Omeprazole interactions to avoid

Many different drugs can interact with omeprazole and cause a variety of unwanted adverse effects

By Stephanie Melby, Pharm.D. | Dec. 6, 2023

Omeprazole is an over-the-counter (OTC) medication known by the brand name Prilosec. Omeprazole belongs to a group of medications called proton pump inhibitors (PPIs). It is one of the most commonly used medications that can treat gastroesophageal reflux disease (GERD) and other stomach acid-related conditions. In addition to GERD, omeprazole is also used for the treatment of Helicobacter pylori (H. pylori), peptic ulcer disease (PUD), duodenal ulcers, gastric ulcers, erosive esophagitis, and Zollinger-Ellison syndrome.

As a medication that lowers stomach acid secretion, certain drug interactions with omeprazole are important to avoid, as people could be at an increased risk of worsening stomach acid symptoms. Some interactions may increase the amount of omeprazole in the body, causing common side effects like nausea, diarrhea, abdominal pain, constipation, headache, and rash.

Key takeaways:

Omeprazole can cause gastrointestinal (GI) side effects, including diarrhea, abdominal pain, nausea, constipation, vomiting, and flatulence. Certain drug interactions can further increase these common GI side effects of omeprazole.
Omeprazole may become less effective due to drug interactions, which can worsen the symptoms of certain stomach acid-related conditions it treats
Omeprazole can affect the metabolism of other medications by either increasing or decreasing the amount of other medications in the body. Dose adjustments may be necessary to lessen or avoid the effects of certain drug interactions with omeprazole.
Healthcare providers may switch omeprazole to a different PPI or a different type of medication to avoid dangerous drug interactions.
If a dangerous mixture of medications has been consumed, seek immediate medical help or contact Poison Control for assistance.

Omeprazole-drug interactions

Many different drugs can interact with omeprazole and cause a variety of unwanted adverse effects. While some drugs may worsen omeprazole side effects or make omeprazole less effective, other drugs can be negatively affected by omeprazole.

Drug metabolism can undergo many different pathways, and cytochrome P450 (CYP) enzymes play a big part in this process. CYP enzymes can affect drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism. There are a variety of CYP enzymes, and drugs may inhibit or induce the enzymes affecting pharmacokinetics (movement of drugs within the body). CYP2C19 is an enzyme that omeprazole competes to inhibit, and this may increase the amounts of other medications that use this enzyme, like diazepam, proguanil, phenytoin, and warfarin. On the other hand, some other medications that are CYP2C19 inducers, like rifampin, can speed up the metabolism of omeprazole and make it less effective in the body. Some of the interactions discussed below are due to this CYP interaction.

Warfarin

Warfarin (Jantoven) and other vitamin K antagonists are commonly used oral anticoagulants, also called blood thinners, that help prevent blood from clotting. Blood thinners need to be closely monitored, as changes in diet, alcohol intake, and medications can lead to serious changes in the thinning or thickening of blood. Omeprazole can increase the amount of warfarin or other vitamin K antagonists in the body. The healthcare clinic monitoring the warfarin dose must be aware of new medication changes. This potential drug interaction with omeprazole can cause the blood to take longer to clot, so people must look out for increased signs of bleeding. Some of these signs of increased bleeding include nosebleeds that do not stop, bleeding gums during teeth brushing, coughing up blood, or vomit that resembles coffee grounds. Prescribers may suggest dose adjustments, especially high doses, or switching medications.

Citalopram and Escitalopram

Citalopram (Celexa) and escitalopram (Lexapro) are commonly used antidepressants that can treat a variety of conditions, such as depression, generalized anxiety disorder, obsessive-compulsive disorder (OCD), and panic disorder. If the dose of citalopram or escitalopram is too high, dangerous side effects can happen, such as serotonin syndrome and heart rhythm disorders. Omeprazole can increase the amount of citalopram or escitalopram in the body and increase the risk of dangerous toxicity. It’s important to keep healthcare professionals up-to-date with current medication lists so dose adjustments can be made. If omeprazole and citalopram are taken together, no more than 20 mg a day should be taken of citalopram. And if omeprazole and escitalopram are taken together, no more than 10 mg a day of escitalopram should be taken. Providers may decide to switch omeprazole to a different PPI or to an H2-antagonist. People should be aware of the signs of citalopram and escitalopram toxicity, such as a fast heart rate, high blood pressure, agitation, or confusion.

Clopidogrel

Clopidogrel (Plavix) is an antiplatelet medication that prevents platelets (a type of blood cell) from sticking together and forming a dangerous blood clot. Clopidogrel can be used to avoid strokes, heart attacks, and other heart problems. Omeprazole can reduce the effect of clopidogrel by decreasing the amount of it in the body, which could lead to a dangerous potential drug interaction, causing a risk for serious cardiovascular events. The combination of clopidogrel and omeprazole is not recommended. Prescribers may recommend a different PPI, such as rabeprazole (Aciphex) or pantoprazole (Protonix), as they are lower-risk medications for this interaction.

Certain Antibiotics

Oral antibiotics can be used to treat various bacterial infections, such as skin infections, strep throat, urinary tract infections, ear infections, and respiratory tract infections. Certain oral antibiotics, such as cefuroxime, cefpodoxime, and doxycycline, interact with omeprazole. This drug interaction is essential to avoid because omeprazole can either decrease the absorption, concentration, or bioavailability of the antibiotic. Omeprazole also interacts with the antibiotic amoxicillin or in people who have a history of allergic reactions to amoxicillin and other penicillins. This combination can lead to a potentially life-threatening allergic reaction, and people should seek immediate medical attention. When being treated for an infection, the prescribing doctor must be aware of all medications being taken to ensure the antibiotic can work effectively and thoroughly treat the infection. This will help prescribers personalize the antibiotic choice based on other medications being taken and the type of infection.

Certain Antifungals

Oral antifungals can be used to treat a variety of fungal infections. Certain oral antifungals, including itraconazole (Sporanox), ketoconazole, posaconazole (Noxafil), and voriconazole (Vfend), interact with omeprazole. Drug interactions with antifungals are important to avoid to ensure proper treatment of the infection and avoid serious adverse effects. For example, when taking omeprazole with ketoconazole or posaconazole, the amount of the antifungal drug can be lowered in the body. Healthcare providers may recommend separating the doses of medications or taking the antifungal drug with an acidic beverage to increase gastric acidity and improve absorption. Sometimes, this type of interaction is less common in antifungal medications that are delayed-release and take longer to absorb in the body. When taking omeprazole with itraconazole or voriconazole, the amount of the antifungal drug can be increased in the body. A prescriber may decide to increase or decrease the dose of an antifungal or omeprazole to manage this interaction. On the other hand, the amount of omeprazole may also be affected by an antifungal drug interaction and needs to be monitored.

Certain HIV Medications

HIV medications can be used either prophylactically or for the treatment of HIV (human immunodeficiency virus) infections. Some examples of HIV medications that can interact with omeprazole include atazanavir (Reyataz), nelfinavir (Viracept), and rilpivirine (Edurant). When taken with omeprazole, the amount of these HIV medications can be decreased in the body. This is a serious interaction, as it can affect keeping the HIV infection under control. It is best to avoid combining these medications, as HIV is a virus that attacks the body’s immune system, and specific medication doses can control the infection and prevent disease progression. Communicating with the healthcare team about all medical conditions and medications is key to avoiding this drug interaction.

Certain Osteoporosis Medications

Alendronate (Fosamax) and risedronate (Actonel), are bisphosphonate derivatives used to treat and prevent osteoporosis. When taken with omeprazole, the therapeutic effects of alendronate and risedronate can be diminished. Prescribers may adjust the dose of omeprazole or change the medication to a H2-antagonist. Older adults and people using higher doses of omeprazole appear to be at the most significant risk of this drug interaction.

Omeprazole-food interactions

Sometimes, interactions with food are an unexpected complication with medications. Omeprazole has unique dietary considerations for people taking it long-term.

Omeprazole and Vitamin B12 Deficiency

While not a typical drug-food interaction, omeprazole can lead to malabsorption issues with dietary vitamin B12. This interaction is more common in long-term use of omeprazole, with usually greater than two years of use. The malabsorption issues can lead to vitamin B12 deficiency. Some signs of vitamin B12 deficiency include anemia, fatigue, pale skin, a sore and red tongue, mouth ulcers, diarrhea, and headaches. People taking omeprazole long-term should have routine blood tests to measure their vitamin B12 levels and take vitamin B12 supplements if necessary.

Other omeprazole interactions

In addition to prescription medications, over-the-counter (OTC) medications and herbal supplements can cause unwanted drug interactions with omeprazole. An important interaction to be aware of is with the supplement St. John’s wort.

Omeprazole and St. John’s Wort

St. John’s wort is a plant that has been used for many years as a supplement for mental health conditions, including depression. While effective for some people, St. John’s wort has many drug interactions as it can speed up the metabolism of many drugs, including omeprazole. This interaction can lessen the effectiveness of omeprazole. It’s best to avoid taking these medications together.

How to minimize omeprazole interactions

A key to minimizing interactions is ensuring healthcare providers know all medical conditions and have a medication list, including prescription drugs, OTC medications, herbal products, and supplements. As seen with omeprazole, even OTC and supplement products can have serious drug interactions. Pharmacists are great resources, as they can provide additional drug information and medical advice when visiting the pharmacy.

Certain medical conditions can impact whether a drug will be safe or not for a person. Omeprazole should be used with caution in people with liver impairment, and often a dose reduction is recommended. PPIs like omeprazole may increase the risk of bone fractures, so individuals with osteoporosis or at risk for osteoporosis should weigh the cons and benefits of omeprazole treatment with their doctor. Long-term use of PPIs also has the possibility of increasing the risk of diarrhea associated with an infection called C. difficile (Clostridium difficile) in the colon, the longest part of the large intestine. Although rare, long-term use of omeprazole may lead to hypomagnesemia (low magnesium levels). People may require magnesium supplementation or need to discontinue omeprazole.

Omeprazole is present in breast milk, so the decision to breastfeed will be determined by a doctor. While certain doses of omeprazole may be acceptable for some breastfeeding women, a few considerations can help make that decision, such as the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the breastfeeding mother.

When to talk to a healthcare provider about omeprazole interactions

Many of the major medication interactions related to omeprazole are listed above. However, numerous more possible drug interactions are not included. It’s important to communicate openly with healthcare professionals about all medical conditions, medications, and supplements to allow for the safest drug management. Other medication options may be better treatment options for some people, including other PPIs (esomeprazole, lansoprazole, rabeprazole, or pantoprazole), H2-antagonists (famotidine, cimetidine, or nizatidine), or antacids like Tums.