Safety of Micafungin in Pediatric Clinical Trials

Background: Pediatric patients with invasive fungal infections are often fragile hosts with multiple underlying conditions. Safety is an important feature of antifungal agents to be used in this setting. This study aims to evaluate safety of micafungin in pediatric patients (<16 years of age), enrolled in different studies including pharmacokinetic evaluations and clinical trials for invasive aspergillosis, candidiasis, and antifungal prophylaxis. Methods: Adverse event (AE) data were pooled from 6 clinical trials conducted in Europe, the Americas, and Asia. Results: A total of 296 patients with a mean +/- standard deviation age of 6.5 +/- 5.1 years received >= 1 dose of micafungin; 66 were <1 year of age; 38 were premature. Other common underlying conditions were hematopoietic stem cell transplantation (33.8%) and hematologic malignancy (29.1%). Approximately 40% of patients were neutropenic at baseline (absolute neutrophil count <500 cells/mm(3)). Median daily micafungin dose was 1.7 mg/kg overall (range, 0.4-8.6 mg/kg) and 2.0 mg/kg (range, 0.8-7.7 mg/kg) for neonates <4 weeks old. Median treatment duration was 15 days (range, 1-425 days). During the study, AEs regardless of causality were recorded in 93.2% of subjects; 26.7% were classified as at least possibly related to study drug; and 34% of subjects had AEs meeting criteria for serious AE; of which, 4.7% of subjects experienced serious AEs at least possibly related to study drug. Study drug was discontinued because of AEs in 7 patients (2.4%). No trends were observed with respect to analysis of AEs by dose or duration of treatment. Conclusions: Micafungin was well tolerated by children of all ages including those with life-threatening underlying conditions. AEs thought to be drug related occasionally lead to discontinuation of the treatment.