Omeprazole

Description

Omeprazole Delayed-Release Capsules contain the active ingredient omeprazole, a substituted benzimidazole with the chemical structure 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 of omeprazole is C17H19N3O3S, and it has a molecular weight of 345.42. The structural formula is represented as follows:

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, with rapid degradation occurring in acidic environments, while it maintains acceptable stability under alkaline conditions.

Omeprazole Delayed-Release Capsules are formulated for oral administration and are available in strengths of 10 mg, 20 mg, or 40 mg of omeprazole, presented as enteric-coated microtablets. The capsules meet the USP Dissolution Test 2 criteria. Inactive ingredients include crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, silicon dioxide, talc, titanium dioxide, and triethyl citrate. The capsule shells are composed of gelatin and may also contain sodium lauryl sulfate. The 20 mg and 40 mg capsules additionally contain yellow iron oxide. The imprinting ink used on the capsules includes ammonium hydroxide, butyl alcohol, black iron oxide, isopropyl alcohol, propylene glycol, and shellac glaze, with the possibility of containing dehydrated alcohol.

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 1 year 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.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

Omeprazole Delayed-Release Capsules are administered orally.

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg once daily for a duration of 4 weeks. In some patients, an additional 4 weeks may be necessary based on clinical 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, administered twice daily for 10 days.

• Amoxicillin: 1000 mg, administered as per the prescribing guidelines.

• Clarithromycin: 500 mg, administered as per the prescribing guidelines.

Dual Therapy:

• Omeprazole Delayed-Release Capsules: 40 mg, administered once daily for 14 days.

• Clarithromycin: 500 mg, administered 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.

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

In patients with pathological hypersecretory conditions, the starting dose is 60 mg once daily; this may vary based on individual patient response and clinical judgment.

Contraindications

Use of this product is contraindicated in the following situations:

Patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation should not use this product due to the risk of severe allergic reactions. Additionally, the use of this product is contraindicated in patients receiving rilpivirine-containing products, as potential drug interactions may occur.

When administered in combination with Omeprazole Delayed-Release Capsules, refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin to ensure safe use.

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 remain vigilant for this potential complication, particularly in patients with risk factors.

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. Treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity, and further evaluation should be considered.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such cases, it is recommended to discontinue Omeprazole Delayed-Release Capsules and refer the patient to a specialist for further evaluation.

Concomitant use of Omeprazole Delayed-Release Capsules with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel.

Long-term daily use of PPIs, 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 Delayed-Release Capsules with St. John’s Wort or rifampin should be avoided due to potential interactions that may affect the efficacy of the medication.

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. It is recommended to temporarily discontinue Omeprazole Delayed-Release Capsules at least 14 days prior to assessing CgA levels.

When used in conjunction with methotrexate, PPIs may elevate and prolong serum concentrations of methotrexate and/or its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of Omeprazole Delayed-Release Capsules should be considered.

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

Side Effects

Most common adverse reactions reported in adults, occurring 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 observed in adults; however, respiratory system events and fever were the most frequently reported reactions in pediatric studies.

Serious adverse reactions warranting caution include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric cancer, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been reported, and treatment should be discontinued and patients evaluated if this occurs. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, and long-term use or multiple daily doses of PPIs may elevate the risk of osteoporosis-related fractures of the hip, wrist, or spine.

Severe cutaneous adverse reactions have been noted; treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been reported, necessitating discontinuation of Omeprazole Delayed-Release Capsules and referral to a specialist for evaluation.

Interactions with other medications are significant; concomitant use of Omeprazole Delayed-Release Capsules with clopidogrel, St. John’s Wort, or rifampin should be avoided. Long-term daily use (exceeding three years) may lead to cyanocobalamin (Vitamin B-12) deficiency due to malabsorption. Rarely, hypomagnesemia and disturbances in mineral metabolism have been reported with prolonged PPI treatment. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors, and it is recommended to temporarily discontinue Omeprazole Delayed-Release Capsules at least 14 days prior to assessing CgA levels. Caution is also advised when using methotrexate concurrently, as PPIs may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity; a temporary withdrawal of Omeprazole Delayed-Release Capsules should be considered during high-dose methotrexate administration. The risk of fundic gland polyps increases with long-term use, particularly beyond one year, thus the shortest duration of therapy is recommended.

In cases of overdosage, reports indicate variable manifestations including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms are generally transient, and no serious clinical outcomes have been reported when Omeprazole Delayed-Release Capsules were 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 evaluate the need for dose modifications based on the specific interactions identified in the prescribing information.

For comprehensive guidance on managing these interactions, including specific recommendations for monitoring and dosage adjustments, 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 Delayed-Release Capsules have been established in pediatric patients aged 1 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 related to the respiratory system were frequently reported across the entire age range of 1 to 16 years. Specifically, fever was commonly reported in patients aged 1 to less than 2 years, while accidental injuries were frequently noted in the 2 to 16 year age group.

It is important to note that the safety and effectiveness of Omeprazole Delayed-Release Capsules have not been established in patients under 1 year of age for any indication. Additionally, the safety and effectiveness of this medication have not been established 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. Furthermore, 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, demonstrating no significant differences in safety and effectiveness when compared to younger subjects. While other clinical experiences have not identified notable differences in response between elderly and younger patients, 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 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. Healthcare providers should remain vigilant in monitoring for any potential increased sensitivity in this population, although current evidence does not necessitate changes in dosing regimens.

Pregnancy

There are no adequate and well-controlled studies with Omeprazole Delayed-Release Capsules in pregnant women. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with the use of omeprazole during the first trimester.

Reproductive 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. However, teratogenicity was not observed in animal reproduction studies with oral esomeprazole, 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. 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. 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 scores, or hospitalization compared to the general population. Another study covering all live births in 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. Additionally, 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. However, in rabbits, omeprazole was associated with 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 resulting 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.

Healthcare professionals should weigh the potential benefits against the risks when considering omeprazole for pregnant patients.

Lactation

There are no adequate and well-controlled studies with Omeprazole Delayed-Release Capsules in nursing mothers. Reproductive studies conducted with omeprazole in rats, administered prior to mating through the lactation period, 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 ranging from 14 to 280 mg/kg/day. However, when maternal administration of esomeprazole was limited to the gestation period, there were no observed effects on bone physeal morphology in the offspring at any age. Given the lack of human data and the findings in animal studies, caution is advised when considering the use of omeprazole in lactating mothers.

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. Regular monitoring of renal function may be advisable in these patients, although specific recommendations are not provided.

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, with symptoms including 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 generally transient, and no serious clinical outcomes have been reported when Omeprazole Delayed-Release Capsules are 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 two 24-month carcinogenicity studies conducted in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44.0, and 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 the development of gastric ECL cell carcinoids in a dose-dependent manner in both male and female rats. The incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently observed in untreated rats. Additionally, ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats receiving 13.8 mg omeprazole/kg/day (about 3.4 times the human dose of 40 mg/day, based on body surface area) for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a notable 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 between treated and control rats diminished (46% versus 26%), yet the treated group still exhibited a higher incidence of hyperplasia. Gastric adenocarcinoma was identified in one rat (2%), although no similar tumors were observed in male or female rats treated for two years. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging. In a separate 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, based on body surface area). No astrocytomas were found in female rats in this study. In a 2-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 of 40 mg/day on a body surface area basis). A 78-week carcinogenicity study in mice did not reveal an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole demonstrated positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and 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.

At oral doses up to 138 mg/kg/day in rats (approximately 34 times the oral human dose of 40 mg on a body surface area basis), omeprazole was found to have no adverse effects on fertility and reproductive performance.

In the aforementioned 24-month carcinogenicity studies in rats, a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals. 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 specific postmarketing experience details are available. 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 are supplied in a tight container that is protected from light and moisture. The recommended storage conditions are at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

For dispensing, it is essential to use a tight and light-resistant container, as specified by USP standards, to ensure the integrity 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.

For the administration of therapy, 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. In contrast, 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 either the omeprazole/clarithromycin/amoxicillin triple therapy or the omeprazole/clarithromycin dual therapy are likely to have clarithromycin-resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing is recommended when feasible. Patients with clarithromycin-resistant H. pylori 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 Lannett Company, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)