What To Know About Plavix (Clopidogrel) and Its Interactions With Proton Pump Inhibitors (PPIs)

Plavix (clopidogrel) is an antiplatelet medication (a type of blood thinner) that is used to prevent certain types of blood clots. If blood clots happen, then they can lead to serious events such as a heart attack or stroke. While Plavix can help prevent these life-threatening problems, it can also cause some problematic side effects, including stomach bleeding.

To help prevent stomach bleeding while on Plavix, many providers will recommend people also take a proton pump inhibitor (PPI). Some PPIs are available over-the-counter, and others require a prescription. Some examples of PPIs include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), and pantoprazole (Protonix).

Unfortunately, PPIs can make Plavix less effective, potentially raising your risk of having a heart attack or stroke. Thankfully, this drug interaction is less likely to happen with certain PPIs and can be avoided. But it’s essential to know which of these stomach-protecting medications are safer to take with Plavix.

Here, we’ll discuss how PPIs interact with Plavix, which ones are safer options, and if other alternatives are available.

What happens when a PPI does interact with Plavix?

For Plavix (clopidogrel) to work properly in the body, it requires a special protein, or enzyme, called CYP2C19 to help the body digest and use it. PPIs, on the other hand, can stop this enzyme from working. If this happens, the CYP2C19 protein won’t be available to digest the Plavix, meaning it won’t work as well.

It’s important to note that this interaction hasn’t been well-studied. Experts worry that not taking PPIs to avoid the interaction could raise the risk of life-threatening stomach bleeding caused by Plavix. Because research is lacking, the American Heart Association (AHA) and American College of Cardiology (ACC) do not offer recommendations about taking PPIs with Plavix. They state this decision should be individualized and based on a person’s risks and medical history.

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Do all PPIs interact with Plavix?

There are six PPIs currently available in the U.S. While all of them carry this warning, the interaction with Plavix is worse with some PPIs than others. Omeprazole (Prilosec) and esomeprazole (Nexium) block more CYP2C19 than others in this medication class, meaning they would be the most likely to stop Plavix from working.

So, which PPIs are safe to use with Plavix?

Currently, the manufacturer of Plavix recommends using pantoprazole (Protonix), lansoprazole (Prevacid), or Dexilant (dexlansoprazole). In their research, these three PPIs had the least effect on the effectiveness of Plavix. Other studies have also suggested rabeprazole (Aciphex) is a safe option to consider. Although lansoprazole is available over-the-counter, it is best to discuss the benefits and risks of each with your provider before purchasing anything on your own.

What can I take instead of a PPI?

If you are taking a PPI along with Plavix to prevent stomach bleeding, it’s best to discuss alternatives with your provider. PPIs are more effective than other types of medications at protecting your stomach.

If you are only using PPIs to treat heartburn or acid reflux, there are some alternatives you could consider. One possible option is to switch to famotidine (Pepcid). Famotidine belongs to a class of medications called histamine-2 antagonists (H2 blockers) and doesn’t interact with Plavix. While it works differently than PPIs, they both work well for relieving and preventing heartburn. 

Other over-the-counter reflux options include antacids, such as Alka-Seltzer, Maalox, Mylanta, Rolaids, and Tums. However, antacids do not last very long, have to be taken multiple times a day, and cannot be used to prevent heartburn. It’s also important to note that they do not work to help protect against stomach bleeding.

Be sure to discuss these potential heartburn alternatives with your provider before making the switch on your own. As discussed earlier, stomach bleeding is a possible side effect of Plavix and can be dangerous. Changing to another stomach medication without your provider’s OK could raise your risk of this complication.

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Written by:

Sonia Amin Thomas, PharmD, BCOP

Sonia Amin Thomas, PharmD, BCOP, has been practicing as a clinical pharmacist for 12 years and in oncology pharmacy for over 10 years. She practices both academic and clinical pharmacy and is board certified as an oncology pharmacist and integrative health coach.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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