Evidence Based
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10 Uses of Omeprazole (Prilosec) & Side Effects

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Medically reviewed by
Evguenia Alechine, PhD (Biochemistry), Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Omeprazole

Omeprazole is available by prescription and is also sold over-the-counter for stomach and gut disorders. It is praised for its anti-ulcer and anti-acid effects. However, omeprazole also protects the stomach from certain painkillers, reduces chemotherapy side effects, and reduces gut bleeding. Read on to learn more about how omeprazole works, its other uses and its side effects.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.

What Is Omeprazole?

Omeprazole is known by the following brand names: Prilosec, Zegerid, and Losec.

Omeprazole is a proton-pump inhibitor, which is a type of drug that blocks the release of acid in the stomach. Stomach acid helps break down proteins from food. However, too much stomach acid can cause problems, like ulcers and heartburn [1].

Omeprazole is FDA-approved for multiple stomach disorders including ulcers, gut bleeding, and GERD.

Omeprazole is available both over-the-counter and as a prescription drug. Over-the-counter omeprazole is only intended for frequent heartburn and acid regurgitation. However, higher doses of omeprazole are prescribed to treat more severe conditions like stomach ulcers and Zollinger-Ellison syndrome [2, 3].

Omeprazole Mechanism of Action

Omeprazole reduces acid release in the stomach by blocking the hydrogen-potassium ATPase, which is an enzyme that increases acid levels. This acid release happens in the parietal cells of the stomach [4].

Omeprazole blocks Hh/Gli1 in esophagus cells. Hh/Gli1 is a pathway involved in cell growth and is found in higher levels in cancer [5, 6].

Omeprazole increases superoxide dismutase and aquaporin-4 in the stomach (mucosal cells). Superoxide dismutase is an important antioxidant enzyme, and aquaporin-4 is a molecule that helps maintain water balance in cells [7, 8].

Proton Pump Inhibitors vs. H2 Receptor Blockers

H2 blockers are a different kind of drug, which has also been used for gut disorders. They block the histamine H2 receptor and reduce stomach acid levels. Proton pump inhibitors block the hydrogen-potassium ATPase, which is the enzyme that produces stomach acid. H2 receptor blockers have largely been displaced by proton-pump inhibitors [9].

In 1,283 patients (randomized controlled trial) with internal stomach bleeding, proton-pump inhibitors significantly reduced acid release and recurrent surgery when compared to H2 blockers [10].

In patients with acid-related disorders, omeprazole is more effective in reducing stomach acid than H2 blockers [11].

Omeprazole healed more ulcers (duodenal), reduced ulcer patientspain, and reduced rates of relapse more than ranitidine, an H2 blocker [12].

Omeprazole vs. Esomeprazole

Esomeprazole (Nexium) is another proton-pump inhibitor chemically similar to omeprazole. In multiple studies of patients with GERD, esomeprazole reduced stomach acid levels more than omeprazole [13, 14].

Uses of Omeprazole

1) Helps Dyspepsia

Dyspepsia is characterized by symptoms of pain, discomfort, belching, or reflux, and is caused by things like ulcers and GERD. Functional dyspepsia has the same symptoms as non-functional dyspepsia, but the causes are different for functional dyspepsia and include things like nervous system dysfunction and sensitivity to certain foods [15].

In 471 patients (randomized controlled trial) with dyspepsia, omeprazole reduced pain at nighttime, especially in those with a high BMI [16].

In 1,262 patients (double-blind randomized controlled trial) with functional dyspepsia, omeprazole showed a modest benefit over placebo. This effect was not seen in patients with poor gut flow and difficulties digesting food [17].

In 24 patients (double-blind randomized controlled trial) with functional dyspepsia, only those who had experienced more than 32 reflux episodes (periods of high stomach acid) had a successful response to omeprazole [18].

In 829 patients (randomized controlled trial) with acid-related symptoms, such as pain, discomfort, bloating, and nausea, omeprazole reduced symptoms more than placebo. The patients who received omeprazole also returned to the doctor less often over the following year [19].

Note: Placebo effect makes up 30 to 40% of the benefit seen in randomized control trials of treating dyspepsia with proton-pump inhibitors like omeprazole [20].

2) Helps Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is a disorder in which the stomach produces too much acid because of either a tumor or enlargement of the pancreas. This leads to ulcers [21].

In a study (prospective) of 116 patients for 114 months, omeprazole reduced the high levels of stomach acid in those with Zollinger-Ellison syndrome without any toxic side effects [22].

In 49 patients with Zollinger-Ellison syndrome, omeprazole reduced stomach acid hypersecretion in 33 patients [23].

In 9 patients with Zollinger-Ellison syndrome, omeprazole reduced acid secretion by 77% to 100%. This effect lasted up to 2 years and treatment showed no negative side effects [24].

In patients with Zollinger-Ellison syndrome, omeprazole was safe and effective for up to 4.5 years at 180 mg, and for 9 years at doses up to 60 mg. A small minority of patients experienced side effects such as a headache, rash, and constipation [22, 25].

In multiple studies, omeprazole became more effective over time, requiring smaller doses than usually prescribed for Zollinger-Ellison syndrome [26, 23].

3) Helps with Gut Bleeding

In patients with gut bleeding, omeprazole was more effective than H2 blockers at preventing rebleeding [10].

In 142 patients (randomized controlled trial) with acute peptic ulcer bleeding, a low dose of omeprazole (intravenous 30 mg once per day for 3 days) prevented peptic ulcer rebleeding [27].

However, in a study (prospective) of healthy patients given high doses of omeprazole (continuous 24 intravenous infusions), the patients still had substantial levels of stomach acid, which can lead to bleeding [28].

In 220 patients (double-blind randomized controlled trial) with gut ulcers and signs of recent bleeding, omeprazole significantly reduced recurrent bleeding and recurrent surgery compared to placebo (but not in those with arterial sprouting or oozing) [29].

In 149 patients (double-blind randomized controlled trial) with a high-risk peptic ulcer, omeprazole decreased the duration of hospital stay (average 11.3 hours less than placebo), rebleeding, and the need for blood transfusions [30].

In 41 patients (randomized controlled trial) with upper gut bleeding, a single dose (80 mg) of omeprazole followed by 3-day treatment (8 mg per hour, intravenously) reduced stomach acid levels more than periodic treatments (40 mg given intravenously every 12 hours) [31].

4) Provides Protection from NSAIDs

NSAIDs, which are common anti-inflammatory drugs (aspirin, ibuprofen, naproxen, etc.), increase the risk of peptic ulcers. Omeprazole is commonly prescribed along with NSAIDs to reduce acid levels and protect the stomach [32, 33].

In patients with inflammatory disorders, omeprazole combined with NSAIDs like ketoprofen prevented ulcers and decreased dyspepsia symptoms [34].

In 156 patients with ulcers (double-blind randomized controlled trial) receiving long-term NSAID treatment, 20 mg of omeprazole reduced ulcers [35].

In 935 patients (randomized controlled trial) taking NSAIDs over a prolonged period of time, omeprazole reduced ulcers, pain, and heartburn. Omeprazole was better tolerated and reduced the return of ulcers compared to misoprostol, another drug used to treat ulcers [36, 37].

In 541 patients (double-blind randomized controlled trial) taking NSAIDs over a prolonged period of time, omeprazole healed and prevented ulcers more effectively than did ranitidine, which is an H2 receptor blocker used to reduce stomach acid levels [38].

5) Helps Heartburn and GERD

In 355 patients with GERD (double-blind randomized controlled trial), 20 mg of omeprazole reduced heartburn, regurgitation, nausea, pain, and difficulty swallowing [39].

In 216 patients with mild GERD (randomized controlled trial), daily omeprazole reduced the return of symptoms compared to taking it as needed [40].

For patients with erosive GERD (meta-analysis), omeprazole reduced symptoms more than H2 blockers or antacids. Omeprazole seems to be the best treatment option for patients with GERD who have not had success with other treatments [41].

In 230 patients with reflux esophagitis, omeprazole use for up to 6.5 years was effective in reducing pain and heartburn, despite periodic relapses. The long-term use of omeprazole (up to 11 years) seems to be safe and helpful for those with reflux esophagitis [42].

In 41 patients (double-blind randomized controlled trial) with GERD, omeprazole was taken for 1 month effectively reduced symptoms. However, relapse occurred rapidly after omeprazole was stopped [43].

6) Helps H. pylori Infections

H. pylori is a bacteria with a high presence in the gut. It is common for people throughout the world. While it does not always lead to symptoms, it can eventually cause ulcers and lead to stomach cancer [44].

Omeprazole given with 2 antibiotics (amoxicillin, clarithromycin, or metronidazole), also known as triple therapy, can eradicate H. pylori. This same treatment seems to also be effective for children with H. pylori [45, 46].

In 89 patients (meta-analysis) with H. pylori, omeprazole given along with 2 antibiotics (clarithromycin and metronidazole) eradicated H. pylori in 85 to 95% of patients [47].

In 40 patients (randomized controlled trial) with ulcers and H. pylori, omeprazole combined only with amoxicillin was as good as triple therapy in eradicating H. pylori [48].

7) Reduces Chemotherapy Side Effects

In 125 rectal-cancer patients (retrospective analysis), omeprazole increased the effectiveness of the chemoradiotherapy and decreased the return of tumors [49].

In 228 cancer patients (double-blind randomized controlled trial) receiving chemotherapy, omeprazole significantly reduced ulcers, pain, and heartburn compared to ranitidine and placebo [50].

In 128 cancer (breast and colon) patients (double-blind randomized controlled trial), omeprazole significantly reduced ulcers, blocked stomach erosion, and reduced pain and heartburn compared to misoprostol, (another drug used to treat ulcers) and placebo [51, 37].

8) Reduces Stomach and Esophagus Inflammation

In 96 patients (double-blind randomized controlled trial) with stomach inflammation, omeprazole reduced inflammation levels by 75% (and by 97.92% when combined with domperidone) [52].

In 196 patients (double-blind randomized controlled trial) with severe inflammation and ulcers of the esophagus, omeprazole significantly reduced symptoms and ulcers [53].

Omeprazole reduced inflammation and cell damage in rats with alcohol-induced stomach inflammation [7, 54].

9) Reduces Peptic Ulcers

Omeprazole healed peptic ulcers in 29 out of 30 patients who previously had no success with other anti-ulcer drugs [55].

In more than 600 patients with stomach ulcers, omeprazole healed ulcers more effectively than ranitidine, an H2 blocker [56].

10) May Reduce Cancer Growth

In 125 rectal-cancer patients (meta-analysis) being treated with chemotherapy, omeprazole decreased the return of tumors [49].

Omeprazole blocked tumor growth in the esophagus (blocks Hh/Gli1 in esophagus cells) [5].

The exact mechanism of omeprazole against tumor growth is unknown. However, omeprazole may sensitize tumors to chemotherapy, induce tumor cell death (apoptosis and autophagy), and may improve the immune response to cancer growth [57, 58, 59, 60].

Side Effects of Omeprazole

In 19,000 individuals who have taken omeprazole, no serious side effects were found. The most common side effects are [61]:

Proton-pump inhibitors can cause fundic gland polyps, which are abnormal growths of tissue at the top of the stomach. Polyps are often harmless but can turn into cancer. These are known to go away after quitting proton-pump inhibitors [62].

Proton-pump inhibitors may also cause higher blood levels of gastrin, a hormone that releases acid in the stomach [63].

Proton-pump inhibitors may increase the risk for community-acquired pneumonia, which is an infection that causes inflammation of the air sacs of the lungs [63].

Eradicating H. pylori may worsen reflux disease by increasing stomach acid levels [64].

Rare Side Effects

  • Multiple studies have linked omeprazole to various types of epidermal necrosis (TEN, ADEN, Stevens-Johnson syndrome), a set of life-threatening conditions [65, 66, 67, 68, 69, 70].
  • Chronic use of omeprazole may be a risk factor for dementia and Alzheimer’s disease [71, 72, 73, 74, 75].
  • Omeprazole increases the risk of bone fractures [75, 76, 77, 78, 79].
  • Omeprazole may cause heart problems, but results are mixed [80, 81, 81, 82].
  • Rarely, patients may develop allergic reactions to omeprazole over time, with symptoms ranging from minor rashes to severe, flu-like symptoms and widespread blisters [83, 84, 85].
  • Omeprazole may cause Clostridium difficile-related diarrhea [86].
  • In patients with H. pylori, omeprazole increased bacterial infection with non-H. pylori species, increased nitrite levels, and reduced vitamin C levels in the stomach [87].
  • Treating patients with H. pylori and inflammation of the esophagus with omeprazole may increase levels of stomach inflammation [88].
  • In 63,397 patients, long-term omeprazole use (average of 3 years) increased the risk of stomach cancer, even after eliminating H. pylori [89].
  • In 17 patients, omeprazole caused inflammation of the kidneys (acute interstitial nephritis) [90].
  • Omeprazole increased impotence and increased male breast tissue (gynecomastia) in 15 men taking 20 to 60 mg [91].
  • In 52 patients with GERD (randomized controlled trial), taking omeprazole at doses ranging from 10 to 20 mg for an average of 2.2 years resulted in weight gain when compared to healthy controls [92].

Omeprazole and Vitamin/Mineral Deficiency

Omeprazole may reduce the absorption of vitamin B12. However, it is unclear whether long-term omeprazole use leads to a full vitamin B12 deficiency [93].

Omeprazole increases the risk of deficiencies of vitamin C, vitamin B12, calcium, iron, and magnesium. This risk is relatively low for most people, but it may be a concern for elderly or malnourished patients, including those on chronic dialysis (filtering of the blood) [94].

In at least 40 cases, proton-pump inhibitors caused magnesium deficiencies. The FDA issued a warning statement in 2011 regarding this possible side effect of proton-pump inhibitors. Cell studies confirmed this blocking of magnesium absorption by omeprazole (blocking TRPM 6 and 7 channels) [95].

However, in 109 patients with Zollinger-Ellison syndrome, continuous omeprazole treatment for 6 years did not reduce iron levels [96].

Omeprazole Use During Pregnancy and Breastfeeding

It is unknown if omeprazole is completely safe to take during pregnancy, however, several studies have found no increased risk to the fetus. Caution is still advised and you should consult with your doctor about your options [97, 98].

Omeprazole is found in breast milk, but it is not enough to be considered a risk to the child. Again caution is advised and you should speak to your doctor [99].

Drug Interactions of Omeprazole

Omeprazole may interact with any drug broken down by the enzymes CYP2C19 or CYP3A4, since omeprazole blocks these enzymes. This increases the amount of the following drugs in the blood [100, 101, 102, 103, 104, 105]:

  • Cilostazol
  • Clopidogrel
  • Diazepam (Valium)
  • Digoxin
  • Disulfiram (Antabuse)
  • Erlotinib
  • Iron-containing medicines (ferrous fumarate, ferrous gluconate, ferrous sulfate, and others)
  • Methotrexate
  • Mycophenolate mofetil
  • Phenytoin
  • St. John’s Wort
  • Tacrolimus
  • Warfarin (Coumadin, Jantoven)
  • Antibiotics (ampicillin, amoxicillin, clarithromycin, rifampin)
  • Antifungal medicine (ketoconazole, voriconazole)
  • HIV or AIDS medication (atazanavir, nelfinavir, saquinavir)

Omeprazole may also interact with any drug broken down by the enzymes CYP1A1 or CYP1A2, as omeprazole activates these enzymes and reduces the amount of the following drugs [106, 107]:

  • Granisetron
  • Phenobarbital
  • Chlorzoxazone
  • Clofibrate
  • Daunorubicin
  • Caffeine
  • Carbamazepine
  • Fluvoxamine
  • Ketoconazole
  • Miconazole

Analyze your genome with SelfDecode and find out if you’re a fast or slow metabolizer for these drugs.

Omeprazole may reduce the absorption of certain drugs that require stomach acids, such as ketoconazole, itraconazole, and indinipur [63, 108].

Ten healthy men were given 40 mg of omeprazole every morning for 10 days. This treatment reduced secretin levels and increased gastrin levels, which may decrease the absorption of some drugs including ketoconazole, cefpodoxime, enoxacin, atazanavir, itraconazole, and dipyridamole [109, 110].

In 93 patients undergoing maintenance hemodialysis, omeprazole reduced the risk of peptic ulcer [111].

Forms and Dosage of Omeprazole

Omeprazole is available in immediate and delayed-release tablets, capsules, orally disintegrating tablets (ODTs), and oral suspensions. The doses available for each form vary, but they come in 10 mg, 20 mg, or 40 mg for the tablets, capsules, and ODTs. Oral suspensions are usually reconstituted to 1 mg/mL or 2mg/mL.

The dosage for omeprazole depends on the condition and doctor recommendation, but the optimal dose for most patients is 20 mg taken either once or twice daily [112, 61].

Genetics Related to Omeprazole

Certain genes may increase or decrease your response to omeprazole:

  • CYP3A4 and CYP2C19: Omeprazole inhibits the enzymes CYP3A4 and CYP2C19, which break down many molecules, including omeprazole. Therefore, your genes for these enzymes may increase or decrease your response to omeprazole [100, 101, 102, 103, 104, 105].
  • CYP1A1 and CYP1A2: Omeprazole activates the enzymes CYP1A1 and CYP1A2, which break down many molecules [106, 107].
  • TRPM6: Variations in the TRPM6 gene, which code for channels (claudin-16) that allow magnesium in and out of the cell, may lead to magnesium deficiency when taking omeprazole [113].

Natural Alternatives

Omeprazole is very effective at reducing stomach acid, but for many it’s not enough.

One study reveals that over 85% of people still experience acid reflux symptoms despite treatment with proton-pump inhibitors (PPIs) [114].

Considering the safety concerns of long-term use and its high cost, it’s no surprise that many are seeking alternative options. In fact, about 42% of people supplement their PPI medication with other treatments [114].

Luckily, there are several natural alternatives that may help reduce stomach acid and protect the gut.

Of course, you should always consult your doctor before changing or stopping your medications. It’s also a good idea to let your doctor know of all the supplements you are currently taking.

Melatonin

Melatonin is mostly known for its role in sleep, but it also has important effects on the stomach. Interestingly, the digestive system is one of the largest producers of melatonin in the body [115, 116].

Research shows that melatonin reduces stomach acid secretion. It also increases nitric oxide, prostaglandin E2, and gastrin, all of which help protect the stomach [117, 118].

One study of 351 people compared the effects of omeprazole to a supplement containing melatonin. All of the patients taking the supplement experienced complete symptom relief after 40 days. Only about 65% of omeprazole users saw symptom relief [119].

However, it’s important to note that the supplement contained other ingredients, like vitamin B6, vitamin B12, L-tryptophan, and folic acid [119].

According to a different study of 36 people, omeprazole is more effective for acid reflux than melatonin alone. However, melatonin did still provide symptom relief. It was also effective when taken in combination with omeprazole [120].

Acupuncture

Researchers are discovering that acupuncture may offer some interesting health benefits.

One study looked at acupuncture in 30 people who did not experience relief from normal doses of PPIs. They found that adding on acupuncture is more effective at controlling acid reflux than doubling the PPI dose [121].

An analysis of 12 trials including 1,235 people also found that acupuncture is safe and effective for acid reflux. However, they state that the quality of existing research is poor and better studies are needed [122].

Shilajit

Shilajit, also known as mumijo, is fairly interesting. It’s a tar-like substance that oozes out of mountain rocks, most notably the Himalayas [123].

This sticky substance is actually a biomass made up of many different plant materials, nutrients, and minerals [123].

Research is exploring the health benefits of shilajit, including its effect on the stomach.

For instance, a study in rats found that shilajit protects against ulcers by reducing stomach acidity. Researchers also found that shilajit reduces stomach acidity more than ranitidine (Zantac) [124].

Limonene

Limonene is a natural compound found in the oils of many citrus fruits.

In one study, 17 out of 19 patients no longer had heartburn symptoms after just 2 weeks of taking daily limonene [125].

A similar study of 13 people found that daily limonene for 2 weeks results in complete relief of all symptoms in almost all participants [125].

Diet and Lifestyle Changes

It’s no surprise that certain foods can exacerbate acid reflux. Avoiding foods that trigger symptoms can be a simple and effective strategy.

Some foods that can worsen GERD symptoms include [126]:

  • Spicy foods
  • Citrus
  • Carbonated beverages
  • Chocolate

On top of that, a low-carb diet may help reduce heartburn. A small study of 8 obese individuals found that a diet restricted to 20 g of carbohydrates per day improves symptoms [127].

Several lifestyle changes can also help. Factors that can worsen GERD symptoms include [126]:

  • Tobacco use
  • Alcohol
  • Obesity
  • Lying down

However, the impact of diet and lifestyle changes is not fully understood.

For instance, a large review was conducted in 2006 that analyzed 100 different GERD studies. Interestingly enough, they found that the only effective diet/lifestyle changes are elevating the head of the bed and weight loss [126].

Understand how your genes may be affecting how you respond to medications (pharmacogenomics) at SelfDecode.

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About the Author

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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