title: Prevalence and risk of potential cytochrome P450-mediated drug-drug interactions in older hospitalized patients with polypharmacy.
abstract: BACKGROUND
  As rates of polypharmacy rise and medication regimens become more complex, the risk of potential cytochrome P450 (CYP)-mediated drug-drug interactions (DDIs) is a growing clinical concern for older adults.
  
  
  OBJECTIVE
  To determine the prevalence of potential CYP-mediated DDIs in older hospitalized adults with polypharmacy and analyze the relationship between the number of drugs dispensed and the probability of these interactions in this high-risk population.
  
  
  METHODS
  A prospective 16-week cohort study was conducted among consecutive new patients aged 65 years and older with polypharmacy (>5 drugs) admitted to a community hospital. The medication profiles of these patients were analyzed with a new multidrug cytochrome-specific software program. The prevalence of potential CYP-mediated DDIs was determined, with the probability calculated as a function of the number of medications dispensed using multivariate Poisson regression adjusted for age and sex. Comparative performance of the software program and a standard 2-drug alert program for detecting these DDIs was evaluated using the Wilcoxon-Mann-Whitney rank-sum test. Pharmacists' decisions to recommend medication adjustment based on the probability of CYP-mediated DDIs were recorded.
  
  
  RESULTS
  The prevalence of potential CYP-mediated DDIs detected among 275 older adults with polypharmacy was 80%. The probability of at least 1 CYP-mediated DDI was 50% for persons taking 5-9 drugs, 81% with 10-14 drugs, 92% with 15-19 drugs, and 100% with 20 or more drugs. Addition of each medication to a 5-drug regimen conferred a 12% increased risk of a potential CYP-mediated DDI after adjustment for age and sex (OR 1.12; 95% CI 1.09-1.14). The multidrug software identified a median increase of 3 (95% CI 2.5-3.5) potential CYP-mediated DDIs per patient, compared to use of the standard 2-drug alert software. Pharmacists targeted patients for medication adjustment or close clinical monitoring in 23% of cases.
  
  
  CONCLUSIONS
  The prevalence of potential CYP-mediated DDIs is high in geriatric patients with polypharmacy. The risk of DDIs increases as a function of the number of medications dispensed. Pharmacists' decision to intervene for potential CYP-mediated DDIs depends on clinical judgment in addition to the output from drug alert software programs, but may be facilitated by a single multicomponent, multidrug potential CYP-mediated DDI assessment.
authors.affiliation: Sir Mortimer-B Davis Jewish General Hospital, Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Doan
authors.forename: Hubert
authors.initials: H
authors.lastname: Zakrzewski-Jakubiak
authors.forename: Julie
authors.initials: J
authors.lastname: Roy
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
authors.forename: Cara
authors.initials: C
authors.lastname: Tannenbaum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006760:Hospitalization; D006764:Hospitals, Community / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D019338:Polypharmacy; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk
chemical_list: D003577:Cytochrome P-450 Enzyme System