Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Sep 2003
Increased warfarin doses and decreased international normalized ratio response after nationwide generic switching.
Our objective was to examine possible changes in the effectiveness of warfarin after a nationwide generic substitution of formulations in 1998. ⋯ Because a general unidirectional change in INR response per unit warfarin dose cannot be explained by biologic mechanisms or confounding, we conclude that slightly reduced bioavailability (within the acceptable bioequivalence range) of the new formulation led to overestimated period 2 doses and reduced apparent warfarin sensitivity in all patient subgroups (by period 1 dose or INR), which was most prominent in those individuals with the lowest maintenance dose requirements.