Voriconazole plasma levels in children are highly variable

Spriet, Isabel; Cosaert, Katrien; Renard, Marleen; Uyttebroeck, Anne; Meyts, Isabelle; Proesmans, Marijke; Meyfroidt, Geert; Hoon, Jan de; Verbesselt, René; Willems, Ludo

doi:10.1007/s10096-010-1079-8

Cited by 27 publications

(22 citation statements)

References 11 publications

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“…Neely et al predicted that when using the recommended dose, around 34% of children Ͼ2 years of age receiving voriconazole would not achieve C trough s of Ͼ1 mg/liter (5). Brüggeman et al showed that in 44% of 18 children and Spriet et al in 31% of 16 children Ͼ2 years of age, the recommended dose resulted in a C trough below the target concentration of 1 mg/liter (4,18). In comparison, our study showed that 60% of 41 patients had an initial C trough below this target concentration, and this data set included 11 patients Ͻ2 years of age.…”

Section: Discussionmentioning

confidence: 46%

Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients

Bartelink

Wolfs

Jonker

et al. 2013

Antimicrob Agents Chemother

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cInvasive fungal infections are of great concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first choice for treating or preventing invasive aspergillosis. Optimum trough levels (C trough s) are between 1 and 5 mg/liter. It is unclear whether these levels are reached with currently advised pediatric dosing schedules. Between 2007 and 2011, 11 patients <2 years of age, 31 between 2 and 12 years, and 20 between 12 and 20 years were (prophylactically or therapeutically) treated with voriconazole in the HSCT unit of UMC Utrecht. For children <2 years of age, the dosage recommended for 2 to 12 years was used. In 34% of children who started with the recommended dose, an adequate C trough was reached irrespective of age or administration route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequate C trough s were reached in 80% of the patients at median doses of 31.5 (age, <2 years), 16 (age, 2 to 12 years), and 9.4 mg/kg of body weight/ day (age, >12 years) (P ‫؍‬ 0.034). The intrapatient variability in C trough ranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a median C trough of 0.5 mg/liter at the initial dose (ranging from 0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was reached. Inter-and intrapatient variability is a major concern in voriconazole treatment and necessitates therapeutic drug monitoring of dosing, especially in young children.

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Section: Discussionmentioning

confidence: 46%

Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients

Bartelink

Wolfs

Jonker

et al. 2013

Antimicrob Agents Chemother

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“…Some studies detected considerable variability in patients receiving voriconazole both between patients and in the same patient. 24,25 Small studies have suggested that there is a relationship between low plasma voriconazole levels and treatment failure and high plasma levels and toxicity. 26,27 However, more recent studies have not been able to identify cutoff levels for toxicity or a clear relationship between the two.…”

Section: Discussionmentioning

confidence: 98%

Voriconazole hepatotoxicity in severe liver dysfunction

Solís‐Muñoz

López

Bernal

et al. 2013

Journal of Infection

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“…Caution must therefore be used in determining dose efficacy as agebased dosing does not necessarily correlate with attainment of trough levels >1 mg/L due to PK considerations (age, hepatic function, non-linear PK, CYP2C19 polymorphisms, etc.) [35,48,49,[102][103][104]. Over one-third of patients 2-12 years of age may not reach this trough concentration target with widely recommended pediatric doses [67,79].…”

Section: Childrenmentioning

confidence: 99%

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections

Job

Olson

Constance

et al. 2016

Expert Review of Anti-infective Therapy

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The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.

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Voriconazole plasma levels in children are highly variable

Abstract: International audienc

Cited by 27 publications

References 11 publications

Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients

Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients

Voriconazole hepatotoxicity in severe liver dysfunction

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections

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