Key takeaways

Omeprazole, a proton pump inhibitor, is commonly used to treat acid-related stomach issues such as heartburn, GERD, and ulcers. It can cause side effects ranging from mild, like headaches and abdominal pain, to severe, such as liver disease and osteoporosis, particularly with long-term use.
Long-term use of omeprazole is linked to serious health risks including bone fractures, low magnesium levels, atrophic gastritis, vitamin B-12 deficiency, and potentially an increased risk of stomach cancer.
Omeprazole may interact adversely with various medications, including HIV drugs, anticoagulants, and certain antibiotics, potentially leading to decreased drug effectiveness or increased risk of side effects.
To minimize side effects, omeprazole should be taken as directed for the shortest time necessary, and patients should consult healthcare professionals before using over-the-counter omeprazole, especially if considering long-term use.

Omeprazole (brand name Prilosec) is a prescription and over-the-counter medication that reduces stomach acidity. Belonging to a family of drugs called proton pump inhibitors, omeprazole partially blocks the stomach’s ability to secrete acid. Most often taken as a capsule or tablet, omeprazole is used to treat heartburn, symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis, gastric ulcers, duodenal ulcers, Helicobacter pylori infections of the stomach lining, and rare medical conditions such as Zollinger-Ellison syndrome that cause excess stomach acid production.

Although omeprazole can be purchased without a prescription, the drug has several side effects, some quite serious. A comprehensive review of side effects, warnings, contraindications, and drug interactions can help determine if omeprazole is the right drug to take.

Common side effects of omeprazole

The most common possible side effects of omeprazole are:

Headache
Abdominal pain
Nausea
Diarrhea
Vomiting
Flatulence
Upper respiratory infection
Constipation

Omeprazole is sometimes combined with the antibiotics clarithromycin and amoxicillin to treat H. pylori infection of the stomach lining, an infection associated with gastritis (irritation of the stomach lining) and ulcer formation. When combined with these antibiotics, the most common adverse effects of omeprazole combination therapies are:

Diarrhea
Taste changes
Headache
Tongue discoloration
Nasal congestion

Serious side effects of omeprazole

Serious side effects are rare for omeprazole and include:

Clostridium difficile infection: C. difficile is a bacterial infection of the colon that causes severe diarrhea and fever.
Liver disease: Omeprazole can alter liver function and sometimes lead to liver disease, death of liver tissues, or potentially fatal liver failure.
Lupus: Omeprazole may cause the onset or worsening of lupus erythematosus, an autoimmune condition marked by rash and skin redness.
Allergic reactions: Hypersensitivity reactions can be mild to severe including anaphylaxis, rapid skin swelling (angioedema), severe skin reactions, trouble breathing, and swelling in the kidney’s filtration tubes (interstitial nephritis).

Some serious adverse effects are associated with long-term use of omeprazole. Because of this, the prescribing information states that omeprazole should be used at the lowest effective dose for the shortest period of time. These effects may include:

Bone fractures: Used chronically, omeprazole reduces calcium in the bloodstream by reducing the digestive system’s absorption of calcium. The body balances this loss by pulling calcium from the bones, leading to osteoporosis and an increased risk of fractures. Patients taking omeprazole continuously over the long-term (one year or longer) may be advised to take calcium supplements and/or prescription medication to help prevent osteoporosis and lower fracture risk.
Growths: Omeprazole has been associated with the development of gastric fundic gland polyps, typically benign growths along the stomach lining. More seriously but more rarely, omeprazole has also been associated with slow-growing tumors (carcinoids) in the duodenum, the first part of the small intestine, in patients with Zollinger-Ellision syndrome.
Low magnesium: Long-term omeprazole use can also lower magnesium levels in the body. Low magnesium (hypomagnesemia) leads to several mild to serious consequences including heart rhythm problems or seizures.
Atrophic gastritis and low vitamin B–12: Chronic omeprazole use may also cause atrophic gastritis (swelling and irritation of the stomach lining). Atrophic gastritis leads to vitamin B-12 deficiency, a condition that eventually causes anemia (a shortage of healthy red blood cells). Over time, atrophic gastritis destroys the stomach lining and raises the risk of stomach cancer.
Weight gain: Long-term use of omeprazole increases the risk of weight gain in patients with GERD.

Omeprazole and weight gain

Significant weight gain has been linked with years-long use of omeprazole and other PPIs (proton pump inhibitors) to treat heartburn or GERD symptoms. The reasons are unclear but are thought to possibly be due to increased food consumption when symptoms are better controlled. Keep in mind that omeprazole is only intended for short-term treatment of heartburn, GERD, and other gastrointestinal conditions. Long-term use is only advised for people with rare medical conditions that cause hypersecretion of stomach acid. If heartburn or GERD requires long-term omeprazole treatment, talk to a healthcare professional about alternative drugs, diets, or lifestyle choices to better manage the symptoms.

Omeprazole and cancer

There is a popular notion that omeprazole and other PPIs may increase the risk of stomach cancer. Research on the association of omeprazole with stomach cancer is mixed. Some studies show omeprazole (or any PPI) can increase the risk of stomach cancer. Omeprazole raises the risk of atrophic gastritis, or irritation and swelling of the stomach lining. Atrophic gastritis is considered a precursor to stomach cancer.

More importantly, omeprazole could mask the symptoms of stomach cancer. This is very important. People could start taking omeprazole for heartburn, but the symptoms may be caused by a malignancy. Symptoms such as frequent heartburn should always be evaluated by a healthcare provider.

How long do omeprazole side effects last?

The body clears omeprazole in a few hours, so many side effects will fade in that time. Because the effects of omeprazole on the stomach lining, however, typically last for three or more days, some gastrointestinal side effects may linger for a few days after discontinuing omeprazole. Side effects caused by combining omeprazole with antibiotics, such as taste perversions or tongue discoloration, will resolve a few days after the antibiotics are discontinued. Serious side effects associated with omeprazole, however, like bone loss, low white blood cell counts, liver disease, or kidney problems, may take longer to resolve. Report side effects to your healthcare provider.

Omeprazole contraindications & warnings

Omeprazole and other proton pump inhibitors are effective medications and have a low incidence of side effects when used in the short-term. However, omeprazole may not be for everyone, particularly when used over the long-term.

Dependency

Chronic use of omeprazole can lead to serious and debilitating side effects. In particular, people taking omeprazole for a long time will develop a kind of physical dependency. Omeprazole creates a feedback loop in the stomach. After chronic use of omeprazole, the stomach begins to overproduce stomach acid. For many people, discontinuing long-term use of omeprazole means a rapid return of acid reflux and heartburn.

Allergies

Omeprazole should not be taken by anyone with severe hypersensitivity to omeprazole or any of the inactive ingredients in the medicine.

People with liver problems

Omeprazole is processed by the liver. Patients with liver problems can generally take omeprazole (if approved by your doctor), but the dose may have to be smaller than usual.

People of Asian descent

People of Asian descent have an increased risk of dementia from proton pump inhibitors such as omeprazole. Compared to other populations, a higher percentage of Asians metabolize omeprazole very slowly—20% compared to around 3%. The prescribing information for omeprazole recommends a lower dose in these patients.

Children

Prescription omeprazole is approved to treat GERD symptoms and erosive esophagitis in children between the ages of 1 and 16. Over-the-counter omeprazole is not, so it should not be given to children. If the liquid formulation (packets for oral suspension) is not available, the medication can be compounded by a compounding pharmacy. Or, the contents of a capsule may be mixed with a tablespoon of applesauce and immediately consumed, along with a glass of water.

Seniors

In clinical trials, omeprazole had the same safety record in older adults as it does for other adults.

Pregnancy and breastfeeding

There are no definitive studies on the safety of omeprazole use during pregnancy. The prescribing information advises that pregnant women should use omeprazole only if it’s absolutely necessary.

Omeprazole is present in breast milk in small amounts. Because of possible risks to the nursing baby, the FDA advises that new mothers taking omeprazole either discontinue nursing or discontinue omeprazole.

Omeprazole interactions

Like all drugs, omeprazole interacts with other drugs or substances.

In general, food does not affect the absorption or effectiveness of omeprazole. However, since the goal is to reduce stomach acid, it’s probably not sensible to take omeprazole and then eat foods that overstimulate stomach acid secretion such as spicy foods, fatty foods, sodas, alcohol, or coffee.

Rilpivirine

The HIV medication rilpivirine is contraindicated for use with omeprazole because omeprazole’s effect on stomach acidity reduces the body’s absorption of rilpivirine. This is equivalent to lowering the dose of rilpivirine, a drug that treats HIV/AIDS, a potentially fatal disease.

Other drugs that are also poorly absorbed by the body when combined with omeprazole include:

Many antifungal medications such as ketoconazole
Some oral antibiotics such as amoxicillin and ampicillin
Some anti-HIV drugs such as atazanavir and nelfinavir
Some cancer drugs such as erlotinib
Thyroid hormones
Some iron supplements

Omeprazole interactions with blood thinners (anticoagulants)

Omeprazole interacts with the blood thinner warfarin, and could potentially cause abnormal bleeding or even death. If you are on omeprazole and warfarin, your doctor will monitor you closely and may need to adjust the dosage of your medication(s).

Omeprazole also interacts with the antiplatelet agents Plavix (clopidogrel) and Pletal (cilostazol). Plavix should not be taken with omeprazole. Another antiplatelet drug should be used. If you take Pletal with omeprazole, the dosage of Pletal must be adjusted.

Omeprazole interactions that increase side effects

Omeprazole raises the toxicity and risk of side effects of some prescription drugs by either increasing their absorption or slowing down the body’s metabolism of the drug. These drugs include:

The immune-suppressing drugs methotrexate and tacrolimus
ADHD medications
Benzodiazepines such as diazepam
Some anticonvulsants such as phenytoin and fosphenytoin
The HIV medication saquinavir
The heart medication digoxin

These drugs can generally be taken with omeprazole, but a healthcare professional may need to monitor therapy and reduce doses if necessary.

Some drugs increase the risk of omeprazole side effects if the two are taken together. These include:

Some cystic fibrosis drugs
Cannabidiol
The antifungal drug voriconazole

Omeprazole interactions that decrease effectiveness

Some drugs speed up the body’s metabolism of omeprazole, reducing its effectiveness. These include:

The antibiotics rifampin, rifapentine, , and rifabutin
Certain types of anticonvulsant drugs
Some types of antiviral drugs such as ritonavir
Barbiturates such as butalbital and phenobarbital
Cystic fibrosis drugs lumacaftor/ivacaftor
St. John’s wort

Omeprazole interactions with diuretics (water pills)

Taking diuretics with omeprazole raises the risk of low magnesium. Therapy may need to be monitored or modified.

How to avoid omeprazole side effects

When taken as directed for a limited time, omeprazole has minimal side effects. A few tips can help keep side effects to a minimum:

1. Take omeprazole as directed

Take the daily dose as prescribed at the time prescribed. Over-the-counter omeprazole should be taken in the morning before breakfast. For prescription omeprazole, the prescribing doctor or other healthcare professional will specify a time of day to take the medication. Don’t increase or decrease the dose. Don’t skip a dose for one or two days or take a double dose in place of a missed dose. The medicine must be taken daily over the full period to realize its full benefits.

2. Avoid taking omeprazole long-term

Only take omeprazole for the short-term, anywhere from 10 days to eight weeks. Very few medical conditions require omeprazole to be taken for longer periods. Continual use of omeprazole not only raises the risk of side effects in general, but it also raises the risk of more serious side effects. If the medicine seems to require long-term use, talk to a healthcare provider about alternative therapies.

3. Tell your doctor about all your medical conditions and medications

Because of the risk of side effects, you should tell your doctor about:

Any physical conditions you may have, particularly
- Chest pain
- Nausea, vomiting, stomach pain, or unexplained weight loss
- Skin rash, tiredness, or joint pain
- Low magnesium levels
- Liver problems
- Pregnancy or breastfeeding
All medications you are currently taking, particularly
- Rilpivirine
- Blood thinners/antiplatelets
- Methotrexate or
- Rifampin
All over-the-counter medications and supplements you take, particularly
- St. John’s wort

4. Talk to a healthcare professional before taking OTC omeprazole

Omeprazole can be easily purchased without a prescription. Still, because of the risk of overuse, physical dependency, and side effects, seek medical advice from a healthcare professional before taking over-the-counter omeprazole. There may be better alternatives including other medications, dietary changes, and lifestyle changes.

5. Take omeprazole 30 to 60 minutes before eating

Chances are the doctor’s prescription, medication guide, or package will have an instruction that reads, “Take before a meal.” The general practice is to take omeprazole 30 to 60 minutes before eating.

6. Avoid acid-raising foods and drugs

Many foods or drugs stimulate the stomach lining to increase acid production. These include spicy foods, fried foods, fatty meats, cheeses, peppers, citrus fruits, chocolate, coffee, alcohol, soda pop, aspirin, peppermint, and some mineral supplements. Eating spicy foods and taking omeprazole will not increase the risk of omeprazole side effects, however, they will increase the amount of acid in the stomach, blunting the effects of the medicine.

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Omeprazole side effects and how to avoid them