title: Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  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.affiliation: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: K
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Shigemura
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: K
authors.initials: K
authors.lastname: Sakashita
authors.forename: K
authors.initials: K
authors.lastname: Koike
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D000077551:Micafungin; D009181:Mycoses / Q000517:prevention & control*; D010949:Plasma / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin