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]-1H-benzimidazole, which functions as a gastric acid secretion inhibitor. The empirical formula is C17H19N3O3S, and it has a molecular weight of 345.42. The structural formula is provided in the official documentation.

Omeprazole USP appears as a white to off-white powder that decomposes upon melting at approximately 150°C to 160°C. It is soluble in dichloromethane and sparingly soluble in methanol and alcohol. 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 either 10 mg or 20 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the granules include colloidal silicon dioxide, dibasic sodium phosphate anhydrous, hydroxypropyl cellulose, hypromellose, hypromellose phthalate, lactose monohydrate, low-substituted hydroxypropyl cellulose, mannitol, microcrystalline cellulose, sodium lauryl sulfate, talc, and triethyl citrate. The capsule shells consist of D&C Red 28, D&C Yellow 10, FD&C Blue 1, FD&C Red 40, gelatin, sodium lauryl sulfate, and titanium dioxide. The imprinting ink is composed of black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. It is important to note that FDA-approved dissolution test specifications may differ from those outlined in the USP.

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 patients aged 2 years and older, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis (EE) due to acid-mediated GERD. It is also indicated for the maintenance of healing of EE due to acid-mediated GERD in this age group.

Furthermore, this drug is 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 once daily for a duration of 4 weeks. In some cases, an additional 4 weeks of treatment 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 delayed-release capsules: 20 mg taken twice daily for 10 days.

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

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

Dual Therapy:

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

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

For the treatment of active benign gastric ulcer, the recommended dosage is 40 mg once daily for a period of 4 to 8 weeks.

In patients with symptomatic gastroesophageal reflux disease (GERD), the dosage is 20 mg once daily for up to 4 weeks.

For the treatment of erosive esophagitis (EE) due to acid-mediated GERD, the recommended dosage is 20 mg once daily for 4 to 8 weeks. If there is no response, an additional 4 weeks of treatment may be warranted.

To maintain healing of EE due to acid-mediated GERD, a dosage of 20 mg once daily is recommended.

In cases of pathological hypersecretory conditions, the starting dose is 60 mg once daily; however, this may vary based on individual patient needs, and healthcare professionals should refer to the full prescribing information for further guidance.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, it should not be administered to patients receiving rilpivirine-containing products due to potential drug interactions. When used in combination with clarithromycin and amoxicillin, refer to the contraindications section of their prescribing information for further guidance.

Warnings and Precautions

In adults, it is important to note that a symptomatic response to treatment does not rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to ensure comprehensive patient evaluation.

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

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

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

The emergence of cutaneous and systemic lupus erythematosus, particularly in the form of new onset or exacerbation of existing disease, has been reported. In such cases, omeprazole should be discontinued, and referral to a specialist for further evaluation is recommended.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential drug interactions. Healthcare professionals should avoid prescribing these medications together.

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 may be warranted in patients on extended 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 drug efficacy.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is crucial to note 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 to ensure accurate diagnostic outcomes.

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.

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

Common adverse reactions reported in adult patients include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 2 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 clinical studies involving this age group.

Serious adverse reactions and warnings include the potential for gastric malignancy, as symptomatic response does not exclude this possibility in adults. Additional follow-up and diagnostic testing should be considered. Acute interstitial nephritis has been observed in patients taking proton pump inhibitors (PPIs). There is also an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term and multiple daily dose PPI therapy may elevate the risk of osteoporosis-related fractures of the hip, wrist, or spine.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus; in such cases, discontinuation of omeprazole and referral to a specialist for evaluation is recommended. Long-term daily use of omeprazole (beyond three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia has been reported with prolonged treatment with PPIs. The risk of fundic gland polyps increases with long-term use, particularly beyond one year, thus the shortest duration of therapy should be utilized.

In cases of overdosage, reports indicate that manifestations can vary and may include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. Symptoms are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken alone.

Additional considerations include the contraindication for patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation, as well as those receiving rilpivirine-containing products. Concomitant use of omeprazole with clopidogrel, St. John's Wort, or rifampin should be avoided due to potential interactions. Furthermore, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; it is advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is also warranted when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

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 evaluate 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 2 to 16 years for the treatment of symptomatic gastroesophageal reflux disease (GERD), the treatment of erosive esophagitis (EE) due to acid-mediated GERD, and the maintenance of healing of EE due to acid-mediated GERD. The use of omeprazole in this age group is supported by adequate and well-controlled studies in adults, as well as uncontrolled safety, efficacy, and pharmacokinetic studies conducted in pediatric and adolescent patients.

In the pediatric population, adverse reactions affecting the respiratory system were frequently reported among patients aged 2 to 16 years. Additionally, accidental injuries were commonly noted in this age group.

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

Geriatric Use

Clinical trials involving over 2000 elderly individuals aged 65 years and older have demonstrated that omeprazole is safe and effective, with no significant differences in safety and effectiveness observed between elderly 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 the elderly, with an increased bioavailability. 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 this population 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. Healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population, although current evidence does not necessitate alterations in dosing.

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 associated with the use of omeprazole 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, 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 indicated population are unknown; however, 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 studies have reported no apparent adverse short-term effects on infants when single doses of oral or intravenous omeprazole were administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. A population-based retrospective cohort study from the Swedish Medical Birth Registry indicated that the incidence of malformations, low birth weight, low Apgar scores, or hospitalization among infants exposed in utero to omeprazole was similar to that observed in the general population. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9%, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole was 3.6%, compared to 5.5% for H2-blockers and 4.1% for unexposed mothers. A small prospective observational cohort study 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.

Given the available data, healthcare professionals should weigh the potential benefits of omeprazole use during pregnancy against the potential risks, considering the individual circumstances of each patient.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. Reproductive studies conducted with omeprazole in rats, administered prior to mating through the lactation period, resulted in 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. However, when maternal administration of esomeprazole was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. Given the lack of data in human subjects and the observed effects in animal studies, caution is advised when considering the use of omeprazole in lactating mothers.

Renal Impairment

There is no specific information regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

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. In terms of non-teratogenic effects, oral administration of omeprazole at 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 a dose-related increase in gastric ECL cell carcinoids at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day, corresponding to about 0.4 to 34 times the human dose of 40 mg/day based on body surface area. The incidence of carcinoids was significantly higher in female rats, which exhibited 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 notable 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%), with no similar tumors 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 singular 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, which equates to approximately 0.1 to 3.9 times the human dose of 40 mg/day based on body surface area. 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, approximately 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 p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

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. 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.

In summary, the findings from the carcinogenicity studies indicate a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia in both male and female rats. It is noteworthy that carcinoid tumors have also been reported in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

No postmarketing experience details are available in the provided data.

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 are supplied in a tight container to ensure protection from light and moisture. It is essential to store the capsules at a temperature range of 20° to 25°C (68 to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are crucial to maintain the integrity and efficacy of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)