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.

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, demonstrating rapid degradation in acidic environments while maintaining acceptable stability in alkaline conditions.

Omeprazole Delayed-Release Capsules are formulated for oral administration and are available in strengths of 10 mg, 20 mg, or 40 mg. Each capsule contains enteric-coated microtablets of omeprazole, along with inactive ingredients such as 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 include sodium lauryl sulfate, with the 20 mg and 40 mg capsules containing yellow iron oxide. The imprinting ink used on the capsules consists of ammonium hydroxide, butyl alcohol, black iron oxide, isopropyl alcohol, propylene glycol, and shellac glaze, and may also contain dehydrated alcohol. Omeprazole Delayed-Release Capsules 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 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 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 of Omeprazole Delayed-Release Capsules administered once daily for a duration of 4 weeks. In certain patients, an additional 4 weeks of treatment may be necessary based on clinical 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, administered as directed.

• Clarithromycin: 500 mg, taken as directed.

Dual Therapy:

• Omeprazole Delayed-Release Capsules: 40 mg, taken 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 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; however, this may vary based on individual patient needs and should be continued as long as clinically indicated.

If an ulcer is present during Triple Therapy, it is advised to continue Omeprazole Delayed-Release Capsules at a dosage of 20 mg once daily for an additional 18 days. For patients undergoing Dual Therapy with an ulcer, the continuation of Omeprazole Delayed-Release Capsules at 20 mg once daily for an additional 14 days is recommended.

In cases where there is no response after the initial treatment, an additional 4 weeks of therapy may be warranted. If recurrence occurs, further courses of treatment lasting 4 to 8 weeks may be considered.

For patients with hepatic impairment (Child Pugh Class A, B, or C) and for Asian patients, the dosage should be reduced to 10 mg once daily.

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 rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to ensure comprehensive patient evaluation (5.1).

Acute interstitial nephritis has been observed in patients receiving proton pump inhibitors (PPIs), including Omeprazole Delayed-Release Capsules. Clinicians should remain vigilant for signs and symptoms of this condition (5.2). Additionally, there is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, necessitating careful monitoring of patients for gastrointestinal symptoms (5.3).

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. It is advisable to assess the need for ongoing therapy in patients at risk for bone fractures (5.4). Furthermore, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been reported; in such cases, discontinuation of Omeprazole Delayed-Release Capsules is recommended, and referral to a specialist for further evaluation is warranted (5.5).

Concomitant use of Omeprazole Delayed-Release Capsules with clopidogrel should be avoided due to potential drug interactions that may diminish the efficacy of clopidogrel (5.6, 7). Long-term daily use of PPIs, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12), necessitating periodic monitoring of vitamin levels (5.7). Hypomagnesemia has been reported rarely with prolonged PPI treatment; clinicians should consider monitoring magnesium levels in patients on long-term therapy (5.8).

Healthcare professionals should also avoid the concomitant use of Omeprazole Delayed-Release Capsules with St. John’s Wort or rifampin due to potential interactions that may affect drug efficacy (5.9, 7). When assessing chromogranin A (CgA) levels for neuroendocrine tumors, it is crucial to temporarily discontinue Omeprazole Delayed-Release Capsules at least 14 days prior to testing, as elevated CgA levels may interfere with diagnostic accuracy (5.10, 7). Additionally, caution is advised when using PPIs alongside methotrexate, as this combination 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 Delayed-Release Capsules should be considered (5.11, 7).

Lastly, the risk of fundic gland polyps increases with long-term PPI use, particularly beyond one year. It is recommended to use the shortest duration of therapy necessary to manage the patient's condition (5.12).

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 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 studies involving this population.

Serious warnings associated with the use of Omeprazole Delayed-Release Capsules include the potential for gastric malignancy. It is important to note that a symptomatic response does not rule out the presence of gastric malignancy, and additional follow-up and diagnostic testing should be considered. 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 doses of PPIs may be associated with an increased risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. Patients should be monitored for signs of cutaneous and systemic lupus erythematosus, which may present as new onset or exacerbation of existing disease; discontinuation of Omeprazole Delayed-Release Capsules and referral to a specialist for evaluation is recommended in such cases. Additionally, daily long-term use of PPIs (e.g., longer than three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Hypomagnesemia has been reported rarely with prolonged treatment with PPIs, and the risk of fundic gland polyps increases with long-term use, especially beyond one year; therefore, the shortest duration of therapy should be utilized.

Reports of overdosage with omeprazole in humans have indicated variable manifestations, 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 Delayed-Release Capsules were taken alone.

Drug Interactions

Clinically significant drug interactions may occur with the use of this medication. It is essential to consult the full prescribing information for a comprehensive list of these interactions.

Healthcare professionals should be vigilant in monitoring patients for potential interactions and consider appropriate dosage adjustments as necessary based on the specific drugs involved.

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 those aged 2 to 16 years.

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 aged 65 years and older 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 seen in young healthy volunteers. Despite these pharmacokinetic changes, no dosage adjustment is necessary for elderly patients.

Healthcare providers should remain vigilant when prescribing omeprazole to geriatric patients, considering the potential for increased sensitivity and the pharmacokinetic alterations that may affect drug metabolism. Regular monitoring may be warranted to ensure optimal therapeutic outcomes in this population.

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 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.

While teratogenicity was not observed in animal reproduction studies with oral esomeprazole magnesium 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. Notably, 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 remain 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 score, or hospitalization compared to the general population. Another study from Denmark indicated 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 reported 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. Additionally, a small prospective observational cohort study indicated 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 disclose any evidence of teratogenic potential; however, 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 resulting from parents treated with omeprazole. Conversely, no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis, although 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 may experience acute interstitial nephritis while taking proton pump inhibitors (PPIs). It is important for healthcare professionals to monitor renal function in these patients and consider the potential risks associated with PPI use. Adjustments to dosing or alternative therapies may be necessary based on the severity of renal impairment and individual patient factors. Regular assessment of kidney function is recommended to ensure safe and effective treatment.

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 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 120 times the usual recommended clinical dose. The manifestations of overdosage were variable and included symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are consistent with those typically observed in normal clinical use of the medication.

It is noteworthy that the symptoms experienced during overdosage were transient, and no serious clinical outcomes have been reported when Omeprazole Delayed-Release Capsules were 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, corresponding to about 0.4 to 34 times the human dose of 40 mg/day on a body surface area basis. 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 the drug 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 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 on a body surface area basis). 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 of 40 mg/day on a body surface area basis). 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 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 in rats was noted 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 postmarketing experience details are available in the provided text.

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. It is important for patients to be fully informed to ensure safe and effective treatment.

Storage and Handling

Omeprazole Delayed-Release Capsules are supplied in a tight container that is protected 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. For dispensing, the capsules should be placed in a tight and light-resistant container, as specified by USP standards.

Additional Clinical Information

Standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical integrity of laboratory procedures. Clinicians should be aware that patients who do not achieve eradication of H. pylori following treatment with omeprazole/clarithromycin/amoxicillin triple therapy or omeprazole/clarithromycin dual therapy are likely to have clarithromycin-resistant H. pylori isolates. Therefore, it is advisable to conduct clarithromycin susceptibility testing when feasible. Patients with clarithromycin-resistant H. pylori should not be treated with regimens that include clarithromycin, such as omeprazole/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy, or any other treatment that relies on clarithromycin as the sole antimicrobial agent.

FDA Insert (PDF)

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

View full prescribing information (PDF)