Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.

Abstract

BACKGROUND:

Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.

• Authors: Judith M Martin, Mercedes Macias-Parra, Peter Mudry, Umberto Conte, Jean L Yan, Ping Liu, M Rita Capparella, Jalal A Aram
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 36 Issue 1 Pg. e1-e13 (01 2017) ISSN: 1532-0987 [Electronic] United States
• PMID: 27636722 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Voriconazole

Topics

• Adolescent
• Antifungal Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Aspergillosis (drug therapy)
• Candidiasis (drug therapy)
• Candidiasis, Invasive (drug therapy)
• Child
• Child, Preschool
• Female
• Humans
• Male
• Prospective Studies
• Voriconazole (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)