Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications Guidance for Industry: Guidance for Industry

Description

FDA is announcing the availability of a guidance for industry entitled “Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications.” ARAs such as antacids, histamine H2-receptor antagonists, and proton pump inhibitors (PPIs) are widely used, and many of these drugs are available over-the-counter. Because ARAs can elevate the gastric pH, concomitant administration of a drug with an ARA could alter the solubility, dissolution, and bioavailability of the drug, potentially resulting in a loss of efficacy for weak-base drugs or increased toxicity for weak-acid drugs. Therefore, it is important to assess the susceptibility of an investigational drug to gastric pH change-mediated DDIs early in drug development, characterize the DDI effect with clinical studies when needed, and communicate the relevant findings in the drug product labeling. This guidance addresses when clinical DDI studies with ARAs should be conducted, the design and conduct of clinical pH-dependent DDI studies, alternative approaches for evaluating pH-dependent DDIs, and extrapolating clinical DDI study results among drug classes of ARAs.

Scope & Applicability

Regulatory Context

• 21CFR201.56§ 201.56 Requirements on content and format of labeling for human prescription drug and biological products.

  (a) General requirements. Prescription drug labeling described in § 201.100(d) must meet the following general requirements:Read full regulation →

• 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .

  The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →

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