Heterogeneity Observed in Reporting on Drug-Drug Interactions With Proton Pump Inhibitors

In a cross-sectional study, there was large heterogeneity of interaction checkers (ICs) and summary of product characteristics (SPCs) in reporting information related to potential drug-drug interactions (DDIs) with proton pump inhibitors (PPIs), according to results published in JAMA Network Open.¹

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PPIs are a commonly prescribed class of drugs. They are used to prevent nonsteroidal and anti-inflammatory drug (NSAID)-induced ulcers, as well as the treatment of acid-related disorders.¹

The wide range of indications for which PPIs are prescribed can lead to adverse outcomes for patients with long-term use. Previous literature has described the significant increase in use of PPIs for “ill-defined indications,” and deemed that educating providers and patients regarding best practices “may be the rational approach to safe and effective PPI therapy.”²

These adverse effects (AEs) include an increased risk of fractures, susceptibility to severe infections, and the reduced effectiveness of co-administered medications. The risk of these drug-related AEs increases for older patients, who are more likely to receive polypharmacy and be affected by multimorbidity, according to the investigators.¹

Given these risks, clinicians must have access to reliable information about interacting drugs, especially in at-risk populations. SPCs and ICs, online databases for health care professionals, are supposed to be consistent and accurate resources—yet their reliability has been found to waver greatly depending on the source of information.¹

This study aimed to assess the agreeability among 5 different ICs open to health care professionals for identifying medicines at interaction risk for omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, as well as classifying the severity of PPI-related DDIs. In addition, the investigators sought to analyze how consistent the information reported by each IC was with the PPIs’ SPCs.¹

Three subscription drug ICs and 2 open-access drug ICs were utilized for the study and were labeled ICs 1-5. SPCs of all the PPIs under investigation were found from the official websites of the European Medicines Agency and the FDA; each SPC contained a section concerning DDIs. The investigators standardized the severity groups for potential DDIs into severe, moderate, minor, and unknown.¹

There was a total of 518 potentially interacting drugs reported with omeprazole, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. The IC that reported the largest number of potential DDIs for all PPIs was IC 1, which identified more than 55% of the total potentially interacting drugs by all ICs.¹

Only a small proportion of the total number of drugs reported as interacting with PPIs was identified simultaneously by all 5 ICs assessed, according to the study authors. Particularly, all ICs recognized only 31 medications, which was 6.0% of the total identified.¹

SPCs reported a smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% for rabeprazole and 7.6% for lansoprazole of the total identified drugs at risk of interaction with PPI. There were also substantial differences between ICs observed regarding the severity of DDIs.¹

The overall level of agreement among the 5 ICs for identifying potentially interacting drugs was poor, and the level of agreement among these in categorizing the severity of potential DDIs was moderate.¹

Heterogeneity among the ICs were attributed to several factors, including the different sources that the ICs draw upon, the differences in the algorithms used to detect interactions, and the frequency that databases are updated with current information.¹

Although the study authors noted that IC 1 consistently reported the highest number of potential DDIs, they discussed that, despite an increased frequency of identified potential DDIs, this does not imply greater reliability or clinical relevance.¹

The results of this study indicate that there is “a need for improved harmonization between different drug information, especially concerning DDIs.”¹ This is especially important in the wake of studies reporting the negative effects that PPIs have on drugs such as palbociclib in patients with breast cancer.³

In that study, the authors “cautioned physicians who prescribe PPIs to patients treated with palbociclib,” and that “they should be advised about the risks of interaction to prevent risks for adverse outcomes.”³

The authors of the current study recommended that future efforts to ensure the reliability and consistency of ICs and SPCs center on improving the algorithms for DDI detection, ensure timely updates of ICs and SPCs, standardizing DDI databases. Additionally, they discuss the need for collaboration among key stakeholders, such as regulatory agencies and healthcare professionals.¹

“To evaluate and prevent clinically relevant DDIs, it is recommended to explore multiple ICs and SPCs as well as to consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions,” the study authors concluded.¹

References

1. Carollo M, Crisafulli S, Selleri M, et al. Agreement of different drug-drug interaction checkers for proton pump inhibitors. JAMA Netw Open. 2024;7(7):e2419851. doi:10.1001/jamanetworkopen.2024.19851

2. Dharmarajan T S. The use and misuse of proton pump inhibitors: an opportunity for deprescribing. Journ Ameri Med Direct Assoc. 2021;22(1):15-22. doi:10.1016/j.amda.2020.09.046

3. Gallagher A. Study: proton pump inhibitor use negatively affects therapeutic benefits of palbociclib for breast cancer. Pharmacy Times. July 26, 2023. Accessed July 12, 2024. https://www.pharmacytimes.com/view/study-proton-pump-inhibitor-use-negatively-affects-therapeutic-benefits-of-palbociclib-for-breast-cancer