The optimal conversion ratio of tacrolimus switching from intravenous to oral tacrolimus administration in hematopoietic cell transplantation patients receiving posaconazole prophylaxis with and without letermovir.

Abstract

Letermovir, a moderate inhibitor of CYP3A4 and inducer of CYP2C9 and CYP2C19, is used for cytomegalovirus prophylaxis following allogeneic hematopoietic stem cell transplantation (HCT). Posaconazole also inhibits CYP3A4, affecting tacrolimus metabolism. This study aimed to examine tacrolimus conversion ratios when switching from continuous intravenous to oral administration in HCT patients receiving posaconazole with and without letermovir. Tacrolimus concentration-to-dose (C/D) ratios before (C/Dciv) and after (C/Dpo) conversion were compared. The median C/Dciv ratios were 20.1 and 22.5 (ng/mL)/(mg/day) for patients with and without letermovir, respectively (P = 0.31). The median C/Dpo ratios were 5.1 and 5.9 (ng/mL)/(mg/day), respectively (P = 0.43). The median (C/Dpo)/(C/Dciv) ratios were 0.25 and 0.24, respectively (P = 0.77), indicating no significant difference in tacrolimus conversion ratios with and without letermovir. Based on these findings, the tacrolimus conversion ratio in patients receiving posaconazole was estimated to be approximately 1:2, regardless of concomitant letermovir use.