Concomitant Treatment with Voriconazole and Flucloxacillin: A Combination to Avoid

Antibiotics

Pieter De Cock¹  Yves Debaveye²  Joost Wauters³  Willy E. Peetermans³  Katrien Lagrou³  Matthias Gijsen⁴  Isabel Spriet⁴  Pieter Van Brantegem⁴  Pieter Annaert⁴  Ruth Van Daele⁴  Roger J. Brüggemann⁵  John Leys⁶  Franky Buyle⁷ 

[1] Department of Basic and Applied Medical Sciences, Ghent University, 9000 Ghent, Belgium;Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium;Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium;Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium;Department of Pharmacy and Radboud Institute for Health Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands;Department of Pharmacy, Antwerp University Hospital, 2650 Edegem, Belgium;Department of Pharmacy, Ghent University Hospital, 9000 Ghent, Belgium;

关键词: drug–drug interaction;    voriconazole;    flucloxacillin;    CYP450 enzymes;    underexposure;   

DOI  :  10.3390/antibiotics10091112

来源: DOAJ

【 摘 要 】

Background: Voriconazole is an antifungal drug used as one of the first-line treatments for invasive aspergillosis. This drug is extensively metabolized, predominantly via cytochrome P450 enzymes. An interaction between flucloxacillin and voriconazole, leading to subtherapeutic voriconazole concentrations, has previously been reported. We aimed to demonstrate that flucloxacillin independently influences voriconazole exposure. Methods: Patients from three Belgian hospitals, treated with a combination of voriconazole and flucloxacillin, were included in this retrospective study. Voriconazole concentrations were collected both in a timeframe with and without flucloxacillin co-treatment. Multivariate analyses were performed to study the independent effect of flucloxacillin treatment on voriconazole exposure and the possible influence of the flucloxacillin dose. Results: Thirty-three patients were included in this study and 145 trough concentrations (51 with, and 94 without concomitant flucloxacillin treatment) were analyzed. The median (IQR) voriconazole trough concentration sampled during flucloxacillin co-treatment was 0.5 (0–1.8) mg/L, whereas samples without flucloxacillin co-treatment had a median (IQR) voriconazole trough concentration of 3.5 (1.7–5.1) mg/L (p = 0.002), while receiving similar voriconazole doses. Subtherapeutic concentrations (<1 mg/L) were observed in 69% and 7% of the samples with flucloxacillin co-treatment versus samples without flucloxacillin co-treatment, respectively. Conclusion: This study shows that flucloxacillin co-treatment independently decreases voriconazole exposure. Caution is needed when these two drugs are administered simultaneously.

【 授权许可】

Unknown