Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

Abstract

INTRODUCTION:

Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients.

METHODS:

We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT.

RESULTS:

During MCFG prophylaxis, infusion reactions or adverse events (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 μg/mL (569 samples) and 9.63 ± 3.62 μg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 μg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids.

CONCLUSIONS:

Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.

• Authors: K Yoshikawa, Y Nakazawa, Y Katsuyama, K Hirabayashi, S Saito, T Shigemura, M Tanaka, R Yanagisawa, K Sakashita, K Koike
• Journal: Infection (Infection) Vol. 42 Issue 4 Pg. 639-47 (Aug 2014) ISSN: 1439-0973 [Electronic] Germany
• PMID: 24567233 (Publication Type: Journal Article)

Chemical References

• Antifungal Agents
• Echinocandins
• Lipopeptides
• Micafungin

Topics

• Adolescent
• Antifungal Agents (administration & dosage, adverse effects, pharmacokinetics)
• Chemoprevention (adverse effects, methods)
• Child
• Child, Preschool
• Drug-Related Side Effects and Adverse Reactions
• Echinocandins (administration & dosage, adverse effects, pharmacokinetics)
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Infant
• Lipopeptides (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Micafungin
• Mycoses (prevention & control)
• Plasma (chemistry)