Adverse Events of Spironolactone

Study Hypothesis
This study hypothesized that analyzing real-world adverse drug event (ADE) reports from the FDA Adverse Event Reporting System (FAERS) could identify both known and previously unrecognized safety signals of spironolactone, particularly rare or underdocumented adverse reactions not listed in drug labels, to enhance its safety assessment and clinical management.
Data Overview: Collection and Processing
The dataset includes 8,566 ADE reports linked to spironolactone extracted from FAERS (2004 Q1–2024 Q3).
Source: Data were retrieved from the public FAERS database, which aggregates voluntary reports from healthcare providers, consumers, and pharmaceutical companies.
Processing: Duplicate entries were removed using CASEID and ISR identifiers (retaining only the most recent reports). ADEs were classified using MedDRA v26.1, and safety signals were detected using four statistical methods (PRR, ROR, BCPNN, EBGM), with signals validated only if all methods met predefined thresholds.
Key Findings
Known ADEs: Consistent with existing labels, hyperkalemia (n=1,308; ROR=90.35) and nipple pain (n=42; ROR=46.19) showed strong signals.
Notable New Signals: Rare but significant associations included male endometriosis (n=7; ROR=13,615.84), 5-alpha-reductase deficiency (n=5; ROR=1,620.81), congenital bulbospinal muscular atrophy (n=6; ROR=402.42), and double-hit lymphoma (n=5; ROR=243.12)—none are currently listed in drug labels.
Interpretation and Usage
The data confirm spironolactone’s known safety profile while highlighting potential new risks, particularly in hormonal and genetic disorders. These signals indicate disproportional reporting, not definitive causality, requiring further validation.

研究假设
本研究假设，通过分析美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System, FAERS）中的真实世界药品不良事件（adverse drug event, ADE）报告，可识别螺内酯（spironolactone）已知及此前未被发现的安全信号，尤其是未列入药品说明书的罕见或记录不足的不良反应，以完善其安全性评估与临床管理。
数据概览：采集与处理
本数据集包含从FAERS（2004年第一季度至2024年第三季度）中提取的8566条与螺内酯相关的ADE报告。
数据来源：数据取自公开的FAERS数据库，该数据库汇总了医疗保健机构、消费者及制药企业提交的自愿报告。
数据处理：使用CASEID与ISR标识符去除重复条目（仅保留最新报告）；采用医学监管活动词典（MedDRA）v26.1对ADE进行分类；采用四种统计方法（比例报告比（Proportional Reporting Ratio, PRR）、报告比值比（Reporting Odds Ratio, ROR）、贝叶斯置信神经网络（Bayesian Confidence Neural Network, BCPNN）、经验贝叶斯几何均值（Empirical Bayes Geometric Mean, EBGM））检测安全信号，仅当所有方法均达到预设阈值时，信号方视为有效。
核心研究发现
已知ADE：与现有药品说明书一致，高钾血症（n=1308；ROR=90.35）与乳头疼痛（n=42；ROR=46.19）呈现强信号。
值得关注的新信号：罕见但具有统计学意义的关联包括男性子宫内膜异位症（n=7；ROR=13615.84）、5α-还原酶缺乏症（n=5；ROR=1620.81）、先天性球脊髓性肌萎缩症（n=6；ROR=402.42）以及双重打击淋巴瘤（n=5；ROR=243.12）——上述不良反应目前均未列入药品说明书。
结果解读与应用
本数据集验证了螺内酯已知的安全性特征，同时揭示了潜在的新型风险，尤其涉及内分泌与遗传相关疾病。需注意的是，此类信号仅提示报告比例失衡，并非确定的因果关联，仍需进一步验证。