Ng Heng Joo, Crowther Mark A
St. Joseph's Hospital, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada.
Am J Geriatr Pharmacother. 2006 Mar;4(1):75-7. doi: 10.1016/j.amjopharm.2006.03.001.
Warfarin and azathioprine may be prescribed concurrently in patients requiring both anticoagulation and immunosuppression. However, a potential interaction between the 2 drugs, resulting in an increased warfarin requirement, may be overlooked in clinical practice.
A 67-year-old woman was treated with warfarin (initial mean dose, 24 mg/wk [3.5 mg/d]) for >3 years for recurrent deep vein thrombosis associated with systemic lupus erythematosus. Soon after commencing warfarin, azathioprine 150 mg/d was introduced for its steroid-sparing effect. Warfarin was titrated to a mean dose of 60 to 75 mg/wk (8.5-10.5 mg/d) over the next 18 months. Her dose of azathioprine was then increased to 200 mg/d. Subtherapeutic international normalized ratio (INR) levels required an increase in the warfarin dose to a mean of 130 mg/wk (18.5 mg/d). Subsequent discontinuation of azathioprine resulted in a dramatic increase in her INR levels (from 1.8 to 14.0 four weeks after discontinuation).
A temporal relationship, demonstrating the interaction between warfarin and azathioprine, was evident at various times during therapy for our patient. This case, together with 7 additional published cases, is comprehensively reviewed here using previously described criteria for establishing a definite interaction between warfarin and other drugs.
The evidence supports a clinically important inhibitory action of azathioprine on warfarin and calls for closer monitoring of INR levels when azathioprine doses are altered during concurrent administration with warfarin.
对于同时需要抗凝和免疫抑制治疗的患者，可能会同时开具华法林和硫唑嘌呤。然而，这两种药物之间潜在的相互作用可能会导致华法林需求量增加，而在临床实践中这一点可能被忽视。
一名67岁女性因系统性红斑狼疮相关的复发性深静脉血栓接受华法林治疗（初始平均剂量为24mg/周[3.5mg/天]）超过3年。在开始使用华法林后不久，引入了硫唑嘌呤，剂量为150mg/天，以发挥其节省类固醇的作用。在接下来的18个月里，华法林的剂量逐渐滴定至平均60至75mg/周（8.5 - 10.5mg/天）。随后她的硫唑嘌呤剂量增加至200mg/天。国际标准化比值（INR）低于治疗水平，需要将华法林剂量增加至平均130mg/周（18.5mg/天）。随后停用硫唑嘌呤导致她的INR水平急剧上升（停药四周后从1.8升至14.0）。
在我们患者的治疗过程中，不同时间都明显存在华法林和硫唑嘌呤相互作用的时间关系。本病例与另外7例已发表病例一起，使用先前描述的用于确定华法林与其他药物之间明确相互作用的标准进行了全面回顾。
证据支持硫唑嘌呤对华法林具有临床上重要的抑制作用，并且在与华法林同时给药期间改变硫唑嘌呤剂量时，需要密切监测INR水平。
