Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation

Abstract: Purpose This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered Cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Methods We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. Results After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. Conclusion POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.