Substituting warfarin products: what's the source of the problem?

Many clinicians have expressed concerns about the bioequivalence of warfarin products, and data suggest that substituting warfarin products may increase the risk of major bleeding and thromboembolic complications. Anecdotal reports and some retrospective studies have reported differences in anticoagulation control after a warfarin product substitution. But the best available evidence-prospective, randomized, blinded clinical trials-has failed to validate these observations. Indeed, interpatient and intrapatient variability in anticoagulation control observed before and after warfarin product substitution is very similar. So, while differences in product standardization, bioavailability, and bioequivalence make a convenient explanation, the problem lies elsewhere. Perhaps poor communication, fractionated systems of care, and errors are the culprits.