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

ABSTRACT

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 four- and two-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 DDI datasets and to conduct real-world studies to generate evidence regarding the frequency and clinical relevance of potential DOAC-related DDIs.

KEYWORDS:

• Direct-acting oral anticoagulants
• drug–drug interactions
• interaction checkers
• summary of product characteristics
• Gwet’s AC1

Declaration of interests

G Trifirò has served, over the last 3 years, on advisory boards/seminars funded by Sanofi, MSD, Eli Lilly, Sobi, Celgene, Daichii Sankyo, Novo Nordisk, Gilead, and Amgen; he is also a scientific coordinator of the academic spin-off ‘INSPIRE srl,’ which has received funding from several pharmaceutical companies (i.e. PTC Pharmaceuticals, Kiowa Kirin, Shonogi, Shire, Novo Nordisk, and Daichii Sankyo) for conducting observational studies. Additionally, he is currently a consultant for Viatris in a legal case concerning an adverse reaction to sertraline. None of these listed activities are related to the topic of the article.

The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethical approval

Ethical approval was not required for this type of study as it did not involve human or animal subjects.

Author contributions

M Carollo: Data extraction, statistical analysis, writing the original draft, and interpretation of data.

S Crisafulli: Data extraction, writing the original draft, and interpretation of data, with a significant methodological contribution.

F Ciccimarra: Data extraction, writing the original draft, and interpretation of data.

G Andò: Critical revision of the manuscript.

I Diemberger: Critical revision of the manuscript.

G Trifirò: Conception and design of the study, interpretation of data, and supervision.

All authors contributed to and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2024.2322134

Additional information

Funding

This paper was not funded.