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FDA Seeks Input on pH-Dependent Drug-Drug Interactions

Posted 21 May 2018 | By Michael Mezher 

FDA Seeks Input on pH-Dependent Drug-Drug Interactions

Following the release of two draft guidances on enzyme- and transporter-based drug-drug interactions (DDIs) last year, the US Food and Drug Administration (FDA) is asking for input on developing new guidance on assessing pH-dependent DDIs.

Those guidances, Clinical Drug Interaction Studies – Study Design, Data Analysis, and Clinical Implications and In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies were developed to aid drugmakers when evaluating investigational products for DDIs.

However, FDA says those guidances do not provide a framework or recommendations for assessing DDIs caused by drug-induced changes in gastric pH.

“For a drug whose solubility is pH-dependent, concomitant administration with an [acid-reducing agent] ARA may affect its absorption and systemic exposure, potentially resulting in loss of efficacy or, in some cases, increased toxicity,” FDA writes.

FDA says this is of particular concern due to the widespread use and over-the-counter availability of drugs such as antacids, histamine H2-receptor antagonists (H2 blockers) and proton pump inhibitors.

As such, FDA is calling for input from the public on a range of questions related to ph-dependent DDIs.n

In particular, FDA is asking what are the characteristics of drugs that are susceptible to pH-dependent DDIs, and whether a stepwise approach can be used to evaluate interaction potential.

FDA is also asking for input on different approaches to evaluating DDIs when it comes to pH-dependent DDIs, study design considerations and whether the findings from a clinical study looking at one ARA drug can be extrapolated for other ARAs in the same or in a different class.

Federal Register Notice

Categories: Regulatory News

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