10 FAQs About Proton Pump Inhibitors (PPIs), Including How PPIs Work
Key takeaways:
Proton pump inhibitors (PPIs) are common medications for treating conditions like heartburn and gastroesophageal reflux disease (GERD). PPIs are available over the counter (OTC) or with a prescription.
PPIs work by lowering the amount of acid in your stomach. This reduces the chance of having acid move up into your esophagus and cause burning or pain.
While PPIs are effective, there are certain interactions and side effects to be aware of. Be sure to check with your healthcare provider and pharmacist before starting treatment with a PPI.
There are many ways to save on PPIs. These medications are available as lower-cost generics. And using GoodRx coupons can help make your medication more affordable.
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Table of contents
Many people experience heartburn from time to time. But if you’re experiencing frequent heartburn, it may be a sign that you have gastroesophageal reflux disease (GERD). People with GERD experience symptoms two to three times per week or more.
There are many medications that can help with heartburn and other GERD symptoms. Proton pump inhibitors (PPIs) are one example.
PPIs are common treatments for heartburn and GERD, and you’ve likely heard some of their names before. But what’s the best way to take PPIs? And how do you get the most out of your medication? Here, we’ll explain what PPIs are and answer 10 frequently asked questions about PPIs.
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What are PPIs?
PPIs are a class of medications that reduce the amount of acid in your stomach. Although there are several different PPIs, they all work in a similar way. Most PPIs are available as oral pills (tablets or capsules) or liquids. Some also come as intravenous (IV) injections.
Some of the most common PPIs are available over the counter (OTC), including:
Omeprazole (Prilosec)
Esomeprazole (Nexium)
Lansoprazole (Prevacid)
There are also some PPIs that are available only with a prescription:
Pantoprazole (Protonix)
Dexlansoprazole (Dexilant)
Rabeprazole (Aciphex)
Higher doses and liquid forms of the OTC medications listed above
1. How do PPIs work?
As mentioned above, PPIs work by reducing the amount of acid in the stomach. They do this by binding to the “proton pump” enzyme (protein) of certain stomach cells.
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The proton pump is part of the last step in the process of making stomach acid. When this pump is blocked, or prevented from working, less stomach acid is produced. And less stomach acid means you’re less likely to have heartburn or other symptoms of GERD. For many people, the benefits of taking PPIs for GERD outweigh the risks.
2. Are PPIs safe?
There are several risks associated with taking PPIs long term (more than 4 months) that may sound scary. But keep in mind that many people take PPIs long term without problems. And over time, untreated GERD can lead to serious problems, such as Barrett’s esophagus.
Some studies have found a link between taking PPIs long term and certain health problems. These problems include pneumonia, bone fractures, and stomach infections and cancer. Dementia and heart attacks have also been mentioned in some of the research.
Another concerning risk of taking PPIs is potential kidney damage. Kidney damage from taking PPIs short term (4 months or less) can be reversed. But it’s possible to develop more permanent kidney problems with long-term use.
The research regarding these risks is conflicting, however. Some studies have found that there is no significant risk of most long-term side effects with PPIs. If you’re concerned about the possible risks, talk with your healthcare provider. They can help you decide if the treatment benefits are worth the risks in your case.
3. What time of the day should I take PPIs?
PPIs tend to work best if you take them on an empty stomach, about 30 to 60 minutes before eating.
If you’re taking a PPI once daily, take it before your first meal of the day. If you take a PPI twice a day, it’s best to take your doses before breakfast and dinner. Taking PPIs at bedtime may be less effective.
4. Should I take PPIs once or twice daily?
It’s usually recommended to start with a once-daily PPI for GERD. But some people may benefit from taking a PPI twice a day.
If you have a stomach ulcer, you might need to take a PPI twice a day, along with other medications, for a few weeks. A healthcare provider may also recommend a twice-daily PPI if once-daily dosages aren't relieving GERD symptoms sufficiently.
5. How long does it take for PPIs to work?
In general, it takes about 3 days of taking a PPI to see noticeable improvements in heartburn and other GERD symptoms. But it’s possible to start feeling the effects earlier. You may even notice some benefits within 1 day of taking certain PPIs. But keep in mind that it can take several weeks for PPIs to fully treat digestive conditions like stomach ulcers.
Exactly how long a PPI takes to work varies by medication. Check with your pharmacist or healthcare provider for details on your specific PPI.
6. Are there any side effects of PPIs that I should know about?
As mentioned above, PPIs have been linked to long-term side effects like bone fractures and kidney damage. But these side effects are rare.
Short-term side effects of PPIs tend to be mild and they often go away on their own. These potential side effects, which can typically be managed at home, include:
PPIs may also cause constipation, but this side effect tends to be less common than diarrhea. If you’re concerned about side effects from your PPI, talk to your healthcare provider. If you feel that your symptoms are severe or life-threatening, seek emergency medical care.
7. What’s the difference between PPIs and H2 blockers?
Histamine-2 (H2) blockers are another group of medications that treat heartburn and GERD. They work a bit differently than PPIs. But both types of medications lower the amount of acid in the stomach. H2 blockers bind to H2 receptors (chemical binding sites) in the stomach, lowering the amount of acid that’s made.
Common H2 blockers include famotidine (Pepcid AC, Zantac 360) and cimetidine (Tagamet HB). These H2 blockers can be purchased OTC. Higher doses and liquid forms are available with a prescription.
Both PPIs and H2 blockers can help with heartburn symptoms. H2 blockers work much faster than PPIs — usually, within about an hour. But PPIs are typically more effective.
8. What happens if you stop taking PPIs?
If you stop taking a PPI, your symptoms may return or worsen (often called acid rebound). This is especially true if you’ve been taking a PPI for longer than 8 weeks (about 2 months). You may experience rebound symptoms for weeks or months after you stop taking the medication.
You can avoid PPI rebound symptoms by slowly stopping treatment over the course of a few weeks, with the help of your healthcare provider. As you gradually stop taking your PPI, your provider may recommend an antacid, like calcium carbonate (Tums), or an H2 blocker for breakthrough heartburn.
9. Do PPIs have any drug interactions?
PPIs interact with medications that need an acidic environment to be absorbed into the bloodstream. Examples of these medications are oral antifungals, like ketoconazole, and protease inhibitors, like ritonavir-boosted atazanavir for HIV.
Sometimes, these interactions can be avoided by taking the medications with an acidic drink, like regular (non-diet) soda. Or you may need to separate doses of your PPI and the interacting medication by a certain amount of time, which varies depending on the medications. Discuss how to best manage PPI interactions with your healthcare provider or pharmacist.
PPIs can also interact with warfarin (Coumadin, Jantoven), clopidogrel (Plavix), many oral cancer medications, and other medications.
Keep in mind: The medications discussed above are not the only ones that can potentially interact with PPIs. Before starting treatment with a PPI, be sure to provide your pharmacist and provider with your full medication list, which should include OTC medications. This will help them give you advice on how to avoid or manage interactions.
10. Can PPIs make gastritis worse?
The short answer is: no. PPIs aren't known to make gastritis (stomach inflammation) worse. In one study, people who took PPIs were less likely to have gastritis than those who didn’t take them. People who took PPIs also had less severe gastritis when it occurred.
Gastritis can have many causes. In some cases, taking a PPI can actually help treat gastritis. Your healthcare provider will help you navigate how to best treat gastritis if you develop it.
How you can save money on PPIs
There are many ways to save on PPIs. GoodRx can help you navigate your options, which may include GoodRx coupons, copay savings programs, and patient assistance programs. You can find PPI prices as low as $7 with a free GoodRx coupon.
Keep in mind that you can also use GoodRx to save on OTC PPIs if your healthcare provider writes you a prescription.
The bottom line
Proton pump inhibitors (PPIs) are effective for treating heartburn and symptoms of gastroesophageal reflux disease (GERD). Experts suggest that, for most people, the benefits of taking PPIs for GERD outweigh the risks. But these medications are not without possible interactions and side effects.
Both short-term and long-term side effects are possible. You shouldn’t abruptly stop taking your PPI if you’ve been taking it for 2 months or longer. Doing so may cause your symptoms to come back or worsen. And it can take a few days of taking a PPI to see improvement in your symptoms.
Be sure to follow your healthcare provider’s instructions for taking your PPI to get the most benefit out of the medication.
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References
Ahmed, A., et al. (2023). Proton pump inhibitors (PPIs). StatPearls.
Chin, T. W., et al. (1995). Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole. Antimicrobial Agents and Chemotherapy.
Clinicalinfo.HIV.gov. (2022). Drug interactions between protease inhibitors and other drugs.
Fashner, J., et al. (2015). Diagnosis and treatment of peptic ulcer disease and H. pylori infection. American Family Physician.
Katz, P., et al. (2022). ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. The American Journal of Gastroenterology.
Nasser, S. C., et al. (2015). Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes. World Journal of Gastroenterology.
National Institute of Diabetes and Digestive and Kidney Diseases. (2019). Treatment of gastritis and gastropathy.
Targownik, L. E., et al. (2022). AGA clinical practice update on de-prescribing of proton pump inhibitors: Expert review. Gastroenterology.
Troxler, R. B., et al. (2014). Sleep and gastroesophageal reflux. Principles and Practice of Pediatric Sleep Medicine.
Wedemeyer, R., et al. (2014). Pharmacokinetic drug interaction profiles of proton pump I\inhibitors: An update. Drug Safety.
