Efficacy and tolerability of the switch from a branded to a generic warfarin sodium product: An observer-blinded, randomized, crossover study

Background: Anticoagulation is an essential part of the management of numerous cardiovascular conditions. Although warfarin sodium has been in clinical use for > 40 years, only 1 proprietary warfarin preparation was in use for long-term anticoagulation in Taiwan until 2001, when the Taiwan Food and Drug Administration approved a new generic formulation. Objective: This study evaluated the efficacy and tolerability of switching from an established dose of the branded warfarin sodium product (in mg/wk) to the same dose of the generic product. Methods: This was a randomized, observer-blinded, crossover study in Taiwanese patients who received a mechanical heart valve to replace an original valve or a previously implanted mechanical valve from March 2003 to August 2004 and had received branded warfarin therapy for >= 2 months postoperatively, with a mean baseline international normalized ratio (INR) in the range from 1.7 to 3.0 in the 8- to 12-week run-in period. Patients were randomized to 1 of 2 treatment sequences, each involving three 28-day periods: the generic product for 1 period followed by the branded product for 2 periods, or the branded product for 1 period followed by the generic product for 2 periods. Prothrombin time and INR were measured, and anticoagulant activity was compared. At each visit, treatment-emergent adverse events were recorded and evaluated by the blinded observer, an internal medicine physician who was not involved in patients' care. Results: Thirty-five patients were enrolled (25 men, 10 women; mean age, 52.4 years [range, 34.5-74.4 years]). All but 2 of the patients had received a replacement for a natural heart valve. Thirty-four patients (16 who received the generic product initially, 18 who received the branded product initially) completed the study without a dose change and were >= 75% compliant with therapy. There was no difference in pooled mean (SE) INR between the 2 products (2.28 [0.06] and 2.27 [0.06], respectively). The 90% CI for the difference was 96.4 to 104.9, well within the range for bioequivalence (80-120). There were no differences in the adverse-event profiles of the 2 formulations. Conclusions: No therapeutic inequivalence was demonstrated in this small, single-blind study, suggesting that the generic and branded warfarin products studied were equally effective in maintaining anticoagulation in patients with mechanical prosthetic heart valves. The 2 products had similar safety profiles. Copyright (c) 2005 Excerpta Medica, Inc.