levels during treatment with flucloxacillin compared with before (p = 0.009) and after flucloxacillin treatment (p = 0.010). In the only available case with concomitant everolimus and flucloxacillin treatment, the same pattern was observed. Conclusions: Flucloxacillin decreases tacrolimus trough levels, possibly through a CYP3A4 and/or P-gp-inducing effect. It is strongly recommended to closely monitor tacrolimus and everolimus trough levels during flucloxacillin treatment and up to 2 weeks after discontinuation of flucloxacillin.

DRUG interactions; DRUG monitoring; TACROLIMUS; GENE expression; GLYCOPROTEINS; GRAFT rejection; IMMUNOSUPPRESSIVE agents; LONGITUDINAL method; STATISTICS; TRANSPLANTATION of organs, tissues, etc.; DATA analysis; RETROSPECTIVE studies; OXACILLIN; DESCRIPTIVE statistics; EVEROLIMUS; CYTOCHROME P-450; PHARMACODYNAMICS

European Journal of Clinical Pharmacology, 2020, Vol 76, Issue 12, p1667

0031-6970

Academic Journal

10.1007/s00228-020-02968-z