5 Must-Know Omeprazole Drug Interactions

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.

Omeprazole Drug Interactions – Acid Suppression

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.

Enzyme Inducers

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.

Clopidogrel and Omeprazole

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).

Citalopram and Omeprazole

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.

Oral Iron Supplements and Omeprazole

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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  1. Cole

    For the Omeprazole+Clopidogrel interaction consider getting a P2Y12 platelet function assay to determine effectiveness of clopidogrel as there are alternative anti-platelet agents that don’t go through CYP2C19 pathway (e.g. ticagrelor).
    Appears to be less of a DDI with prasugrel vs clopidogel w/ concurrent omeprazole use (proceed with caution). And platelet function testing may be warranted regardless. Very important topic, thanks for sharing!

  2. Linda McMahan, RPh, BCGP

    Hey Eric,
    Along with the iron issue, I always thought that calcium required an acid environment also. Of course one could use calcium citrate, but I frequently see calcium carbonate or oyster shell (gasp!). As always thanks for sharing your knowledge.

  3. William Larson

    Hi Eric. I would include the rilpivirine and omperazole interaction. It’s highly significant because it results in lowered absorption of rilpivirine, which could lead to failure of ARV therapy and viral resistance.

    • Eric Christianson

      Thanks for sharing! Agree!


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Written By Eric Christianson

April 19, 2020

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