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

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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.

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Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    K. Yoshikawa, Y. Nakazawa, K. Hirabayashi, S. Saito, T. Shigemura, M. Tanaka, R. Yanagisawa, K. Sakashita & K. Koike

  2. Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan

    Y. Katsuyama

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  1. K. Yoshikawa
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  2. Y. Nakazawa
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  3. Y. Katsuyama
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  7. M. Tanaka
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  9. K. Sakashita
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Correspondence to Y. Nakazawa.

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Yoshikawa, K., Nakazawa, Y., Katsuyama, Y. et al. Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation. Infection 42, 639–647 (2014). https://doi.org/10.1007/s15010-014-0601-9

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