Dexilant Vs. Protonix: What Is The Difference Between The Two PPIs?

In our latest question and answer, the pharmacist discusses whether or not there is a difference between two PPI drugs, Dexilant and Protonix.

Dexilant Vs. Protonix: What Is The Difference Between The Two PPIs?
Jan 19, 2020

Wally asked

My health plan is suggesting a switch from Dexilant to Protonix. Can you let me know if there is a difference between these two?

At a glance

  • Studies report that all PPIs have similar effectiveness.
  • Dexilant and Protonix are metabolized similarly and have no significant difference in number of drug interactions.
  • Dexilant and Protonix are both PPIs (proton pump inhibitors) and work the same way.
  • While Protonix is available generically, Dexilant is only available as a brand name drug. For most individuals, Dexilant will have a higher co-pay on their insurance plan when compared to pantroprazole (the generic for Protonix).
  • Studies have shown that there is no clinically signficant difference in effectiveness between PPI drugs.
  • Dexilant and Protonix have a similar side effect profile and number of drug interactions.
  • Dexlant can be taken with or without food while Protonix should be taken 30 to 60 minutes before food for maximum effectiveness.


Dexilant (dexlansoprazole) and Protonix (pantoprazole) are both PPIs (proton pump inhibitors) used to reduce stomach acid.

PPIs are most commonly taken to treat relatively simple stomach acid-related disorders, like heartburn, but are also used to treat more complicated matters such as peptic ulcer disease and GERD (gastroesophageal reflux disease).

While there are a few PPIs available over the counter, like Prilosec (omeprazole) and Nexium (esomeprazole), many are still only available via a prescription.

Now, based on your question, you health plan is suggesting the switch from Dexilant to Protonix due to the high cost of Dexilant. This is a good thing! They likely have a pharmacist or other medical provider looking at opportunities to save you (and them) some money by suggesting a cost-effective alternative that is equally effective than what you are already taking.

If you have the opportunity to discuss this recommended alternative with your health plan's pharmacist, I recommend doing so! They have your specific prescription data and plan information and are going to be your best resource here. They're also the drug information experts and can help answer any questions you have!

Generic Availability

Before we get into detail regarding the differences between Dexilant and Protonix (of which there aren't many), the most significant one is that while Protonix is available generically (as pantoprazole), Dexilant is not. It is only available as a brand name medication. This means that not only does the drug itself cost significantly more than pantoprazole, but your copay is likely higher.

While your copay structure will depend on your specific insurance plan, it isn't uncommon for brand name drugs to have a copay of $50 to $100 or more! Generics are almost always less expensive.

Side Effects

The side effect profiles of Dexilant and Protonix are essentially the same.

They are both well tolerated, with minor stomach disturbances being the most commonly reported (e.g. nausea, diarrhea). Other common side effects include:

  • Dizziness
  • Headache
  • Dry mouth
  • Headache
  • Abdominal pain

PPI drugs are well-known to have some potential problems if you take them for a long time (like increased risk of bone fractures) but that is a topic for another article. When used in the short-term, they are considered well-tolerated.


Taking Them

If there is one notable difference between Protonix and Dexilant, it is that Dexilant has a different release mechanism than Protonix. Due to this, there is a (small) but notable difference in recommendation of how to physically take them.

Protonix is a 'delayed-release' tablet and contains an enteric coating, allowing it to pass through the stomach intact (i.e. your stomach acid will not cause the tablet to dissolve). This reduces drug loss in the stomach and increases the total amount that gets absorbed.

In order for the delayed-releases tablets to be most effective, it is recommended to take Protonix 30 to 60 minutes before food, on an empty stomach.

Dexilant contains two different types of drug granules and has a 'dual release' mechanism. The first type of granule releases the drug within one hour of taking it while the second granule type release of medicine about 4-5 hours later. Studies have not shown that this has any therapeutic benefit. Even the Dexilant manufacturer website has the disclaimer:

The link between two releases and therapeutic benefit is not known.

I do want to point out that even though this release mechanism likely doesn't have any therapeutic benefit over other PPI drugs that don't use it, there is a slight advantage of using it. That advantage is that Dexilant can be taken without regard to food. If you take it with food, it will not decrease its effectiveness, the same of which can't be said for other PPI drugs.

  1. Protonix Prescribing Information. AccessFDA
  2. Dexilant Prescribing Information. AccessFDA
  3. Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid-related disorders. UpToDate (Subscription required)
  4. Comparative Effectiveness of Management Strategies For Gastroesophageal Reflux Disease. PubMed
  5. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. AJG

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