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Updated: Jul 18, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Comparative assessment of four drug interaction compendia
1Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, University of South Australia, GPO Box 2471, Adelaide SA 5001, Australia. agnes.vitry@unisa.edu.au
Aims:
To assess the consistency of inclusion and grading of major drug interactions for 50 drugs in four leading international drug interaction compendia. METHODS Four international drug interaction compendia were compared: the drug interactions appendix of the British National Formulary, the interaction supplement in the French drug compendium Vidal, and two US drug interaction compendia, Drug Interaction Facts and the Micromedex (Drug-Reax) program. Major interactions were defined as potentially hazardous in BNF or with the warning 'contraindication' or 'avoid' in Vidal or with the significance grading 1 or 2 in DIF. Major interactions for a list of 50 drugs were searched in all four compendia.
Results:
A total of 1264 interactions meeting the inclusion criteria were identified for these 50 drugs. After deletion of 169 duplicates, 1095 interactions were included in the analysis. Of the drug interactions classified as major in any one compendium between 14% and 44% were not listed in the other compendia. The grading systems used for the severity and the quality of the supporting evidence in Micromedex and DIF were inconsistent.
Conclusions:
There is a lack of consistency in the inclusion and grading of drug interactions of major significance for 50 drugs across the four drug compendia examined. This may reflect the lack of standardization of the terminology used to classify drug interactions and the lack of good epidemiological evidence on which to base the assessment of the clinical relevance of drug interactions.
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