Therapeutic drug monitoring of posaconazole delayed release tablet while managing COVID-19–associated mucormycosis in a real-life setting

Abstract

Background: Along with COVID-19 pandemic, India has faced an outbreak of COVID-19–associated mucormycosis (CAM). Due to restricted availability of amphotericin B during this outbreak, clinicians were forced to use posaconazole or isavuconazole preparations as first-line or alternate therapy in many patients. We planned an early monitoring of posaconazole trough level while using delayed release (DR) tablet as first-line or alternate therapy. Objectives: Primary objective of the study was to determine percentage of patients achieving arbitrarily decided therapeutic posaconazole levels (≥1.2 μg/ml) after using standard dosages of posaconazole. Secondary objective was to identify potential factors associated with sub-therapeutic posaconazole levels. Methods: We performed retrospective chart review of the hospitalised patients, who received posaconazole DR tablet as first-line or alternate therapy to treat CAM during outbreak period (March 1 to May 31, 2021). High-performance liquid chromatographic (HPLC) method was used to measure trough level of posaconazole. Results: Posaconazole serum levels of 29 patients were analysed, who received posaconazole DR tablet. Majority (n = 23) were male with the median (range) age 53 (24–86) years. The mean (SD) posaconazole level was 1.66 (0.76) μg/ml. Sub-therapeutic posaconazole trough level was observed in 7 (24.1%) patients. Relatively younger patients were associated with lower posaconazole level (p =.046). Except two patients, all the patients tolerated posaconazole well. Conclusions: The study supports the posaconazole trough level measurement on day 4 while using posaconazole DR tablet as first-line or alternate therapy to treat mucormycosis during limited supply of amphotericin B.