Optimising Seniors’ Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug–Drug and Drug–Drug–Gene Interactions

Abstract

Many individuals ≥65 have multiple illnesses and polypharmacy. Primary care physicians prescribe >70% of their medications and renew specialists’ prescriptions. Seventy-five percent of all medications are metabolised by P450 cytochrome enzymes. This article provides unique detailed tables how to avoid adverse drug events and optimise prescribing based on two key databases. DrugBank is a detailed database of 13,000 medications and both the P450 and other complex pathways that metabolise them. The Flockhart Tables are detailed lists of the P450 enzymes and also include all the medications which inhibit or induce metabolism by P450 cytochrome enzymes, which can result in undertreatment, overtreatment, or potentially toxic levels. Humans have used medications for a few decades and these enzymes have not been subject to evolutionary pressure. Thus, there is enormous variation in enzymatic functioning and by ancestry. Differences for ancestry groups in genetic metabolism based on a worldwide meta-analysis are discussed and this article provides advice how to prescribe for individuals of different ancestry. Prescribing advice from two key organisations, the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium is summarised. Currently, detailed pharmacogenomic advice is only available in some specialist clinics in major hospitals. However, this article provides detailed pharmacogenomic advice for primary care and other physicians and also physicians working in rural and remote areas worldwide. Physicians could quickly search the tables for the medications they intend to prescribe.