title: Posaconazole therapeutic drug monitoring in pediatric patients and young adults with cancer.
abstract: BACKGROUND
  Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescents, and young adults with cancer. At St. Jude Children's Research Hospital, the recommended posaconazole dose in patients weighing less than 34 kg is 18-24 mg/kg daily, given in 4 divided doses. For patients aged 13 years or older or those weighing 34 kg or more, the recommended dose is 800 mg daily, given orally in 4 divided doses.
  
  
  OBJECTIVE
  To determine whether the current posaconazole dosing guidelines achieve target posaconazole plasma concentrations of 0.7 μg/mL or greater.
  
  
  METHODS
  This retrospective clinical study examined data from patients who received treatment-dose posaconazole and had at least 1 posaconazole plasma concentration measurement.
  
  
  RESULTS
  Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5-23.2). Twenty-one of 33 patients (63.6%) had posaconazole concentrations of 0.7 μg/mL or greater (median 1.4; range 0.7-2.98) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg/day. Patients with concentrations less than 0.7 μg/mL (median 0.4; range 0.025-0.69) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg/day; p = 0.02). Of the 12 patients with concentrations less than 0.7 μg/mL, 7 (58.3%) were aged 13 years or older.
  
  
  CONCLUSIONS
  The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients younger than 13 years than in those 13 years or older. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent, and young adult patients with cancer, with routine therapeutic drug monitoring to ensure adequate concentrations.
authors.affiliation: Department of Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, MO, USA. Valeria.Bernardo@ssmhc.com
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Bernardo
authors.forename: Shane J
authors.initials: SJ
authors.lastname: Cross
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flynn
authors.forename: James M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Knapp
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pauley
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Molinelli
authors.forename: William L
authors.initials: WL
authors.lastname: Greene
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000097:blood / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D014230:Triazoles / Q000097:blood* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole