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Last Update: February 7, 2023.

Continuing Education Activity

Omeprazole is a proton-pump inhibitor used to manage and treat several conditions, including uncomplicated heartburn, peptic ulcer disease, gastrointestinal reflux disease, Zollinger-Ellison syndrome, multiple endocrine adenomas, systemic mastocytosis, erosive esophagitis, gastric ulcers, and helicobacter pylori infection. This activity reviews the indications, mechanism of action, administration, dosage, contraindications, interactions, and potential adverse effects of omeprazole therapy. It also highlights other key elements of omeprazole therapy in the clinical setting as it relates to the essential points needed by members of an interprofessional team managing the care of patients with peptic ulcers and other related conditions and sequelae.


  • Describe the mechanism of action of omeprazole.
  • Identify the administration options for omeprazole.
  • Outline potential adverse effects associated with omeprazole therapy.
  • Review the importance of improving care coordination amongst interprofessional team members to improve outcomes for patients receiving omeprazole.
Access free multiple choice questions on this topic.


FDA-approved Indication

  • Omeprazole is indicated for the short-term treatment of peptic ulcer disease in adults, where most patients heal within four weeks.[1]
  • Patients with duodenal ulcer disease and H. pylori infection that is active for up to one year may benefit from combination therapy of omeprazole with clarithromycin, amoxicillin, and metronidazole. Studies show a reduced recurrence of duodenal ulcers with H. pylori treatment and a reduced rate of clarithromycin resistance with quadruple therapy.[2][3]
  • Omeprazole is also indicated for gastric ulcers in adults.
  • Omeprazole is indicated for gastroesophageal reflux disease in pediatric and adult populations.[4]
  • Omeprazole is also indicated for healing erosive esophagitis in both adults and children.[5]
  • Omeprazole is indicated for conditions prone to hypersecretion, such as Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis in adults.[6]
  • Uncomplicated heartburn (OTC use)

Non-FDA-approved Indications

  • Barrett esophagus[7]
  • Stress ulcer prophylaxis[8]

Mechanism of Action

Omeprazole is a proton pump inhibitor. It is a substituted benzimidazole that belongs to the antisecretory class of compounds. It inhibits the parietal cell H+ / K+ ATP pump, the final step of acid production. In turn, omeprazole suppresses gastric basal and stimulates acid secretion. The inhibitory effects of omeprazole occur rapidly within 1 hour of administration, with the maximum effect occurring in 2 hours. The inhibitory effects last for approximately 72 hours after administration, followed by a return to baseline activity in 3 to 5 days. The effects will plateau on the fourth day with daily use of the medication.[9]

Omeprazole is extensively metabolized by the hepatic cytochrome P450 enzyme system, mainly via CYP2C19 and CYP3A4 isozymes. Urinary excretion is a primary route for the excretion of omeprazole metabolites. Omeprazole has a short half-life of a half-hour to an hour in healthy subjects and about three hours half-life for patients with hepatic impairment. However, the pharmacological effect of omeprazole lasts much longer as the drug preferentially concentrates in parietal cells, where it forms a covalent linkage with H+/K+ ATPase, which it irreversibly inhibits.[10]


Absorption: Delayed-release Omeprazole capsules contain enteric-coated granules that only release omeprazole once the drug leaves the stomach. Once the drug is released, it is rapidly absorbed. It has an absolute bioavailability of 30 to 40 % (20 to 40 mg oral dose), and the peak plasma concentration is attained in 0.5 to 3.5 hours; peak plasma concentration and AUC are increased proportionally up to 40 mg. However, due to saturation of the first-pass effect above a 40 mg dose, those increase greater than linear at a dose above 40 mg.

Distribution: Plasma protein binding is approximately 95%.

Metabolism: It is metabolized mainly via the cytochrome P450 system.

Elimination: It is eliminated mainly in urine as an unchanged drug and its metabolites. Its plasma half-life is 0.5 to 1 hour after oral administration in healthy subjects.[11]


The administration route for omeprazole heavily depends on the diagnosis of a medical condition and the patient's preference. It is available as a delayed-release oral suspension, capsules, tablets, and orally disintegrating tablets.

  • The recommended oral dose for treating symptomatic GERD absent esophageal lesions is 20 mg daily for up to 4 weeks. However, therapy may extend to 8 weeks if erosive lesions are present.
  • For H. pylori infection, the recommended adult oral regimen is 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg plus metronidazole 500 mg, each given twice daily for fourteen days. If an ulcer is present on initial diagnosis, then it is recommended to provide an additional 18 days of omeprazole 20 mg once daily. Clinicians should expect antimicrobial resistance; if treatment fails, susceptibility testing should be performed, and the treatment should be adjusted accordingly.
  • The recommendation for patients with hypersecretory diseases is to start at 60 mg once daily, followed by the individualization of dosage based on the patient's need and clinical response. If the daily dose exceeds 80 mg, they should divide the dosage throughout the day. Long-term treatment with omeprazole is not recommended; eventually, switching to an H2 inhibitor is preferred.

Omeprazole should be ingested 30 to 60 minutes before meals. It may be taken with antacids. When taken twice daily, the first dose should be before breakfast and the second dose before dinner. The capsule and tablet should be swallowed whole, not crushed or chewed. However, it is permissible to open the capsule and mix the contents with one tablespoon of applesauce, soft enough to be swallowed without chewing. The suspension should be left to thicken for two to three minutes, following reconstitution and administration within 30 minutes. Drink with a glass of cool water to ensure the complete swallowing of the pellets.

Omeprazole therapy should be at the lowest dose possible for the shortest duration; physicians have looked into deprescribing proton pump inhibitors if patients are on it long-term. One group recommends deprescribing PPIs, meaning reducing the dose, stopping completely, or using "on-demand" dosing in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis and who have achieved symptomatic resolution. The clinician should monitor symptoms at four weeks, 12 weeks, and 6 to 12 months. But these recommendations do not apply to patients who have or had Barrett's esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers.[12]

Specific Patients Population 

  • Patient with Hepatic Impairment: As per the manufacturer's label, the bioavailability in patients with hepatic impairment increased by 100 % compared to the I.V. dose due to a decrease in the first-pass effect. Plasma half-life also increased to 3 hours instead of 0.5 to 1 hour. Dose reduction should be considered for patients with hepatic impairment. 
  • Patient with Renal Impairment: There is no dose adjustment guidance in the manufacturer label for patients with renal impairment or with creatinine clearance ranging between 10 to 62 mL/min/1.73 m2. A slight increase in bioavailability was observed in the patient with renal impairment as a primary route of excretion of omeprazole metabolites; their elimination slowed in proportion to the decreased creatinine clearance.
  • Pregnant Women: Omeprazole crosses the placenta and is pregnancy safety category C.[13] Some PPIs are considered pregnancy category B, with a  better safety profile established.
  • Breastfeeding Women: Limited information indicates that maternal omeprazole doses of 20 mg daily would not cause any adverse effects in breastfed infants.[14]
  • Pediatric Patients: The dosage depends on the child's weight for pediatric patients between the ages of 1 and 16.
    • Between 5 to 10 kg: 5 mg daily
    • Between 10 to 20 kg: 10 mg daily
    • More than 20 kg: 20 mg daily
  • Geriatric Patients: The bioavailability is increased in geriatric patients as the rate of elimination decreases in the geriatric population. There is 76% drug bioavailable when a single dose of 40 mg oral buffered solution is administered to healthy elderly volunteers versus 58% in young volunteers at the same dose.

Adverse Effects

Omeprazole is considered a benign drug; however, the primary adverse effects reported in drug labeling include headache (6.9%), abdominal pain (5.2%), diarrhea (3.7%), nausea (4.0%),  vomiting (3.2%), and flatulence (2.7%) in adults. Other than these adverse effects, cough, rash, asthenia, back pain, regurgitation, upper respiratory infection, constipation, and dizziness are also reported in 1 to 2 % of patients.

The major adverse effects in the pediatric population are similar to adults; the most frequent events were reportedly fever and respiratory infections.

Proton pump inhibitors (PPI) therapy may correlate with an increased risk of Clostridioides difficile (C. diff) associated diarrhea.[15] 

There are rare reports of hypomagnesemia with prolonged treatment with PPIs.[16]

Avoid concomitant use of omeprazole with St John’s wort or rifampin and other CYP450 inducers due to the potential reduction in omeprazole concentration.[17]

There is an increased risk of drug resistance or toxic effect of antiretroviral medicines when used with omeprazole.

Patients on warfarin could experience increased INR, resulting in bleeding when used with omeprazole.

Some evidence has shown a diminished antiplatelet activity of clopidogrel due to impaired CYP2C19 function when used in conjunction with 80 mg omeprazole.[18]

According to product labeling, warnings and precautions are advised for patients who develop acute tubulointerstitial nephritis,  cyanocobalamin (vitamin B12) deficiency, and cutaneous or systemic lupus erythematosus while on omeprazole.

Long-term and multiple daily dose PPI treatment may have connections with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. However, newer studies show that long-term PPI use does not correlate with changes in bone mineral density or bone strength that would predispose to increased fracture risk, suggesting this relationship is not causal.[19][20]

Drug Interactions

Coadministration with Amoxicillin: Combine therapy of omeprazole and amoxicillin may lead to serious fatal hypersensitivity reactions in patients on penicillin therapy. These reactions are more common in patients with a history of hypersensitivity reactions to penicillins, cephalosporins, or other allergens. During combined therapy, if such reactions occur, amoxicillin therapy should be discontinued, and appropriate therapy should be implemented.

Coadministration with Clarithromycin: Combine therapy of omeprazole and clarithromycin may increase the plasma levels of omeprazole and clarithromycin.

CYP2C19 Substrates: Omeprazole competitively inhibits CYP2C19, which may increase the plasma concentration of other CYP2C19 substrates like diazepam, proguanil, moclobemide, phenytoin, and warfarin.[21]


Omeprazole is contraindicated in patients with a history of hypersensitivity to the drug or any excipients from the dosage form. Hypersensitivity reactions like anaphylactic shock, angioedema, interstitial nephritis, anaphylaxis, urticaria, and bronchospasm may occur. According to product labeling, omeprazole is contraindicated in patients taking dosage forms containing rilpivirine.


When using omeprazole, patients should be monitored for signs and symptoms of gastroesophageal reflux disease and peptic ulcer disease.

Physicians should also monitor for C. difficile-associated diarrhea and hypomagnesia when patients are on omeprazole long-term.

Omeprazole is listed in Beers criteria, and care should be taken when used in the geriatric population for more than eight weeks and reassess the need for continuation of treatment.[22]

Monitor INR and prothrombin time in patients using warfarin and omeprazole.

Caution should be exercised when co-administered with CYP2C19 substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam, digoxin).[23]


Omeprazole overdose of up to 2400 mg (120 times higher than recommended clinical dose) has been reported. The adverse reactions like confusion, drowsiness, tachycardia, blurred vision, headache, dry mouth, nausea, vomiting, diaphoresis, and flushing were seen with overdose. These symptoms were transient, and no serious clinical outcomes were observed with monotherapy. No specific antidote for omeprazole overdosage is known. Dialysis may not be helpful as omeprazole is extensively protein bound. Symptomatic and supportive care is recommended with an overdose.[24]

Enhancing Healthcare Team Outcomes

Omeprazole was the first proton pump inhibitor discovered in 1979, and it has revolutionized the management of numerous gastrointestinal diseases. Its efficacy compared to new proton pump inhibitors has been studied. One study showed the superiority of esomeprazole for the Japanese population, especially with CYP2C19 polymorphism over omeprazole and other proton pump inhibitors.[25] Studies have shown equivalent efficacy when comparing omeprazole and rabeprazole.[26] Comparative studies with multiple proton pump inhibitors, including omeprazole, have shown greater cost-effectiveness and management of symptoms when using esomeprazole.[27][28][29]

Healthcare workers, including physicians, nurse practitioners, physician assistants, etc., should avoid empirical prescriptions of omeprazole. Given the number of potential adverse events associated with long-term proton pump inhibitor use, it is recommended that clinicians prescribe the lowest effective dose of omeprazole for the shortest period and monitor the patients to adjust the dose according to their needs. Nursing staff should counsel patients, ensure proper medicine administration, and monitor patients for therapeutic insufficiency. Pharmacists should check for drug-drug interactions, verify the dose, and inform the prescriber of any adverse events. All clinicians, specialists, nursing staff, PAs, and pharmacists must collaborate as an interprofessional team and coordinate the treatment plan to enhance patient outcomes using omeprazole. [Level 5]

Review Questions


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Laine L, Suchower L, Frantz J, Connors A, Neil G. Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials. Am J Gastroenterol. 1998 Nov;93(11):2106-12. [PubMed: 9820381]
Prasertpetmanee S, Mahachai V, Vilaichone RK. Improved efficacy of proton pump inhibitor - amoxicillin - clarithromycin triple therapy for Helicobacter pylori eradication in low clarithromycin resistance areas or for tailored therapy. Helicobacter. 2013 Aug;18(4):270-3. [PubMed: 23356886]
Bianchi Porro G, Pace F, Peracchia A, Bonavina L, Vigneri S, Scialabba A, Franceschi M. Short-term treatment of refractory reflux esophagitis with different doses of omeprazole or ranitidine. J Clin Gastroenterol. 1992 Oct;15(3):192-8. [PubMed: 1479161]
Sontag SJ, Hirschowitz BI, Holt S, Robinson MG, Behar J, Berenson MM, McCullough A, Ippoliti AF, Richter JE, Ahtaridis G. Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study. Gastroenterology. 1992 Jan;102(1):109-18. [PubMed: 1727744]
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Cooper BT, Neumann CS, Cox MA, Iqbal TH. Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's oesophagus. Aliment Pharmacol Ther. 1998 Sep;12(9):893-7. [PubMed: 9768533]
Levy MJ, Seelig CB, Robinson NJ, Ranney JE. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci. 1997 Jun;42(6):1255-9. [PubMed: 9201091]
Sachs G, Wallmark B. The gastric H+,K+-ATPase: the site of action of omeprazole. Scand J Gastroenterol Suppl. 1989;166:3-11. [PubMed: 2557669]
Howden CW. Clinical pharmacology of omeprazole. Clin Pharmacokinet. 1991 Jan;20(1):38-49. [PubMed: 2029801]
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Kahrilas PJ, Shaheen NJ, Vaezi MF., American Gastroenterological Association Institute. Clinical Practice and Quality Management Committee. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology. 2008 Oct;135(4):1392-1413, 1413.e1-5. [PubMed: 18801365]
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Belhocine K, Vavasseur F, Volteau C, Flet L, Touchefeu Y, Bruley des Varannes S. Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole. BMC Gastroenterol. 2014 Jul 15;14:128. [PMC free article: PMC4110066] [PubMed: 25027286]
Çelebi A, Aydın D, Kocaman O, Konduk BT, Şentürk Ö, Hülagü S. Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease. Turk J Gastroenterol. 2016 Sep;27(5):408-414. [PubMed: 27782887]
Miner P, Katz PO, Chen Y, Sostek M. Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol. 2003 Dec;98(12):2616-20. [PubMed: 14687806]
Röhss K, Lind T, Wilder-Smith C. Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with gastro-oesophageal reflux symptoms. Eur J Clin Pharmacol. 2004 Oct;60(8):531-9. [PubMed: 15349707]

Disclosure: Neal Shah declares no relevant financial relationships with ineligible companies.

Disclosure: William Gossman declares no relevant financial relationships with ineligible companies.

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