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Proton Pump Inhibitors (PPI) Interactions

People who take proton pump inhibitors (PPIs) may need to limit or avoid their exposure to certain medicines or foods due to potential interactions. Patients should discuss all medications and supplements they are taking, as well as any dietary restrictions, with their doctor prior to taking a PPI.

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Eating certain foods, taking certain medications or supplements, or even enjoying your morning cup of coffee can interact with a proton pump inhibitor (PPI), causing unwanted side effects. This is known as a drug or food interaction.

These interactions can cause symptoms to worsen, stop other medications from working properly, or increase the effects of PPIs or other drugs on the body. Some of these interactions are mild, while others can result in severe complications.

Patients should discuss all medications and supplements they are currently taking or plan to take with their doctor before taking a PPI.

They should also be informed on what foods or drinks, including alcohol, to limit or avoid while taking PPIs in order to maximize the medication’s effects and prevent potential side effects.

In certain cases, where the risk of interactions is high and changes cannot be made to existing medications, a doctor may recommend an alternative to taking PPIs. Patients should not start or stop taking PPIs or any other medications without first speaking with their doctor.

Drug-Drug Interactions

PPIs can potentially interact with a variety of medications. Patients should use caution when taking PPIs simultaneously with other prescription and non-prescription medicines, as well as certain supplements.

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PPIs work to alter the pH of the stomach, thereby potentially changing the way certain drugs work within the body, including the way they are absorbed, filtered, activated or bonded.

Sometimes, changing the dosages or spacing out when to take the medications may be enough to help prevent interactions. Other times, a certain PPI may need to be avoided altogether, and another medication prescribed in its place.

The following charts can be used as a guide to know where to start when discussing the potential for drug-drug interactions with your doctor.

Omeprazole (Prilosec) & Esomeprazole (Nexium)
Drug Interactions What Happens What Can Be Done
Clopidogrel (Plavix) – blood thinner Omeprazole and esomeprazole block the enzyme CYP2C19, which is needed to activate clopidogrel, thereby decreasing its presence in the blood. Take pantoprazole (Protonix) instead.
Diazepam (benzodiazepine) – anxiety; Warfarin (Coumadin, Jantoven) – blood thinner; Citalopram (Celexa) – depression; Phenytoin (Dilantin, Phenytek) – seizures Omeprazole blocks elimination (metabolism) of these drugs, potentially increasing their presence in the blood. Take pantoprazole (Protonix) instead.
All PPIs
Drug Interactions What Happens What Can Be Done
Nelfinavir (Aricept); Rilpivirine (Edurant) – antiretroviral drugs used to treat HIV PPIs reduce stomach acid, thereby increasing stomach pH, which can lead to decreased absorption of these medications. Take an H2 blocked instead.
Harvoni (ledipasvir and sofosbuvir) – used to treat hepatitis C Gastric acid is needed for absorption of this drug, and PPIs decrease this acid. Take an H2 blocker instead, or decrease omeprazole to 20mg daily.
Methotrexate (Trexall) – chemotherapy drug used to treat cancer, including leukemia, and certain types of arthritis PPIs block the active secretion of the medication in renal tubules, which are essential components of the kidneys and are used for filtration. Take an H2 blocker instead, or watch out for signs and symptoms of methotrexate toxicity.
Digoxin (Lanoxin, Digitek) – used to treat congestive heart failure and abnormal heart rhythms Increased absorption of the medication can occur due to altered gastric pH levels. Take an H2 blocker instead.

PPIs and Clopidogrel

The FDA issued a strong warning in 2009, advising patients taking clopidogrel to avoid also taking certain PPIs, especially omeprazole (Prilosec) and esomeprazole (Nexium), as they may reduce clopidogrel’s effectiveness by 50 percent.

The FDA warned against patients taking a certain blood thinner at the same time as PPIs, especially Prilosec.

Clopidogrel — sold under the brand names Ceruvin, Clopilet and Plavix — is intended to prevent blood clots from forming in patients who are at high risk of heart attack and stroke.

Clopidogrel, however, is hard on the stomach lining and intestines, and has been found to increase a patient’s risk of gastrointestinal bleeding. This side effect is further aggravated by the use of aspirin, which is commonly prescribed in conjunction with clopidogrel.

To discourage gastrointestinal problems, doctors often prescribed clopidogrel, or dual clopidogrel-aspirin therapy, along with a PPI. But PPIs, especially omeprazole, have been found to block a certain enzyme called CYP2C19.

CYP2C19 is necessary in the metabolism (or chemical transformation) of many different medications. Likewise, it is essential to the activation of clopidogrel and its anti-blood clotting effects.

Without this enzyme, the drug cannot metabolize properly, thereby negating its effects and putting patients at risk of developing blood clots.

Food and Drink Interactions

Although certain foods and drinks do not directly interact with PPIs, a patient’s diet can have an effect on the underlying condition PPIs are used to treat. This can potentially diminish or negate the effects of the PPI.

Certain foods and drinks can contribute to acid reflux flare-ups.

acid reflux icons
The most common triggers of acid reflux complications include:
  • Citrus fruits
  • Peppermint
  • Caffeinated drinks (i.e. coffee and soda)
  • Chocolate
  • Sugary foods
  • Spicy foods
  • Red and processed meats
  • Tomatoes and tomato-based products
  • High-fat or greasy (fried) foods

Long-term PPI-use is also associated with certain nutritional deficiencies. PPIs can decrease absorption of vitamin B12 and iron leading to health complications. Patients taking PPIs should, therefore, discuss appropriate diet and/or supplement options with their doctor.

PPIs and Alcohol

Drinking alcohol should be avoided or limited in people taking PPIs. This is partially due to possible interactions that may occur with the medication itself.

For example, lansoprazole (Prevacid) is known to cause drowsiness and dizziness, and omeprazole (Prilosec) can cause nausea and headaches. Consuming alcohol can intensify these side effects, especially when a patient is already prone to these symptoms.

Drinking alcohol while taking PPIs can result in increased side effects and the worsening of gastrointestinal problems.

It’s also possible alcohol will worsen the conditions PPIs are intended to treat, such as heartburn caused by acid reflux (GERD) and stomach ulcers.

PPIs work by reducing or limiting the amount of acid produced in the stomach. Alcohol can further aggravate certain gastrointestinal problems by causing excess acid production and irritation to the stomach lining, thereby negating the effects of the medication.

Patients with alcohol problems, dehydration or low blood sodium levels are at a greater risk of developing complications. These patients should avoid drinking alcohol while taking PPIs.

Please seek the advice of a medical professional before making health care decisions.

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9 Cited Research Articles

  1. Bardot, J. (2017, August 14). Can You Take Lansoprazole and Drink Alcohol? Retrieved from
  2. Harvard Health Publishing. (2011, April). Proton-pump inhibitors. Harvard Medical School. Harvard University. Retrieved from
  3. Vanderhoff, B. T. MD and Tahboub, R. M. MD. (2002, July 15). Proton Pump Inhibitors: An Update. American Family Physician. Retrieved from
  4. Wiley, F., PharmD, CGP, RPh. (2015, October 20). What Are Proton Pump Inhibitors (PPIs)? Everyday Health. Retrieved from
  5. Obert, L. DNP and Obert, J. MD. (2016, February 1). PPIs and Antacids: How to Avoid Interactions. Contemporary Clinic. Retrieved from
  6. Ogawa, R. and Echizen, H. (2010, August). Drug-drug interaction profiles of proton pump inhibitors. U.S. National Library of Medicine. Retrieved from
  7. Madanick, R. D. MD. (2011, January). Proton pump inhibitor side effects and drug interactions: Much ado about nothing? Cleveland Clinic Journal of Medicine. Retrieved from
  8. Frank, S. A. (2007, January). Digesting the Complexity of PPI Management and Care. Practical Gastroenterology. Retrieved from
  9. Nall, R. RN, BSN, CCRN. (2017, July 11). Best Alcoholic Beverages for People with GERD. Healthline. Retrieved from
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