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

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

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)1667-1673
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Issue number12
DOIs
Publication statusPublished - 25-Jul-2020

Keywords

  • Tacrolimus
  • Everolimus
  • Flucloxacillin
  • Drug-drug interaction
  • Blood trough levels
  • Therapeutic drug monitoring
  • P-GLYCOPROTEIN
  • CYTOCHROME-P450 3A4
  • TRANSPLANT PATIENTS
  • DRUG-INTERACTIONS
  • EVEROLIMUS
  • CYCLOSPORINE
  • SIROLIMUS
  • MANAGEMENT
  • INHIBITORS

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