Voriconazole dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre

Boast, Alison; Curtis, Nigel; Cranswick, Noel; Gwee, Amanda

doi:10.1093/jac/dkw056

Cited by 49 publications

(54 citation statements)

References 34 publications

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“…Similar to the findings of many previous studies (14,15), 50% of children could not reach the target range at the initial trough concentration. The initial trough concentrations ranged from 0.02 to 9.35 mg/liter with high inter-and intraindividual variability.…”

Section: Discussionsupporting

confidence: 90%

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Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China

Dai

Zou

et al. 2018

Antimicrob Agents Chemother

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Voriconazole is a broad-spectrum triazole antifungal and the first-line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients 2 to 14 years old who were subjected to voriconazole trough concentration monitoring from 1 June 2015 to 1 December 2017. A total of 138 voriconazole trough concentrations from 42 pediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35 mg/liter, with high inter- and intraindividual variability. Only 50.0% of children achieved the target range (1.0 to 5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) received an adjusted dose according to trough concentrations. Children <6, 6 to 12, and >12 years old required a median oral maintenance dose to achieve the target range of 11.1, 7.2, and 5.3 mg/kg twice daily, respectively (P = 0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P = 0.033 and 0.003, respectively). Affecting factors such as administration routes and coadministration with proton pump inhibitors (PPIs) explained 55.3% of the variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

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Section: Discussionsupporting

confidence: 90%

“…2. The study of Boast et al (15) showed that patients Ͻ6, 6 to 12, and Ͼ12 years of age required median intravenous doses of 8.8, 7.5, and 4.0 mg/kg twice daily, respectively, and these results were significant. These results were consistent with those obtained in our study.…”

Section: Discussionmentioning

confidence: 97%

Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China

Dai

Zou

et al. 2018

Antimicrob Agents Chemother

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“…Our patient's final therapeutic dose (54 mg/kg/ day) was large compared to those reported in other published studies among pediatric patients. 1,[11][12][13] Use of every-8-hour dosing with the oral formulation was deemed necessary after multiple dosage adjustment using every 12 hours failed to overcome rapid hepatic clearance known to occur in infants.…”

Section: Discussionmentioning

confidence: 99%

Voriconazole: Poor Oral Bioavailability and Possible Renal Toxicity in an Infant With Invasive Aspergillosis

Walldorf¹,

Kishk²,

Campbell³

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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Voriconazole is the recommended agent of choice for treatment of invasive aspergillosis; however, achieving therapeutic serum concentrations while avoiding toxicity, both with intravenous and oral formulations, is challenging in infants. We report the case of an infant with confirmed invasive aspergillosis who developed renal toxicity possibly associated with IV voriconazole. Renal function improved upon withdrawal of the IV agent and switch to the oral formulation. The infant subsequently required large oral weight-based dosing to achieve therapeutic voriconazole serum concentrations. This case illustrates a rare side effect associated with voriconazole as well as the issues surrounding the pharmacokinetic profile of voriconazole in a pediatric patient.

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“…Higher doses are used clinically in select patients, generally under the guidance of TDM. Institutional processes that result in delays in obtaining results may significantly impact TDM utilization, dosing practices, and patient outcomes [83, 118,207]. Recent dosing IV and oral experience for IFI in this age group include loading and maintenance doses up to 7-9 mg/kg [132,204,208].…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…There is no FDA-approved dosing regimen for children <12 years of age, with the voriconazole label simply stating that safety and efficacy have not been established in this population [36]. A number of retrospective studies have additionally suggested that IV maintenance doses exceeding 8 mg/kg are necessary for children <6 years of age [11,104,207,209]. For serious Candida spp.…”

Section: Pediatric Dosingmentioning

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 dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre

Abstract: There is significant intra- and inter-individual variability in voriconazole concentrations in children, particularly in children <6 years of age. This warrants repeated TDM throughout treatment. Standardized guidelines for TDM and dose adjustment are required in children.

Cited by 49 publications

References 34 publications

Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China

Therapeutic Drug Monitoring of Voriconazole in Children from a Tertiary Care Center in China

Voriconazole: Poor Oral Bioavailability and Possible Renal Toxicity in an Infant With Invasive Aspergillosis

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

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