A Comparison of Common Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are used to treat gastroesophageal reflux disease (GERD) and other conditions. Common PPIs include:

• AcipHex (rabeprazole)
• Dexilant (dexlansoprazole)
• Nexium (esomeprazole)
• Prevacid (lansoprazole)
• Prilosec (omeprazole)
• Protonix (pantoprazole)

These medications work similarly, but some are more effective than others. There are also differences in additional conditions and ages they treat, warnings, and interactions.

This article discusses the differences between common PPIs. It explains the approved uses for each PPI, compares the dosage strength of common PPIs, and describes the similarities and differences in warnings and drug interactions.

Proton Pump Inhibitor Comparison

PPIs are generally taken once a day as their effects are meant to last close to 24 hours. The main differences between common PPIs include the conditions and ages they are approved to treat and whether or not they require a prescription. Here is a closer look at the differences and similarities among PPIs.

AcipHex

AcipHex (raberprazole) is available by prescription only. It is approved for treating GERD, peptic and esophageal ulcers, erosive esophagitis (EE), Helicobacter pylori (H. pylori) infections, and Zollinger-Ellison syndrome (a hypersecretory condition) in adults.

It is also approved in adolescents ages 12 and up for short-term treatment of GERD.

Dexilant

Dexilant (dexlansoprazole) is available by prescription only. It is approved for treating GERD and EE. It is also used to prevent EE from returning.

Nexium

Nexium (esomeprazole) is available over-the-counter (OTC) and by prescription. It is used to treat GERD, stomach and peptic ulcers, EE, and Zollinger-Ellison syndrome.

Nexium is also approved to help prevent NSAID-associated gastric ulcers. It is also prescribed in combination with antibiotics to treat H. pylori infection.

Prevacid

Prevacid (lansoprazole) is available OTC and by prescription. It is approved to treat GERD, EE, and Zollinger-Ellison syndrome, and to prevent and treat duodenal and gastric ulcers. It is also prescribed with antibiotics to treat H. pylori infection.

Prevacid is also approved for the short-term treatment of GERD and EE in children ages 1 and older. 

Prilosec

Prilosec (omeprazole) is available OTC and by prescription. In adults, it is approved to treat GERD, EE, gastric and duodenal ulcers, Zollinger-Ellison syndrome, and, when combined with antibiotics, H. Pylori infection.

Prilosec is also approved to treat GERD and EE in children ages 1 to 16. 

Protonix

Protonix (pantoprazole) is available by prescription only and is approved to treat GERD, EE, and Zollinger-Ellison syndrome in adults.

Protonix is also approved for the short-term treatment of GERD and EE in children ages 5 and older. 

How PPIs Compare by Dose

While all PPIs work similarly, some are more effective than others. Researchers compare the potency of AcipHex, Nexium, Prevacid, and Protonix based on milligram (mg) equivalence to Prilosec.

Doses and their Prilosec equivalence (PE) are as follows:

Comparative dosing information is not available for Dexilant. One study found 60 mg Dexilant was superior to 20 mg Prilosec, 40 mg Nexium, 40 mg Protonix, 30 mg Prevacid, and 20 mg Aciphex for treating EE. However, the precise mg-per-mg comparison has not been evaluated.

PPI Warnings

All PPIs come with a warning that symptom relief can mask stomach cancer, and additional follow-up and diagnostic testing should be considered.

All PPIs also carry increased risks of:

• Clostridioides difficile-associated diarrhea
• Chronic inflammation of the stomach lining
• Bone fractures and osteoporosis
• Magnesium deficiency, though rare

AcipHex and Nexium both also carry a warning of a type of kidney damage known as acute interstitial nephritis. 

AcipHex is associated with new-onset cutaneous and systemic lupus erythematosus and an increased risk of fundic gland polyps.

Daily, long-term use (three years or more) of Nexium or AcipHex is linked to vitamin B-12 (cyanocobalamin) deficiency due to malabsorption. 

AcipHex and Protonix are also associated with the potential for false positives on urine screens for tetrahydrocannabinol (THC). 

PPI Drug Interactions

Some PPIs also have different drug interactions. Common drug interactions among most PPIs include:

• Antiretroviral drugs like atazanavir, nelfinavir, and saquinavir
• Medications in which gastric pH is important for bioavailability (such as ampicillin esters, digoxin, erlotinib, iron salts, ketoconazole, mofetil, and mycophenolate)
• Methotrexate
• Warfarin

Since PPIs are metabolized in the liver, you should avoid drinking alcohol while taking them.

Different drug interactions for individual PPIs include the following:

• Cilostazol, a vasodilator, may interact with Nexium and Prilosec.
• Clopidogrel, an anti-platelet, may interact with Nexium and Prilosec.
• Rifampin, an antibiotic, may interact with Nexium and Prilosec.
• St. John’s wort, an herbal remedy for depression, may interact with Nexium and Prilosec.
• Tacrolimus, an immunosuppressant, may interact with Prilosec, Prevacid, Dexilant, and Nexium.
• Theophylline, a bronchodilator, may interact with Prevacid.

In addition, Prilosec may interfere with drugs metabolized by cytochrome P450 (such as diazepam, warfarin, phenytoin, cyclosporine, disulfiram, and benzodiazepines) as well as combined inhibitors of CYP 2C19 and 3A4 (such as voriconazole).

Prilosec and AcipHex may also interact with diagnostic investigations for neuroendocrine tumors.

What Is the Most Effective PPI?

The most effective PPI will likely vary depending on your condition, including severity and how long you'll need treatment.

One review from 2017 looked at the effectiveness of PPIs, including esomeprazole, rabeprazole, lansoprazole, omeprazole, and pantoprazole. It concluded that esomeprazole (40 mg per day) was most effective as a first-line treatment for GERD when used for four to eight weeks. However, it noted that esomeprazole is more expensive than omeprazole (40 mg per day), another PPI that's effective at relieving symptoms and well-tolerated.

Your healthcare provider can help you determine the most effective medication at the lowest dose and cost that's appropriate for you.

Long-Term Use of Proton Pump Inhibitors

PPIs are not meant to be taken for long periods of time, even though some are available over the counter. In fact, the American College of Gastroenterology recommends discontinuing PPIs after eight weeks of treatment for GERD.

Chronic PPI use is associated with increased risks for:

• Dementia
• Fractures
• Heart attack
• Kidney disease
• Stomach cancer

However, a large clinical trial suggests these risks may not be related to PPI use. The study, involving more than 17,000 people, found similar rates of these complications in those taking Protonix or a placebo.

While the study authors conclude PPIs are not associated with long-term harm other than gastric infections, it is important to note the research only compared Protonix to placebo. It is unclear if the same is true for all PPIs.

Always speak to your healthcare provider about the medications that you are taking. It's reasonable to ask about the risks and benefits of taking PPI. If the benefits outweigh the risks for you, consider the lowest possible effective dose.

Which PPI Is Right for Me?

Talk with your healthcare provider about which PPI would work best for you. They will help you make the best decision based on factors such as your condition, your age, and cost. They'll also take into consideration how long you've had symptoms, whether you've tried other medications before, and whether your condition requires a prescription.

If you have a prescription for a PPI, review it with your healthcare provider periodically. They will help determine if it's still effective and make sure that you aren't taking it for longer than necessary.

Summary

Proton pump inhibitors (PPIs) treat gastroesophageal reflux disease and other conditions such as esophageal ulcers, peptic ulcers, H. pylori infections, and Zollinger-Ellison syndrome. PPIs differ in the conditions and ages that they are approved to treat. They may require a prescription, or they may be available over the counter.

Some PPIs may be more effective for you than others, depending on why you need them and how long you'll be taking them. Check with your healthcare provider to find out which PPI is right for you.