European Journal of Clinical Pharmacology

, Volume 68, Issue 12, pp 1667–1676

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

  • Paulo Roque Obreli-Neto
  • Alessandro Nobili
  • André de Oliveira Baldoni
  • Camilo Molino Guidoni
  • Divaldo Pereira de Lyra Júnior
  • Diogo Pilger
  • Juliano Duzanski
  • Mauro Tettamanti
  • Joice Mara Cruciol-Souza
  • Walderez Penteado Gaeti
  • Roberto Kenji Nakamura Cuman
Pharmacoepidemiology and Prescription

DOI: 10.1007/s00228-012-1309-3

Cite this article as:
Obreli-Neto, P.R., Nobili, A., de Oliveira Baldoni, A. et al. Eur J Clin Pharmacol (2012) 68: 1667. doi:10.1007/s00228-012-1309-3

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.

Keywords

Drug interactions Drug toxicity Age Outpatients Cohort studies Pharmacovigilance 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Paulo Roque Obreli-Neto
    • 1
  • Alessandro Nobili
    • 2
  • André de Oliveira Baldoni
    • 3
  • Camilo Molino Guidoni
    • 3
  • Divaldo Pereira de Lyra Júnior
    • 4
  • Diogo Pilger
    • 5
  • Juliano Duzanski
    • 6
  • Mauro Tettamanti
    • 2
  • Joice Mara Cruciol-Souza
    • 7
  • Walderez Penteado Gaeti
    • 1
  • Roberto Kenji Nakamura Cuman
    • 1
  1. 1.Department of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil
  2. 2.Laboratory of Quality Assessment of Geriatric Therapies and Services, and Drug Information Services for the ElderlyIstituto di Ricerche Farmacologiche “Mario Negri”MilanoItaly
  3. 3.Department of Pharmaceutical SciencesUniversity of São PauloRibeirão PretoBrazil
  4. 4.Laboratory of Teaching and Research in Social PharmacyFederal University of SergipeSão CristóvãoBrazil
  5. 5.Department of MedicinesFederal University of BahiaSalvadorBrazil
  6. 6.Department of PharmacyFaculdades Integradas de OurinhosOurinhosBrazil
  7. 7.Department of Pharmaceutical SciencesState University of LondrinaLondrinaBrazil

Personalised recommendations