Voriconazole Therapeutic Drug Monitoring Practices in Intensive Care

Wanrooy, Marjolijn J. P. van; Rodgers, Michael G. G.; Span, L. F. R.; Zijlstra, Jan G.; Uges, Donald; Kosterink, Jos G. W.; Werf, Tjip S. van der; Alffenaar, Jan‐Willem C.

doi:10.1097/ftd.0000000000000284

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…The 46% of non-therapeutic voriconazole levels was a little higher than reported in the majority of other studies, which ranged from 23 to 37% [ 9 , 18 , 22 – 25 ]. To our knowledge, only three studies reported percentages greater than 40% [ 26 – 28 ].…”

Section: Discussionmentioning

confidence: 53%

“…This study had a large percentage of drug levels that were measured early, which could be a reflection of ICU practices, as nearly half of patients in this study were critically ill. A retrospective study of voriconazole in an ICU reported that 49% of the drug levels measured for TDM were too early [ 18 ]. Given the frequency of pre-steady state TDM in real-life ICU settings, we aimed to evaluate the utility of early drug measurements.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies have assessed other patient populations, such as the critically ill, who may have the lowest rates of attaining therapeutic drug levels of posaconazole [ 17 ]. TDM practices can be different in the intensive care unit (ICU) as opposed to other less emergent settings, as seen with the high rate of drug levels drawn on day 1 or 2 of therapy [ 18 ]. While guidelines recommend waiting until steady state for first TDM measurement [ 1 ], studies have not evaluated whether this is strictly adhered to in routine practice and what the implications on efficacy are if it is not.…”

Section: Introductionmentioning

confidence: 99%

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Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Schoeppler

Jaeger

et al. 2017

Ann Clin Microbiol Antimicrob

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BackgroundTherapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability. However, its benefits on clinical outcomes are still being defined. Additionally, TDM data are limited for posaconazole IV and delayed-release tablet formulations among specific patient populations, including critically ill. The aim of this study was to determine the percentage of therapeutic posaconazole and voriconazole drug levels across all formulations in a real-world clinical setting and elucidate factors affecting attainment of target concentrations.MethodsThis study was a retrospective cohort study conducted at the University of Colorado Hospital between September 2006 and June 2015 that evaluated patients who received posaconazole or voriconazole TDM as part of routine care.ResultsVoriconazole (n = 250) and posaconazole (n = 100) levels were analyzed from 151 patients. Of these, 54% of voriconazole and 69% of posaconazole levels were therapeutic. For posaconazole, 14/38 (37%), 28/29 (97%) and 27/33 (82%) levels were therapeutic for the oral suspension, IV, and delayed-release tablet, respectively. Intravenous and delayed-release tablet posaconazole were 20 fold (p < 0.01) and sevenfold (p = 0.002) more likely than the oral suspension to achieve a therapeutic level. Subsequent levels were more likely to be therapeutic after dose adjustments (OR 3.31; 95% CI 1.3–8.6; p = 0.02), regardless of timing of initial non-therapeutic level. In a multivariable logistic regression analysis, no characteristics were independently predictive of therapeutic voriconazole levels and only absence of H2RA/PPI use was independently predictive of therapeutic posaconazole levels. There was no correlation between survival and therapeutic drug levels for either voriconazole (p = 0.67) or posaconazole (p = 0.50).ConclusionsA high percentage of drug levels did not achieve TDM targets for voriconazole and posaconazole oral suspension, supporting the need for routine TDM for those formulations. The utility of TDM for the IV and delayed-release tablet formulations of posaconazole is less apparent.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Schoeppler

Jaeger

et al. 2017

Ann Clin Microbiol Antimicrob

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“…Therapeutic monitoring of VCZ levels has been investigated due to the effects of its non-linear pharmacokinetics, especially in children [ 187 ], the elderly [ 37 ], patients in Intensive Care Units (ICU), and for hematological and inflammatory diseases [ 188 , 189 ]. The central monitoring measures have been the evaluation of CYP2C19 polymorphisms [ 190 ] and plasma drug concentration [ 189 , 191 ], in addition to the evaluation of liver function and other measures [ 192 , 193 ]. Monitoring VCZ plasma concentrations is carried out with well-standardized Liquid Chromatography coupled with Mass Spectrometry and High-Performance Liquid Chromatography methods [ 194 , 195 ].…”

Section: Voriconazolementioning

confidence: 99%

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections

et al. 2023

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Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

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“…In practice, despite several examples of efficient dose adaptation, particularly in critically ill patients, 171 the effective rate of dose adaptation after TDM is variable 170,332 (51% or 38%), including in children. 361 A cross-sectional survey of TDM practices in Australia concluded that only 35% of clinical practices were consistent with current TDM recommendations.…”

Section: Tdm For Af Drugsmentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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Voriconazole Therapeutic Drug Monitoring Practices in Intensive Care

Cited by 9 publications

References 21 publications

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections

Antifungal Drugs TDM: Trends and Update

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