St. Elizabeth Healthcare, Edgewood Anticoagulation Clinic, Edgewood, KY, USA.
Ann Pharmacother. 2011 Nov;45(11):e58. doi: 10.1345/aph.1Q242. Epub 2011 Oct 18.
To report a case of a probable interaction between warfarin and extended-release niacin that may have led to synergistic coagulopathy and to inform health care providers of a need for more frequent monitoring of international normalized ratio (INR) in patients taking these drugs concomitantly.
A 69-year-old white female whose anticoagulation treatment had been stable for 18 months with warfarin 2.5 mg daily (17.5 mg/wk) presented to an anticoagulation clinic with a critically elevated INR of greater than 12.3 after a dose increase in extended-release niacin (Niaspan) from 500 mg to 1000 mg daily the previous week. Extended-release niacin 500 mg daily had not affected the patient's INR for the previous 3 months; the most recent INR before this episode was 2.4. Warfarin was withheld and extended-release niacin was discontinued. The INR 2 days later was 4.8 and, with titration of warfarin to the previous maintenance dose of 2.5 mg daily, the INR was 2.3.
Common drug interaction resources do not consistently list an interaction between warfarin and extended-release niacin. The mechanism of niacin-induced coagulopathy is theorized to be related to diminished coagulation factors, and limited data suggest that this may be more pronounced with extended-release niacin. Because of the described effects of niacin on the coagulation cascade and the possibility for pharmacokinetic interactions, there is a potential for synergistic coagulopathy when combined with warfarin therapy. For patients taking both medications, more frequent INR monitoring than that which drug interaction references suggest may be advised. An objective causality assessment (Horn Drug Interaction Probability Scale) revealed that the interaction was probable.
An interaction between niacin and warfarin likely elevated the INR in this patient because of synergistic coagulopathy and pharmacokinetic effects of niacin. Increased frequency of INR monitoring may be advised for patients taking these drugs concomitantly.
报告 1 例可能由华法林与烟酸缓释剂相互作用导致协同性凝血功能障碍的病例，以提醒医务人员在同时使用这些药物时，需要更频繁地监测国际标准化比值（INR）。
一位 69 岁白人女性，每日服用华法林 2.5 毫克（每周 17.5 毫克），抗凝治疗已稳定 18 个月。上周，她将烟酸缓释剂（Niaspan）剂量从每日 500 毫克增加到 1000 毫克后，出现 INR 严重升高至超过 12.3。在过去的 3 个月中，每日服用 500 毫克的烟酸缓释剂并未影响患者的 INR；在此事件之前的最近一次 INR 为 2.4。停用华法林并停止使用烟酸缓释剂。两天后 INR 为 4.8，将华法林滴定至之前的维持剂量 2.5 毫克/日，INR 为 2.3。
常见的药物相互作用资源并未一致列出华法林和烟酸缓释剂之间的相互作用。烟酸引起凝血功能障碍的机制理论上与凝血因子减少有关，有限的数据表明，这种作用在烟酸缓释剂中更为明显。由于烟酸对凝血级联的描述性影响以及与药代动力学相互作用的可能性，当与华法林联合使用时，可能会出现协同性凝血功能障碍。对于同时服用这两种药物的患者，建议比药物相互作用参考建议更频繁地监测 INR。客观的因果关系评估（Horn 药物相互作用可能性量表）显示，该相互作用很可能导致了患者 INR 的升高。
烟酸和华法林之间的相互作用可能导致了该患者 INR 的升高，原因是协同性凝血功能障碍和烟酸的药代动力学作用。对于同时服用这些药物的患者，建议增加 INR 监测的频率。
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