Saito Kazuki, Nihei Satoru, Asaka Junichi, Kudo Kenzo
Department of Pharmacy, Iwate Medical University Hospital, Iwate, Japan;
Department of Pharmacy, Iwate Medical University Hospital, Iwate, Japan.
In Vivo. 2025 May-Jun;39(3):1458-1469. doi: 10.21873/invivo.13947.
BACKGROUND/AIM: The concurrent use of vascular endothelial growth factor (VEGF) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) raises concerns regarding the increased risk of adverse drug reactions (ADRs) due to potential pharmacodynamic interactions. However, no studies have specifically addressed this issue. The objective of this study was to investigate whether the combination of these drugs increased the risk of ADRs.
Disproportionality analysis was conducted on ADR reports from the Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS) databases. The concomitant signal score and Ω shrinkage measure were used to identify safety signals associated with the drug combination. Additionally, logistic regression analysis focused on reports of ADRs related to cancer treatment and assessed the significance of the adjusted reporting odds ratio (aROR) for the interaction between these drugs.
Disproportionality analysis included ADR data from the JADER (=1,509,399) and FAERS (=38,610,433) databases. The concomitant signal score and Ω shrinkage measure identified a signal for gastrointestinal perforation in both databases. Logistic regression on cancer treatment-related ADRs (JADER: =255,177; FAERS: =1,167,941) showed a synergistic increase in gastrointestinal perforation risk with the drug combination [aROR for interaction term: JADER: 1.74 (95% confidence interval (CI)=1.45-2.07); FAERS: 1.49 (95% CI=1.29-1.72)].
The combination of VEGF inhibitors and NSAIDs is associated with an increased risk of gastrointestinal perforation, a serious and potentially fatal ADR. Therefore, caution is warranted when prescribing a combination of these drugs.
背景/目的：血管内皮生长因子（VEGF）抑制剂与非甾体抗炎药（NSAIDs）同时使用引发了人们对因潜在药效学相互作用导致药物不良反应（ADR）风险增加的担忧。然而，尚无研究专门探讨这一问题。本研究的目的是调查这些药物联合使用是否会增加ADR风险。
对来自日本药品不良反应报告（JADER）和美国食品药品监督管理局不良事件报告系统（FAERS）数据库的ADR报告进行不成比例分析。使用伴随信号评分和Ω收缩测量来识别与药物联合相关的安全信号。此外，逻辑回归分析聚焦于与癌症治疗相关的ADR报告，并评估这些药物之间相互作用的调整报告比值比（aROR）的显著性。
不成比例分析纳入了JADER（=1,509,399）和FAERS（=38,610,433）数据库的ADR数据。伴随信号评分和Ω收缩测量在两个数据库中均识别出胃肠道穿孔信号。对与癌症治疗相关的ADR进行逻辑回归分析（JADER：=255,177；FAERS：=1,167,941）显示，药物联合使用会使胃肠道穿孔风险协同增加[aROR交互项：JADER：1.74（95%置信区间（CI）=1.45 - 2.07）；FAERS：1.49（95% CI = 1.29 - 1.72）]。
VEGF抑制剂与NSAIDs联合使用与胃肠道穿孔风险增加相关，胃肠道穿孔是一种严重且可能致命的ADR。因此，开具这些药物的联合处方时需谨慎。
