Omeprazole

Description

The active ingredient in omeprazole delayed-release capsules USP is a substituted benzimidazole, specifically 5-methoxy-2 [(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl sulfinyl]-1 H-benzimidazole, which functions as an inhibitor of gastric acid secretion. The empirical formula of omeprazole is C17H19N3O3S, with a molecular weight of 345.42.

Omeprazole appears as a white to off-white crystalline powder that decomposes at approximately 155°C. It is classified as a weak base, exhibiting solubility characteristics that include being freely soluble in ethanol and methanol, slightly soluble in acetone and isopropanol, and very slightly soluble in water. The stability of omeprazole is pH-dependent; it is rapidly degraded in acidic environments but maintains acceptable stability in alkaline conditions.

Omeprazole is formulated as delayed-release capsules for oral administration, with each capsule containing 40 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the granules include hypromellose, magnesium carbonate light, methacrylic acid copolymer dispersion, sodium lauryl sulfate, sugar spheres (sucrose and starch, corn), talc, and triethyl citrate. The capsule shells consist of gelatin, black iron oxide, iron oxide red, potassium hydroxide, propylene glycol, shellac, sodium lauryl sulfate, and titanium dioxide. Omeprazole delayed-release capsules USP comply with USP Dissolution Test 2.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcers in adults. It is also indicated for the eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults. Additionally, this drug is used for the treatment of active benign gastric ulcers in adults.

In pediatric populations, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) in patients aged 1 year and older, as well as for the treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients aged 1 month and older. Furthermore, it is indicated for the maintenance of healing of EE due to acid-mediated GERD in patients aged 1 year and older.

This drug is also indicated for the treatment of pathologic hypersecretory conditions in adults. There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg administered orally once daily for a duration of 4 weeks. In some cases, an additional 4 weeks may be necessary based on the patient's response.

For the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

Triple Therapy:

• Omeprazole delayed-release capsules: 20 mg orally twice daily for 10 days.

• Amoxicillin: 1000 mg orally.

• Clarithromycin: 500 mg orally.

Dual Therapy:

• Omeprazole delayed-release capsules: 40 mg orally once daily for 14 days.

• Clarithromycin: 500 mg orally three times daily for 14 days.

In the case of active benign gastric ulcer, the recommended dosage is 40 mg administered orally once daily for a period of 4 to 8 weeks.

For symptomatic gastroesophageal reflux disease (GERD), the dosage is 20 mg orally once daily for up to 4 weeks. In patients with erosive esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg orally once daily for 4 to 8 weeks. For the maintenance of healing of EE due to acid-mediated GERD, a dosage of 20 mg orally once daily is recommended.

For pathological hypersecretory conditions, the starting dose is 60 mg administered orally once daily. The dosage may vary based on individual patient needs and should be adjusted as clinically indicated.

All dosages should be administered orally.

Contraindications

Use is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, the use of this product is contraindicated in patients receiving rilpivirine-containing products due to potential drug interactions. When administered in combination with omeprazole, refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin for further guidance.

Warnings and Precautions

In adults, the symptomatic response to treatment with omeprazole delayed-release capsules does not exclude the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to rule out this condition.

Acute interstitial nephritis has been observed in patients receiving proton pump inhibitors (PPIs), including omeprazole. Clinicians should remain vigilant for signs and symptoms of this condition.

There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Healthcare providers should monitor patients for gastrointestinal symptoms and consider this risk when prescribing omeprazole.

Long-term use of PPIs, particularly at multiple daily doses, may be linked to an increased risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. It is advisable to assess the need for continued therapy in patients at risk for fractures.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus while on omeprazole. In such cases, it is essential to discontinue the medication and refer the patient to a specialist for further evaluation.

Concomitant use of omeprazole with clopidogrel is not recommended due to potential interactions that may diminish the effectiveness of clopidogrel. Healthcare professionals should avoid this combination.

Long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin B-12 levels may be warranted in patients on prolonged therapy.

Hypomagnesemia has been reported rarely in patients undergoing prolonged treatment with PPIs. Clinicians should consider monitoring magnesium levels in patients receiving long-term therapy.

The concomitant use of omeprazole with St. John's Wort or rifampin should be avoided due to potential interactions that may affect the efficacy of omeprazole.

Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors. It is recommended to temporarily discontinue omeprazole delayed-release capsules at least 14 days prior to assessing CgA levels to ensure accurate diagnostic results.

When used alongside methotrexate, omeprazole may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of omeprazole should be considered.

The risk of developing fundic gland polyps increases with long-term use of omeprazole, particularly beyond one year. It is advisable to use the shortest duration of therapy necessary to manage the patient's condition.

Side Effects

Most common adverse reactions reported in adults, with an incidence of 2% or greater, include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 1 to 16 years, the safety profile is similar to that of adults; however, respiratory system events and fever were the most frequently reported reactions in pediatric studies.

Serious adverse reactions associated with the use of omeprazole include gastric malignancy, where symptomatic response does not preclude the presence of malignancy, necessitating additional follow-up and diagnostic testing. Acute interstitial nephritis has also been observed in patients taking proton pump inhibitors (PPIs). Furthermore, there is an increased risk of Clostridium difficile-associated diarrhea with PPI therapy.

Long-term and multiple daily dose PPI therapy may be associated with an increased risk of osteoporosis-related bone fractures, particularly of the hip, wrist, or spine. Other notable adverse reactions include cutaneous and systemic lupus erythematosus, which may present as new onset or exacerbation of existing disease; in such cases, discontinuation of omeprazole delayed-release capsules and referral to a specialist for evaluation is recommended.

Patients using omeprazole for an extended period (e.g., longer than three years) may experience cyanocobalamin (Vitamin B-12) deficiency due to malabsorption. Hypomagnesemia has been reported rarely with prolonged treatment. Additionally, interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John's Wort, or rifampin should be avoided. There may also be interactions with methotrexate, where concomitant use may elevate serum concentrations and potentially lead to toxicity, warranting consideration of a temporary withdrawal of omeprazole during high-dose methotrexate administration.

Increased levels of Chromogranin A (CgA) due to omeprazole may interfere with diagnostic investigations for neuroendocrine tumors; therefore, it is advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. The risk of fundic gland polyps increases with long-term use, particularly beyond one year.

In cases of overdosage, reports have indicated a range of symptoms, including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

Clinically important drug interactions should be reviewed in the full prescribing information. It is essential for healthcare professionals to consider the potential for both pharmacodynamic and pharmacokinetic interactions when prescribing medications.

Pharmacodynamic interactions may lead to additive or synergistic effects, which could enhance therapeutic outcomes or increase the risk of adverse effects. Monitoring for signs of increased effects or toxicity is recommended when combining drugs with similar mechanisms of action.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of a drug, potentially necessitating dosage adjustments. Healthcare providers should assess the need for dose modifications based on the specific interactions identified in the prescribing information.

For comprehensive guidance on managing drug interactions, including specific recommendations for dosage adjustments and monitoring parameters, refer to the full prescribing information.

Packaging & NDC

The table below lists all NDC Code configurations of Omeprazole, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of omeprazole have been established in pediatric patients aged 1 month to 16 years for the treatment of symptomatic gastroesophageal reflux disease (GERD), treatment of erosive esophagitis (EE) due to acid-mediated GERD, and maintenance of healing of EE due to acid-mediated GERD. However, for patients less than 1 year of age, omeprazole is only indicated for the treatment of EE due to acid-mediated GERD; its safety and effectiveness for symptomatic GERD and maintenance of healing of EE in this age group have not been established.

In the broader pediatric population (1 month to 16 years), adverse reactions affecting the respiratory system were frequently reported. Specific age-related adverse events included otitis media, which was commonly reported in infants aged 1 month to less than 1 year, and fever, which was frequently observed in children aged 1 to less than 2 years. Additionally, accidental injuries were frequently reported in the age group of 2 to 16 years.

The safety and effectiveness of omeprazole have not been established for several indications in pediatric patients, including the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcers, and pathological hypersecretory conditions. Furthermore, omeprazole has not been studied in patients less than 1 month of age for any indication.

Geriatric Use

Clinical trials involving over 2000 elderly individuals (≥ 65 years of age) have demonstrated that omeprazole is safe and effective, with no significant differences in safety and effectiveness observed between elderly patients and younger subjects. While other clinical experiences have not identified notable differences in response between these age groups, it is important to acknowledge that some older individuals may exhibit greater sensitivity to the medication.

Pharmacokinetic studies indicate that the elimination rate of omeprazole is somewhat decreased in geriatric patients, with an increased bioavailability noted. Specifically, the plasma clearance of omeprazole in elderly patients is approximately 250 mL/min, which is about half that observed in younger volunteers. Additionally, the plasma half-life of omeprazole in the elderly averages one hour, which is roughly twice that of young healthy volunteers.

Despite these pharmacokinetic changes, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. However, healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. However, reproduction studies in rats and rabbits have shown dose-dependent embryo-lethality at doses approximately 3.4 to 34 times the oral human dose of 40 mg, based on body surface area for a 60 kg person.

Teratogenicity was not observed in animal reproduction studies with oral esomeprazole magnesium administered during organogenesis at doses about 68 times and 42 times, respectively, the oral human dose of 40 mg. Changes in bone morphology were noted in offspring of rats dosed throughout most of pregnancy and lactation at doses equal to or greater than approximately 34 times the oral human dose of 40 mg. However, when maternal administration was limited to gestation only, no effects on bone physeal morphology in the offspring were observed at any age.

The estimated background risks of major birth defects and miscarriage for the indicated population are unknown, but all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Several epidemiological studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those of women exposed to H2-receptor antagonists or other controls. A population-based retrospective cohort study from the Swedish Medical Birth Registry reported on 955 infants whose mothers used omeprazole during pregnancy, revealing similar rates of malformations, low birth weight, low Apgar score, or hospitalization compared to the general population. However, the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed group than expected.

A population-based retrospective cohort study in Denmark reported an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. Another retrospective cohort study indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. A small prospective observational cohort study following 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group.

Several studies have indicated no apparent adverse short-term effects on the infant when single doses of oral or intravenous omeprazole were administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Reproductive studies conducted with omeprazole in rats did not reveal any evidence of teratogenic potential, although in rabbits, omeprazole produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring from parents treated with omeprazole. Conversely, no effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal survival and developmental delays at high doses, but when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (approximately 34 times the oral human dose of 40 mg on a body surface area basis) during lactation demonstrated dose-related embryo/fetal toxicity and postnatal developmental toxicity.

Additionally, effects on maternal bone were observed in pregnant and lactating rats when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times the oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). However, when maternal administration of esomeprazole was limited to gestation only, there were no observed effects on bone physeal morphology in the offspring at any age.

Given the lack of data on excretion in human breast milk and the potential risks indicated in animal studies, caution is advised when considering the use of omeprazole or esomeprazole in lactating mothers.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Reports have been documented regarding overdosage with omeprazole in humans, with doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations of overdosage have been variable, but commonly reported symptoms include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are consistent with those observed in normal clinical experience.

It is noteworthy that the symptoms associated with omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. Currently, there is no specific antidote available for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable.

In the event of an overdosage, treatment should focus on symptomatic and supportive care. Healthcare professionals are advised to contact the Poison Control Center at 1-800-222-1222 for the most current information regarding the management of poisoning or overdosage.

Nonclinical Toxicology

In nonclinical studies, omeprazole demonstrated no teratogenic effects. At oral doses up to 138 mg/kg/day in rats, which is approximately 34 times the human dose of 40 mg on a body surface area basis, omeprazole did not affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed a dose-related increase in gastric ECL cell carcinoids at daily doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day, with a notably higher incidence in female rats, correlating with elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. ECL cell hyperplasia was noted in all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a significant increase in ECL cell hyperplasia was recorded at the end of the first year (94% in treated rats versus 10% in controls). By the second year, the difference diminished (46% in treated versus 26% in controls), yet hyperplasia remained more prevalent in the treated group. Gastric adenocarcinoma was identified in one rat (2%), but no similar tumors were observed in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were detected in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose of 40 mg/day). No astrocytomas were found in female rats during this study. In a separate two-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were observed in either sex at the high dose of 140.8 mg/kg/day (about 34 times the human dose). A 78-week carcinogenicity study in mice did not indicate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week study involving p53 (+/-) transgenic mice did not yield positive results.

Omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay and in one of two in vivo mouse micronucleus tests, as well as in an in vivo bone marrow cell chromosomal aberration assay. Conversely, omeprazole was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies aligns with findings from other studies involving long-term treatment with proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Medication Guide and Instructions for Use. This information is essential for understanding the proper use of the medication, potential side effects, and any necessary precautions. Emphasizing the importance of this material can help ensure that patients are well-informed and can engage in their treatment plan effectively.

Storage and Handling

Omeprazole delayed-release capsules USP are supplied in a tight container that is designed to protect the contents from light and moisture. It is essential to store the capsules at a controlled room temperature of 25°C (68°F to 77°F). Temporary excursions in temperature are permissible, provided they remain within the range of 15°C to 30°C (59°F to 86°F). Proper storage conditions are crucial to maintain the integrity and efficacy of the product.

Additional Clinical Information

Standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical accuracy of laboratory procedures. In studies involving omeprazole/clarithromycin dual therapy, clarithromycin pretreatment resistance rates were observed at 3.5% (4 out of 113 subjects), while in omeprazole/clarithromycin/amoxicillin triple therapy studies, the resistance rate was 9.3% (41 out of 439 subjects). Notably, amoxicillin pretreatment susceptible isolates (≤ 0.25 µg/mL) were identified in 99.3% (436 out of 439) of patients participating in the triple therapy studies.

For treatment regimens, the dual therapy consists of omeprazole 40 mg once daily and clarithromycin 500 mg three times daily for 14 days, followed by omeprazole 20 mg once daily for an additional 14 days. The triple therapy involves omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily for 10 days, followed by omeprazole 20 mg once daily for another 18 days. Clinicians should counsel patients that those who do not achieve eradication of H. pylori after the triple or dual therapy may harbor clarithromycin-resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing is recommended when feasible, and patients with such resistance should not be treated with regimens that include clarithromycin as the sole antimicrobial agent.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Omeprazole as submitted by Lupin Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)