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Clin Ther. 2005 Mar;27(3):309-19.

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

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Institute of Clinical Medicine,Medical College, National Cheng Kung University, Tainan, Taiwan.



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.


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.


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.


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.


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.

[Indexed for MEDLINE]

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