Wei Shaokui, Niu Manette T, Dores Graça M
Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Drugs Real World Outcomes. 2021 Jun;8(2):253-262. doi: 10.1007/s40801-021-00242-x. Epub 2021 Mar 15.
Digoxin immune fab products, DigiBind and DigiFab, are antidotes for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose. Although approved by the US Food and Drug Administration (FDA) in 1986 (DigiBind) and 2001 (DigiFab), there remains a paucity of literature describing the safety of these products in the postmarketing setting.
We sought to assess US adverse event (AE) reports submitted to the FDA Adverse Event Reporting System (FAERS) for DigiBind and DigiFab in the postmarketing period.
We searched reports for DigiBind and DigiFab submitted from the time of each product approval through December 31, 2019. Descriptive statistics were used to assess AE reports for DigiBind and DigiFab. Empirical Bayes geometric means (EBGMs) and their 90% confidence intervals were computed to identify disproportionate (i.e., at least twice the expected) reporting of DigiBind and DigiFab. Reports describing selected AEs and death outcomes were individually reviewed.
A total of 78 DigiBind and 43 DigiFab reports were identified, of which 68 DigiBind (87.2%) and 27 DigiFab (62.8%) reports were serious. Among the most frequently reported AEs for both products [DigiBind, DigiFab, respectively] were cardiac (bradycardia [3.8%, 3.9%], cardiac arrest [3.3%, 3.9%], and hypotension [2.4%, 2.6%]) and non-cardiac (nausea [1.9%, 2.6%] and hyperkalemia [1.4%, 1.9%]) events. These AEs were labeled events or confounded by indication for use (digoxin toxicity). Nineteen (24.4%) DigiBind and 13 (30.2%) DigiFab reports described an outcome of death, of which seven (53.8%) DigiFab reports were attributed to poisoning with non-digoxin cardiac glycosides. No deaths could be attributed to DigiBind or DigiFab administration.
Our analysis did not identify new safety concerns for DigiBind or DigiFab. Most AEs reported were labeled events or confounded by indication for use.
地高辛免疫Fab产品，即DigiBind和DigiFab，是用于治疗有危及生命或潜在危及生命的地高辛中毒或过量患者的解毒剂。尽管分别于1986年（DigiBind）和2001年（DigiFab）获得美国食品药品监督管理局（FDA）批准，但在上市后环境中描述这些产品安全性的文献仍然匮乏。
我们试图评估上市后期间提交给FDA不良事件报告系统（FAERS）的关于DigiBind和DigiFab的美国不良事件（AE）报告。
我们检索了从每种产品获批之时至2019年12月31日提交的关于DigiBind和DigiFab的报告。使用描述性统计来评估DigiBind和DigiFab的AE报告。计算经验贝叶斯几何均值（EBGMs）及其90%置信区间，以识别DigiBind和DigiFab的不成比例（即至少是预期的两倍）报告。对描述选定AE和死亡结局的报告进行单独审查。
共识别出78份DigiBind报告和43份DigiFab报告，其中68份DigiBind报告（87.2%）和27份DigiFab报告（62.8%）为严重报告。两种产品最常报告的AE [分别为DigiBind、DigiFab] 是心脏相关的（心动过缓 [3.8%，3.9%]、心脏骤停 [3.3%，3.9%] 和低血压 [2.4%，2.6%]）以及非心脏相关的（恶心 [1.9%，2.6%] 和高钾血症 [1.4%，1.9%]）事件。这些AE是标记事件或因使用指征（地高辛中毒）而混淆。19份（24.4%）DigiBind报告和13份（30.2%）DigiFab报告描述了死亡结局，其中7份（53.8%）DigiFab报告归因于非地高辛强心苷中毒。没有死亡可归因于DigiBind或DigiFab的给药。
我们的分析未发现DigiBind或DigiFab有新的安全问题。报告的大多数AE是标记事件或因使用指征而混淆。
