Prilosec vs Pepcid: Similarities and Differences

By Zina Semenovskaya, MD
Medically reviewed checkmarkMedically reviewed
July 11, 2022

Prilosec and Pepcid are two common medications for treating heartburn and acid reflux.

While they produce a similar effect—reducing acid in the stomach—they work differently.

In this article, we’ll discuss the differences between Prilosec vs Pepcid, including their side effects, effectiveness, and important interactions and warnings you need to know.

Pepcid vs Prilosec

Pepcid and Prilosec are popular medications used to treat heartburn, acid reflux, and gastroesophageal reflux disease (GERD).

Both medications are available over-the-counter or with a prescription.

While they have a similar effect on the symptoms of acid reflux, they are not in the same drug class and work differently.

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What is Pepcid

Pepcid is the brand name for famotidine.

It is a histamine-2 blocker (H2 blocker), meaning it works by inhibiting histamine at the H2-receptor site in parietal cells in the stomach.

This blocks the production of acid and addresses symptoms of acid reflux and GERD.

Pepcid is approved by the U.S. Food and Drug Administration (FDA) for the treatment of:

  • GERD
  • Gastric ulcers
  • Duodenal ulcers
  • Erosive esophagitis
  • Zollinger-Ellison syndrome (a rare condition that produces too much stomach acid)
  • Heartburn

Pepcid is available as a pill, chewable tablet, or liquid.

OTC versions of Pepcid are lower doses than prescription versions.

What is Prilosec

Prilosec is the brand name for omeprazole.

It is a proton pump inhibitor (PPI) and works by blocking acid production in the stomach.

When acid levels decrease, it reduces common signs of acid reflux such as heartburn and feelings of acid in the throat.

Prilosec is also used to treat other conditions such as:

  • Stomach ulcers
  • Duodenal ulcers
  • GERD
  • Erosive esophagitis
  • Zollinger-Ellison syndrome

Prilosec is available as a pill or powder.

Over-the-counter Prilosec is not the same as prescription-strength pills, which usually have a higher dosage and are meant to be taken longer-term.

Possible side effects of Pepcid

Pepcid is generally well-tolerated.

It can cause a few common side effects:

Possible side effects of Prilosec

Prilosec may cause mild side effects such as:

  • Headache
  • Nausea
  • Vomiting
  • Constipation
  • Diarrhea
  • Flatulence

Are Pepcid and Prilosec the Same Thing?

Pepcid and Prilosec are not the same thing.

While both treat GERD and acid reflux, they are different drug types and have different mechanisms to reduce stomach acid.

Both are available OTC and by prescription, but neither are quick-acting antacids. 

Which is better?

There are a few pros and cons when it comes to Pepcid vs Prilosec.

  • How fast do they work? Pepcid takes about an hour to start working, with the peak effect occurring 1-3 hours after taking. Prilosec may take 1-4 days before it reaches full effectiveness for managing GERD or reflux symptoms.
  • Take with or without food? Pepcid can be taken with or without food. If you eat a meal that seems to cause reflux, you can take it when you are done eating and it will still work. Prilosec must be taken on an empty stomach before you eat.
  • Long-term use? Prilosec works better for longer-lasting relief, whereas Pepcid kicks in faster but may not be as effective long term. Still, everyone responds differently to drugs, and a medical provider can determine which one is best for long-term treatment of GERD, reflux, or other conditions.

A small study of 98 people compared Pepcid and Prilosec for the purpose of treating GERD and found that Prilosec was more effective.

Interactions and Warnings

Pepcid and Prilosec have important interactions and warnings to be aware of.

Interactions can include:

  • Pepcid: Cefditorin, cefpodoxime, itraconazole, ketoconazole, atazanavir, delavirdine, other antacids
  • Prilosec: Ampicillin, flurazepam, calcium carbonate, ketoconazole, citalopram, vitamin B12, cycloSPORINE, diazepam, digoxin, methotrexate, disulfiram, gefitinib, indinavir, iron salts, phenytoin, triazolam, warfarin, Plavix, St. John’s wort

To avoid drug interactions, tell your healthcare provider and pharmacist about any other medications, supplements, or vitamins that you take.

Both medications also come with some serious warnings:

  • Pepcid: Stomach cancer, central nervous system side effects
  • Prilosec: Stomach cancer, kidney damage, severe C. difficile diarrhea, bone fractures (especially in the spine, wrist, and hip), lupus, vitamin B12 deficiency, magnesium deficiency

Prilosec is not indicated for pregnant persons or those who are breastfeeding.

Prilosec can pass through breast milk.

Prilosec is also not safe for people who have osteoporosis or may be at high risk for it since it can increase the risk of a serious fracture.

Pepcid is pregnancy category B, which means that it can be safely used during pregnancy.

Still, check with healthcare providers to ensure it does not interact with other medical considerations for pregnancy.

People who breastfeed should check with their medical provider before taking Pepcid, since a small amount may pass through the breast milk.

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How K Health Can Help

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Frequently Asked Questions

Which is better Prilosec or Pepcid?
Each medication is more effective at a different thing: For more immediate relief of acid reflux or heartburn, Pepcid may be better. For longer-term relief from GERD, Prilosec may be more effective. A healthcare provider will recommend the medication that is best for you based on your health history, symptoms, and other medications that you take.
Why you should not take Prilosec?
Prilosec should not be taken by people who have certain kidney problems, osteoporosis, or who are pregnant or breastfeeding.
Should you take Pepcid and Prilosec?
Pepcid and Prilosec should not be taken together.
What is the safest antacid to take?
There are many types of antacids, and each works differently to neutralize stomach acid from causing painful burning as it comes up the throat. The safest antacid depends on your medical history, current health conditions, and any prescriptions you take. A medical provider can determine which antacid is safest for your situation.
K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Zina Semenovskaya, MD

Dr. Semenovskaya specializes in emergency medicine, and received her medical degree from Weill Cornell Medical College. She is currently the medical director at Remote Emergency Medicine Consulting, LLC and splits her time working clinically as an emergency medicine attending in California and Alaska. She is the first of our doctors to be fluent in Russian.

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