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

Abstract

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.

Keywords

• mycoses
• children
• cancer
• voriconazole
• safety