TY - JOUR
T1 - 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
AU - Nakashima, Toshihisa
AU - Kawasaki, Azusa
AU - Inamoto, Yoshihiro
AU - Ito, Ayumu
AU - Fukuda, Takahiro
AU - Hashimoto, Hironobu
N1 - Publisher Copyright:
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PY - 2025/10/1
Y1 - 2025/10/1
N2 - 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.
AB - 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.
KW - allogeneic hematopoietic cell transplantation
KW - drug-drug interaction
KW - letermovir
KW - posaconazole
KW - tacrolimus
UR - https://www.scopus.com/pages/publications/105018028953
UR - https://www.scopus.com/pages/publications/105018028953#tab=citedBy
U2 - 10.1093/jjco/hyaf101
DO - 10.1093/jjco/hyaf101
M3 - Article
C2 - 40493965
AN - SCOPUS:105018028953
SN - 0368-2811
VL - 55
SP - 1189
EP - 1193
JO - Japanese journal of clinical oncology
JF - Japanese journal of clinical oncology
IS - 10
ER -