title: Voriconazole dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre.
abstract: Therapeutic drug monitoring (TDM) of voriconazole is recommended to achieve trough concentrations of 1-5 mg/L. In children, this is challenging due to age-related variability in voriconazole pharmacokinetics. This study describes our experience with voriconazole, focusing on dosing regimens, dose adjustment and TDM.
  
  
  
  We reviewed the medical records of immunocompromised children who received voriconazole from July 2009 to January 2015 and had TDM. Demographic, clinical and voriconazole dosing and monitoring data were collected.
  
  
  
  Fifty-five children received 62 courses of voriconazole and had TDM, with a total of 256 samples taken. Only 71.0% of courses (44/62) had TDM at the correct time, and at least one therapeutic level was achieved in only 52.3% (23/44) of these. Twenty-six courses had at least one sub-therapeutic level and in only 61.5% was the dose adjusted. Patients aged <6, 6-12 and >12 years required median intravenous doses of 8.8, 7.5 and 4.0 mg/kg twice daily, respectively (P < 0.001). With oral administration, patients aged 6-12 and >12 years required median doses of 4.7 and 4.3 mg/kg twice daily, respectively (P = 0.307). Levels within the target range were observed to fall below 1 mg/L in 36.4% of unchanged dosing regimens. Photosensitive skin reactions (20.0%) and hepatotoxicity (12.7%) were the most frequent adverse events and occurred in children with voriconazole levels <5 mg/L.
  
  
  
  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.
authors.affiliation: Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Boast
authors.affiliation: Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Flemington, Victoria, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
authors.affiliation: Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Flemington, Victoria, Australia.
authors.forename: Noel
authors.initials: N
authors.lastname: Cranswick
authors.affiliation: Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia Murdoch Children's Research Institute, Flemington, Victoria, Australia amanda.gwee@rch.org.au.
authors.forename: Amanda
authors.initials: A
authors.lastname: Gwee
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010949:Plasma / Q000737:chemistry; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole