Voriconazole as primary antifungal prophylaxis in children undergoing allo-SCT

Abstract

Invasive fungal disease (IFD) causes significant morbidity and mortality among children undergoing allo-SCT. In this prospective pilot study, we analyze voriconazole as primary antifungal prophylaxis. From October 2004 to July 2010, 56 children o18 years of age were enrolled in this study. Patients received voriconazole doses of 5 mg/ kg per 12 h (n ¼ 23) or 7 mg/kg per 12 h (n ¼ 33), with a limiting dose of 200 mg/12 h, from day À1 to day þ 75 or later in patients with active acute GVHD. Patients were followed up for IFD for 6 months. In this series, 37 (66.1%) patients successfully completed treatment (85.7% during neutropenic period) without empirical or preemptive antifungal therapy, adverse effects or IFD. Nine (16.1%) children needed preemptive (n ¼ 2) or empirical (n ¼ 7) antifungal therapy, and one (1.8%) of them developed a fatal probable IFD during the study period. A total of 10 (17.8%) children developed adverse effects related to voriconazole prophylaxis, leading to definitive withdrawal on median day 26.5 (in 7 patients after granulocytic recovery). The most frequent adverse effect was persistent elevation of hepatic enzymes in seven (12.5%) children. There were no differences between doses of 5 and 7 mg/kg per 12 h. Our results suggest that voriconazole can be safely used as primary antifungal prophylaxis in children undergoing allo-SCT.

ESCMID guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp.

“…Clinical trials in adults with inclusion of paediatric patients [99] PK studies in children: [96,97] Safety and efficacy in children [ [83] PK studies in children: [84][85][86][87][88] TDM dosing target: [89][90][91] Safety/efficacy in children: [84][85][86][87][88][89][136][137][138] Allogeneic HSCT Itraconazole suspension 2.5 mg/kg Q12 h for patients ‡2 years of age; to be started after completion of the conditioning regimen; studied until at least day +100 (B-II)…”

Voriconazole Prophylaxis in Children With Cancer

“…15 Our findings demonstrate the changing epidemiology of iMi at our institution after voriconazole prophylaxis was established as part of the standard supportive care of patients with aMl. Our study describes the largest cohort of pediatric aMl patients (n = 117) to receive voriconazole prophylaxis during chemotherapy.…”

Voriconazole-induced Phototoxicity in Children

“…In one study, no statistical difference in safety and efficacy was observed between voriconazole doses of 5 and 7 mg/kg/dose bid in children receiving antifungal prophylaxis after allo-SCT. 16 Shima et al 17 showed that children aged <3 years require significantly higher doses of voriconazole to obtain C trough within a target range of 1-5 μg/mL than older children. Neely et al 18 showed that C trough of >1 μg/mL causes a significant benefit in survival.…”