How Acid-Reducing Drugs Like PPIs Interfere With Your Medications — And the FDA’s Stance

 If you’ve ever taken a proton pump inhibitor (PPI) for heartburn or acid reflux, you’re in good company. These acid-reducing medications are widely used and available over the counter. But here’s something you might not know: they can alter how your body absorbs other drugs—and the FDA is taking notice. 

Why this Matters 

PPIs and other acid-reducing agents (ARAs) work by decreasing stomach acidity. While that’s great for soothing heartburn, it can backfire for other medications. A less acidic stomach environment may: 

• Reduce absorption of some drugs, making them less effective.
• Increase absorption of others, raising the risk of side effects.

Beyond pH changes, PPIs like omeprazole can also influence liver enzymes and drug transporters, further affecting how medications are metabolized and eliminated. 

The FDA’s New Guidance

In March 2023, the FDA issued updated recommendations: Drug developers must now assess potential interactions between new oral medications and acid-reducing drugs early in the process, providing the legal framework to ensure that any acid-mediated drug-drug interactions (DDIs) are well-characterized and clearly reflected in labeling. 

What Our Analysis Revealed

We examined all FDA-approved oral drugs from 2021, 2023, and the first eight months of 2024. Key takeaways included: 

• 56 of 134 new approvals were oral medications.
• About half had been evaluated for ARA interactions.
• Evaluation methods ranged from clinical DDI studies to in vitro assays and predictive modeling.
• A few products were approved with post-marketing commitments, indicating ongoing investigation into potential interactions.

Revealed No Single Approach, But a Clear Priority 

There’s no standardized approach for assessing ARA interactions. Some sponsors conducted dedicated clinical trials; others leveraged modeling or integrated findings from broader clinical studies. In some cases, no additional testing was needed when absorption was shown to be pH-independent. 

What’s clear: accounting for these interactions is now a regulatory expectation, especially for drugs where bioavailability is a critical factor. 

Want the Full Breakdown? We shared these findings at the ASCPT 2025 Annual Meeting in our poster presentation — and it’s available for download if you’re curious to dive deeper into the data and methodology. 

Written By:

Sunny Le 

Director, Pharmacokinetics

BioPharma Services, Inc., a HEALWELL AI and clinical trial services company, is a full-service Contract Clinical Research Organization (CRO) based in Toronto, Canada, specializing in Phase 1 clinical trials 1/2a, Human Abuse Liability(HAL) and Bioequivalence clinical trials for international pharmaceutical companies worldwide. BioPharma Services conducts clinical research operations from its Canadian facility, with access to healthy volunteers and special populations.