Omeprazole
- 40 mg lyophilized vial (IV)
- 10 mg, 20 mg and 40 mg standard and extended release capsules, tablets (PO)
Executive Summary
(July 5, 2023)
Omeprazole is the most prescribed proton pump inhibitor (PPI) worldwide. It reduces gastric acid secretion by irreversibly blocking the H+/K+ ATPase enzyme within the gastric parietal cells (9).
Globally, PPIs are commonly prescribed and administered in the ED for a variety of conditions, including gastrointestinal bleeding, gastroesophageal reflux disease, dyspepsia, etc. Nevertheless, there is no need to initiate PPI therapy within the first hours of emergency care, and no benefit has been proven in providing acute symptomatic relief in the ED.
PPIs are frequently initiated in the ED as prophylaxis for stress peptic ulcer disease in critically ill patients with favorable outcomes (12).
The acute management of upper gastrointestinal bleeding in the ED typically involves the empiric administration of an IV PPI bolus (such as omeprazole) followed by continuous infusion or intermittent boluses. However, the benefits of emergent administration are questionable, as it does not reduce mortality, rebleeding, use of hemoderivatives, or need for surgery (1, 2, 4, 6). On the other hand, it has been associated with a reduced incidence of high-risk stigmata of hemorrhage (4, 6).
Resuscitation and bleeding control of hemorrhagic shock should be prioritized, and the administration of omeprazole should not delay upper endoscopy or standard management for severe hemorrhage (eg., administration of hemoderivatives).
Adult dose for peptic ulcer bleeding
Intermittent dosing (3, 14)
80 mg IV, followed by 40 mg every 6 hours IV.
Therapy is usually started empirically in upper GI bleeding before endoscopic visualization.
Adult dose
Adult dose for peptic ulcer bleeding
Intermittent dosing (3, 14)
80 mg IV, followed by 40 mg every 6 hours (days 0 to 3 of the index endoscopy).
High-risk patients should receive 40 mg every 12 hours from days 4 to 14 of the index endoscopy.
Continuous infusion (13, 14)
80 mg IV, followed by 8 mg/hr of continuous infusion for 3 days.
High-risk patients should receive 40 mg every 12 hours from days 4 to 14 of the index endoscopy.
Therapy is usually started empirically in upper GI bleeding before endoscopic visualization
Adult dose for stress peptic ulcer disease prophylaxis
40 mg IV or PO, every 24 hours
Indications
US-FDA labeled (15)
Peptic ulcer disease, treatment of duodenal or gastric ulcers
Gastroesophageal reflux disease (GERD)
Erosive esophagitis and heartburn
Gastric hypersecretion (Zollinger-Ellison syndrome)
Off-label
Aspiration prophylaxis in patients undergoing anesthesia
Functional dyspepsia
NSAIDs induced ulcers primary prevention
Stress ulcer prophylaxis in select critically ill patients
PPIs overview
Mechanism of action (9)
The H+/K+ ATPase pump is responsible for pumping protons (hydrogen ions) from the parietal cell into the stomach lumen, which leads to the secretion of hydrochloric acid (HCl) into the stomach. This pH decrease serves multiple purposes, including digestion and protection against foreign pathogens.
Omeprazole works by irreversibly binding to and inhibiting the activity of the H+/K+ ATPase pump. By inhibiting the activity of the H+/K+ ATPase pump, omeprazole blocks the final step in the production of stomach acid, leading to a significant decrease in the amount of acid secreted into the stomach.
Omeprazole versus other PPIs
To this date, omeprazole remains the most prescribed PPI in the United States, ranking as the 8th most prescribed medication in 2020 (11). It is likely the most prescribed PPI globally as well, being the first PPI introduced to the market in the 1980s and having a significantly lower cost compared to other PPIs (e.g., 3 to 5 times lower than esomeprazole).
All PPIs have a similar efficacy in equivalent doses (9).
Esomeprazole is a newer PPI that may produce better acid suppression than omeprazole, with similar results treating conditions such as GERD and esophagitis. It may be used as a valid alternative to omeprazole, considering its higher cost.
Appropriateness use and prescription of PPIs in the Emergency Department
Studies have shown a high rate of inappropriate usage of PPIs in the ED (10).
In the vast majority of cases, the administration of PPIs in the emergency department is unnecessary.
While it is not mandatory to initiate PPIs pre-endoscopically for upper gastrointestinal bleeding, EMDrugs recommends starting PPIs prior to the index endoscopy due to their potential benefits and the frequent occurrence of unexpected delays, especially in hospitals with limited resources.
For mild gastrointestinal disorders, PPIs can be initiated upon discharge.
As stress ulcer prophylaxis in critically ill patients, PPIs can be administered in the ICU if the transfer will occur shortly.
Omeprazole and peptic ulcer bleeding
The use of omeprazole in the management of peptic ulcer bleeding (PUB) has faced challenges due to the lack of evidence demonstrating a reduction in mortality, need for hemoderivatives, or surgery before the index endoscopy (1, 2, 4, 6).
While omeprazole may reduce the incidence of high-risk stigmata of hemorrhage (4, 6), it has not been found to decrease the risk of rebleeding before index endoscopy (1, 2, 4).
A recent systematic review of PPI treatment initiated prior to endoscopic diagnosis in UGB concluded with moderate-certainty evidence that it likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy, with insufficient level of evidence to conclude other significant outcomes such as rebleeding, need for surgery or mortality (16).
The European Society of Gastrointestinal Endoscopy (13) and the American College of Gastroenterology (14) offer different recommendations regarding the pre-endoscopic administration of omeprazole.
ESGE advises the use of high-dose omeprazole (80 mg bolus followed by 8 mg/h for 72 hours) in patients with active bleeding and those exhibiting a non-bleeding visible vessel or adherent clot.
In contrast, ACG has not definitively recommended the routine use of pre-endoscopic PPI therapy in patients with upper gastrointestinal bleeding. However, it acknowledges the potential benefits in individuals displaying evidence of high-risk stigmata of recent hemorrhage.
These recommendations emphasize the necessity for further research to establish the role of omeprazole in the management of peptic ulcer bleeding.
In conclusion, PPIs are an affordable and safe intervention that may provide pre-endoscopic benefits and constitute a key component in the long-term treatment of peptic ulcer disease, but they do not necessarily need to be started before endoscopic diagnosis.
Appropriate dose and administration scheme of omeprazole for peptic ulcer bleeding (PUB)
The optimal dose and administration scheme of omeprazole and other PPIs for PUB remain a topic of debate.
The majority of omeprazole studies have utilized either an 80 mg bolus followed by 40 mg every 12 hours PO or IV, or an 80 mg bolus followed by an 8 mg/hr continuous infusion.
A 2014 systematic review and meta-analysis comparing intermittent and continuous PPI therapy for high-risk bleeding ulcers concluded that both regimens demonstrate comparable efficacy in terms of rebleeding within 3, 7 and 30 days, mortality, urgent interventions, blood transfusion and hospital length of stay (8).
The 2021 Guidelines from the European Society of Gastrointestinal Endoscopy and the American College of Gastroenterology recommend continuous infusion or intermittent administration as acceptable strategies based on current evidence (13, 14).
In conclusion, available data has prompted the preference for bolus intermittent administration in emergency medicine practice due to its ease of use and the preservation of intravenous lines for more substantial interventions.
PPIs and acute symptomatic management in the ED
The inappropriate use of PPIs in the ED has been reported to be high, indicating their frequent overprescription (19).
No studies have demonstrated that PPIs provide acute symptomatic relief for dyspepsia or pain when administered in the emergency department. In a study involving patients with dyspeptic pain in the ED who received a conventional cocktail (antacid + antispasmodic), two randomized groups were formed: one received placebo and the other received a high dose of IV pantoprazole (80mg). The study showed no significant differences in symptomatic relief between the two groups (7).
Studies comparing different PPIs for symptom relief in patients with reflux esophagitis evaluate treatment response within 7 days or longer. Esomeprazole appears to provide faster symptom relief compared to pantoprazole, lansoprazole, and omeprazole. This effect has been attributed to esomeprazole's faster onset of antisecretory activity, which is quicker than that of omeprazole, lansoprazole, and pantoprazole. Esomeprazole also leads to a rapid increase in pH to >4 on the first day of treatment (5). However, there were no significant differences in the rate of endoscopic healing at week 8 among the four groups.
Renal, hepatic and age adjustments
No renal adjustment needed.
No hepatic adjustment needed.
Older adult: no adjustment needed.
⚠ Cautions
Excluding anaphylaxis and hypersensitivity reactions, omeprazole does not have any major short-term adverse effects or warnings for use in the acute setting or emergency department.
It is worth considering the appropriateness of long-term prescription from the ED.
For prolonged prescriptions, arrange gastroenterology outpatient follow-up to prevent long-term adverse effects.
Significant drug interactions
EMDrugs is currently reviewing drug interactions with omeprazole that are worth considering to prevent unexpected adverse events.
Adverse effects associated with prolonged use of PPIs
EMDrugs is currently reviewing this topic to provide better understanding of the appropriateness of PPIs prescription in the ED.
Pregnancy and lactation
Pregnancy risk classification
AU TGA pregnancy category: B3
US FDA pregnancy category: C
Lactation
Limited data suggest omeprazole may be present in human milk. There are no clinical data on the effects of omeprazole on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition (15).
Very low risk. Safe, compatible with breastfeeding (17).
References
Daneshmend TK, Hawkey CJ, Langman MJ, et al. Omeprazole versus placebo for acute upper gastrointestinal bleeding: Randomized double blind controlled trial. BMJ 1992;304:143–7.
PubmedHawkey GM, Cole AT, McIntyre AS, et al. Drug treatments in upper gastrointestinal bleeding: Value of endoscopic findings as surrogate end points. Gut 2001;49:372–9.
PubmedLin HJ, Lo WC, Cheng YC, Perng CL. Role of intravenous omeprazole in patients with high-risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial. Am J Gastroenterol. 2006;101(3):500-505. doi:10.1111/j.1572-0241.2006.00399.x
PubmedLau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. NEngl J Med 2007;356:1631–40.
PubmedZheng RN. Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis. World J Gastroenterol. 2009 Feb 28;15(8):990-5. doi: 10.3748/wjg.15.990. PMID: 19248200; PMCID: PMC2653397.
Pubmed Central (Open Access)Sreedharan A, Martin J, Leontiadis GI, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;2010(7):CD005415. Published 2010 Jul 7. doi:10.1002/14651858.CD005415.pub3
PubmedMusikatavorn K, Tansangngam P, Lumlertgul S, Komindr A. A randomized controlled trial of adding intravenous pantoprazole to conventional treatment for the immediate relief of dyspeptic pain. Am J Emerg Med. 2012;30(9):1737-1742. doi:10.1016/j.ajem.2012.02.001
PubmedSachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174(11):1755-1762. doi:10.1001/jamainternmed.2014.4056
PubmedBrunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th edition. McGraw Hill; 2017.
McGraw-HillGranero-Melcon B, Morrás I, Galán-DeJuana M, Abad-Santos F. Appropriateness of the use of proton pump inhibitors in the Emergency Department of a Spanish university hospital. Rev Esp Enferm Dig. 2018;110(12):755-761. doi:10.17235/reed.2018.5468/2018
Revista Español de Enfermedades Digestivas (Open Access)US Department of Health & Human Services. Medical Expenditure Panel Survey (MEPS) 2013-2020. Agency for Healthcare Research and Quality (AHRQ).
MEPS (Open Access)Putnam J, Wolfson AB. Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients. Acad Emerg Med. 2020;27(7):634-636. doi:10.1111/acem.13914
Wiley (Open Access)Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021. Endoscopy. 2021;53(3):300-332. doi:10.1055/a-1369-5274
European Society of Gastrointestinal Endoscopy (Open Access)Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding [published correction appears in Am J Gastroenterol. 2021 Nov 1;116(11):2309]. Am J Gastroenterol. 2021;116(5):899-917. doi:10.14309/ajg.0000000000001245
American Journal of Gastroenterology (Open Access)NIH-NLM (National Institutes of Health - National Library of Medicine). DailyMed. Label: Omeprazole capsule, delayed release. Updated February 2022. Accessed June 1, 2023.
DailyMedKanno T, Yuan Y, Tse F, Howden CW, Moayyedi P, Leontiadis GI. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2022;1(1):CD005415. Published 2022 Jan 7. doi:10.1002/14651858.CD005415.pub4
PubmedAPILAM (Association for promotion of and cultural and scientific research into breastfeeding). e-lactancia. Omeprazole. Updated May 2022. Accessed July 5, 2023.
E-lactancia (Open Access)
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