J Pharm Pharmaceut Sci (www.cspsCanada.org) 15(2) 344 - 354, 2012 Prevalence and Predictors of Potential Drug-Drug Interactions in the Elderly: A Cross-Sectional Study in the Brazilian Primary Public Health System Paulo Roque Obreli Neto1, Alessandro Nobili2, Srecko Marusic3, Diogo Pilger4, Camilo Molino Guidoni5, André de Oliveira Baldoni5, Joice Mara Cruciol-Souza6, Alessandra Negri da Cruz7, Walderez Penteado Gaeti1, Roberto 1 Kenji Nakamura Cuman 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, Milano, Italy. 3Department of Clinical Pharmacology, University Hospital Dubrava, Zagreb, Croatia. 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. Received, November 2, 2011; Revised, April 9, 2012; Accepted, April 30, 2012; Published, May 2 , 2012. ABSTRACT- Purpose. The primary objective of this study was to investigate the prevalence of clinically important potential drug-drug interactions (DDIs) in elderly patients attending the public primary health care system in Brazil. The secondary objective was to investigate possible predictors of potential DDIs. Methods. A cross-sectional study was carried out in 5 Brazilian cities located in the Ourinhos Micro-region, Sao Paulo State, between November 2010 and April 2011. The selected sample was divided according to the presence (exposed) or absence (unexposed) of one or more potential DDIs (defined as the presence of a minimum 5-day overlap in supply of an interacting drug pair). Data were collected from medical prescriptions and patients’ medical records. Potential DDIs (rated major or moderate) were identified using 4 DDI-checker programs. Logistic regression analysis was used to study potential DDI predictors. Results. The prevalence of clinically important potential DDIs found during the study period was 47.4%. Female sex (OR = 2.49 [95% CI 2.29–2.75]), diagnosis of ≥ 3 diseases (OR = 6.43 [95% CI 3.25–12.44]), and diagnosis of hypertension (OR = 1.68 [95% CI 1.23– 2.41]) were associated with potential DDIs. The adjusted OR increased from 0.90 [95% CI 0.82–1.03] in patients aged 60 – 64 years to 4.03 [95% CI 3.79 – 4.28] in those aged 75 years or older. Drug therapy regimens involving ≥ 2 prescribers (OR = 1.39 [95% CI 1.17–1.67]), ≥ 3 drugs (OR = 3.21 [95% CI 2.78–3.59]), ≥ 2 ATC codes (OR = 1.19 [95% CI 1.12–1.29]), ≥ 2 drugs acting on cytochrome P450 (OR = 2.24 [95% CI 2.07–2.46]), and ATC codes B (OR = 1.89 [95% CI 1.05–2.08]) and C (OR = 4.01 [95% CI 3.55–4.57]) were associated with potential DDIs. Conclusion. Special care should be taken with the prescription and therapeutic follow-up of patients who present characteristics identified as predictors. Knowledge of potential DDI predictors could aid in developing preventive practices and policies that allow public health services to better manage this situation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page. ____________________________________________________________________________________ INTRODUCTION all hospitalizations in older patients and representing an estimated cost of more than Earlier studies have reported that 54.4–80.0% U$1 billion per year to health care systems (4- of elderly Latin American outpatients presented 6). Several factors influence the occurrence of with one or more potential drug-drug potential DDIs in elderly patients (7-9). interactions (DDIs) (1,2), and the elderly _____________________________________ population is increasing rapidly in Latin Corresponding Author: Paulo Roque Obreli Neto, American countries (3). DDIs present Department of Pharmacology and Therapeutics, State University of Maringá, Avenue Colombo 5790, Maringá, deleterious outcomes, causing roughly 2.8% of PR, Brazil; E-mail: [email protected] 344 J Pharm Pharmaceut Sci (www.cspsCanada.org) 15(2) 344 - 354, 2012 Knowledge of predictors of potential DDIs prevention and surveys of disease spread, and could aid in developing preventive practices drug dispensation. Family physicians, general and policies (9). However, to the authors’ practitioners, and nurses provide primary health knowledge, drug utilization studies analyzing care interventions (consultations, exams, these predictors in elderly patients at the education groups, and vaccinations), and primary health care level in Latin American pharmacies within BHUs provide patients with countries are scarce. the drugs prescribed by these professionals. A previous drug utilization study conducted in a tertiary hospital setting in Brazil, a Latin Inclusion and exclusion criteria American country, indicated that patient According to the threshold set by the United characteristics, prescriber characteristics, and Nations Programme on Ageing, patients aged drug characteristics influenced the occurrence over 60 years were considered elderly (10). The of potential DDIs (8), but these findings cannot use of a cut-off of 60 years instead of 65 years be extrapolated to the primary health care level. augmented the sample size of the study. Up to 70.0% of Latin American patients are Patients ≥ 60 years of age with at least one attended at the primary care level, reinforcing prescription for 2 or more drugs (prescribed the need to study potential DDI predictors in both within and across prescriptions) collected this setting. in participating BHU pharmacies were eligible The primary objective of this study was to for inclusion in the study. investigate the prevalence of clinically The Brazilian public health system does not important potential DDIs in elderly patients employ software to create electronic drug attending the public primary health care system prescriptions. Drug prescriptions are hand- in a south-eastern region of Brazil. The written by the physicians. According to secondary objective was to investigate possible Brazilian legislation, prescriptions must be predictors of potential DDIs. signed and dated by the physician, legible, and written in ink, with no sign of tampering (e.g. METHODS different handwriting or written in different ink colours) or erasures (e.g. scribble and blots), to Study design be considered valid (11). Exclusion criteria This study was approved by the Research included signs of prescription tampering or Ethical Committee of the State University of erasure and illegibility. Maringa, Brazil (CAAE 0010-10). The research followed a cross-sectional study model, with Data collection the selected sample group divided between The Brazilian public primary health care system patients receiving drug therapies with one or has no administrative prescription database. more potential DDI (exposed) and those Thus, data collection was carried out by receiving drug therapies with no potential DDI analyzing patients’ drug prescriptions and (unexposed). The study was carried out medical records. between November 2010 and April 2011, using At the time of dispensing the medication, data from the public primary health care system the employees of participating BHU pharmacies in 5 Brazilian cities located in the Ourinhos (51 employees) registered patient identification Micro-region, Sao Paulo State. The Ourinhos (name, date of birth, and sex) and Micro-region has an estimated population of complementary information (drug dispensation 280,000 individuals (28,929 over the age of 60 amount and date) in the prescriptions and years), attended by 36 Basic Health Units retained them. Three researchers (NN, JV and (BHUs). Twenty-seven BHUs participated in GS) were responsible for weekly collection of the study. these prescriptions and determination of those The Brazilian Public Health System eligible for inclusion in the study. Information provides free access to primary, secondary, and from eligible prescriptions (name, date of birth, tertiary care to all inhabitants, including the sex, names of the drugs prescribed, amount of supply of drugs by pharmacies located in health drug dispensed, prescribers’ identification, date establishments. Primary care offered to of prescription, and date of dispensation) was outpatients in BHUs involves health education, collected and entered into an electronic 345 J Pharm Pharmaceut Sci (www.cspsCanada.org) 15(2) 344 - 354, 2012 database developed for the purpose of this study sensitivity in the survey (18). These 4 DDI- to rapidly access and assess this information. checker programs have been widely used in All prescriptions were classified according to previous published studies and represent the the first level of the Anatomical Therapeutic programs most used by Latin American Chemical (ATC) classification system, as pharmacists. The drug therapy regimen of each recommended by the World Health patient was typed and evaluated independently Organization (12). In this system, active by the four researchers mentioned above using substances are divided into different groups the 4 DDI-checker programs, to avoid possible according to the organ or system on which they mistakes in the typing and evaluation process. act and their therapeutic, pharmacological