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Adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

Although the prevalence of drug–drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions.

Methods

A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged ≥60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression.

Results

A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age ≥80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0–6.1, p < 0.01], a Charlson comorbidity index ≥4 (OR 1.3; 95 % CI 1.1–1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9–3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1–1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44).

Conclusions

The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.

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Acknowledgments

We acknowledge the clinical pharmacists and physicians involved in the study. This study was supported by Fundação de Apoio ao Desenvolvimento Científico (FADEC).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, State University of Maringá, Avenue Colombo 5790, 87020-290, Maringá, PR, Brazil

    Paulo Roque Obreli-Neto, Walderez Penteado Gaeti & Roberto Kenji Nakamura Cuman

  2. Laboratory of Quality Assessment of Geriatric Therapies and Services, and Drug Information Services for the Elderly, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy

    Alessandro Nobili & Mauro Tettamanti

  3. Department of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil

    André de Oliveira Baldoni & Camilo Molino Guidoni

  4. Laboratory of Teaching and Research in Social Pharmacy, Federal University of Sergipe, São Cristóvão, SE, Brazil

    Divaldo Pereira de Lyra Júnior

  5. Department of Medicines, Federal University of Bahia, Salvador, BA, Brazil

    Diogo Pilger

  6. Department of Pharmacy, Faculdades Integradas de Ourinhos, Ourinhos, SP, Brazil

    Juliano Duzanski

  7. Department of Pharmaceutical Sciences, State University of Londrina, Londrina, PR, Brazil

    Joice Mara Cruciol-Souza

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  1. Paulo Roque Obreli-Neto
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  2. Alessandro Nobili
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Correspondence to Paulo Roque Obreli-Neto.

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Obreli-Neto, P.R., Nobili, A., de Oliveira Baldoni, A. et al. Adverse drug reactions caused by drug–drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmacol 68, 1667–1676 (2012). https://doi.org/10.1007/s00228-012-1309-3

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