Detection and prevention of drug-drug interactions in the hospitalized elderly: utility of new cytochrome p450-based software

Abstract

Background: Polypharmacy increases the risk of cytochrome P450-based drug-drug interactions (CYP450-DDIs), leading to decreased therapeutic efficacy or increased drug toxicity.

Objective: The aims of this study were to investigate the utility of a new CYP450-DDI software, InterMED-Rx, in aiding pharmacists in detecting CYP450-DDIs in hospitalized elderly patients and to ascertain pharmacists' agreement on how to intervene for each CYP450-DDI.

Methods: A consensus panel of geriatric pharmacists first established guidelines for managing clinically relevant pharmacokinetic CYP450-DDIs. A prospective study was then conducted of patients newly admitted to a geriatric hospital whose pharmaceutical profile underwent analysis with InterMED-Rx. Rates and types of interventions were recorded.

Results: Pharmacists' interrater agreement on how to manage CYP450-DDIs was initially only moderate (Cohen's κ, 0.51; 95% CI, 0.39-0.62), but improved subsequent to deliberation (Cohen's κ, 0.79; 95% CI, 0.70-0.88). Persistent disagreement involved interactions between 2 drugs with similar affinities for the same cytochrome. One hundred patients with polypharmacy (≥5 medications) aged 82.3 years (range, 65-96), with a mean (SD) of 12.2 (4.1) drugs (range, 5-27) were recruited for the prospective study. Eighty percent of patients had at least 1 CYP450 DDI detected with InterMED-Rx. A total of 238 CYP450-DDIs were identified involving CYP3A4 (70.2%), CYP2D6 (22.7%), and CYP2C9 (3.4%) substrates or inhibitors. Nineteen percent of patients received immediate medication adjustment, and 39% required follow-up of clinical signs, symptoms, and laboratory tests to determine whether future modification was needed. More than one half (56%) of all patients who required clinical follow-up had further medication adjustment prior to discharge.

Conclusions: Use of the InterMED-Rx software identified elderly patients at risk for pharmacokinetic interactions and facilitated interventions aimed at reducing adverse drug events. Although consensus can be reached among pharmacists on how to intervene for many CYP450-DDI scenarios, certain situations allow for multiple intervention strategies.