Exploring the Reliability of Detecting Drug-Drug Interactions that Increase the Risk of Gestational Diabetes in Adverse Event Reporting Systems.

IF 3.8 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Safety Pub Date : 2025-09-02 DOI:10.1007/s40264-025-01607-9

Robiyanto Robiyanto, Jim W Barrett, Lovisa Sandberg, Boukje C Raemaekers, G Niklas Norén, Catharina C M Schuiling-Veninga, Eelko Hak, Eugène P van Puijenbroek

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引用次数: 0

Abstract

Background: Adverse event reporting systems are an important source of safety signals for drug use in pregnancy, but their usefulness in the identification of potential drug-drug interactions (DDIs) remains unclear.

Objective: Our objective was to explore the reliability of signal detection for pharmacokinetic DDIs during pregnancy in adverse event reporting systems, focusing on potential interactions between antipsychotics (APs) or antidepressants (ADs) and drugs modifying cytochrome P450 (CYP450) activity, increasing the occurrence of gestational diabetes mellitus (GDM).

Methods: Reports related to the use of drugs during pregnancy were identified in VigiBase, the World Health Organization (WHO) global database of adverse event reports. Potential interacting drugs were selected based on WHO Drug Standardised Drug Groupings for CYP450 isoenzymes involved in the metabolic pathway of the AP or AD of interest. We conducted statistical interaction analysis using the omega disproportionality measure and including concomitant medication to identify potential DDIs, followed by a case series review for supporting evidence. Evaluation was subjective by author consensus.

Results: Of the 30 drug-drug-event combinations considered, statistical signals emerged for escitalopram, citalopram, and sertraline and the simultaneous use of CYP2D6 inhibitors with a higher relative reporting rate of GDM. However, case series review of reports did not support the existence of these DDIs because of uncertainties regarding the actual timing of medication use reported as concomitant.

Conclusion: Statistical signals of DDIs between ADs and potential interacting drugs during pregnancy were identified but not pursued further after case reviews. Uncertainty around medication use and event timing affected the reliability of the outcomes. These findings highlight the need to validate signals using detailed report data and stress the importance of accurate medication reporting.

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探索在不良事件报告系统中检测增加妊娠糖尿病风险的药物-药物相互作用的可靠性。

背景：不良事件报告系统是妊娠期用药安全信号的重要来源，但其在识别潜在药物-药物相互作用（ddi）方面的用途尚不清楚。目的：探讨不良事件报告系统中妊娠期ddi药代动力学信号检测的可靠性，重点关注抗精神病药（APs）或抗抑郁药（ADs）与改变细胞色素P450 （CYP450）活性的药物之间潜在的相互作用，增加妊娠期糖尿病（GDM）的发生。方法：在世界卫生组织（WHO）全球不良事件报告数据库VigiBase中识别与妊娠期间药物使用相关的报告。根据WHO药物标准化药物分组，选择可能与AP或AD代谢途径相关的CYP450同工酶的相互作用药物。我们使用omega歧化测量法进行统计交互分析，并包括伴随用药来识别潜在的ddi，随后进行病例系列回顾以支持证据。评价是主观的作者共识。结果：在所考虑的30种药物-事件联合用药中，艾司西酞普兰、西酞普兰和舍曲林同时使用CYP2D6抑制剂出现统计学信号，GDM的相对报告率较高。然而，对报告的病例系列审查并不支持这些ddi的存在，因为报道的伴随用药的实际时间存在不确定性。结论：妊娠期ad与潜在相互作用药物之间ddi的统计信号已确定，但在病例回顾后未进一步探讨。药物使用和事件发生时间的不确定性影响了结果的可靠性。这些发现强调了使用详细报告数据验证信号的必要性，并强调了准确用药报告的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Safety 医学-毒理学

CiteScore

7.60

自引率

7.10%

发文量

112

审稿时长

6-12 weeks

期刊介绍： Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.