Pharmacovigilance assessment of the association between Fournier's gangrene and other severe genital adverse events with SGLT-2 inhibitors
Pharmacovigilance assessment of the association between Fournier's gangrene and other severe genital adverse events with SGLT-2 inhibitors
复制标题
DOI：
10.1136/bmjdrc-2019-000725
复制
发表时间：
2019-10-01
影响因子：
4.1
通讯作者：
Raschi, Emanuel
中科院分区：
文献类型：
--
作者：
Fadini, Gian Paolo;Sarangdhar, Mayur;Raschi, Emanuel
目的 钠 - 葡萄糖协同转运蛋白2抑制剂（SGLT2i）对糖尿病患者具有心肾保护作用。通过诱导糖尿，SGLT2i易引发生殖器感染。此外，已有罕见的福尼尔坏疽（FG）病例报道。我们旨在通过美国食品药品监督管理局（FDA）不良事件（AE）报告系统（FAERS）对此类关联进行调查。
研究设计与方法 我们挖掘截至2018年第3季度（在FDA就SGLT2i相关的FG发出警告之前）的FAERS数据，以检索包含FG作为AE以及SGLT2i作为可疑或伴随用药的报告，并计算比例报告比值（PRR）。
结果 我们检索到47例与SGLT2i相关的FG病例以及17例生殖器区域的其他严重AE病例。FG患者比其他生殖器严重AE患者大约年长10岁。总体而言，77%的病例发生在男性中。3名患者同时接受了全身性免疫抑制药物治疗。与其他药物相比，SGLT2i的报告频率增加，PRR范围为5 - 10。当限定在SGLT2i可用的时期、针对降糖药物或具有糖尿病适应证的药物的报告以及对FG定义进行细化后，FG与SGLT2i的不均衡报告仍然显著且具有一致性。FG与银屑病以及免疫抑制剂和SGLT2i的联合使用存在不均衡关联。
结论 尽管无法证明因果关系，但SGLT2i可能易引发FG和其他生殖器严重AE。由于SGLT2i的使用预计将显著增加，临床医生应了解这些严重（尽管罕见）的AE及其诱发因素。
Objective Sodium glucose cotransporter-2 inhibitors (SGLT2i) exert cardiorenal protection in people with diabetes. By inducing glycosuria, SGLT2i predispose to genital infections. In addition, rare occurrence of Fournier's gangrene (FG) has been reported. We aimed to investigate such association through the U.S. Food and Drug Administration (FDA) adverse event (AE) reporting system (FAERS).Research design and methods We mined the FAERS up to 2018q3 (before FDA warning about SGLT2i-associated FG) to retrieve reports including FG as an AE and SGLT2i as suspect or concomitant drugs, and calculated proportional reporting ratios (PRR).Results We retrieved 47 cases of FG and 17 cases of other severe AEs of the genital area associated with SGLT2i. Patients with FG were similar to 10 years older than those with other severe genital AEs. Overall, 77% occurred in men. Three patients were concomitantly treated with systemic immunosuppressive drugs. Increased reporting frequency emerged for SGLT2i compared with other drugs, with a PRR ranging from 5 to 10. The disproportional reporting of FG with SGLT2i remained robust and consistently significant when restricting to the period when SGLT2i were available, to reports filed for glucose-lowering medications or for drugs with the diabetes indication, and after refining the definition of FG. FG was disproportionally associated with psoriasis and with the combination of immunosuppressants and SGLT2i.Conclusions Although causality cannot be demonstrated, SGLT2i may predispose to FG and other severe genital AEs. Since the use of SGLT2i is expected to increase significantly, clinicians should be aware of these severe, although rare, AEs and their predisposing factors.