Important Drug Interactions for the Stomach-Acid–Suppressing Drug Omeprazole

Patients taking the commonly used stomach-acid–suppressing drug omeprazole should be aware that it has clinically important interactions with many other prescription medications.

Omeprazole belongs to the family of drugs known as proton pump inhibitors. It is available as a single-active-ingredient drug by prescription under the brand name PRILOSEC and over-the-counter (OTC) under the brand name PRILOSEC OTC, as well as in multiple prescription and OTC generic versions. The prescription versions are approved by the Food and Drug Administration (FDA) to treat several stomach-acid disorders, including ulcers in the stomach and duodenum (the first part of the small intestine) and gastroesophageal reflux disease.[1] Over-the-counter omeprazole is FDA-approved only for treatment of frequent heartburn (occurs two or more days a week).[2]

Omeprazole also is a component of several combination prescription drugs, including a two-drug combination containing the antacid sodium bicarbonate (brand name ZEGERID) that is approved to treat the same stomach-acid disorders for which Prilosec is approved.[3]

An OTC omeprazole-sodium bicarbonate combination product is sold under the brand name ZEGERID OTC for treatment of frequent heartburn.[4]

Interacting Drugs[5],[6]

The Table below provides examples of 19 widely used prescription oral drugs that have clinically important interactions with omeprazole. The following are some particularly notable omeprazole drug interactions.

Antiviral drugs

Omeprazole can interact with several antiviral drugs used to treat HIV infection. For most of these interacting antiviral drugs — including indinavir (CRIXIVAN) and rilpivirine (COMPLERA, EDURANT, JULUCA, ODEFSEY) — concomitant use with omeprazole decreases blood levels of the antiviral drug, which may reduce the effectiveness of the antiviral drug and promote the development of HIV antiviral drug resistance. In the case of rilpivirine, the product labeling for omeprazole warns that the two drugs should not be used concomitantly because the interaction is so significant.

For the antiviral drug saquinavir (INVIRASE), concomitant use with omeprazole has the opposite effect: It can lead to increased blood levels of saquinavir and saquinavir-related toxicity.

Methotrexate

Concomitant use of proton pump inhibitors like omeprazole with methotrexate (OTREXUP, RASUVO, TREXALL, XATMEP) — which is used to treat the autoimmune diseases rheumatoid arthritis, psoriasis and several types of cancer — may increase methotrexate in the blood to toxic levels. This interaction is most likely to occur when methotrexate is administered in high doses.

Methotrexate toxicity can cause a wide range of serious and life-threatening adverse effects, including

• anemia (low red blood cell levels);
• low white blood cell levels, which can lead to serious infections;
• low blood platelet levels, which can lead to bleeding;
• liver damage; and
• kidney failure.[7]

Warfarin

Concomitant use of omeprazole and the anticoagulant (blood thinner) warfarin (COUMADIN, JANTOVEN) can increase blood levels of warfarin. This can increase the risk of bleeding complications. Patients who take warfarin should undergo more frequent monitoring of warfarin levels during therapy with omeprazole and initially after discontinuing omeprazole.

Phenytoin

Concomitant use of omeprazole with the seizure drug phenytoin (DILANTIN, PHENYTEK) can increase blood levels of phenytoin, potentially resulting in phenytoin toxicity. Signs of phenytoin toxicity include loss of muscle coordination, involuntary repetitive eye movements, slurred speech, sleepiness and confusion.

Examples of Drugs That Have Clinically Important Interactions With Omeprazole

†Combination drug product that contains one or more other active ingredients
*Designated as Limited Use
*Designated as Limited Use **Designated as Do Not Use

What You Can Do

If you need treatment with omeprazole, review all your other medications with your doctor to assess your risk for potentially significant drug interactions. If you are taking certain medications that interact with omeprazole, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug, or your doctor may advise you to take a different drug for your stomach-acid condition. Be aware that other drugs not listed in this article also may have dangerous interactions with omeprazole.
 

References

[1] Covis Pharma. Label: omeprazole (PRILOSEC). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6761f84-53ac-4745-a8c8-1e5427d7e179&type=display. Accessed August 5, 2020.

[2] The Proctor & Gamble Manufacturing Company. Label: omeprazole (PRILOSEC OTC). December 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=35a79458-79f6-44d6-b74c-b4f4aaf0dde0&type=display. Accessed August 5, 2020.

[3] Salix Pharmaceuticals. Label: omeprazole and sodium bicarbonate (ZEGERID). September 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021636s020,021849s015lbl.pdf. Accessed August 5, 2020.

[4] Bayer Healthcare. Label: omeprazole and sodium bicarbonate (ZEGERID OTC). November 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=32bed6d8-8a9a-4fb0-a2f6-045892011ee4&type=display. Accessed August 5, 2020.

[5] Covis Pharma. Label: omeprazole (PRILOSEC). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6761f84-53ac-4745-a8c8-1e5427d7e179&type=display. Accessed August 5, 2020.

[6] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “omeprazole.” Accessed July 17, 2020.

[7] Orion Corporation. Label: methotrexate tablets. February 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8f1260de-b60c-4f0e-8af6-0e957b0a281b. Accessed July 17, 2020.