Svendsen Kristian, Wood Mollie, Olsson Erika, Nordeng Hedvig
Hospital Pharmacy of Tromsø, Sykehusapotek Nord HF, Norway, Postboks 6147 Langnes, 9291, Tromsø, Norway.
Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, School of Pharmacy & PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Eur J Clin Pharmacol. 2018 May;74(5):627-636. doi: 10.1007/s00228-017-2407-z. Epub 2017 Dec 30.
Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender.
All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis.
Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys).
Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.
尽管美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）对甲氧氯普胺的长期使用发出了警告，但对于甲氧氯普胺所致神经学不良药物反应（ADR）的发病时间（TTO）却知之甚少。本研究的目的，首先是评估甲氧氯普胺所致神经学ADR的报告是否比其他药物更为常见，其次是描述神经学ADR的发病时间如何因年龄和性别而有所不同。
从世界卫生组织全球ADR数据库Vigibase®中提取1967年至2016年5月期间所有以甲氧氯普胺为可疑/相互作用药物的ADR报告。以神经学ADR的TTO作为结果，年龄、性别和ADR类型作为预测因素，拟合Cox比例风险模型。比较不同年龄和性别的神经学ADR的比例报告率（PRR）。分析中排除了律师报告。
共识别出47,000多份与甲氧氯普胺有关的ADR报告。超过三分之一（35.6%）的报告来自律师。总体而言，大多数ADR以及具体的神经学ADR发生在使用甲氧氯普胺的前5天内（中位数为1天）。TTO随年龄增长而增加。甲氧氯普胺所致神经学ADR的报告频率是其他药物的两到四倍，在儿童中观察到的PRR最高（女孩为4.24，男孩为4.60）。
大多数药物不良反应发生在使用甲氧氯普胺治疗的前5天内。在治疗的最初几天，需要使用甲氧氯普胺的患者应密切监测神经学ADR。
