An update on drug–drug interactions associated with proton pump inhibitors

ABSTRACT

Introduction

Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug–drug interactions have been described with PPIs, but all the described interactions do not have clinical significance.

Areas covered

This review will discuss the latest updates on drug–drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics.

Expert opinion

Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.

In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.

KEYWORDS:

• CYP2C19
• peptic ulcer
• gastroesophageal reflux
• Helicobacter
• antifungal
• antibiotics
• antiplatelet agents
• antidiabetics
• oncology drugs

Article highlights

• Numerous drug–drug interactions have been reported with PPIs, the most frequent mechanism being the increase in gastric pH, which alters the absorption and bioavailability of numerous treatments with pH-dependent solubility.

• Some formulations have been developed to prevent these gastric pH-dependent drug–drug interactions. Their efficacy should be further demonstrated large-scale comparative prospective studies.

• Another frequent mechanism is the competitive inhibition of cytochromes P450, notably CYP2C19 and CYP3A4

• Some PPIs, omeprazole, esomeprazole, and lansoprazole, have high CYP2C19 inhibitory potential. The others, pantoprazole, rabeprazole, and dexlansoprazole, have a low CYP2C19 inhibitory potential, and may be preferred according to the co-prescribed treatments.

• All described drug–drug interactions do not have significant clinical impact, but clinicians should be careful with the potentially clinically significant ones. They must also understand that because of the retrospective nature of most of the studies assessing clinical relevance, the level of evidence is quite low.

• According to the co-prescribed drugs, dose adjustment or therapeutic drug monitoring may be required.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.