Accumulating Evidence for a Drug-Drug Interaction Between Methotrexate and Proton Pump Inhibitors
Accumulating Evidence for a Drug-Drug Interaction Between Methotrexate and Proton Pump Inhibitors
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DOI：
10.1634/theoncologist.2011-0431
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发表时间：
2012-04-01
期刊：
影响因子：
5.8
通讯作者：
Korvick, Joyce
中科院分区：
文献类型：
--
作者：
Bezabeh, Shewit;Mackey, Ann Corken;Korvick, Joyce
背景。已知许多药物可通过各种机制与甲氨蝶呤相互作用。本文的目的是根据甲氨蝶呤（主要是高剂量）和质子泵抑制剂 (PPI) 之间可能存在药物相互作用的不断积累的证据，告知从业者新的标签变更。方法。检索了美国食品和药物管理局 (FDA) 不良事件报告系统 (AERS) 自发不良事件报告数据库和已发表的文献，以查找报告甲氨蝶呤和质子泵抑制剂之间相互作用的病例。结果。对 AERS 数据库和现有文献的检索发现了一些药物间相互作用的个案报告，以及三项额外的支持性研究，这些研究表明了相互作用的潜在潜在机制。结论。有证据表明，甲氨蝶呤（主要是高剂量）与质子泵抑制剂（如奥美拉唑、埃索美拉唑和泮托拉唑）合用可能会降低甲氨蝶呤的清除率，导致甲氨蝶呤和/或其代谢物羟基甲氨蝶呤的血清水平升高，可能导致甲氨蝶呤毒性。在一些病例报告中，当用组胺 H-2 阻滞剂替代 PPI 时，没有发现甲氨蝶呤毒性。根据审查的数据，FDA 更新了甲氨蝶呤标签，以纳入大剂量甲氨蝶呤和 PPI 之间可能存在的药物相互作用。医生应警惕同时接受大剂量甲氨蝶呤和 PPI 治疗的患者可能存在的药物相互作用。
Background. A number of medications are known to interact with methotrexate through various mechanisms. The aim of this article is to apprise practitioners of a new labeling change based on the accumulating evidence for a possible drug-drug interaction between methotrexate (primarily at high doses) and proton pump inhibitors (PPIs).Methods. The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database of spontaneous adverse event reports and the published literature were searched for cases reporting an interaction between methotrexate and PPIs.Results. A search of the AERS database and existing literature found several individual case reports of drug-drug interactions and three additional supportive studies that suggest potential underlying mechanisms for the interaction.Conclusion. There is evidence to suggest that concomitant use of methotrexate (primarily at high doses) with PPIs such as omeprazole, esomeprazole, and pantoprazole may decrease methotrexate clearance, leading to elevated serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. In several case reports, no methotrexate toxicity was found when a histamine H-2 blocker was substituted for a PPI. Based on the reviewed data, the FDA updated the methotrexate label to include the possible drug-drug interaction between high-dose methotrexate and PPIs. Physicians should be alerted to this potential drug-drug interaction in patients receiving concomitant high-dose methotrexate and PPIs.