Omeprazole Drug Interactions

Instructor: Rachel Torrens

Rachel is a Nurse Practitioner with experience working as a high school teacher, skin surgery center, and as a family NP.

Omeprazole, a proton-pump inhibitor, is used on a daily basis to treat acid-reflux. However, this common medication interacts with a significant amount of other medications. In this lesson learn the details of omeprazole drug interactions.

Proton-pump Inhibitors: A Common Medication

You're watching TV, munching nachos and relaxing. A commercial comes on describing a new medication to treat heartburn. You hear a super-fast voice rattling off all the do's and don'ts of taking this medication, but you're more concerned with getting back to your show. When all of the sudden, you feel a burning right in the middle of your chest. The pain is unbelievable, and you wish you had paid more attention to that ad!

Acid-reflux is a serious health problem which can lead not only to incredible discomfort but long-term health problems if not treated. Proton-pump inhibitors (PPIs) are a very common type of medication used to treat acid-reflux. In fact, millions of people in the United States use PPIs! One of the first PPIs to come to market was omeprazole. Omeprazole is generally considered a safe drug. So much so that, in 2003 omeprazole was approved to be sold over-the-counter.

Omeprazole was one of the first proton-pump inhibitors.

The Problem with PPIs

The reality is that, omeprazole when taken alone is very safe. However, if taken along with another medication it can cause problems. Omeprazole interacts with over 150 different medications. Some of these interactions are major, necessitating a change in medication, while other interactions are minor. But why in the world does omeprazole interact with so many medications?

Well, the interactions usually stem from one of two causes.

  1. gastric pH changes
  2. liver processing

Gastric pH Changes

The goal of omeprazole is to treat acid-reflux, which is accomplished by increasing the gastric pH. In other words, omeprazole makes the stomach less acidic. The problem is that many other medications require a low pH to break the medication down into usable parts. If the pH is raised by omeprazole, then the medication cannot be broken down and can't enter the body. The bioavailability of many medications is decreased because omeprazole increases the pH of the stomach. Bioavailability is the amount of effective medication able to enter the bloodstream.

Liver Processing

Omeprazole is processed in the liver. Many other medications are also processed in the liver. Therefore if two drugs requiring liver processing are ingested at the same time, then one or both drugs' processing will be affected. Depending on the chemical structure of the drug either omeprazole or the other drug will be processed first. Whichever drug is processed second will be in the body longer than normal which may lead to complications.

Omeprazole drug interactions usually occur in one of the two following organs: the stomach or liver.
organ diagram

Major Interaction Medications

Some medications have major interactions with omeprazole. The medications are divided into two categories: those affected by the gastric pH change and those affected by liver processing. Keep in mind that a healthcare provider will likely not give these medications with omeprazole if there is a choice.

Drugs Classes Affected by the Gastric pH Change

Chemotherapy Agents

A large majority of chemotherapy agents used in the treatment of cancer have a decreased bioavailability due to the pH change caused by omeprazole. Examples include erlotinib and dasatinib.


Many of the drugs used to treat Human Immunodeficiency Virus are affected by the gastric pH change. However, different antiretrovirals are affected differently. For example, atazanavir, indinavir, and nelfinavir become less bioavailable. So the blood levels of these drugs is markedly less in patients also taking omeprazole, meaning the antiretroviral is rendered ineffective. Other antiretrovirals, such as saquinavir, increase in bioavailability with the pH change which can lead to toxic blood levels.


Antifungals are medications used to eliminate fungal infection. These medications have a decreased effect due to decreased bioavailability. Examples include ketoconazole and itraconazole.

Heart Medications

Two more medications which react with omeprazole are digoxin and nisoldipine. Digoxin is a very old heart medication, which is commonly used to treat congestive heart failure or atrial fibrillation. Taking digoxin with omeprazole has been shown to increase blood levels of digoxin, and therefore close monitoring of the patient is essential.

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