Chan T Y
Department of Clinical Pharmacology, The Chinese University of Hong Kong.
Ann Pharmacother. 1995 Dec;29(12):1274-83. doi: 10.1177/106002809502901214.
To review the mechanisms and clinical significance of adverse interactions between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) and discuss how these interactions can be avoided.
Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles.
All articles were considered for inclusion in the review. Pertinent information was selected for discussion.
All NSAIDs can prolong bleeding time by inhibiting platelet function. High-dose aspirin has a direct hypoprothrombinemic effect. Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of warfarin, but the mechanism is not known. The clinical relevance of protein binding displacement in the interaction between warfarin and NSAIDs has been overstated, although a significant one may be more likely in the presence of high concentrations of NSAIDs in patients with slow elimination of warfarin (e.g., those with severe heart failure or impaired liver function). NSAIDs can induce gastrointestinal bleeding, which is likely to be more severe if warfarin is also given.
The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided. Patients should be closely monitored for anticoagulant control and bleeding complications during the combined use of warfarin and NSAIDs.
回顾华法林与非甾体抗炎药（NSAIDs）之间不良相互作用的机制及临床意义，并讨论如何避免这些相互作用。
通过检索MEDLINE（1976年至今）以及相关文章的参考文献列表，确定了以往关于华法林与NSAIDs相互作用的研究或不良相互作用的报告。
所有文章均被纳入综述考虑范围。选取相关信息进行讨论。
所有NSAIDs均可通过抑制血小板功能延长出血时间。大剂量阿司匹林具有直接的低凝血酶原血症作用。保泰松及其类似物通过抑制华法林的肝脏代谢，经药代动力学相互作用增强华法林的低凝血酶原血症作用。甲芬那酸也可增强华法林的抗凝作用，但其机制尚不清楚。尽管在华法林清除缓慢的患者（如重度心力衰竭或肝功能受损者）中，高浓度NSAIDs存在时更可能发生显著的蛋白结合置换，但在华法林与NSAIDs相互作用中，蛋白结合置换的临床相关性已被夸大。NSAIDs可诱发胃肠道出血，若同时使用华法林，出血可能更严重。
由于这些患者出血风险增加，一般不鼓励联合使用华法林与NSAIDs。在接受华法林治疗且需要使用NSAIDs的患者中，应避免使用保泰松及其类似物、大剂量阿司匹林、甲芬那酸、过量使用外用的水杨酸甲酯以及与消化性溃疡出血风险较高相关的NSAIDs。在联合使用华法林与NSAIDs期间，应密切监测患者的抗凝控制情况及出血并发症。
