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An Optimized Voriconazole Dosing Strategy to Achieve Therapeutic Serum Concentrations in Children Younger than 2 Years Old. Pharmacotherapy 2016 10;36(10):1102-1108 PMID: 27548272

Pubmed ID

27548272

DOI

10.1002/phar.1829

Abstract

STUDY OBJECTIVE: To describe our experience with voriconazole in three patients younger than 2 years using an optimized dosing strategy for voriconazole that incorporates intensive therapeutic drug monitoring (TDM).

DESIGN: Case series.

SETTING: Large pediatric hospital.

PATIENTS: Three patients younger than 2 years who received voriconazole therapy and had serum trough concentrations measured between January 1, 2010, and October 31, 2015.

MEASUREMENTS AND MAIN RESULTS: A clinical practice guideline developed at our institution was used to standardize initial dosing, appropriate use and timing of TDM, and dosage modifications based on TDM. TDM was used to guide dosing to achieve a target voriconazole serum trough concentration of 2-6 μg/ml. Voriconazole samples were assayed by using a high-performance liquid chromatography analytical method with solid-phase extraction. Initial dosages for the three patients were 9 mg/kg intravenously every 12 hours (one patient) and 9 mg/kg enterally twice/day (two patients). Multiple dose escalations and a more frequent dosing interval were required to achieve trough concentrations within the target range. The final dosages were 12 mg/kg intravenously every 8 hours, 17.7 mg/kg enterally 3 times/day, and 8.5 mg/kg enterally 3 times/day, respectively. In addition to voriconazole trough concentrations, TDM included evaluations for drug toxicities. Visual, neurologic, or hepatic adverse effects were not encountered in the three patients.

CONCLUSION: Our data support higher initial doses and perhaps a 3 times/day dosing schedule to achieve voriconazole serum concentrations in the target range for children younger than 2 years. Implementation of a clinical practice guideline with the participation of pharmacists specializing in pharmacokinetics allows for effective use of voriconazole in young children.

Author List

Zembles TN, Thompson NE, Havens PL, Kaufman BA, Huppler AR

Authors

Peter L. Havens MD Professor in the Pediatrics department at Medical College of Wisconsin
Anna H. Huppler MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Bruce A. Kaufman MD Professor in the Neurosurgery department at Medical College of Wisconsin
Nathan Thompson MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




Scopus

2-s2.0-84990831275   4 Citations

MESH terms used to index this publication - Major topics in bold

Antifungal Agents
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Drug Monitoring
Female
Hospitals, Pediatric
Humans
Infant
Male
Pharmacists
Pharmacy Service, Hospital
Practice Guidelines as Topic
Professional Role
Voriconazole
jenkins-FCD Prod-336 69ef4a6b262d135130251597d5d39873903802b5