Hope K A, Havrda D E
Department of Pharmacy Practice, College of Pharmacy, University of Oklahoma, Oklahoma City 73190, USA.
Ann Pharmacother. 2001 Feb;35(2):183-7. doi: 10.1345/aph.10207.
To discuss the effect on the international normalized ratio (INR) when patients are converted from therapy with Coumadin to generic warfarin.
Two cases at a family medicine center anticoagulation clinic in Oklahoma City, OK, in which subtherapeutic INR values occurred after a switch from Coumadin to generic warfarin, while all other variables were kept consistent demonstrate the need for close monitoring of the INR when patients are switched between brands of warfarin.
Warfarin is a narrow therapeutic index drug since small changes in systemic concentration can lead to significant variation in phamacodynamic response. In March 1997, the Food and Drug Administration (FDA) approved generic warfare based on the FDA and United States Pharmacopoeia (USP) standards. Due to different specifications between Dupont Pharma and the USP, content uniformity may differ between brand and generic forms of warfarin. United studies have demonstrated bioequivalence between brand and generic. The two cases presented demonstrate the potential for fluctuations in the INR when switching between generic and brand. Thus, these eases illustrate the need for close monitoring if a change is made.
While considered bioequivalent by the FDA, switching between Coumadin and generic warfarin may lead to significant changes in the INR, warranting dose alterations due to different content uniformity specifications between Dupont Pharma and the USP. Patients switching between Coumadin and generic warfarin should have their INR monitored more carefully.
探讨患者从使用香豆素类药物转换为使用华法林通用名制剂时，对国际标准化比值（INR）的影响。
俄克拉何马城一家家庭医学中心抗凝门诊的两例病例显示，从香豆素类药物转换为华法林通用名制剂后，出现了INR值低于治疗水平的情况，而所有其他变量均保持一致，这表明当患者在不同品牌的华法林之间转换时，需要密切监测INR。
华法林是一种治疗指数狭窄的药物，因为全身浓度的微小变化可能导致药效学反应的显著差异。1997年3月，美国食品药品监督管理局（FDA）根据FDA和美国药典（USP）标准批准了华法林通用名制剂。由于杜邦制药公司的产品与USP的规格不同，华法林品牌制剂和通用名制剂的含量均匀度可能存在差异。联合研究表明品牌制剂和通用名制剂具有生物等效性。所呈现的两例病例表明，在通用名制剂和品牌制剂之间转换时，INR可能会出现波动。因此，这些病例说明如果进行了转换，就需要密切监测。
虽然FDA认为两者具有生物等效性，但在香豆素类药物和华法林通用名制剂之间转换可能会导致INR出现显著变化，由于杜邦制药公司的产品与USP的含量均匀度规格不同，需要调整剂量。在香豆素类药物和华法林通用名制剂之间转换的患者，应更密切地监测其INR。
