Which Acid-Reducing Drugs Are Safe With Plavix?

Answer

Thanks so much for reaching out to us! Your question touches on a classic drug-drug interaction that essentially all pharmacists and pharmacy students alike are taught to look out for, and that is the interaction between Plavix (clopidogrel) and PPIs, proton pump inhibitors, like Prilosec (omeprazole).

I just want to give you a little background on the interaction.

Why Proton Pump Inhibitors Interact With Plavix

Plavix is a prodrug, meaning that it is converted in our system to the active form of the drug as it is metabolized. In other words, the drug does not work until our body metabolizes it.

The metabolism of Plavix happens via several different liver enzymes, but it is predominately metabolized by CYP2C19.

Proton pump inhibitors, especially Prilosec, can inhibit CYP2C19.

This inhibition of CYP2C19 means that Plavix can't be changed to its active form, and therefore, may not be effective. This would put whoever is taking the drug at serious risk since it wouldn't be having the intended clinical effect.

The prescribing information for Plavix specifically warns about this interaction:

The metabolism of clopidogrel can also be impaired by drugs that inhibit CYP2C19, such as omeprazole [Prilosec] or esomeprazole [Nexium]. Avoid concomitant use of Plavix with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of Plavix.

Now, I think it is important to point out that there is some data to suggest that the interaction between PPIs (even omeprazole) and Plavix is not clinically significant.

For example, in one large study published in the New England Journal of Medicine, 3761 patients being treated with clopidogrel were assigned to either omeprazole or placebo (i.e., no PPI). The study found that there was no significant difference in cardiovascular events and there was a lower rate of gastrointestinal bleeding episodes in patients assigned to omeprazole. It concluded:

Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI.

Nevertheless, this study had some limitations, which is why it does not rule out the potential of a clinically significant interaction.

Alternative Acid-Reducer Drug Options

So, getting into what you asked about, you do have some options if your doctor doesn't want you taking Prilosec or Nexium due to the interaction I talked about above. Your options include:

• Switch to another PPI (proton pump inhibitor) that is less likely to interact with Plavix.
• Switch to a combination of fast-acting acid neutralizers (e.g., Tums) and an H2-blocker (e.g., Pepcid).

Let's start with alternative PPIs.

Most literature suggests that two PPIs are the most likely to interact with Plavix due to their strong CYP2C19 inhibition and those are the two you mentioned in your question (Prilosec and Nexium).

There are other PPI options that inhibit CYP2C19 to a far lesser degree, or not at all. These options include:

• Protonix (pantoprazole)
• Aciphex (rabeprazole)
• Prevacid (lansoprazole)
• Dexilant (deslansoprazole)

Protonix is known as a weak inhibitor of CYP2C19, while Prevacid, Dexilant, and Aciphex are not thought to inhibit CYP2C19 to a clinically significant degree.

If you want to try an alternative PPI to Prilosec or Nexium, since they tend to be the most effective at treating acid-related gastrointestinal symptoms, your best options, being on Plavix, are Prevacid, Dexilant and Aciphex. They are the least likely to cause an interaction.

Moving on to your other options, you could also try using both a fast-acting acid-neutralizing medication, like Tums or Rolaids, for immediate relief, and use an H2-blocker, like Pepcid (famotidine) or Zantac (ranitidine) twice a day, consistently.

H2-blockers are effective medications to help reduce acid-related conditions, like GERD (gastroesophageal reflux disease), they just don't tend to be as effective as PPIs. Adding on a medication like Tums if your symptoms are particularly bad, can help as well.

You mentioned that you have tried Pepcid, but don't mention how you were taking it. Taking it twice a day, alongside an acid-neutralizer, may be more effective compared to how you have been taking it.

Final Words

I highly recommend talking to your doctor about your options.

You may be able to continue on another PPI drug if your symptoms are particularly bad, and, as I wrote about above, there are options that are not thought to interact with Plavix. Otherwise, an H2-blocker is probably your best bet.

I hope you found this helpful, and please, reach out again if anything comes up!