Author: [AUTHOR] Published on 3/17/2023 6:00:00 AM
FDA Announces Availability of a Final Guidance on pH-Dependent Drug Interactions
On March 13, 2023, the FDA announced the availability of a final guidance for industry entitled
Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications, replacing the December 2020 draft guidance. This guidance describes the FDA’s recommendations regarding: (1) when clinical drug-drug interactions with acid-reducing agents are needed; (2) the design of such clinical drug-drug interaction studies; (3) how to interpret the study results; and (4) communicating findings in drug product labeling.
Elevation of gastric pH by acid-reducing agents can affect the solubility and dissolution characteristics of some orally administered drugs. As a result, concomitant administration of a drug with an acid-reducing agent could alter the bioavailability of the drug, potentially resulting in a loss of efficacy for weak-base drugs or increased adverse events for weak-acid drugs. Acid-reducing agents such as antacids, histamine H2-receptor antagonists, and proton pump inhibitors are widely used, and these drugs are available through prescription and also over the counter. Consequently, there is a potential risk for clinically significant drug-drug interactions with concomitant administration of drugs with acid-reducing agents. It is important to assess the susceptibility of an investigational drug to drug-drug interactions mediated by gastric-pH changes early in drug development, characterize the drug interaction effect with clinical studies when needed, and communicate the relevant findings and mitigation options where available in the drug product labeling.
The “Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications” guidance is available at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-gastric-ph-dependent-drug-interactions-acid-reducing-agents-study-design-data-analysis. Please refer to the final guidance for more details.
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.