title: Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children.
abstract: OBJECTIVE
  To describe the safety and efficacy of voriconazole in children treated within the compassionate release program.
  
  
  METHODS
  Children received voriconazole on a compassionate basis for treatment of an invasive fungal infection if they were refractory to or intolerant of conventional antifungal therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h i.v. on Day 1 followed by 4 mg/kg every 12 h i.v. thereafter. When feasible the route of administration of voriconazole was changed from i.v. to oral (100 or 200 mg twice a day for patients weighing < 40 or > or = 40 kg, respectively). Outcome was assessed by investigators at the end of therapy or at the last visit as success (complete or partial response), stable infection, or failure, based on protocol-defined criteria.
  
  
  RESULTS
  Sixty-nine children (ages 9 months to 15 years; median, 7 years) received voriconazole; 58 had a proven or probable fungal infection. Among these 58 patients 27 had hematologic malignancies and 13 had chronic granulomatous disease as the most frequent underlying conditions. Forty-two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis and 4 had other invasive fungal infections. The median duration of voriconazole therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or partial response. Four patients (7%) had a stable response, 25 (43%) failed therapy and 4 (7%) were discontinued from voriconazole because of intolerance. Success rates were highest in patients with chronic granulomatous disease (62%) and lowest in patients with hematologic malignancies (33%). Two patients experienced treatment-related serious adverse events (ulcerated lips with rash, elevated hepatic transaminases or bilirubin). A total of 23 patients had voriconazole-related adverse events, 3 (13%) of which caused discontinuation of voriconazole therapy. The most commonly reported adverse events included elevation in hepatic transaminases or bilirubin (n = 8), skin rash (n = 8), abnormal vision (n = 3) and a photosensitivity reaction (n = 3).
  
  
  CONCLUSIONS
  These data support the use of voriconazole for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy.
authors: Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. walsht@mail.nih.gov
authors: Thomas J
authors: TJ
authors: Walsh
authors: Irja
authors: I
authors: Lutsar
authors: Timothy
authors: T
authors: Driscoll
authors: Bertrand
authors: B
authors: Dupont
authors: Maureen
authors: M
authors: Roden
authors: Parvis
authors: P
authors: Ghahramani
authors: Michael
authors: M
authors: Hodges
authors: Andreas H
authors: AH
authors: Groll
authors: John R
authors: JR
authors: Perfect
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D007223:Infant; D008297:Male; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D017211:Treatment Failure; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole