Exploring the level of agreement among different drug-drug interaction checkers: a comparative study on direct oral anticoagulants

Background: Direct oral anticoagulants (DOACs) may be involved in drug-drug interactions (DDIs) potentially increasing the risk of adverse drug reactions. This study aimed to evaluate the level of agreement among interaction checkers (ICs) and DOACs' summary of product characteristics (SPCs), in listing DDIs and in attributing DDIs' severity. Research design and methods: The level of agreement among five ICs (i.e. INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com) in identifying potential DDIs and in attributing severity categories was evaluated using Gwet's AC1 on all five ICs and by comparing groups of 4- and 2-pair sets of ICs. Results: A total of 486 potentially interacting drugs with dabigatran, 556 for apixaban, 444 for edoxaban, and 561 for rivaroxaban were reported. The level of agreement among the ICs in identifying potential DDIs was poor (range: 0.12-0.16). Similarly, it was low in 4 and 2-sets analyses. The level of agreement among the ICs in classifying the severity of potential DDIs was poor (range: 0.32-0.34), also in 4 and 2-sets analyses. Conclusions: The heterogeneity among different ICs and SPCs underscores the need to standardize DDIs datasets and to conduct real-world studies to generate evidence regarding the frequency and clinical relevance of potential DOACs-related DDIs.