Can You Take Plavix And Omeprazole Together?

Hello and thank you for your question!

The interaction between Plavix (clopidogrel), an antiplatelet drug and omeprazole, a proton pump inhibitor, is one of the more well-known interactions to clinicians.

While we appear to not fully understand the complete mechanism behind the interaction, numerous studies have shown that taking Plavix and omeprazole together reduces the effectiveness of Plavix. In other words, omeprazole can reduce the antiplatelet effect of Plavix and increase the risk for cardiovascular events.

Therefore, in most cases, these two drugs should be avoided and if Plavix is necessary, an alternative proton pump inhibitor or acid-reducing medication should be considered. Simply separating their administration (e.g. taking Plavix first, then omeprazole 12 hours later) doesn't seem to avoid the interaction.

How Does The Interaction Work?

Plavix is a prodrug, meaning that it must be metabolized in the body to its active form. It is inactive until it is transformed. In most cases, a liver enzyme is what transforms a prodrug, like Plavix, to its active form.

The enzyme CYP2C19 is the predominant liver enzyme that converts/transforms Plavix. Once transformed, it is then active, and starts producing its clinical effect, binding to platelet receptors, inhibiting platelet aggregation.

Omeprazole can inhibit the liver enzyme CYP2C19. If this enzyme is inhibited, Plavix cannot be transformed to its active form (remember, it is a prodrug) and therefore, will not work to inhibit platelet aggregation.

What Do The Studies Say?

There have been many, many studies looking into the potential interaction between Plavix and omeprazole (and PPI drugs in general). Most have shown that there is a clinically significant interaction, with a real world impact.

One such study found a statistically significant increase in the rate of heart attacks (i.e. myocardial infarctions) in those taking PPIs (with the exception of one specific one, pantoprazole) and Plavix together. It concluded:

Among patients receiving clopidogrel [Plavix] following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.

Another study found similar results, that taking Plavix and a PPI together (most individuals in the study took omeprazole), increased the risk of complications and hospital readmission. It concluded:

Concomitant use of clopidogrel [Plavix] and PPI after hospital discharge for ACS [acute coronary syndrome] was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.

There are countless other studies and clinical articles to go through, but the overwhelming majority have found a significant interaction between Plavix and omeprazole.

What Is Recommended?

The evidence for the interaction is so overwhelming, the FDA published labeling changes in the prescribing information for Plavix warning against taking it with omeprazole:

Omeprazole, a moderate CYP2C19 inhibitor, reduces the pharmacological activity of Plavix. Avoid using omeprazole concomitantly or 12 hours apart with Plavix. Consider using another acid-reducing agent with less CYP2C19 inhibitory activity

If possible, it is recommended to avoid taking Plavix and omeprazole together. If a PPI (proton pump inhibitor) must be used, Protonix (pantoprazole) seems to be the least likely to cause a significant interaction (a study published in the American Heart Journal discusses this).

Other acid-reducing medications, like H2 blockers (e.g. Pepcid and Zantac) may be better choices still.

Now, in your question, you specifically asked about separating administration of Plavix and omeprazole to different times in the day. Unfortunately, it doesn't appear as though this technique will avoid the interaction.

The inhibition of the liver enzyme CYP2C19 by omeprazole seems to last a considerable amount of time...more than 12 hours at least.

Studies have specifically looked at this and the general conclusion is that omeprazole reduces the activity of the antiplatelet effects of Plavix, regardless of administration timing. This probably means that the activity of CYP2C19 is reduced for more than 24 hours after taking omeprazole.

Therefore, your best bet would be to avoid being on both meds, and use an alternative acid-suppression medication.

Thanks again for your question!