Yokota Hayato, Akamine Yumiko, Hatakeyama Harumi, Kagaya Hideaki, Sakamoto Sho, Saito Mitsuru, Takeda Masahide, Sato Kazuhiro, Nakayama Katsutoshi, Kikuchi Masafumi
Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan.
Department of Respiratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
J Pharm Health Care Sci. 2025 Mar 13;11(1):20. doi: 10.1186/s40780-025-00427-4.
Azole antifungals are the standard treatment for pulmonary mycosis, which may develop during long-term immunotherapy for kidney transplant. Isavuconazole (ISCZ) is a cytochrome P450 (CYP) 3 A inhibitor that has a risk of interacting with the immunosuppressive drug tacrolimus (TAC). We report a case of simple pulmonary aspergilloma with renal dysfunction due to increased trough levels of TAC after ISCZ coadministration.
A male in his 60s was treated with TAC 3.0 mg/day orally to prevent graft rejection after kidney transplantation. He received a loading dose of ISCZ 600 mg/day orally for two days, followed by a maintenance dose of 200 mg/day for simple pulmonary aspergilloma. The TAC trough concentration increased markedly from 2.4 to 9.9 ng/mL on day 6 after coadministration. The creatinine level increased from 0.70 to 1.08 mg/dL, suggesting renal dysfunction due to TAC. Subsequently, the TAC dosage was reduced, leading to a decreased blood TAC concentration and improved renal function. The patient's genotype was CYP3A5*1/*3.
In the early stages of ISCZ treatment, the blood TAC concentration is higher, and CYP3A5 polymorphisms may partially explain the extent of this interaction. We recommend more careful monitoring of TAC and serum creatinine levels for approximately one week after ISCZ administration.
唑类抗真菌药是肺真菌病的标准治疗药物,肺真菌病可能在肾移植长期免疫治疗期间发生。艾沙康唑(ISCZ)是一种细胞色素P450(CYP)3A抑制剂,有与免疫抑制药物他克莫司(TAC)相互作用的风险。我们报告1例在联合使用ISCZ后因TAC谷浓度升高导致肾功能不全的单纯性肺曲菌球病例。
一名60多岁男性在肾移植后口服TAC 3.0mg/天以预防移植物排斥反应。他因单纯性肺曲菌球接受了为期2天的口服ISCZ负荷剂量600mg/天治疗,随后维持剂量为200mg/天。联合用药后第6天,TAC谷浓度从2.4显著升高至9.9ng/mL。肌酐水平从0.70mg/dL升至1.08mg/dL,提示TAC导致肾功能不全。随后,降低了TAC剂量,导致血TAC浓度下降,肾功能改善。患者的基因型为CYP3A5*1/*3。
在ISCZ治疗早期,血TAC浓度较高,CYP3A5基因多态性可能部分解释这种相互作用的程度。我们建议在使用ISCZ后约一周内更密切地监测TAC和血清肌酐水平。