Detailed evaluation of 2 years TDM of voriconazole in a 2000-bed tertiary care center

Ref ID: 19358

Author:

K. Vanstraelen, K. Lagrou, J. Maertens, L. Willems and
I. Spriet

Author address:

University Hospitals Leuven – Research Centre for Clinical
Pharmacy, Leuven, Belgium; University Hospitals Leuven –
Clinical Department of Laboratory Medicine, Leuven, Belgium
and University Hospitals Leuven – Hematology ward, Belgium

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Retrospective evaluation of two years therapeutic drug
monitoring (TDM) of voriconazole in a tertiary care center.
Methods Patients treated with voriconazole, with at least 1 vorico-
nazole trough level (VTL), were included. VTLs were determined
using LC-MSMS (Pauwels et al. 2012, Clin Chim Acta) with 1-
5,5 mg/L as therapeutic interval (Pascual et al. 2008, CID). Statisti-
cal analyses were performed using SPSS 20.0 for Windows, p < 0.05 was considered significant. Results 726 VTLs were obtained from 185 patients (table 1). 28 VTLs (4,7%) were below the limit of quantification of 0.2 mg/L. 589 samples (81.1%) were obtained during hospitalization (table 2), the others were from ambulatory patients, with little information available, resulting in median VTLs of 2.2 and 1.7 mg/L respectively (p = 0.000). During hospitalization, 117 VTLs (19.9%) were below 1 mg/L and 260 VTLs (44.1%) below 2 mg/L (Trifilio et al, 2007, Cancer). Additionally, 91 VTLs (15.5%) were supratherapeutic. No correlations were seen with age (R² = 0.008), body weight (R² = 0.000) and daily dose expressed in mg/kg (R² = 0.011) or mg (R² = 0.008), confirming the unpredictable dose-exposure relationship. Daily dose (mg) and body weight were only weakly correlated (R² = 0.270), possibly due to the use of standard doses instead of exact doses calculated on body weight. 129 patients (69.7%) had at least one follow-up level. 56 (43.5%) had a non-therapeutic first VTL, which remained non-therapeutic in the follow-up level in 41.1%. No clear correlation was found between the initial and follow-up VTL (R² = 0.378). Remarkably, 24.5% and 29% of initial subtherapeutic and supratherapeutic VTL were not fol- lowed by a control VTL. Intravenously administered (IV) voriconazole (328 VTLs; 55.7%) results in higher VTLs (table 2). Also omeprazole elevates VTLs vs. ranitidine and pantoprazole (Boyd et al, 2012, AAC). No difference was seen in VTLs between pantoprazole and ranitidine co-administra- tion, suggesting no need for voriconazole dose adjustment when combining with pantoprazole. Also, more co-administration with omeprazole (39.1% vs. 26%, p = 0.019), and less with pantoprazole (34.5% vs. 51.2%, p = 0.005) was seen in case of supratherapeutic VTLs vs. (sub-)therapeutic VTLs. As shown in table 2, dose and route of administration of omeprazole are also important.

Abstract Number: o2.1

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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