Subtherapeutic INR Values Associated with a Switch to Generic Warfarin

Abstract

OBJECTIVE: To discuss the effect on the international normalized ratio (INR) when patients are converted from therapy with Coumadin to generic warfarin. CASE SUMMARY: 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. DISCUSSION: Warfarin is a narrow therapeutic index drug since small changes in systemic concentration can lead to significant variation in pharmacodynamic response. In March 1997, the Food and Drug Administration (FDA) approved generic warfarin based on the FDA and United States Pharmacopeia (USP) standards. Due to different specifications between Dupont Pharma and the USP, content uniformity may differ between brand and generic forms of warfarin. Limited 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 cases illustrate the need for close monitoring if a change is made. CONCLUSIONS: 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.