title: Incidence and predictors of adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study.
abstract: OBJECTIVE
  The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs.
  
  
  METHODS
  A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors.
  
  
  RESULTS
  A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]).
  
  
  CONCLUSIONS
  The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil. paulorobreli@yahoo.com.br
authors.forename: Paulo Roque
authors.initials: PR
authors.lastname: Obreli Neto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nobili
authors.forename: Divaldo Pereira
authors.initials: DP
authors.lastname: de Lyra
authors.forename: Diogo
authors.initials: D
authors.lastname: Pilger
authors.forename: Camilo Molino
authors.initials: CM
authors.lastname: Guidoni
authors.forename: André
authors.initials: A
authors.lastname: de Oliveira Baldoni
authors.forename: Joice Mara
authors.initials: JM
authors.lastname: Cruciol-Souza
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: de Carvalho Freitas
authors.forename: Mauro
authors.initials: M
authors.lastname: Tettamanti
authors.forename: Walderez Penteado
authors.initials: WP
authors.lastname: Gaeti
authors.forename: Roberto Kenji
authors.initials: RK
authors.lastname: Nakamura Cuman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000554:Ambulatory Care Facilities / Q000706:statistics & numerical data; D001938:Brazil; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010045:Outpatients / Q000706:statistics & numerical data*; D058007:Physicians, Primary Care; D019338:Polypharmacy; D011446:Prospective Studies