Safety and outcome of treatment with voriconazole in a large cohort of immunocompromised children and adolescents

Objectives: Post-marketing data on safety and outcome of voriconazole (VCZ) treatment in pediatric patients is limited. We performed a retrospective, single center analysis of safety, tolerance and antifungal efficacy in a large cohort of children and adolescents requiring VCZ therapy.Patients and methods: The cohort included 107 patients (0.2-18 years of age) with hematological disorders (85; 42 post allo-HSCT), primary immunodeficiencies (9), AIDS (4), metabolic diseases (5) and solid tumors (4) who received 252 courses of VCZ for possible (12) and probable/proven (25) invasive fungal diseases (IFDs), as primary (127) or secondary (79) prophylaxis or as empiric therapy (9). VCZ was given IV (10) and (37)/or (205) PO at recommended dosages until intolerance or maximum efficacy. IFDs and outcomes were assessed by EORTC/MSG consensus criteria.Results: VCZ was administered at a median maintenance dosage of 5.9 mg/kg twice daily (range, 2.2-22.0) for a median of 65 days (range 1-1,002). While on treatment, increases in hepatic transaminases, serum bilirubin and alkaline phosphatase, skin eruptions and neurological adverse events (AEs) were observed in 53.5, 23.6, 10.9, 5.6 and 4.8% of courses, respectively. At end of treatment (EOT), mean alkaline phosphatase, aspartate aminotransferase and serum bilirubin values were slightly elevated relative to baseline (p<0.01). AEs prompting discontinuation of VCZ occurred in 18 courses (7.1%). Treatment success was observed in 16/37 patients with proven/probable/possible IFDs, and in 187/215 courses of empiric therapy and prophylaxis. Overall survival was 97.6% at EOT and 92.1% at 3 month post EOT, respectively.Conclusions: VCZ displayed acceptable clinical safety and tolerance and was effective in the management of IFDs in severely immunocompromised children and adolescents.