Adverse drug reactions are the fourth leading cause of death in the U.S., claiming more 100,000 lives each year. More than 2 million cases of adverse drug reactions are reported in the U.S. anually, with more than 100,000 people dying annually from ADRs, according to the U.S Food and Drug Administration. The F.D.A. estimates that there may be as many as 350,000 unreported additional cases of adverse drug events each year. The health care costs of ADRs are estimated by the F.D.A. to be greater than $136 billion each year.
Genetic variation can affect the way medications are metabolized
Ethnic groups differ in their genetic makeup. Some traits are common among certain groups while others are not. Pharmacogenetics takes into account this genetic variation as it pertains to the administration of medications. Selecting medicines that are compatible with an individual’s genetic makeup may reduce the occurrence of ADRs.
Several changes take place as drugs are metabolized, depending on the pathways of the drug and the metabolizing enzymes. Most drugs are converted to inactive metabolites. In other drugs, the metabolite characteristics remain the same as those of the parent drug.
As some medicines are metabolized, the metabolites become more potent than the original drug, develop new pharmacologic actions or become toxic. Flavin-containing monooxygenase and cytochrome P450 enzymes that include gene CYP2D6 are important in hepatic drug assimilation. Pharmacogenetic adverse drug effects occur because of an individual’s genetic response to these enzymes.
Gene CYP2D6 is a metabolic catalyst for many commonly prescribed medicines such as codeine. Patients who cannot metabolize CYP2D6 may not feel any pain-relieving effects from codeine, or worse, have a toxic reaction to the drug. Those taking warfarin, a commonly prescribed anticoagulant, are at risk if genetic variations cause a reaction to gene VKORC1, which affects the way the body processes vitamin K. Optimal dosing takes into account the interaction of variants of gene VKORC1 and the CYP2C9 genotype. A 43 percent reduction in risk of hospitalization for bleeding or thromboembolism was reported when genotyping for warfarin was implemented.
The Importance of Pharmacogenetic Testing
Pharmacogenetic testing provides patients with a genetic profile that can be used by health care providers to reduce the occurrence of ADRs. Although genetic risk factors in assimilating and metabolizing medicines are known to physicians, pharmacists and other health care providers, many medications are prescribed without determining a patient’s genetic profile. This may be due in part to a lack of education about pharmacogenetics and lack of training in how to interpret results.
Pharmacists who receive pharmacogenetic training can assist patients in completing a genetic profile and interpreting the results. The results can then be made available to physicians so that prescription medications are tailored to the individual’s genetic make-up, reducing the potential for an adverse drug event. Patient confidence increases adherence to drug treatment plans, contributing to a healthier outcome.