Akamatsu Hayato, Nakagawa Hiroo, Matsumaru Ichiro, Hashizume Junya, Harasawa Hitomi, Kodama Yukinobu, Miura Takashi, Ohyama Kaname
Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Department of Cardiovascular Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
J Pharm Health Care Sci. 2023 Apr 1;9(1):11. doi: 10.1186/s40780-023-00279-w.
Fluconazole (FLCZ) inhibits cytochrome P450 (CYP) 2C9, 2C19, and 3A4 and has a drug-drug interaction that potentiates the effects of warfarin and prolong the prothrombin time-international normalized ratio (PT-INR). Although a drug-drug interaction have been reported between FLCZ and warfarin, the effects of the timing of their administration on this interaction have not yet been investigated.
A female patient in her 30s with Marfan syndrome had undergone the Bentall procedure with a mechanical valve and total arch replacement for acute aortic dissection Stanford A type and rupture of the ascending aorta. Warfarin was administered to prevent thromboembolism. She was hospitalized 1 year ago for graft infection caused by Candida albicans, and treatment with FLCZ was initiated. She received FLCZ 200 mg once a day in the morning and warfarin 1.75 mg once a day in the evening, and the PT-INR remained stable at approximately 2.0 and within the therapeutic range. However, 42 days after changing the timing of administration of warfarin from evening to morning, the PT-INR was prolonged by approximately 3-fold to 6.25. The PT-INR then decreased to the previous level by changing the timing of administration of warfarin from morning to evening.
The timing of administration of FLCZ and warfarin may affect the magnitude of drug-drug interaction.
氟康唑（FLCZ）可抑制细胞色素P450（CYP）2C9、2C19和3A4，并存在药物相互作用，可增强华法林的作用并延长凝血酶原时间-国际标准化比值（PT-INR）。虽然已有报道称FLCZ与华法林之间存在药物相互作用，但它们给药时间对这种相互作用的影响尚未得到研究。
一名30多岁患有马凡综合征的女性患者因急性A型斯坦福主动脉夹层和升主动脉破裂接受了带机械瓣膜的Bentall手术及全主动脉弓置换术。给予华法林以预防血栓栓塞。她1年前因白色念珠菌引起的移植感染住院，并开始接受FLCZ治疗。她每天早上服用一次FLCZ 200mg，每天晚上服用一次华法林1.75mg，PT-INR保持稳定在约2.0且在治疗范围内。然而，将华法林的给药时间从晚上改为早上42天后，PT-INR延长了约3倍至6.25。随后通过将华法林的给药时间从早上改为晚上，PT-INR降至先前水平。
FLCZ和华法林的给药时间可能会影响药物相互作用的程度。
