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Br J Clin Pharmacol. 2015 Oct;80(4):808-17. doi: 10.1111/bcp.12600. Epub 2015 May 19.

Number of drugs most frequently found to be independent risk factors for serious adverse reactions: a systematic literature review.

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Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Research Centre of Emergency Medicine, Aarhus University Hospital, Aarhus, Denmark.
Hospital Pharmacy, Central Denmark Region, Aarhus, Denmark.
Department of Biochemistry and Department of Biomedicine, Aarhus University Hospital, Aarhus, Denmark.


In order to reduce the numbers of medication errors (MEs) that cause adverse reactions (ARs) many authors have tried to identify patient-related risk factors. However, the evidence remains controversial. The aim was to review systematically the evidence on the relationship between patient-related risk factors and the risk of serious ARs. A systematic search in Pubmed, Embase, Cochrane Systematic Reviews, Psychinfo and SweMed+ was performed. Included full text articles were hand searched for further references. Peer reviewed papers including adults from primary and secondary healthcare were included if they clearly defined seriousness of the ARs and described correlations to risk factors by statistical analysis. A total of 28 studies were identified including 85,212 patients with 3385 serious ARs, resulting in an overall frequency of serious ARs in 4% of patients. Age, gender and number of drugs were by far the most frequently investigated risk factors. The total number of drugs was the most consistent correlated risk factor found in both univariate and multivariate analyses. The number of drugs is the most frequently documented independent patient-related risk factor for serious ARs in both the general adult population as well as in the elderly. The existing evidence is however conflicting due to heterogeneity of populations and study methods. The knowledge of patient-related risk factors for experiencing ARs could be used for electronic risk stratification of patients and thereby allocation of healthcare resources to high risk patients.


drug-related side effects and adverse reactions; medication errors; risk factors

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