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Individualization with pharmacogenetics
Get used to the word "pharmacogenetics" — the discipline of studying genetic variation and its effect on responses to drugs. Warfarin dosing may be one of the first clinical applications of pharmacogenetics as it now appears that genetic testing may help predict an individual patient's response to the oral anticoagulant. Warfarin dosing can vary as much as 10 times from individual to individual, and currently, slow titration with frequent testing is the only way to safely initiate therapy. A new study, however, uses pharmacogenetic testing to estimate the appropriate warfarin dose. Reviewing data from more than 4000 patients, algorithms were developed based on clinical variables only or clinical variables plus genetic information (CYP2C9 and VKORC1). Compared to algorithms employing clinical data alone, algorithms employing genetic information more accurately identified a larger proportion of patients who would require low-dose (49.4% vs 33.3%; P < 0.001) or high-dose warfarin (24.8% vs 7.2%; P < 0.001). The authors conclude that pharmacogenetic algorithms for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than algorithms derived from clinical data alone or a fixed-dose approach, particularly for those that require 49 mg or more per week or 21 mg or less per week. (N Engl J Med 2009;360:753-764). Although pharmacogenetic testing is not yet widely available and may be difficult to obtain prior to initiating warfarin therapy, an accompanying editorial states "pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not 'average.'" (N Engl J Med 2009;360:811-813).