Prevalence of potentially harmful multidrug interactions on medication lists of elderly ambulatory patients

Abstract

Background: It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. Methods: Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. Results: MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. Conclusions: An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.