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 g/mol.

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.

Each Omeprazole Delayed-Release Capsule is designed for oral administration and contains either 10 mg, 20 mg, or 40 mg of omeprazole, formulated as enteric-coated microtablets. The inactive ingredients in the microtablets include crospovidone, glyceryl behenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, silicon dioxide, talc, titanium dioxide, and triethyl citrate. The capsule shells consist of gelatin, titanium dioxide, sodium lauryl sulfate, synthetic black iron oxide, shellac glaze, and other inactive components, with the 20 mg and 40 mg capsules also containing yellow iron oxide. Omeprazole Delayed-Release Capsules comply with USP Dissolution Test 2.

Uses and Indications

This drug is indicated for the treatment of duodenal ulcers and gastric ulcers in adults. It is also indicated for the treatment of gastroesophageal reflux disease (GERD) in both pediatric patients and adults. Additionally, this drug is indicated for the maintenance of healing of erosive esophagitis in pediatric patients and adults, as well as for the treatment of pathological hypersecretory conditions in adults.

Limitations of use include the lack of established safety and effectiveness of Omeprazole Delayed-Release Capsules in pediatric patients under 1 year of age. There are no specific teratogenic effects associated with this drug.

Dosage and Administration

For the short-term treatment of active duodenal ulcer, the recommended dosage is 20 mg administered once daily for a duration of 4 weeks. Some patients may require an additional 4 weeks of treatment based on clinical response.

In the context of H. pylori eradication to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available. For triple therapy, the regimen includes Omeprazole Delayed-Release Capsules at a dosage of 20 mg, taken twice daily for 10 days, in conjunction with Amoxicillin at 1000 mg and Clarithromycin at 500 mg, both administered as per their respective dosing guidelines. For dual therapy, Omeprazole Delayed-Release Capsules should be given at a dosage of 40 mg once daily for 14 days, alongside Clarithromycin at 500 mg, taken three times daily for the same duration.

For the treatment of gastric ulcer, the recommended dosage is 40 mg once daily for a period of 4 to 8 weeks. In cases of gastroesophageal reflux disease (GERD), a dosage of 20 mg once daily for 4 to 8 weeks is advised. For the maintenance of healing of erosive esophagitis, a dosage of 20 mg once daily is recommended.

In patients with pathological hypersecretory conditions, the dosage may vary with individual patient needs, typically starting at 60 mg once daily.

For pediatric patients aged 2 to 16 years, the dosing for GERD and maintenance of healing of erosive esophagitis is weight-based. For those weighing less than 20 kg, the dosage is 10 mg once daily, while patients weighing 20 kg or more should receive 20 mg once daily.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to any component of the formulation. This is due to the potential for severe allergic reactions, which may pose significant health risks.

Warnings and Precautions

Patients receiving Omeprazole Delayed-Release Capsules should be monitored for the possibility of concomitant gastric malignancy. A symptomatic response to therapy does not exclude the presence of gastric cancer; therefore, appropriate diagnostic evaluations should be considered in patients presenting with alarming symptoms, such as unexplained weight loss, persistent vomiting, or gastrointestinal bleeding (5.1).

Long-term treatment with Omeprazole Delayed-Release Capsules has been associated with the development of atrophic gastritis, as evidenced by gastric corpus biopsies. Healthcare professionals should be aware of this potential outcome and consider periodic assessments of gastric mucosal health in patients undergoing extended therapy (5.2).

When prescribing Omeprazole Delayed-Release Capsules in combination with clarithromycin and/or amoxicillin, it is essential to consult the full prescribing information for each medication. This ensures that all potential interactions and contraindications are adequately addressed, optimizing patient safety and therapeutic efficacy (5.3, 5.4).

Side Effects

Patients receiving Omeprazole Delayed-Release Capsules may experience a range of adverse reactions. The most common adverse reactions, occurring in 2% or more of participants, 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 reported as the most frequently noted reactions in clinical studies involving this age group.

In cases of overdosage, reports have indicated symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were generally transient, and no serious clinical outcomes have been documented when Omeprazole Delayed-Release Capsules were taken alone.

It is important to note that patients with known hypersensitivity to any component of the formulation should avoid using Omeprazole Delayed-Release Capsules. Additionally, symptomatic response to therapy does not exclude the possibility of concomitant gastric malignancy. Long-term treatment with Omeprazole Delayed-Release Capsules has also been associated with the observation of atrophic gastritis in gastric corpus biopsies.

Drug Interactions

Omeprazole Delayed-Release Capsules may interact with various medications, affecting their pharmacokinetics and pharmacodynamics.

Pharmacodynamic Interactions

• Warfarin: Concomitant use of Omeprazole Delayed-Release Capsules and warfarin may necessitate monitoring of INR and prothrombin time due to the potential for increased anticoagulant effect.

Pharmacokinetic Interactions

• Drugs Affected by Gastric pH: Omeprazole Delayed-Release Capsules may interfere with the absorption of drugs whose bioavailability is influenced by gastric pH, such as ketoconazole, ampicillin esters, and iron salts, due to its inhibition of gastric acid secretion.

• Cytochrome P450 Metabolized Drugs: Omeprazole Delayed-Release Capsules can prolong the elimination of drugs metabolized by cytochrome P450, including diazepam, warfarin, phenytoin, cyclosporine, disulfiram, and benzodiazepines. Monitoring is advised to determine the need for possible dose adjustments when these medications are co-administered.

• Voriconazole: Voriconazole may increase plasma levels of omeprazole, which could necessitate monitoring for potential effects.

• Atazanavir and Nelfinavir: Omeprazole Delayed-Release Capsules may reduce plasma levels of atazanavir and nelfinavir, potentially diminishing their therapeutic effects.

• Tacrolimus: The use of Omeprazole Delayed-Release Capsules may increase serum levels of tacrolimus, which could lead to toxicity; therefore, monitoring of tacrolimus levels is recommended.

• Saquinavir: Omeprazole Delayed-Release Capsules may increase plasma levels of saquinavir, warranting careful monitoring for adverse effects.

Healthcare professionals should consider these interactions when prescribing Omeprazole Delayed-Release Capsules and adjust dosages or monitor patients accordingly to ensure safety and efficacy.

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 use of Omeprazole Delayed-Release Capsules in pediatric and adolescent patients aged 2 to 16 years for the treatment of gastroesophageal reflux disease (GERD) is supported by extrapolated results from adequate and well-controlled studies conducted in adults, as well as safety and pharmacokinetic studies specifically performed in this age group. However, the safety and effectiveness of Omeprazole Delayed-Release Capsules for the treatment of GERD in patients younger than 1 year of age have not been established. Additionally, the safety and effectiveness of Omeprazole Delayed-Release Capsules for other pediatric indications remain unproven.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals (≥ 65 years of age) in clinical trials conducted in the U.S. and Europe. The results indicated no significant differences in safety and effectiveness between elderly patients and younger subjects. While other clinical experiences have not identified notable differences in response between these age groups, it is important to acknowledge that greater sensitivity in some older individuals cannot be entirely excluded.

Pharmacokinetic studies have demonstrated 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 changes, 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

Pregnancy Category C. Reproductive studies in rats and rabbits, as well as multiple cohort studies involving pregnant women, have not demonstrated an increased risk of congenital anomalies or adverse pregnancy outcomes associated with omeprazole use during the first trimester. However, there are no adequate and well-controlled studies on the use of omeprazole in pregnant women, and animal reproduction studies are not always predictive of human response. Therefore, omeprazole should be used during pregnancy only if clearly needed.

The majority of reported experiences with omeprazole during human pregnancy involve first trimester exposure, with the duration of use often unspecified (e.g., intermittent vs. chronic). An expert review by the Teratogen Information System (TERIS) concluded that therapeutic doses of omeprazole during pregnancy are unlikely to pose a substantial teratogenic risk, although the quantity and quality of data were assessed as fair. In utero exposure to omeprazole has not been associated with an increased risk of malformations (odds ratio 0.82, 95% CI 0.50–1.34), low birth weight, or low Apgar scores.

While the overall malformation rate was reported at 4.4% (95% CI 3.6–5.3), the malformation rate for first trimester exposure to omeprazole was 3.6% (95% CI 1.5–8.1). The relative risk of malformations associated with first trimester exposure compared to non-exposed women was 0.9 (95% CI 0.3–2.2), effectively ruling out a relative risk greater than 2.5 for all malformations. Rates of preterm delivery, growth retardation, spontaneous and elective abortions, gestational age at delivery, and mean birth weight did not differ significantly between omeprazole-exposed and control groups.

Notably, several studies have indicated 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 sections under general anesthesia. However, reproductive studies in animals have shown that omeprazole can produce dose-related increases in embryo lethality, fetal resorptions, and pregnancy loss in pregnant rabbits at doses approximately 5.5 to 56 times the human dose. Additionally, in rats treated with omeprazole at doses about 5.6 to 56 times the human dose, there was evidence of dose-related embryo/fetal toxicity and postnatal developmental toxicity in offspring.

In summary, while the available data suggest that omeprazole may not pose a significant teratogenic risk when used during pregnancy, it should be prescribed with caution and only when clearly indicated.

Lactation

Omeprazole concentrations have been measured in breast milk following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was found to be less than 7% of the peak serum concentration, corresponding to approximately 0.004 mg of omeprazole in 200 mL of milk.

Due to the excretion of omeprazole in human milk and the potential for serious adverse reactions in nursing infants, as well as the potential for tumorigenicity demonstrated in rat carcinogenicity studies, lactating mothers should carefully consider whether to discontinue breastfeeding or to discontinue the drug. This decision should take into account the importance of omeprazole to the mother’s health.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 indicated instances of overdosage with omeprazole in humans, with doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations of overdosage have been variable, including symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms are generally transient, and no serious clinical outcomes have been reported when Omeprazole Delayed-Release Capsules were ingested alone.

Management of Overdosage

There is currently no specific antidote for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable. In cases of overdosage, treatment should focus on symptomatic and supportive care. Healthcare professionals should also consider the possibility of multiple drug ingestion, as this may complicate the clinical picture.

For guidance on the management of any drug overdose, including omeprazole, it is advisable to contact a Poison Control Center at 1-800-222-1222 for current treatment recommendations.

Animal Studies

Toxicological studies in animals have demonstrated that single oral doses of omeprazole at 1350 mg/kg in mice, 1339 mg/kg in rats, and 1200 mg/kg in dogs were lethal. Observed effects in these animals included sedation, ptosis, tremors, convulsions, decreased activity, reduced body temperature, and alterations in respiratory rate, including increased depth of respiration. These findings underscore the importance of careful monitoring and management in cases of suspected overdosage.

Nonclinical Toxicology

Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (approximately 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (also about 56 times the human dose on a body surface area basis) did not reveal any evidence of teratogenic potential. However, in rabbits, omeprazole administered at doses ranging from 6.9 to 69.1 mg/kg/day (approximately 5.5 to 56 times the human dose on a body surface area basis) resulted in 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 at doses of 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis).

Omeprazole at oral doses up to 138 mg/kg/day in rats (approximately 56 times the human dose on a body surface area basis) was found to have no effect on fertility and reproductive performance.

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day (about 0.7 to 57 times a human dose of 20 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats, with a markedly higher incidence in female rats, which exhibited higher blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. ECL cell hyperplasia was present in all treated groups of both sexes. In one study, female rats treated with 13.8 mg omeprazole/kg/day (approximately 6 times a human dose of 20 mg/day, based on body surface area) for one year and followed for an additional year without the drug did not show carcinoids. An increased incidence of treatment-related ECL cell hyperplasia was noted at the end of one year (94% in treated rats vs 10% in controls). By the second year, the difference between treated and control rats was smaller (46% vs 26%) but still indicated more hyperplasia in the treated group. Gastric adenocarcinoma was observed in one rat (2%), with no similar tumors noted in male or female rats treated for two years. Historically, no similar tumors have been reported in this strain of rat, although the interpretation of a single tumor finding is challenging. In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were identified in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.2 to 6.5 times the human dose on a body surface area basis), while no astrocytomas were observed in female rats. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in either sex at the high dose of 140.8 mg/kg/day (about 57 times the human dose on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not demonstrate increased tumor occurrence, although the study was inconclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was also not positive.

Omeprazole exhibited 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. It 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 the 24-month carcinogenicity studies in rats, a dose-related significant 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

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. Commonly reported adverse reactions include headache, diarrhea, nausea, vomiting, constipation, flatulence, abdominal pain, and dizziness.

Additionally, rare cases of interstitial nephritis have been documented. There have been reports of Clostridium difficile-associated diarrhea in patients receiving proton pump inhibitors. Prolonged therapy with proton pump inhibitors has been associated with hypomagnesemia, which may lead to hypocalcemia and/or hypokalemia. Acute kidney injury has also been reported in patients receiving proton pump inhibitors. Furthermore, cases of cutaneous and systemic lupus erythematosus have been observed in patients treated with proton pump inhibitors.

Patient Counseling

Healthcare providers should advise patients to take Omeprazole Delayed-Release Capsules before eating to ensure optimal effectiveness. It is important to inform patients that the capsules must be swallowed whole and should not be chewed or crushed, as this can affect the medication's action.

For patients who experience difficulty swallowing capsules, healthcare providers can recommend an alternative method. Patients may open the capsule and add the contents, which consist of microtablets, to one tablespoon of applesauce in an empty bowl. It is crucial that the applesauce is not hot and is soft enough to swallow without chewing. After adding the microtablets to the applesauce, patients should mix the two thoroughly and swallow the mixture immediately with a glass of cool water to ensure complete ingestion of the microtablets.

Healthcare providers should emphasize that the microtablets/applesauce mixture should not be stored for future use, as it is intended for immediate consumption. This guidance will help ensure that patients receive the full benefit of their medication while minimizing any potential issues related to administration.

Storage and Handling

Omeprazole Delayed-Release Capsules are supplied in a tight container that is designed to protect the product from light and moisture. It is essential to store the capsules at a temperature range of 15°C to 30°C (59°F to 86°F) to maintain their efficacy and stability. Proper storage conditions are crucial to ensure the integrity of the medication throughout its shelf life.

Additional Clinical Information

Clarithromycin pretreatment resistance rates were observed at 3.5% (4/113) in studies involving omeprazole/clarithromycin dual therapy and 9.3% (41/439) in studies utilizing omeprazole/clarithromycin/amoxicillin triple therapy. In the latter studies, amoxicillin pretreatment susceptible isolates (≤ 0.25 μg/mL) were present in 99.3% (436/439) of patients. The reference methodology for susceptibility testing of Helicobacter pylori is agar dilution minimum inhibitory concentrations (MICs), and standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical integrity of laboratory procedures.

Clinicians should counsel patients that those not successfully eradicated of H. pylori after receiving omeprazole/clarithromycin/amoxicillin triple therapy or 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 avoid treatment with omeprazole/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy, or any 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 Contract Pharmacy Services-PA. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)