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 an inhibitor of gastric acid secretion. The empirical formula is C17H19N3O3S, and it has a molecular weight of 345.42. The structural formula is provided in the accompanying documentation.

Omeprazole USP appears as a white to off-white powder that melts between 150°C and 160°C with decomposition. It exhibits solubility characteristics of being soluble in dichloromethane, sparingly soluble in methanol and alcohol, and very slightly soluble in water.

Omeprazole USP is formulated as delayed-release capsules intended for oral administration. Each capsule contains either 10 mg, 20 mg, or 40 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients include crospovidone, hypromellose, magnesium stearate, mannitol, meglumine, methacrylic acid copolymer, poloxamer, povidone, and triethyl citrate. The capsule shells are composed of D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, yellow iron oxide, gelatin, silicon dioxide, sodium lauryl sulfate, and titanium dioxide.

The imprinting ink used on the capsules contains D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, n-butyl alcohol, pharmaceutical glaze, propylene glycol, SDA-3A alcohol, and synthetic black iron oxide. Omeprazole delayed-release capsules comply with the 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 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

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

For the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

Triple Therapy:

• Omeprazole delayed-release capsules: 20 mg

• Amoxicillin: 1000 mg

• Clarithromycin: 500 mg Each medication should be taken orally twice daily for 10 days.

Dual Therapy:

• Omeprazole delayed-release capsules: 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 orally once daily for a period of 4 to 8 weeks. For symptomatic gastroesophageal reflux disease (GERD), a dosage of 20 mg orally once daily for up to 4 weeks is advised.

For erosive esophagitis (EE) due to acid-mediated GERD, the initial dosage is 20 mg orally once daily for 4 to 8 weeks. If there is no response, an additional 4 weeks of treatment may be warranted. In instances of recurrence, further courses of 4 to 8 weeks may be considered.

To maintain healing of EE due to acid-mediated GERD, a dosage of 20 mg orally once daily is recommended. For patients with hepatic impairment (Child-Pugh Class A, B, or C) and Asian patients, the dosage may be reduced to 10 mg once daily.

For pathological hypersecretory conditions, the starting dose is 60 mg orally once daily, with adjustments made based on individual patient needs as clinically indicated.

All medications should be administered orally.

Contraindications

Use is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, the use of this product is contraindicated in patients receiving rilpivirine-containing products due to potential drug interactions. When administered 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 recognize 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.

Acute tubulointerstitial nephritis has been reported in patients receiving treatment. If this condition is suspected, it is crucial to discontinue the medication and conduct a thorough evaluation of the patient.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should be vigilant for this potential complication, particularly in patients with risk factors.

Long-term use of PPIs, especially at multiple daily doses, may elevate the risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. It is advisable to assess the need for ongoing therapy in patients at risk for bone fractures.

Severe cutaneous adverse reactions may occur; therefore, treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity. Further evaluation by a specialist may be warranted in these cases.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such instances, discontinuation of omeprazole is recommended, and referral to a specialist for evaluation should be considered.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel. Additionally, the long-term use of omeprazole (beyond three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12), necessitating monitoring for this deficiency.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with prolonged PPI treatment. Clinicians should monitor patients for signs of these conditions.

Interactions with other medications, such as St. John’s Wort or rifampin, should be avoided due to potential adverse effects. Furthermore, when assessing chromogranin A (CgA) levels for neuroendocrine tumors, it is essential to temporarily discontinue omeprazole at least 14 days prior to testing, as elevated CgA levels may interfere with diagnostic accuracy.

Concomitant use of omeprazole 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.

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

Side Effects

Most common adverse reactions reported in adults, 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 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. Long-term and multiple daily doses of PPIs may also be linked to an increased 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 (beyond three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia and other 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 stop omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of omeprazole should be considered. The risk of fundic gland polyps increases with long-term use, particularly beyond one year, thus the shortest duration of therapy is recommended.

Reports of overdosage with omeprazole have been received, with manifestations varying but including 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 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.

Pharmacodynamic interactions may lead to enhanced effects or increased toxicity when this medication is used concurrently with other agents. Careful monitoring of the patient's clinical status is advised to mitigate potential adverse effects.

Pharmacokinetic interactions may alter the absorption, distribution, metabolism, or excretion of this medication or concomitant drugs. Dosage adjustments may be necessary based on the specific interaction and the clinical scenario.

Healthcare professionals should remain vigilant and consider both the pharmacodynamic and pharmacokinetic profiles of all medications prescribed to ensure patient safety and therapeutic 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 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 across the entire age group of 2 to 16 years. Additionally, accidental injuries were commonly noted in this demographic.

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 the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, active benign gastric ulcers, or pathological hypersecretory conditions in pediatric patients.

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 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

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 the administration of oral esomeprazole, an enantiomer of omeprazole, in rats and rabbits 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 were observed in the offspring at any age.

The estimated background risks of major birth defects and miscarriage for the general 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 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 at oral doses up to 138 mg/kg/day (approximately 34 times the oral human dose of 40 mg) and in rabbits at doses up to 69.1 mg/kg/day (also about 34 times the oral human dose) during organogenesis did not reveal any evidence of teratogenic potential. However, in rabbits, omeprazole administered during organogenesis at doses ranging from 6.9 to 69.1 mg/kg/day 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 from parents treated with omeprazole at doses of 13.8 to 138 mg/kg/day.

Given the potential risks observed in animal studies, healthcare professionals should weigh the benefits and risks of omeprazole use in pregnant patients and consider alternative therapies when appropriate.

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 not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 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.

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

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 demonstrated 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. Notably, the incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently observed in untreated rats. Additionally, ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats 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 marked increase in treatment-related ECL cell hyperplasia was recorded at the end of the first year (94% in treated rats versus 10% in controls). By the second year, the difference between treated and control rats diminished (46% versus 26%), yet 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 a single tumor finding challenging.

In a 52-week toxicity study involving 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 0.1 to 3.9 times the human dose). No astrocytomas were detected in female rats during this study. Conversely, in a separate two-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 34 times the human dose). A 78-week carcinogenicity study in mice did not indicate 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 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 material can help ensure that patients are well-informed and can engage in their treatment plan effectively.

Storage and Handling

Omeprazole delayed-release capsules are supplied in a tight container to ensure protection 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

Serum chromogranin A (CgA) levels may increase due to drug-induced decreases in gastric acidity when patients are treated with omeprazole. This elevation can lead to false positive results in diagnostic tests for neuroendocrine tumors. Clinicians are advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider repeating the test if initial results are elevated. For serial testing, it is important to use the same commercial laboratory, as reference ranges may differ.

Patients should be counseled to use the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy necessary for their condition. Prolonged use of PPIs should be avoided unless medically indicated. If patients exhibit signs of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and referral to a specialist is recommended. Most patients show improvement within 4 to 12 weeks after stopping the PPI. Additionally, for those on long-term treatment or taking medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels before and during PPI therapy may be warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)