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Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications Guidance for Industry Draft Guidance for Industry November 2020

GUIDANCE DOCUMENT

• Docket Number: FDA-2020-D-1794
• Issued by: Center 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.

 

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