title: An Optimized Voriconazole Dosing Strategy to Achieve Therapeutic Serum Concentrations in Children Younger than 2 Years Old.
abstract: 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).
  
  
  
  Case series.
  
  
  
  Large pediatric hospital.
  
  
  
  Three patients younger than 2 years who received voriconazole therapy and had serum trough concentrations measured between January 1, 2010, and October 31, 2015.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pharmacy, Children's Hospital and Health System, Milwaukee, Wisconsin. tzembles@chw.org.
authors.forename: Tracy N
authors.initials: TN
authors.lastname: Zembles
authors.affiliation: Department of Pediatrics, Critical Care Medicine, Medical College of Wisconsin, Children's Hospital and Health System, Children's Research Institute, Milwaukee, Wisconsin.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Thompson
authors.affiliation: Department of Pediatrics, Infectious Disease, Medical College of Wisconsin, Children's Hospital and Health System, Children's Research Institute, Milwaukee, Wisconsin.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Havens
authors.affiliation: Department of Neurosurgery, Medical College of Wisconsin, Children's Hospital and Health System, Milwaukee, Wisconsin.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Kaufman
authors.affiliation: Department of Pediatrics, Infectious Disease, Medical College of Wisconsin, Children's Hospital and Health System, Children's Research Institute, Milwaukee, Wisconsin.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Huppler
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D008297:Male; D010595:Pharmacists / Q000458:organization & administration; D010607:Pharmacy Service, Hospital / Q000458:organization & administration; D017410:Practice Guidelines as Topic; D024382:Professional Role; D065819:Voriconazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: dosing; guideline; pediatrics; therapeutic drug monitoring; voriconazole