title: Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.
abstract: Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited.
  
  
  
  Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored.
  
  
  
  Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established.
  
  
  
  Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.
authors.affiliation: From the *Division of General Academic Pediatrics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; †Pediatric Infectious Diseases Department, Instituto Nacional de Pediatria, Mexico City, Mexico; ‡Department of Pediatric Oncology, University Children's Hospital Brno, Brno, Czech Republic; §Antifungal Clinical Development, Pfizer Inc., New York, New York; ¶Global Established Pharma-Biostatistics, Pfizer Inc., New York, New York; ‖Department of Clinical Pharmacology, Pfizer Inc., Groton, Connecticut; **Global Established Pharma, Pfizer PFE, Paris, France; and ††Global Medical Affairs, Pfizer Inc., Groton, Connecticut.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Martin
authors.forename: Mercedes
authors.initials: M
authors.lastname: Macias-Parra
authors.forename: Peter
authors.initials: P
authors.lastname: Mudry
authors.forename: Umberto
authors.initials: U
authors.lastname: Conte
authors.forename: Jean L
authors.initials: JL
authors.lastname: Yan
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: M Rita
authors.initials: MR
authors.lastname: Capparella
authors.forename: Jalal A
authors.initials: JA
authors.lastname: Aram
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D002177:Candidiasis / Q000188:drug therapy; D058365:Candidiasis, Invasive / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D065819:Voriconazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole