Proton Pump Inhibitors are one of the most commonly used medication classes for GERD and other gastrointestinal disorders. While they don’t have a ton of significant drug interactions, there are some important ones that you should know. I outline my top 5 PPI drug interactions you should pay attention to.
Acid Suppression
There are a few medications that require an acidic environment in the stomach for absorption. PPIs cause a rise in pH and help lower GI acidity. Oral cefuroxime (podcast), the HIV medication atazanavir, ketoconazole, and erlotinib (oncology agent) are examples of medications that can have their absorption reduced when the pH of the gut rises. This can potentially lead to subtherapeutic concentrations and treatment failure.
Clopidogrel
This interaction depends upon who you talk to and which study you look at. It is plausible that omeprazole and esomeprazole can reduce the effectiveness of clopidogrel. My best advice is to ensure that both medications are truly necessary. If a patient has a solid indication for both medications and they have been on them for a long time, I usually leave it alone if the PPI is at the minimum effective dose. Alternatively, we could consider switching esomeprazole or omeprazole to pantoprazole or rabeprazole to help reduce the drug interaction potential.
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Enzyme Inducers
While I readily acknowledge that enzyme inducers aren’t used all that often, we must remember that the beneficial effects of many PPIs can be stifled by the use of these types of medications. Rifampin and St John’s Wort are two of the most notorious enzyme inducers that can cause PPI drug interactions. These medications can reduce the concentration of commonly used omeprazole and esomeprazole. In most cases, we will attempt to avoid the use of rifampin and St John’s Wort rather than discontinue a PPI that may be necessary. Alternatively, pantoprazole is less likely to be affected by rifampin. PPIs are often overutilized so assessing continued need is important and may also allow us to avoid this interaction.
Citalopram and CYP2C19
QTc prolongation is a risk and this risk may increase with rising citalopram concentrations. Omeprazole and esomeprazole can inhibit CYP2C19 and potentially increase citalopram levels (great board exam question). Alternatively, pantoprazole and rabeprazole avoid inhibiting CYP2C19 and would be less likely to interact with citalopram.
Oral Iron Supplements and PPIs
While the significance of this interaction is generally not catastrophic, it should be considered. All PPIs may reduce the absorption of oral iron supplements. We can monitor this by checking iron labs (such as ferritin) as well as a CBC. If iron stores are not rising and hemoglobin is not improving (in iron deficiency anemia), we should take a look and see if acid-suppressing therapy might be contributing to a lack of absorption. Using a more absorbable form of iron or adding a vitamin C supplement are considerations.
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