Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Paulo Roque Obreli-Neto1, Alessandro Nobili2, Divaldo Pereira de Lyra Júnior3, Diogo Pilger4, Camilo Molino Guidoni5, André de Oliveira Baldoni5, Joice Mara Cruciol-Souza6, Ana Luiza de Carvalho Freitas7, Mauro Tettamanti8, Walderez Penteado Gaeti1, Roberto Kenji Nakamura Cuman1

1Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil.
2Laboratory of Quality Assessment of Geriatric Therapies and Services, and Drug Information Services for the Elderly, Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Milano, Italy.
3Laboratory of Teaching and Research in Social Pharmacy, Federal University of Sergipe, São Cristóvão, SE, Brazil.
4Department of Medicines, Federal University of Bahia, Salvador, BA, Brazil.
5Department of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.
6Department of Pharmaceutical Sciences, State University of Londrina, Londrina, PR, Brazil.
7Department of Pharmacy, Faculdades Integradas de Ourinhos, Ourinhos, SP, Brazil.
8Laboratory of Geriatric Neuropsychiatry, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy.


Purpose. 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]). Conclusion. 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.

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J Pharm Pharm Sci, 15 (2): 332-343, 2012

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