Omeprazole

Description

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

Omeprazole, USP 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.

Each omeprazole delayed-release capsule is designed for oral administration and contains either 10 mg, 20 mg, or 40 mg of omeprazole. The capsules also include several inactive ingredients: acetone, di-sodium hydrogen phosphate dihydrate, FD&C blue 1, gelatin, hydroxypropyl cellulose, hypromellose, hypromellose phthalate, polyethylene glycol, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide, and triethyl citrate. The 10 mg and 40 mg capsule shells contain FD&C red 3 and FD&C green 3, while the 20 mg capsule shell includes iron oxide red and iron oxide yellow. The capsule is printed with black pharmaceutical ink, which consists of black iron oxide, potassium hydroxide, propylene glycol, and shellac. Omeprazole Delayed-Release Capsules USP comply with USP Dissolution Test 2.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcer 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 ulcer 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 management 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 Helicobacter pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

Triple Therapy:

• Omeprazole: 20 mg orally twice daily for 10 days.

• Amoxicillin: 1000 mg orally twice daily for 10 days.

• Clarithromycin: 500 mg orally twice daily for 10 days.

Dual Therapy:

• Omeprazole: 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 recommended 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 advised.

For pathological hypersecretory conditions, the starting dose is 60 mg administered orally once daily, with adjustments made based on individual patient response.

All dosages should be taken 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, it is important to note that a symptomatic response to treatment 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 tubulointerstitial nephritis has been reported in patients receiving treatment. If this condition is suspected, it is imperative to discontinue the medication and evaluate the patient accordingly.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should be vigilant for signs of this infection, particularly in patients receiving long-term PPI therapy.

Long-term use of PPIs, especially at multiple daily doses, may increase the risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. It is advisable to assess the patient's bone health and consider alternative therapies when appropriate.

Severe cutaneous adverse reactions may occur; therefore, treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation by a specialist may be warranted.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such cases, discontinuation of omeprazole is recommended, and referral to a specialist for evaluation should be considered.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel. Healthcare providers should avoid this combination.

Long-term daily use of omeprazole, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin B-12 levels is recommended in patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported, albeit rarely, with prolonged PPI treatment. Clinicians should monitor 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.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is essential to be aware that increased levels of Chromogranin A (CgA) may interfere with test results. Omeprazole should be temporarily discontinued at least 14 days prior to assessing CgA levels.

When administering high doses of methotrexate, caution is advised as the concomitant use of PPIs may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. A temporary withdrawal of omeprazole should be considered in these cases.

Finally, the risk of fundic gland polyps increases with long-term use of PPIs, particularly beyond one year. It is recommended to use the shortest duration of therapy necessary to manage the patient's condition effectively.

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. Specifically, otitis media was commonly reported in infants aged 1 month to less than 1 year, while fever was frequently noted in children aged 1 to less than 2 years. Accidental injuries were also reported frequently among children aged 2 to 16 years.

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying malignancy, necessitating further diagnostic testing. Acute tubulointerstitial nephritis requires discontinuation of treatment and patient evaluation. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, as well as a potential for long-term use to lead to bone fractures, particularly in relation to osteoporosis.

Severe cutaneous adverse reactions have been reported, and treatment should be discontinued at the first signs or symptoms of such reactions or any signs of hypersensitivity. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been observed, necessitating discontinuation of omeprazole and referral to a specialist for evaluation. Long-term use of omeprazole may also lead to cyanocobalamin (Vitamin B-12) deficiency, particularly when used for longer than three years, and hypomagnesemia has been reported rarely with prolonged PPI treatment.

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John's Wort, or rifampin should be avoided. Furthermore, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations, potentially leading to toxicity.

In cases of overdosage, reports indicate variable manifestations including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. Symptoms were generally transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Long-term use of omeprazole may also increase the risk of fundic gland polyps, particularly beyond one year of therapy, thus it is recommended to use the shortest duration of therapy necessary.

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, necessitating careful monitoring of therapeutic outcomes and potential adverse effects. In cases where such interactions are identified, dosage adjustments may be warranted to mitigate risks.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of concomitantly administered drugs. These interactions may require modifications in dosing regimens or increased frequency of monitoring to ensure therapeutic efficacy and safety.

Healthcare providers are advised to consult the complete prescribing information for a comprehensive list of drug interactions and specific recommendations regarding dosage adjustments and monitoring protocols.

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. In patients aged 1 month to less than 1 year, omeprazole is indicated specifically for the treatment of EE due to acid-mediated GERD.

Adverse reactions have been reported in the pediatric population, with respiratory system events frequently noted across the entire age range of 1 month to 16 years. In the 1 month to less than 1 year age group, otitis media was commonly reported, while fever was frequently observed in children aged 1 to less than 2 years. Additionally, accidental injuries were frequently reported in the 2 to 16 year age group.

It is important to note that the safety and effectiveness of omeprazole have not been established in patients less than 1 year of age for the treatment of symptomatic GERD or for the maintenance of healing of EE due to acid-mediated GERD. Furthermore, omeprazole has not been established for use in pediatric patients for the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcers, or pathological hypersecretory conditions. The safety and effectiveness of omeprazole have not been established in patients less than 1 month of age for any indication.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals (≥ 65 years of age) in clinical trials conducted in the U.S. and Europe. The results indicated no significant differences in safety and effectiveness 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 greater sensitivity in some older individuals cannot be entirely excluded.

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

Despite these pharmacokinetic variations, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. Healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population, although the overall safety profile appears consistent with that of younger patients.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant patients. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with omeprazole use during the first trimester. 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 esomeprazole magnesium, an enantiomer of omeprazole, when administered during organogenesis at doses about 68 times and 42 times the oral human dose of 40 mg for rats and rabbits, respectively. 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 general 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, showing similar rates of malformations, low birth weight, low Apgar scores, or hospitalization compared to the general population. Another study from Denmark reported an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%, comparable to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

A retrospective cohort study indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole, compared to 5.5% for H2-blockers and 4.1% for unexposed mothers. A small prospective observational cohort study involving 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens and 2.8% in disease-paired controls.

Furthermore, several studies have reported 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 was associated with dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions.

In summary, while the available data suggest that omeprazole does not significantly increase the risk of major congenital malformations when used during pregnancy, caution is advised, and the potential risks should be weighed against the benefits of treatment.

Lactation

Limited data suggest that omeprazole may be present in human milk. However, there are no clinical data available regarding the effects of omeprazole on breastfed infants or on milk production.

When considering the use of omeprazole in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition should be taken into account.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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, including symptoms such as 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

Omeprazole has been evaluated for its potential teratogenic effects, but no specific information is available regarding such effects.

In terms of non-teratogenic effects, studies have demonstrated that omeprazole administered 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, did not adversely affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed that omeprazole, at daily doses ranging from 1.7 to 140.8 mg/kg/day (approximately 0.4 to 34 times the human dose of 40 mg/day based on body surface area), resulted in a dose-related increase in gastric ECL cell carcinoids in both male and female rats. Notably, the incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. Additionally, ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day (about 3.4 times the human dose) for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a marked increase in treatment-related 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 observed in one rat (2%), but no similar tumors were identified in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of a single tumor 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). No astrocytomas were found in female rats in this study. Conversely, a two-year carcinogenicity study in Sprague-Dawley rats at the high dose of 140.8 mg/kg/day did not reveal any astrocytomas in either sex. A 78-week carcinogenicity study in mice did not demonstrate an increased incidence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Animal pharmacology and toxicology assessments indicated that omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, 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. Furthermore, the significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats aligns with findings from other studies involving fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

No specific postmarketing experience details are available in the extracted data. As such, there are no reported adverse events or case reports to summarize.

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

The product is supplied in a tightly closed container to ensure its integrity. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the product from light and moisture to maintain its efficacy. For dispensing, a tight, light-resistant container is recommended to further safeguard the product from environmental factors.

Additional Clinical Information

Standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical accuracy of laboratory methods. 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 higher at 9.3% (41 out of 439 subjects). Notably, amoxicillin pretreatment susceptible isolates (≤ 0.25 mcg/mL) were identified in 99.3% (436 out of 439) of patients participating in the triple therapy studies.

For administration, the dual therapy regimen 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 regimen includes 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, warranting susceptibility testing. Patients with such resistance should avoid treatment 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 Zydus Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)