GUIDANCE DOCUMENT
Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications Guidance for Industry Draft Guidance for Industry November 2020
Not for implementation. Contains non-binding recommendations.
This guidance is being distributed for comment purposes only.
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All written comments should be identified with this document's docket number: FDA-2020-D-1794
- Docket Number:
- FDA-2020-D-1794
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Guidance Issuing OfficeCenter for Drug Evaluation and Research
Elevation of gastric pH by acid-reducing agents (ARAs) can affect the solubility and dissolution characteristics of orally administered drug products. As a result, concomitant administration of a drug with an ARA 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. ARAs such as antacids, histamine H2-receptor antagonists (H2 blockers), and proton pump inhibitors (PPIs) are widely used, and many of these drugs are available over the counter. , Consequently, there is an increased risk for clinically significant drug-drug interactions (DDIs) with concomitant administration of drugs with ARAs. Therefore, it is important to assess the susceptibility of an investigational drug to DDIs mediated by gastric-pH changes (referred to as pH-dependent DDIs) early in drug development, characterize the DDI effect with clinical studies when needed, and communicate the relevant findings in the drug product labeling.