Are brand-name and generic warfarin interchangeable?

Abstract

Although Health Canada approved generic warfarins in Year 2000, there is still controversy over the interchangeability of these products with brand-name Coumadin. Since a large population of patients require warfarin and it has a narrow margin of efficacy and safety, it is vital to ensure that generic brands can be safely interchanged with Coumadin. Multiple N-of-1 randomized double blind crossover trials switched outpatients between generic warfarin and Coumadin over a period of thirty weeks. Study patients were on each drug for 5 × 3-week periods with International Normalized Ratio (INR) measurements twice per period. Outcomes included mean INR results and proportion of dosage adjustments that were required with each brand. Inter-patient and intra-patient differences between generic warfarin and Coumadin were compared. Study patient results were also compared with those of a retrospective control group, maintained on Coumadin only. The 6 patients (96% power to detect a difference of greater than 0.5 INR units between warfarin brands) showed no significant difference between warfarin brands in terms of mean INR results (p = 0.485) and proportion of dosage adjustments required with each brand (p = 0.264). Study patients experienced less inter- and intra-subject INR variation than the historical control group, though the difference was not statistically significant. Patients can safely and effectively switch between generic warfarin and Coumadin. Clinical Pharmacology & Therapeutics (2004) 75, P27–P27; doi: 10.1016/j.clpt.2003.11.103