Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin

Dionysios Neofytos, MD, MPH Yao-Ting Huang, PhD, MPH Kim Cheng, Medical Student Nina Cohen, PharmD Miguel Perales, MD Juliet N. Barker, MD Sergio Giralt, MD Ann Jakubowski, MD, PhD Genovefa Papanicolaou, MD

Abstract: 

Background. Intermittent administration of high-dose IV micafungin (IA HD IV MICA) may be an alternative in allogeneic stem cell transplantation (allo SCT) antifungal treatment and prophylaxis. Although variable doses of MICA at different intervals have been tried, the maximally tolerated dose and minimal dosing intervals for MICA to achieve maximal efficacy without compromising safety remain to be defined.

Methods. This is a retrospective observational study to describe the safety (defined as liver, renal and cardiac toxicity, infusion-related reactions, and death) and efficacy (defined as breakthrough invasive fungal infections –IFIs- in patients that received MICA as prophylaxis) of IA HD IV MICA (defined as ≥5 doses of ≥300 mg MICA ×2 and/or 3 weekly) in a cohort of allo SCT recipients from January 2009 to July 2014.

Results. A total of 104 allo SCT recipients received IA HD IV MICA; 83 (79.8%) patients as prophylaxis. The average and maximal calculated daily MICA doses were 1.78 and 3.59 mg/kg, respectively. IA HD IV MICA was administered for ≤4, 5–8, 9–12, and >12 weeks in 41, 28, 20, and 15 patients, respectively. Large variability in the MICA dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg ×3 weekly.

Liver function tests (LFTs) decreased from baseline to end-of-treatment (EOT; P < .001). For patients with abnormal baseline liver function (49, 47%), LFTs improved from baseline to EOT (P ≤ .005). MICA duration and/or dosing algorithms were not associated with liver toxicity at the EOT in multivariate analyses. There were no significant changes in renal function and cardiac events, infusion-related reactions or deaths were not observed during the study period. Five (6.0%) of 83 patients in the prophylaxis group developed a breakthrough IFI. In exploratory analyses, there was no significant association between clinical failure and MICA dosing.

Conclusion. In this largest cohort of allo SCT recipients treated with IA HD IV MICA to date, 300mg of micafungin administered ×2 and/or 3 weekly was well tolerated and a relatively effective antifungal prophylactic strategy. These findings should be taken with caution considering a number of limitations and until prospective data are available.

Disclosures.D. Neofytos, Astellas: Consultant and Scientific Advisor, Consulting fee; G. Papanicolaou, Astellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Pfizer: Grant Investigator, Research grant

2015

Full conference title: 

IDWeek 2015 San Diego, CA
    • IDWeek 2015