Clinical applications of pharmacogenomics guided warfarin dosing

To assess the state of the literature concerning pharmacogenomic testing in patients requiring vitamin K antagonists, specifically warfarin.

We conducted a literature search of MEDLINE and International Pharmaceutical Abstracts using the following words: warfarin, pharmacogenetic, and pharmacogenomic. The search results were reviewed by the authors and papers concerning pharmacogenomic testing in warfarin dosing were procured and reviewed. Additionally bibliographies of papers procured were also examined for other studies. The authors focused on clinical trials concerning the use of pharmacogenomic testing in warfarin dosing.

Although numerous studies have demonstrated that a significant portion of warfarin dosing variability can be explained by genetic polymorphisms, few prospective studies have been conducted that examine the integration of this information in practical dosing situations. Those that have, have shown that using pharmacogenomic information improves initial dosing estimates and decreases the need for frequent clinic visits and laboratory testing. Data showing a reduction in serious bleeding events is sparse. Cost-effectiveness analyses have generally shown a small but positive effect with pharmacogenomic testing in patients receiving warfarin.

Several studies have shown that pharmacogenomic testing for warfarin dosing is more accurate that other dosing schemes. Pharmacogenomic testing improves time to a therapeutic international normalized ratio while requiring fewer dosing adjustments. Patients who require higher or lower than usual doses seem to benefit the most. The cost-effectiveness of pharmacogenomic testing as well as preventing of outcomes such as bleeding or thrombosis are not yet elucidated. Pharmacists, especially those in a community setting can play a role in this new technology by educating prescribers and patients concerning pharmacogenomic testing, and by developing and using dosing protocols that incorporate its use.