Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Ministry of Education, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu, Sichuan, China.
Expert Opin Drug Saf. 2024 Apr;23(4):513-525. doi: 10.1080/14740338.2024.2327503. Epub 2024 Mar 27.
The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned.
The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs.
Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia.
The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies.
The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.
本研究旨在探讨他克莫司（FK506）、环孢素（CsA）、硫唑嘌呤（AZA）、霉酚酸酯（MMF）、环磷酰胺（CTX）和甲氨蝶呤（MTX）等药物的新的和严重不良事件（AE），这些事件以前没有引起关注。
选择 2016 年 1 月至 2022 年 12 月的 FAERS 数据进行比例失调分析，以发现传统免疫抑制剂药物的潜在风险。
与 CsA 相比，FK506 更频繁地发生移植排斥反应，与肾功能损害、COVID-19、巨细胞病毒感染和曲霉感染更相关。然而，CsA 具有较高的感染相关死亡率。此外，我们还发现了其他药物中一些以前研究中很少报道的严重和罕见的 AE。例如，AZA 与肝脾 T 细胞淋巴瘤密切相关，死亡率较高，而 MTX 与低纤维蛋白原血症密切相关。
本研究的 AE 报告结果基本与既往研究一致，但也存在一些重要的安全性信号，与既往发表的研究结果不一致或未提及。
意见部分讨论了一些局限性和缺点，并提出了需要投入更多努力的领域，以提高免疫抑制剂药物的安全性。
