A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug–Drug Interactions with Orally Administered Medications

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Abstract

Background and Objective

Several review articles have been published discussing gastric acid-related drug–drug interactions (DDIs) mediated by coadministration of antacids, histamine H ₂ receptor antagonists, or proton pump inhibitors, but are not sufficiently comprehensive in capturing all documented DDIs with acid-reducing agents (ARAs) and tend to focus on gastric pH-dependent DDIs and/or basic drugs. Subsequently, several new drugs have been approved, and new information is available in the literature. The objective of this systematic review is to comprehensively identify oral medications that have clinically meaningful DDIs, including loss of efficacy or adverse effects, with gastric ARAs, and categorize these medications according to mechanism of interaction.

Methods

An indepth search of clinical data in the PDR3D: Reed Tech Navigator™ for Drug Labels, University of Washington Drug–Drug Interaction Database, DailyMed, Drugs@FDA.gov, and UpToDate ^®/Lexicomp ^® Drug and Drug Interaction screening tool was conducted from 1 June to 1 August 2018. The PDR3D, University of Washington Drug–Drug Interaction Database, and DailyMed were searched with terms associated with gastric acid and ARAs. Conflicting findings were further investigated using the UpToDate ^®/Lexicomp ^® screening tool. Clinical relevance was assessed on whether an intervention was needed, and prescribing information and/or literature supporting the DDI.

Results

Through the search strategy, 121 medications were found to clinically meaningfully interact with ARAs. For 38 medications the mechanism of interaction with ARAs was identified as gastric pH dependent, and for 83 medications the interaction was found to be not gastric pH mediated, with mechanisms involving metabolic enzymes, transporters, chelation, and urine alkalization. Additionally, 109 medications were studied and did not have a clinically meaningful interaction with ARAs.

Conclusion

This review may provide a resource to healthcare professionals in aiding the care of patients by increasing awareness of interactions with ARAs and may also identify and potentially aid in avoiding clinically relevant DDIs and preventing risk of treatment failure and/or adverse effects. Advances in non-clinical predictions of gastric pH-mediated DDIs may guide the need for a future clinical evaluation.

Electronic supplementary material

The online version of this article (10.1007/s40262-019-00844-3) contains supplementary material, which is available to authorized users.

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Most cited references 35

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Author and article information

Contributors

Mats Någård: mats.nagard@astrazeneca.com

Journal

Journal ID (nlm-ta): Clin Pharmacokinet

Journal ID (iso-abbrev): Clin Pharmacokinet

Title: Clinical Pharmacokinetics

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0312-5963

ISSN (Electronic): 1179-1926

Publication date (Electronic): 2 December 2019

Publication date PMC-release: 2 December 2019

Publication date (Print): 2020

Volume: 59

Issue: 4

Pages: 447-462

Affiliations

[1 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, University of Pittsburgh School of Pharmacy, ; 37 S. New York Rd, Galloway, NJ 08205 USA

[2 ]GRID grid.418152.b, Quantitative Clinical Pharmacology, Early Clinical Development, Innovative Medicines (IMed) Biotech Unit, , AstraZeneca LP, ; One MedImmune Way, Gaithersburg, MD 20878 USA

Article

Publisher ID: 844

DOI: 10.1007/s40262-019-00844-3

PMC ID: 7109143

PubMed ID: 31788764

SO-VID: e972433c-fbde-4d0c-a21d-9bc730bd0ccc

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Funding

Funded by: FundRef http://dx.doi.org/10.13039/100004325, AstraZeneca;

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A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug–Drug Interactions with Orally Administered Medications

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Abstract

Background and Objective

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Results

Conclusion

Electronic supplementary material

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Most cited references 35

Membrane transporters in drug development.

Polypharmacy in elderly patients.

Intraluminal pH of the human gastrointestinal tract.

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Cited by 26

Most referenced authors 1,048