Abstract
The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy.
Highlights
IntroductionWarfarin and tamoxifen are widely prescribed and clinically important drugs for the treatment of conditions that require anticoagulation and estrogen receptor (ER)-positive breast cancer, respectively
Warfarin and tamoxifen are widely prescribed and clinically important drugs for the treatment of conditions that require anticoagulation and estrogen receptor (ER)-positive breast cancer, respectively.The clinical response and efficacy of both drugs are variable likely due in part to genetic differences in pharmacogenes that mediate their metabolism and clearance
The dangerously high adverse event rate with warfarin usage has led to a number of studies, both in vitro and in vivo, examining the pathways and determinants that govern the observed variation in warfarin dose response, and development of more predictive dosing algorithms, including those that take into account patient-specific pharmacogenomic information
Summary
Warfarin and tamoxifen are widely prescribed and clinically important drugs for the treatment of conditions that require anticoagulation and estrogen receptor (ER)-positive breast cancer, respectively. The clinical response and efficacy of both drugs are variable likely due in part to genetic differences in pharmacogenes that mediate their metabolism and clearance. While genomics-based clinical guidelines have been established for several drugs, whether pharmacogenomics can be used to personalize treatment for individual patients remains controversial for warfarin and tamoxifen. This review aims to discuss the evidence to date that seek to correlate pharmacogenomic testing and the clinical outcomes in the context of each drug. We will provide clinical insights and future perspectives based on our experiences with the implementation of personalized medicine strategies for warfarin and tamoxifen within a large acute care hospital setting
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