Understanding Adverse Drug Reactions in Older Adults Through Drug-Drug Interactions

Eur J Intern Med. 2014 Nov;25(9):843-6. doi: 10.1016/j.ejim.2014.10.001. Epub 2014 Oct 11.


Aims: The aims of this study are to evaluate prevalence and characteristics of adverse drug reactions (ADRs) and to evaluate the potential contribution of specific medications, therapeutic categories and drug-drug interactions (DDIs) in older adults.

Methods: All ADR reporting forms of persons aged 65+ years collected by the pharmacovigilance of one of the main hospitals in Italy during 2013 were evaluated. DDIs were analysed by a computerized prescription system (INTERCheck) and based on the interactions' database managed by the Istituto di Ricerche Farmacologiche Mario Negri. DDIs were classified according to their clinical relevance as contraindicated, major, and moderate.

Results: Amongst all the ADR reporting forms (n=1014) collected during 2013, 343 affected older adults. The most frequent ADRs were: haemorrhages (n=122, 35.5%), allergic reactions (n=56, 16.3%), and elevated International Normalized Ratio (INR>6, n=54, 15.7%). The specific medications that contributed to ADRs were warfarin (42.5%), acenocumarol (9%), and allopurinol (8.5%); while the therapeutic categories were haematological agents (67%) and proton pump inhibitors (13%). A total of 912 DDIs were found; one third of them were contraindicated or major and 31.5% of them potentially contributed to ADRs; of these, the most frequent were: warfarin and heparin (contraindicated, n=5); warfarin and a statin (major, n=38); warfarin and a proton pump inhibitor (moderate, n=40). At least one DDI contributed to 66 haemorrhages out of 122 (54%) and to 41 elevated INR out of 54 (76%).

Conclusion: DDIs significantly contribute to the onset of ADRs in older adults and intervention programmes, e.g., the employment of a computerized system, may reduce the burden of iatrogenic illnesses in the elderly.

Keywords: Adverse drug reaction; Drug–drug interaction; Elderly.

MeSH terms

  • Acenocoumarol / adverse effects
  • Age Factors
  • Aged
  • Allopurinol / adverse effects
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / etiology
  • Drug Interactions*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Hematologic Agents / adverse effects
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • International Normalized Ratio
  • Italy / epidemiology
  • Male
  • Prevalence
  • Proton Pump Inhibitors / adverse effects
  • Warfarin / adverse effects


  • Hematologic Agents
  • Proton Pump Inhibitors
  • Warfarin
  • Allopurinol
  • Acenocoumarol