Micafungin – Overview of Safety in Pediatric Patients

Background and aims: Children at risk of invasive fungal infections are often fragile hosts with multiple underlying conditions. Since drug safety is critical in such patients, we evaluated the safety of micafungin, a novel antifungal agent, by pooling pediatric safety data from clinical trials.

Methods: Adverse event (AE) data were pooled from clinical trials conducted in Europe, the Americas and Asia. Results: 296 patients received at least one dose of micafungin. The mean±SD age was 6.5±5.1 years; 66 patients were <1 year. Common underlying conditions were malignancies (37.5%) and hematopoietic stem cell transplantation (33.8%). Neutropenia (ANC<500 cells/µL) at baseline was present in 40% of patients. Overall, the median maximum daily micafungin dose was 1.7mg/kg (interquartile range [IQR]: 1.0–2.4mg/kg). Median treatment duration was 15 days (IQR: 6–29 days). Consistent with the multi-morbid underlying conditions of this population, AEs, irrespective of causality, were experienced by most (93.2%) patients, and a large proportion of these (34.1%) were serious. Few AEs were considered by the investigator to be treatment related or led to treatment discontinuation (see table). No trends were seen with analysis of AEs by dose or duration of treatment.

Conclusions: Micafungin has a favorable safety profile in pediatric patients with complex and life-threatening underlying conditions.

Incidence of AEs (N=296)
All causality (≥20%)	vomiting (31.8%), pyrexia (22.3%), diarrhea (21.6%), nausea (21.3%), hypokalemia (20.9%)
At least possibly related* to micafungin (≥2%)	hypokalemia (3.0%), ALT increased (3.0%), hyperbilirubinemia (2.0%), AST increased (2.0%), LFT abnormal (2.0%), AP increased (2.0%), hypertension (2.0%)
At least possibly related* to micafungin and leading to treatment discontinuation (7 patients)	neutropenia, AST/ALT increased, rash, (3 patients with underlying leukemia/ANCT); jaw and joint pain, hyperbilirubinemia, creatinine increased (3 patients with underlying HSCT); creatinine increased (1 patient with premature birth).
ALT/AST: alanine/aspartate aminotransferase; ANCT: antineoplastic chemotherapy; HSCT: hematopoietic stem cell transplant; LFT: liver function tests; *Investigator-assessed causal relationship.