title: Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin.
abstract: BACKGROUND
  The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug-drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting.
  
  
  METHODS
  This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2-3 times weekly) in patients with acute leukemia and allogeneic SCT recipients.
  
  
  RESULTS
  A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection.
  
  
  CONCLUSIONS
  In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings.
authors.affiliation: Infectious Diseases Service.
authors.forename: Dionysis
authors.initials: D
authors.lastname: Neofytos
authors.affiliation: Infectious Diseases Service.
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Infectious Diseases Service.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Infectious Diseases Service.
authors.forename: Nina
authors.initials: N
authors.lastname: Cohen
authors.affiliation: Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Juliet
authors.initials: J
authors.lastname: Barker
authors.affiliation: Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.affiliation: Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Ann
authors.initials: A
authors.lastname: Jakubowski
authors.affiliation: Infectious Diseases Service Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Genovefa
authors.initials: G
authors.lastname: Papanicolaou
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000503:physiopathology; D007938:Leukemia / Q000150:complications / Q000382:microbiology; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D008111:Liver Function Tests; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D009181:Mycoses / Q000382:microbiology / Q000517:prevention & control*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
keywords: high-dose; intermittent; micafungin; transplant