As a component of individualized medicine, pharmacogenetics (PGx) focuses on how genetic factors influence individual responses to specific medications. The clinical goals of pharmacogenetics are to identify the right drug at the right dose for each patient. The majority of known PGx-related variability is due to variation in genes encoding drug metabolizing enzymes. Variable drug metabolism can result in adverse drug events, ineffective therapies, and noncompliance with therapy. Pharmacogenetic variability can also be due to genetic variation in genes encoding drug transporters, drug targets, and proteins involved in immune response. Drugs with known pharmacogenetic variability may be labeled with PGx-related information. One example is clopidogrel which was updated in March 2010 by the FDA to contain information regarding response to clopidogrel in cytochrome P450 2C19 (CYP2C19) poor metabolizers. It has been demonstrated that individuals with reduced function CYP2C19 alleles do not effectively convert clopidogrel to its active metabolite, and this is associated with an increased rate of subsequent cardiovascular events and death. Other examples of pharmacogenetic-related drug labeling include warfarin and CYP2C9 and VKORC1 variation, psychiatric medications and CYP2C19/CYP2C9/CYP2D6 variation, thiopurines and TPMT variation, hypersensitivy to carbamazepine and abacavir due to HLA-B variation, and irinotecan and UGT1A1 variation. These and other examples are the basis for different clinical applications in pharmacogenetics with the ultimate goal of utilizing genetic information to determine the appropriate drug and dose for each patient.
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