Top 5 CYP2C19 Drug Interactions

CYP2C19 Drug Interactions

Here’s a list of some of the most common CYP2C19 drug interactions that I have seen in clinical practice.

Citalopram and Omeprazole Interaction

Omeprazole can significantly increase the concentration of citalopram. Because of this drug interaction, there is a greater risk for citalopram toxicity and QTc prolongation. Omeprazole inhibits CYP2C19 which is an important breakdown pathway for citalopram.

In addition, the close relative to citalopram, escitalopram can have its concentrations increased by the omeprazole inhibition of CYP2C19. Here’s more info on that specific interaction.

Clopidogrel and Omeprazole Interaction

This interaction is caused by the same CYP2C19 inhibition that causes the citalopram interaction. However, the (possible) clinical outcome is different. Because clopidogrel is a prodrug, it needs to be activated by CYP2C19. Without CYP2C19 activity, the drug does not have its platelet inhibitory activity. The clinical risk is that inadequate concentrations of the active metabolite of clopidogrel could lead to an increased risk of heart attack or stroke. The debate about the clinical significance of this interaction is still ongoing, but in my opinion, it would be safest to avoid it if possible.


Similar to the citalopram interaction, cilostazol’s concentrations can be increased by CYP2C19 inhibition. Cilostazol is occasionally used in the setting of intermittent claudication due to peripheral arterial disease.

Enzyme Inducers

Enzyme inducers like St. Johns Wort and rifampin have the potential to increase the metabolism of omeprazole by inducing CYP2C19 which ultimately leads to lower concentrations and the risk for treatment failure. St Johns Wort and rifampin are seldom used in clinical practice, but if you ever see orders for these agents, you must pay attention to the risk for drug interactions.

Diazepam and CYP2C19 Inhibitors

A drug like omeprazole inhibits CYP2C19. I wouldn’t call this a clinically earth-shattering interaction, but diazepam is broken down by CYP2C19 to a certain extent. The possibility exists that omeprazole could increase the concentrations of diazepam. In my practice, I have not personally seen this issue, but the potential exists.

I talk more about CYP2C19 drug interactions and the overall pharmacology of omeprazole in this episode of my podcast Real Life Pharmacology.

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Written By Eric Christianson

February 7, 2021

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