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 molecular formula of omeprazole is C17H19N3O3S, with 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; it is rapidly degraded in acidic environments but maintains acceptable stability under 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 10 mg and 20 mg capsules include crospovidone, dibasic sodium phosphate, hypromellose, magnesium hydroxide granules (with corn starch), methacrylic acid and ethyl acrylate copolymer dispersion, polyethylene glycol, polysorbate 80, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, purified water, silicon dioxide, sodium lauryl sulfate, sugar spheres (sucrose, corn starch, and purified water), talc, and titanium dioxide. The capsule shells for both dosages contain gelatin and titanium dioxide. The ink used for printing the capsules consists of black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. Omeprazole delayed-release capsules 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 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 treatment of pathologic hypersecretory conditions in adults.

No teratogenic or nonteratogenic effects have been reported.

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 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 consists of:

• Omeprazole: 20 mg

• Amoxicillin: 1000 mg

• Clarithromycin: 500 mg

Each medication should be taken twice daily for a total of 10 days.

Dual Therapy includes:

• Omeprazole: 40 mg once daily for 14 days

• Clarithromycin: 500 mg three times daily for 14 days

In the case 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.

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. For the maintenance of healing of EE due to acid-mediated GERD, a dosage of 20 mg once daily is advised.

In patients with pathological hypersecretory conditions, the starting dose is 60 mg once daily. This dosage may vary based on individual patient needs and should be continued as long as clinically indicated.

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 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 crucial to discontinue the medication and evaluate the patient accordingly.

There is an increased risk of Clostridium difficile-associated diarrhea associated with proton pump inhibitor (PPI) therapy. Clinicians should be vigilant for symptoms of diarrhea and consider this risk when prescribing PPIs.

Long-term use of PPIs, particularly at multiple daily doses, may be linked to an elevated risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. Healthcare providers should assess the need for ongoing therapy and consider alternative treatments when appropriate.

Severe cutaneous adverse reactions may occur. It is essential to discontinue the medication 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, discontinuation of omeprazole is recommended, and referral to a specialist for evaluation is advised.

Concomitant use of omeprazole with clopidogrel should be avoided 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 may be warranted 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 is contraindicated due to potential interactions that may affect the efficacy of omeprazole.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is important 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.

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 PPI use, 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 2 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 attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric malignancy, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, 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 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 reported; 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 noted, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Long-term daily use of omeprazole, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rare cases of hypomagnesemia and mineral metabolism disturbances have been reported 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. 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. Furthermore, the use of omeprazole with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity; thus, a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

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

Reports of overdosage with omeprazole have included symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

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

Pharmacodynamic interactions may lead to additive or synergistic effects, necessitating careful monitoring of therapeutic outcomes and potential adverse effects. In cases where such interactions are identified, dosage adjustments may be required to mitigate risks.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of concomitantly administered drugs. These interactions may necessitate 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 delayed-release capsules 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 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 use of omeprazole is contraindicated in patients less than 1 month of age for any indication.

Geriatric Use

Clinical trials involving over 2000 elderly individuals (≥65 years of age) have demonstrated that omeprazole exhibits comparable safety and effectiveness profiles when administered to geriatric patients versus younger subjects. While no significant differences in response have been identified between these groups, it is important to acknowledge that some elderly patients may exhibit greater sensitivity to the drug, although this has not been definitively established.

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

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

Pregnancy

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

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

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

Several 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 malformation, low birth weight, low Apgar score, 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%, similar 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.

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 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 at doses equal to or greater than 138 mg/kg/day, but when maternal administration of esomeprazole was confined to gestation only, no effects on bone physeal morphology in the offspring were observed at any age.

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, the developmental and health benefits of breastfeeding should be weighed 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 no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular assessment of renal function may be warranted to ensure safe and effective use of the medication in patients with reduced kidney function.

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 observed in normal clinical experience.

It is noteworthy that the symptoms associated with omeprazole overdosage were transient, and no serious clinical outcomes have been reported when omeprazole was 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 information is available regarding such effects.

In terms of non-teratogenic effects, studies have shown 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. 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 in 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 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 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 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). No astrocytomas were found in female rats in this study. Conversely, in a separate two-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were observed in either sex at the high dose of 140.8 mg/kg/day (about 34 times the human dose). A 78-week carcinogenicity study in mice did not demonstrate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week study involving p53 (+/-) transgenic mice did not yield positive 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 aligns with findings from other studies involving 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 have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Medication Guide and Instructions for Use. This information is essential for understanding the proper use of the medication, potential side effects, and any necessary precautions. It is important for patients to be fully informed to ensure safe and effective treatment.

Storage and Handling

Omeprazole delayed-release capsules, USP are supplied in a tight container that must be 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. 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)