Shiraishi Chihiro, Kato Hideo, Ino Kazuko, Iwamoto Takuya
Department of Pharmacy, Mie University Hospital, Mie, Japan.
Division of Clinical Medical Science, Department of Clinical Pharmaceutics, Mie University Graduate School of Medicine, Mie, Japan.
Front Microbiol. 2025 Feb 24;16:1525991. doi: 10.3389/fmicb.2025.1525991. eCollection 2025.
Isavuconazole, a broad-spectrum triazole approved by the United States Food and Drug Administration (FDA) in 2015, moderately inhibits cytochrome P450 3A4. Although antifungal agents are often used concomitantly with cyclosporine, the effect of switching from voriconazole to isavuconazole on the blood cyclosporine level remains unclear.
A 63-year-old Japanese male was administered oral cyclosporine (10:00 and 21:00) for severe aplastic anemia. Following pneumonia with positive antigen and an elevated β-D-glucan level, antifungal therapy was initiated. After switching from voriconazole (10:00 and 21:00) to isavuconazole (approximately 08:00), the blood cyclosporine level decreased by more than half. Although the blood cyclosporine level decreased after switching to isavuconazole, the dose of cyclosporine was not increased because of its possible effect on renal function. Considering the inhibitory effects on the gastrointestinal tract, a physiologically based pharmacokinetic analysis estimated that isavuconazole increased the area under the curve (AUC) and of cyclosporine by 1.48-fold and 1.84-fold, respectively, although assuming no change in gastrointestinal metabolism, these effects were minimal. For interaction with voriconazole considering gastrointestinal metabolism, the predicted increases in AUC and were 3.74-fold and 3.86-fold, respectively. The FDA Adverse Event Reporting System database included 9,144 reports on cyclosporine and 174 on cyclosporine with voriconazole, but none concomitant with isavuconazole. The reporting odds ratios for cyclosporine and isavuconazole could not be assessed because of insufficient reports.
The interaction of isavuconazole with cyclosporine was weaker than that with voriconazole. Maintaining a two-hour dosing interval between isavuconazole and cyclosporine may minimize gastrointestinal drug interactions.
艾沙康唑是一种广谱三唑类药物，于2015年获美国食品药品监督管理局（FDA）批准，对细胞色素P450 3A4有中度抑制作用。尽管抗真菌药物常与环孢素联合使用，但从伏立康唑换用艾沙康唑对血中环孢素水平的影响尚不清楚。
一名63岁日本男性因严重再生障碍性贫血接受口服环孢素治疗（上午10:00和晚上21:00各一次）。在出现抗原阳性且β - D - 葡聚糖水平升高的肺炎后，开始抗真菌治疗。从伏立康唑（上午10:00和晚上21:00各一次）换用艾沙康唑（约上午08:00）后，血中环孢素水平下降超过一半。尽管换用艾沙康唑后血中环孢素水平下降，但由于可能对肾功能有影响，未增加环孢素剂量。考虑到对胃肠道的抑制作用，基于生理的药代动力学分析估计，尽管假设胃肠道代谢无变化且这些影响较小，但艾沙康唑使环孢素的曲线下面积（AUC）和峰浓度（ ）分别增加了1.48倍和1.84倍。对于考虑胃肠道代谢的与伏立康唑的相互作用，预测的AUC和峰浓度增加分别为3.74倍和3.86倍。FDA不良事件报告系统数据库中有9144份关于环孢素的报告以及174份关于环孢素与伏立康唑联用的报告，但没有环孢素与艾沙康唑联用的报告。由于报告不足，无法评估环孢素与艾沙康唑的报告比值比。
艾沙康唑与环孢素的相互作用比与伏立康唑的相互作用弱。在艾沙康唑和环孢素之间保持两小时的给药间隔可能会使胃肠道药物相互作用最小化。
