与硝苯地平相关的药物不良反应：基于FAERS、JADER和CVARD数据库的药物警戒分析

The Adverse Drug Reactions of Nifedipine: A Pharmacovigilance Analysis Based on FAERS, JADER, and CVARD Databases

摘要: 目的：尽管硝苯地平广泛用于高血压和心绞痛治疗，但其超说明书使用(尤其在妊娠期及精神领域)的系统性安全风险证据仍然匮乏。本研究旨在通过分析二十年的真实世界不良事件(AEs)数据，完善其风险–获益评估。方法：采用四种不成比例性分析算法(ROR、PRR、BCPNN、EBGM)，分析FAERS、JADER、CVARD三大药物不良反应数据库中大量的硝苯地平相关报告。通过MedDRA v26.1术语标准化及多算法验证(阈值：ROR/PRR 95% CI > 1, BCPNN IC025 > 0, EBGM05 > 2)确保信号可靠性。结果：妊娠相关AEs呈现强信号强度：围产期心肌病、先兆子痫和出生体重偏轻的婴儿。血管事件与胎儿心脏事件为关键风险。性别差异显著：女性妊娠暴露风险升高，男性心脏骤停关联性更强。自杀完成作为新发信号(两种性别均有阳性信号)值得关注。结论：本研究揭示了硝苯地平既往未明确的产科与精神领域风险。其与超说明书的早产及自杀既遂的关联性挑战现有的安全范式，敦促修订监测指南并开展机制研究。研究结果支持修订药品说明书及对高危人群实施定向监测，弥合临床试验与真实世界药物治疗的关键证据鸿沟。

Abstract: Objective: Although nifedipine is widely used for the treatment of hypertension and angina, systematic safety evidence regarding its off-label use (particularly during pregnancy and in psychiatric domains) remains insufficient. This study aims to enhance its risk-benefit assessment by analyzing 20 years of real-world adverse event (AE) data. Methods: Four disproportionate analysis algorithms (ROR, PRR, BCPNN, and EBGM) were employed to analyze a large number of nifedipine-related reports from three major pharmacovigilance databases: FAERS, JADER, and CVARD. Signal reliability was ensured through MedDRA v26.1 term standardization and multi-algorithm validation (thresholds: ROR/PRR 95% CI > 1, BCPNN IC025 > 0, EBGM05 > 2). Results: Pregnancy-related AEs showed strong signal intensity, including peripartum cardiomyopathy, preeclampsia, and low birth weight infants. Vascular events and fetal cardiac events were identified as key risks. Gender differences were significant: female pregnancy exposure carried an elevated risk, while male patients had a stronger association with cardiac arrest. Completed suicide emerged as a new signal (positive signals in both genders) worthy of attention. Conclusion: This study reveals previously unrecognized obstetric and psychiatric risks associated with nifedipine. Its association with off-label use in preterm birth and completed suicide challenges existing safety paradigms, urging the revision of monitoring guidelines and further mechanistic research. The findings support the revision of drug labeling and the implementation of targeted monitoring for high-risk populations, bridging the critical evidence gap between clinical trials and real-world drug therapy.