Safety and efficacy of intermittent intravenous administration of high-dose micafungin Journal Article


Authors: Neofytos, D.; Huang, Y. T.; Cheng, K.; Cohen, N.; Perales, M. A.; Barker, J.; Giralt, S.; Jakubowski, A.; Papanicolaou, G.
Article 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. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Keywords: adult; aged; major clinical study; allogeneic stem cell transplantation; drug tolerability; drug efficacy; drug safety; drug withdrawal; liver function; treatment duration; drug megadose; drug eruption; liver toxicity; multiple myeloma; creatinine; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; acute leukemia; myelodysplastic syndrome; lymphoma; liver function test; observational study; antibiotic prophylaxis; mycosis; micafungin; drug intermittent therapy; chronic leukemia; human; male; female; priority journal; article; intermittent
Journal Title: Clinical Infectious Diseases
Volume: 61
Issue: Suppl. 6
ISSN: 1058-4838
Publisher: Oxford University Press  
Date Published: 2015-12-01
Start Page: S652
End Page: S661
Language: English
DOI: 10.1093/cid/civ818
PROVIDER: scopus
PUBMED: 26567284
PMCID: PMC5006190
DOI/URL:
Notes: Article -- Export Date: 7 January 2016 -- Source: Scopus
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MSK Authors
  1. Sergio Andres Giralt
    1053 Giralt
  2. Miguel-Angel Perales
    915 Perales
  3. Juliet N Barker
    335 Barker
  4. Yao-Ting Huang
    28 Huang
  5. Kimberly   Cheng
    1 Cheng