Abstract
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.
Funder
University Medical Center Groningen
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology,General Medicine
Reference30 articles.
1. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group (2009) KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 9:S1–S155
2. Brunet M, van Gelder T, Åsberg A, Haufroid V, Hesselink DA, Langman L, Lemaitre F, Marquet P, Seger C, Shipkova M (2019) Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report. Ther Drug Monit 41:261–307
3. Moes D, Swen J, den Hartigh J, van der Straaten T, van der Heide JJH, Sanders J, Bemelman F, de Fijter J, Guchelaar H (2014) Effect of CYP3A4* 22, CYP3A5* 3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus pharmacokinetics in renal transplantation. CPT Pharmacometrics Syst Pharmacol 3:1–12
4. Moes DJA, Guchelaar H, de Fijter JW (2015) Sirolimus and everolimus in kidney transplantation. Drug Discov Today 20:1243–1249
5. Lempers VJ, Martial LC, Schreuder MF, Blijlevens NM, Burger DM, Aarnoutse RE, Brüggemann RJ (2015) Drug-interactions of azole antifungals with selected immunosuppressants in transplant patients: strategies for optimal management in clinical practice. Curr Opin Pharmacol 24:38–44
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献