Drug interactions that matter

Drug–drug interactions arise when the effects of one drug are altered by the co-administration of another. The clinical response seen depends on many factors, including individual patient characteristics such as age, co-morbidities and pharmacogenetics. The number of potential drug interactions is extensive, but the incidence in published studies implies that many of these are not clinically relevant. Interactions are generally classified as pharmacokinetics-related, where drug absorption, distribution, metabolism or excretion are affected, or pharmacodynamics-related, when drugs with similar pharmacological actions are co-prescribed. In recent years we have developed a greater understanding of the mechanisms of drug interactions, including Phase I metabolic reactions involving the family of cytochrome P450 isoenzymes. Furthermore, the drug transporter P-glycoprotein expressed in many tissues, has been shown to play an important role in drug–drug interactions and, like the cytochrome P450 system, also exhibits genetic polymorphism. With an ageing population, an increasing number of new drugs and more polypharmacy, increasing efforts are needed to avoid drug interactions. Although computerized programmes can help to reduce the number of drug interactions, a risk–benefit evaluation by the prescribing physician is also required. This article outlines the main mechanisms involved in clinically relevant drug interactions.