Omeprazole is one of the most commonly used medications for heartburn and other GI conditions. In addition to being very commonly prescribed, it is available over-the-counter which allows for widespread use throughout the public without much supervision at times. That lack of oversight may lead to an increased risk for clinically significant drug interactions. Here are my top 5 omeprazole drug interactions that I’ve seen in clinical practice.


There are a few medications that require an acidic environment in the stomach for absorption. Oral cefuroxime and the HIV medication atazanavir are two examples that can have their absorption reduced. This can potentially lead to subtherapeutic concentrations and treatment failure.


While I readily acknowledge that enzyme inducers aren’t used all that often, we must remember that the beneficial effects of omeprazole 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 reduce the concentration of omeprazole. 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. PPIs are often overutilized so assessing continued need is important and may allow us to avoid this interaction.


This interaction depends upon who you talk to and which study you look at. It is plausible that omeprazole 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 and they have been on them for a long time, I usually leave it alone if the omeprazole is at the minimum effective dose. Dose reductions and trial discontinuation may be considered in patients with less severe GI symptoms (i.e. dyspepsia).


QTc prolongation is a risk and this risk may increase with rising citalopram concentrations. Omeprazole can inhibit CYP2C19 and potentially increase citalopram levels. I discuss clinical options in this previous post.


While the significance of this interaction is generally not catastrophic, it should be considered. Omeprazole 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. Looking at the need for omeprazole is an important consideration. Using a more absorbable form of iron or adding a vitamin C supplement are considerations.

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