Study Identifies Significant Drug-Drug Interactions in Older Adults

October 13, 2021

Drug-drug interactions (DDIs), common in older people, are associated with an increased risk of adverse drug events and hospitalization. Authors of an article in the October issue of JAMDA developed a validated list of potentially clinically significant DDIs in older adults. This list can be used in clinical practice and education to support the identification and management of these interactions or to assess prevalence in epidemiological and intervention studies.

In An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People, the authors asked experts to score (on a 5-point Likert scale) the severity of potential harm relating to 154 DDIs identified from a literature review. Those with a score of 4 or 5 were included on the final list. DDIs with a median score of 3 were discussed at a consensus meeting and included on the list if 75% or more of participants voted for their inclusion in the final round.

Consensus was reached on 66 potentially clinically significant DDIs. Most concerned cardiovascular, antithrombotic, and central nervous system drugs. In all, the list includes 30 pharmacokinetic DDIs, 24 pharmacodynamic DDIs, 9 DDIs that are both pharmacodynamic and pharmacokinetic in nature, and 3 for which the mechanism isn’t fully understood. The final list includes information on the mechanism of interaction, harm, and management. The panel also recommended treatment modifications (such as dose reduction, discontinuation, or substitution) for three-quarters of the DDIs on the list.

“These clinically significant DDIs are particularly important to detect, as they are a preventable cause of morbidity and mortality,” the authors said. This list, they further noted, “can be used to educate and assist healthcare professionals to detect potentially clinically significant DDIs. It could also be used to determine the prevalence of DDIs in epidemiological and intervention studies, as requested by recent core outcome sets.”

This study was conducted by researchers at several institutions, including Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Geriatrics, University Medical Center Utrecht, Utrecht, The Netherlands; Ageing Clinical & Experimental Research (ACER), University of Aberdeen, United Kingdom; Clinical Pharmacy Research Group, Louvain Drug Research Institute, Universite catholique de Louvain, Brussels, Belgium; and Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.

Get more information on the findings above and more details about the study. To contact the researchers or JAMDA editors for an interview, please email



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AMDA – The Society for Post-Acute and Long-Term Care Medicine is the only medical specialty society representing the community of over 50,000 medical directors, physicians, nurse practitioners, physician assistants, and other practitioners working in the various post-acute and long-term care (PALTC) settings. Dedicated to defining and improving quality, we advance our mission through timely professional development, evidence-based clinical guidance, and tireless advocacy on behalf of members, patients, families, and staff. Visit for more information.