Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 1;7(7):e2419851.
doi: 10.1001/jamanetworkopen.2024.19851.

Agreement of Different Drug-Drug Interaction Checkers for Proton Pump Inhibitors

Massimo Carollo  1 , Salvatore Crisafulli  2 , Margherita Selleri  1 , Luca Piccoli  1 , Luca L'Abbate  1 , Gianluca Trifirò  1
Affiliations

Agreement of Different Drug-Drug Interaction Checkers for Proton Pump Inhibitors

Massimo Carollo et al. JAMA Netw Open. .

Abstract

Importance: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions.

Objective: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs.

Design, setting, and participants: This cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023.

Main outcomes and measures: The main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients.

Results: Considering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32).

Conclusions and relevance: This cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Trifirò reported serving on advisory boards and seminars funded by Sanofi, MSD, Eli Lilly and Co, Sobi, Celgene, Daichii Sankyo, Novo Nordisk, Gilead, and Amgen; serving as a scientific coordinator for INSPIRE srl, which has received funding from several pharmaceutical companies (eg, PTC Pharmaceuticals, Kiowa Kirin, Shonogi, Shire, Novo Nordisk, and Daichii Sankyo) for conducting observational studies; and consulting for Viatris in a legal case concerning an adverse reaction to sertraline outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Matrices Showing the Numbers of Drugs Listed as Potentially Interacting With Proton Pump Inhibitors by Each Interaction Checker (IC), Stratified by Proton Pump Inhibitor
Figure 2.
Figure 2.. Severity Category Distribution by Interaction Checker (IC) of the 5 Proton Pump Inhibitors Under Study
See this image and copyright information in PMC

Comment in

References

    1. Heidelbaugh JJ, Inadomi JM. Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients. Am J Gastroenterol. 2006;101(10):2200-2205. doi:10.1111/j.1572-0241.2006.00839.x - DOI - PubMed
    1. Dharmarajan TS. The use and misuse of proton pump inhibitors: an opportunity for deprescribing. J Am Med Dir Assoc. 2021;22(1):15-22. doi:10.1016/j.jamda.2020.09.046 - DOI - PubMed
    1. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014;37(4):201-211. doi:10.1007/s40264-014-0144-0 - DOI - PMC - PubMed
    1. Ben Ghezala I, Luu M, Bardou M. An update on drug-drug interactions associated with proton pump inhibitors. Expert Opin Drug Metab Toxicol. 2022;18(5):337-346. doi:10.1080/17425255.2022.2098107 - DOI - PubMed
    1. Fossmark R, Martinsen TC, Waldum HL. Adverse effects of proton pump inhibitors-evidence and plausibility. Int J Mol Sci. 2019;20(20):5203. doi:10.3390/ijms20205203 - DOI - PMC - PubMed