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Expert Opin Drug Saf. 2012 Jan;11(1):83-94. doi: 10.1517/14740338.2012.631910. Epub 2011 Oct 25.

Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions.

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University of Verona, Faculty of Medicine, Department of Public Health and Community Medicine, Section of Pharmacology, p.le L.A. Scuro 10, 37134 Verona, Italy.



Drug-drug interactions (DDIs) arise in numerous different ways, involving pharmacokinetic or pharmacodynamic mechanisms. Adverse drug reactions are a possible consequence of DDIs and health operators are often unaware of the clinical risks of certain drug combinations. Many papers on drug interactions have been published in recent years, but most of them focused on potential DDIs while few studies have been conducted on actual interactions.


This paper reviews the epidemiology of actual DDIs in outpatients as well as in hospital settings and in spontaneous reporting databases. The incidence of actual DDIs is consistently lower than that of potential DDIs. However, the absolute number of patients involved is high, representing a significant proportion of adverse drug reactions. The importance of risk factors such as age, polypharmacy and genetic polymorphisms is also evaluated. The relevance and efficacy of tools for recognizing and preventing DDIs are discussed.


Potential DDIs far outnumber actual drug interactions. The potential for an adverse interaction to occur is often theoretical, and clinically important adverse effects occur only in the presence of specific risk factors. Several studies have shown the efficacy of computers in early detection of DDIs. However, a correct risk-benefit evaluation by the prescribing physician, together with a careful clinical, physiological and biochemical monitoring of patients, is essential. Future directions of drug interaction research include the increasing importance of pharmacogenetics in preventing DDIs and the evaluation of interactions with biological drugs.

[Indexed for MEDLINE]

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