title: Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age: a retrospective analysis and literature review.
abstract: OBJECTIVE
  Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD).
  
  
  METHODS
  This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy.
  
  
  CONCLUSIONS
  A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8-10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively.
  
  
  CONCLUSIONS
  Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.
authors.affiliation: Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jancel
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Shaw
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Hallahan
authors.affiliation: Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kim
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Freeman
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Department of Pharmacotherapy, University of North Texas System College of Pharmacy, Fort Worth, TX, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Penzak
mesh_terms: D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D009181:Mycoses / Q000188:drug therapy*; D012189:Retrospective Studies; D013535:Suspensions / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000935:Antifungal Agents; D013535:Suspensions; D014230:Triazoles; C101425:posaconazole
keywords: paediatric; pharmacokinetics; posaconazole; therapeutic drug monitoring