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). 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.

Accumulated safety data of micafungin in therapy and prophylaxis in fungal diseases.

OBJECTIVE: To define better the safety profile of micafungin, an analysis of micafungin clinical trial safety data was undertaken. RESEARCH DESIGN AND METHODS: Adverse event data were pooled worldwide from 17 clinical efficacy and safety studies. Adverse events were coded using the Medical Dictionary for Regulatory Activities version 5.0. RESULTS: In the pooled clinical trial data set, 3028 patients received at least one dose of micafungin. The mean age of patients was 41.4 years; with 296 (9.8%) children (< 16 years) and 387 (12.8%) elderly patients (≥ 65 years). Common underlying conditions were hematopoietic stem cell and other transplantations (26.1%), malignancies (20.8%) and HIV (32.9%). Mean exposure was 18 days for adults and 29 days for children. The most frequently reported treatment-related adverse events were nausea (2.8%), vomiting (2.5%), phlebitis (2.5%), hypokalemia (2.1%), fever/pyrexia (2.1%) and diarrhea (2%), as well as increases in alkaline phosphatase (2.7%), aspartate aminotransferase (2.3%) and alanine aminotransferase (2%). Although elderly adults had a higher incidence of renal impairment (1%) compared with non-elderly adult (0.1%) and pediatric patients (0.3%), there were no clear trends showing an association between higher doses of micafungin or longer treatment durations and increased incidence rates of treatment-related adverse events. CONCLUSIONS: Analysis of a large database demonstrated a favorable clinical safety profile for micafungin similar to other echinocandins.