Omeprazole

Description

Omeprazole delayed-release capsules USP contain the active ingredient omeprazole, a substituted benzimidazole with the chemical structure 5-methoxy-2[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]-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, with rapid degradation occurring in acidic environments, while it maintains acceptable stability under alkaline conditions.

The formulation is provided in delayed-release capsules for oral administration, available in strengths of 10 mg, 20 mg, and 40 mg of omeprazole USP, presented as enteric-coated granules. Inactive ingredients in the capsules include anhydrous lactose, cetyl alcohol, di-sodium hydrogen phosphate dihydrate, hypromellose, hypromellose phthalate, mannitol, simethicone emulsion 30%, sodium lauryl sulfate, and sugar spheres.

The capsule shells vary by strength: the 10 mg capsules contain FD&C Red No. 40, FD&C Yellow No. 6, D&C Yellow No. 10, gelatin, FD&C Blue No. 1, sodium lauryl sulfate, and titanium dioxide; the 20 mg capsules include FD&C Blue No. 1, gelatin, sodium lauryl sulfate, and titanium dioxide; and the 40 mg capsules consist of FD&C Red No. 40, FD&C Yellow No. 6, D&C Yellow No. 10, gelatin, FD&C Blue No. 1, sodium lauryl sulfate, and titanium dioxide. The imprinting ink used on the capsules contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, and potassium hydroxide.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcers in adults. It is also indicated for the eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults. Additionally, this drug is used for the treatment of active benign gastric ulcers in adults.

In pediatric patients aged 2 years and older, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) and for the maintenance of healing of erosive esophagitis (EE) due to acid-mediated GERD. Furthermore, it 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

Omeprazole delayed-release capsules USP are available in a dosage strength of 20 mg. The specific route of administration, method, and frequency have not been detailed in the provided information. Healthcare professionals are advised to refer to established guidelines or clinical protocols for the appropriate administration of this medication, ensuring that the dosage aligns with the patient's clinical condition and therapeutic needs.

Contraindications

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

Warnings and Precautions

Gastric malignancy should be considered in adults presenting with symptoms, as a symptomatic response does not rule out the presence of gastric cancer. Additional follow-up and diagnostic testing are recommended to ensure proper evaluation (5.1).

Acute interstitial nephritis has been observed in patients receiving proton pump inhibitors (PPIs), necessitating careful monitoring of renal function (5.2).

There is an increased risk of Clostridium difficile-associated diarrhea in patients undergoing PPI therapy. Healthcare professionals should be vigilant for signs of diarrhea and consider this risk when prescribing PPIs (5.3).

Long-term use of PPIs, particularly at multiple daily doses, may be associated with an elevated risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. Patients should be assessed for bone health, especially those on prolonged therapy (5.4).

The occurrence of cutaneous and systemic lupus erythematosus has been reported, with new onset or exacerbation of existing disease noted in some patients. In such cases, omeprazole should be discontinued, and referral to a specialist for further evaluation is advised (5.5).

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness 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). Monitoring of vitamin B-12 levels is recommended for patients on extended therapy (5.7).

Hypomagnesemia has been reported rarely in patients undergoing prolonged treatment with PPIs. Regular monitoring of magnesium levels may be warranted in these patients (5.8).

Healthcare professionals should avoid the concomitant use of omeprazole with St. John’s Wort or rifampin due to potential interactions that may affect drug efficacy (5.9, 7).

Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels to ensure accurate diagnostic results (5.10, 7).

Concomitant use of PPIs with methotrexate 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 should be considered (5.11, 7).

Side Effects

In clinical trials and postmarketing experiences, the most commonly reported adverse reactions among adult patients include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 2 to 16 years, the safety profile is similar to that of adults; however, respiratory system events and fever were noted as the most frequently reported reactions in pediatric studies.

Serious adverse reactions have also been identified. Patients taking proton pump inhibitors (PPIs) may experience acute interstitial nephritis. Additionally, there is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term use of PPIs, particularly at multiple daily doses, may be linked to an elevated risk of osteoporosis-related fractures of the hip, wrist, or spine.

Other important considerations include the potential for gastric malignancy; a symptomatic response does not exclude the possibility of gastric malignancy, necessitating further follow-up and diagnostic testing. Patients may also develop cutaneous and systemic lupus erythematosus, with new onset or exacerbation of existing disease, warranting 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). Hypomagnesemia has been reported rarely with prolonged PPI treatment. Furthermore, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; therefore, it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels.

Concomitant use of PPIs with methotrexate 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 should be considered.

In instances of overdosage, reports have indicated doses up to 2400 mg (120 times the usual recommended clinical dose). Manifestations of overdosage were variable and included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. Symptoms were generally 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 consult this resource to identify and understand the potential interactions that may affect patient management and treatment outcomes. Monitoring and dosage adjustments may be necessary based on the specific interactions identified.

Packaging & NDC

The table below lists all NDC Code configurations of Omeprazole, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

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

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

The safety and effectiveness of omeprazole delayed-release capsules have not been established in patients younger than 1 year of age for the treatment of symptomatic GERD, maintenance of healing of EE due to acid-mediated GERD, treatment of active duodenal ulcer, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcer, or pathological hypersecretory conditions. Furthermore, omeprazole is contraindicated 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 from these studies indicate that there are no significant differences in safety and effectiveness between elderly patients and younger subjects. However, it is important to note that while clinical experience has not identified distinct differences in response, a greater sensitivity in some older individuals cannot be entirely ruled out.

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. Healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population, ensuring that treatment is tailored to the individual needs of geriatric patients.

Pregnancy

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

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

The estimated background risks of major birth defects and miscarriage for the general population are unknown, but 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. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes.

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 section under general anesthesia. Additionally, no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day or in rabbits at doses up to 86 mg/kg/day during organogenesis.

A pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day showed decreased neonatal and early postnatal survival at doses equal to or greater than 138 mg/kg/day. Effects on maternal bone were also observed in pregnant and lactating rats at these doses. Given the available data, healthcare professionals should weigh the potential benefits against the risks when considering omeprazole for use in pregnant patients.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. Animal studies have indicated that omeprazole may affect offspring, as changes in bone morphology were observed in the offspring of rats dosed during pregnancy and lactation at doses approximately 34 times the oral human dose of 40 mg. Additionally, dose-related embryo/fetal toxicity and postnatal developmental toxicity were noted in offspring from parents treated with omeprazole throughout the lactation period.

Effects on maternal bone health have also been documented in pregnant and lactating rats, particularly with esomeprazole magnesium administered at oral doses ranging from 14 to 280 mg/kg/day. A statistically significant decrease in maternal femur weight of up to 14% was observed in rats dosed from gestational day 7 through weaning on postnatal day 21 at doses equal to or greater than 138 mg/kg/day. Given these findings, 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 the use of PPIs. 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 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 approximately 120 times the usual recommended clinical dose. The manifestations of overdosage have been variable, but commonly reported symptoms include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are consistent with those observed in normal clinical experience see Adverse Reactions (6).

It is noteworthy that the symptoms associated with omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. Currently, there is no specific antidote available for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable.

In the event of an overdosage, treatment should focus on symptomatic and supportive care. Healthcare professionals are advised to contact the Poison Control Center at 1-800-222-1222 for the most current information regarding the management of poisoning or overdosage.

Nonclinical Toxicology

In two 24-month carcinogenicity studies conducted in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44, 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 this effect 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 across both sexes.

In one of the studies, female rats received a dose of 13.8 mg omeprazole/kg/day (approximately 3.4 times the human dose of 40 mg/day, based on body surface area) for one year, followed by an observation period of an additional year without drug administration. No carcinoids were detected in these rats. An increased incidence of treatment-related ECL cell hyperplasia was recorded at the end of the first year, with 94% of treated rats exhibiting hyperplasia compared to 10% of controls. By the second year, the difference between treated and control rats diminished (46% vs. 26%), although the treated group still showed a higher prevalence of hyperplasia. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were identified in male or female rats treated for the full 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 identified in a small number of male rats 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 observed in female rats during this study. Furthermore, a 2-year carcinogenicity study in Sprague-Dawley rats revealed no instances of astrocytomas 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 demonstrate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, 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.

Regarding reproductive toxicity, omeprazole administered at oral doses up to 138 mg/kg/day in rats (approximately 34 times the oral human dose of 40 mg, based on body surface area) did not affect fertility or reproductive performance. In summary, the 24-month carcinogenicity studies in rats indicated a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia in both male and female animals.

Postmarketing Experience

No postmarketing experience details are available in the provided data.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Medication Guide and Instructions for Use. This information is essential for understanding the proper use of the medication, potential side effects, and any necessary precautions. Emphasizing the importance of this documentation 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 designed to protect the contents from light and moisture. It is essential to store the capsules at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). 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 Mas Management Group, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)