A retrospective study on the impact of glucocorticoids on the efficacy of posaconazole in the prevention/treatment of invasive fungal infections in patients with hematological malignancies

Posaconazole (PCZ) has been used to prevent and treat invasive fungal infections in immunocompromised patients with hematological malignancies. There is a significant correlation between plasma drug concentration and the efficacy of posaconazole.

This study aimed to investigate the effects of glucocorticoid on PCZ C_min and on the outcome of PCZ prevention/treatment of invasive fungal infections.

We conducted a retrospective study at a tertiary hospital, examining patients who were administered posaconazole oral suspension between September 2021 and September 2023, to assess the effect of glucocorticoid on the plasma drug concentration and antifungal effect of posaconazole.

(Ⅰ) The concomitant usage of glucocorticoid reduced PCZ C_min from 1310.00 (648.48，2550.00) ng/mL to 1085.00 (529.79，1767.50) ng/mL (p = 0.032), and the C_min/Dose (C/D) decreased from 2.14 (0.98, 4.10) ng/mL/mg to 1.66 (0.86, 2.73) ng/mL/mg (p = 0.038). (Ⅱ) There was a significant difference in PCZ C_min between patients on low-dose glucocorticoids and those on medium & high-dose glucocorticoids (1271.14 vs 720.19 ng/mL, p < 0.001). (Ⅲ) PCZ C_min was significantly lower in patients with longer glucocorticoid duration than with shorter (p = 0.013). (Ⅳ) Compared with PCZ alone, the concomitant usage of PPIs, glucocorticoids, and PPIs & glucocorticoids significantly reduced PCZ C_min (p < 0.001, p= 0.001, p= 0.001).

The concomitant usage of glucocorticoid can significantly reduce PCZ C_min, and this decrease has a correlation with the dose and duration of glucocorticoid. However, glucocorticoid may not affect the clinical outcome of posaconazole in the prevention/treatment of invasive fungal infections.