Safety and pharmacokinetic profiles of repeated-dose micafungin in children and adolescents treated for invasive candidiasis.

ABSTRACT

BACKGROUND: Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida spp. OBJECTIVE: To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable or suspected invasive candidiasis. METHODS: Micafungin safety and pharmacokinetics were assessed in 2 phase I, open-label, repeat-dose trials. In Study 2101, children aged 2-16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10-14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. RESULTS: Safety was analyzed in 78 and 9 children in Studies 2101 and 2102, respectively. Although adverse events (AEs) were experienced by most children (2101 n=62; 2102 n=9), micafungin-related AEs were less common (2101 n=28; 2102 n=1), and the number of patients discontinuing due to AEs was low (2101 n=4; 2102 n=1). The most common micafungin-related AEs were infusion-associated symptoms, pyrexia and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. CONCLUSIONS: In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support US dosing recommendations in children.