Evidence of pharmacogenetics in aiding polypharmacy outcomes

Many drugs interact with the same enzymes and transporters. As a result, variation in the genes encoding these proteins can affect risks of side effects and likelihood of treatment success for patients taking many medications. These interactions may be different and not necessarily predicted from trials of single drugs. Knowing a patient’s genotypes for pharmacogenes can help optimize these treatment regimes. PharmGKB provides resources for exploring these relationships between genetic variation and drug response.

The recent article, “Potential utility of precision medicine for older adults with polypharmacy: a case series study” illustrates increased risk of hospitalization in patients taking multiple medications who also have variants in cytochrome P450 genes. Finkelstein, et al. present the cases of 3 older adults with chronic heart and lung disease, who were taking between 17 and 26 medications each. One of these patients had genotypes predicting normal metabolizer status for CYP2C19, CYP2C9, CYP2D6, and CYP3A4/5. This patient had no hospitalizations in the previous 5 years. The other two patients, one who was a CYP2D6 rapid metabolizer and the other who was a CYP3A4/5 poor metabolizer, had 6 and 23 hospitalizations related to adverse cardiovascular events. While this is a small number of cases, it illustrates the power of pharmacogenomics in optimizing medication regimes in cases of polypharmacy.