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 in alkaline conditions. The dissolution test for omeprazole should be conducted in accordance with USP Test 2.

Omeprazole is formulated as delayed-release capsules intended for oral administration. Each capsule contains 10 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the 10 mg capsule include hypromellose, magnesium oxide, methacrylic acid copolymer dispersion type C, povidone, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide, and triethyl citrate. The capsule shells consist of gelatin, iron oxide black, iron oxide red, iron oxide yellow, and titanium dioxide. The black ink used for printing the 10 mg capsules contains black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. The sugar spheres are composed of maize starch and sucrose.

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 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 management of pathologic hypersecretory conditions in adults. There are no teratogenic or nonteratogenic effects mentioned in the available data.

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 treatment 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 initial dosage is 20 mg once daily for 4 to 8 weeks. If there is no response, an additional 4 weeks of treatment may be warranted. In cases 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 once daily is recommended.

For pathological hypersecretory conditions, the starting dose is 60 mg once daily, with adjustments made based on individual patient needs and clinical indications, as detailed in the full prescribing information.

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 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 extended treatment using PPIs. 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

Patients receiving treatment with omeprazole may experience a range of adverse reactions. Common adverse reactions reported include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence.

In pediatric patients aged 2 to 16 years, the safety profile of omeprazole is similar to that observed in adults; however, respiratory system events and fever were noted as the most frequently reported reactions in clinical studies involving this population.

Serious adverse reactions have also been identified. Gastric malignancy should be considered in adults, as symptomatic response does not exclude its presence; therefore, additional follow-up and diagnostic testing may be warranted. Acute tubulointerstitial nephritis has been reported, necessitating discontinuation of treatment and evaluation of affected patients. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, which should be monitored.

Long-term use of omeprazole, particularly at multiple daily doses, may be associated with an increased risk of osteoporosis-related bone fractures, specifically of the hip, wrist, or spine. Severe cutaneous adverse reactions have been observed; treatment should be discontinued at the first signs or symptoms of such reactions or any signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been reported, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia and disturbances in mineral metabolism have been reported with prolonged PPI treatment. The risk of fundic gland polyps increases with long-term use, particularly beyond one year; therefore, the shortest duration of therapy is recommended.

Interactions with other medications have been noted. Concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Additionally, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; it is advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is also warranted when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

In cases 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 consider the potential for both pharmacodynamic and pharmacokinetic interactions when prescribing medications.

Pharmacodynamic interactions may occur when drugs with similar effects are used concurrently, potentially leading to enhanced therapeutic effects or increased risk of adverse reactions. Monitoring for signs of increased effects or toxicity is advised.

Pharmacokinetic interactions can arise from alterations in drug absorption, distribution, metabolism, or excretion. These interactions may necessitate dosage adjustments or increased monitoring of drug levels to ensure therapeutic efficacy while minimizing the risk of toxicity.

Healthcare providers are encouraged 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, maintenance of healing of EE due to acid-mediated GERD, treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcers, or pathological hypersecretory conditions. Furthermore, the safety and effectiveness of omeprazole have not been established in patients less than 1 month of age for any indication.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals (≥65 years of age) in clinical trials conducted in the U.S. and Europe. The data from these studies indicate that there are 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 ruled out.

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

Despite these pharmacokinetic differences, 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, although the overall safety profile appears consistent with that of younger 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 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. Nonetheless, 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. 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; however, 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 reported 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. In rabbits, omeprazole administered during organogenesis at doses ranging from 6.9 to 69.1 mg/kg/day (approximately 3.4 to 34 times the oral human dose of 40 mg) 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 mg/kg/day (about 3.4 to 34 times the oral human dose of 40 mg).

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 (about 68 times the oral human dose) or in rabbits at doses up to 86 mg/kg/day (about 42 times the oral human dose). However, a pre- and postnatal developmental toxicity study in rats indicated decreased neonatal/early postnatal survival at doses equal to or greater than 138 mg/kg/day (about 34 times the oral human dose). Additionally, body weight and body weight gain were reduced, and neurobehavioral or general developmental delays were evident at doses equal to or greater than 69 mg/kg/day (about 17 times the oral human dose).

Decreased femur length, width, and thickness of cortical bone, as well as decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity, were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times the oral human dose). Physeal dysplasia in the femur was observed in offspring of rats treated with esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day. Effects on maternal bone were also observed in pregnant and lactating rats when esomeprazole magnesium was administered at doses of 14 to 280 mg/kg/day.

Given the potential risks, healthcare professionals should carefully consider the benefits and risks of omeprazole use in pregnant patients.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. In reproductive studies conducted with omeprazole in rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole administered prior to mating through the lactation period. Changes in bone morphology were noted in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole.

Additionally, effects on maternal bone were observed in pregnant and lactating rats in the pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day. A statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day when administered from gestational day 7 through weaning on postnatal day 21.

Given the lack of human data and the observed effects in animal studies, caution is advised when considering the use of omeprazole in lactating mothers.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 120 times the usual recommended clinical dose. The manifestations of overdosage are variable and may include symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are similar to those observed in normal clinical use. It is noteworthy that the symptoms experienced 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. Therefore, in the event of an overdosage, the recommended course of action is to provide symptomatic and supportive treatment.

In cases of over-exposure, it is advisable 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

No teratogenic effects were observed in the studies conducted. 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 affect fertility or reproductive performance.

In two separate 24-month carcinogenicity studies involving rats, omeprazole was administered at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day, corresponding to about 0.4 to 34 times the human dose of 40 mg/day based on body surface area. These studies revealed a dose-related occurrence of gastric ECL cell carcinoids in both male and female rats, with a significantly higher incidence noted in female rats, attributed to elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. Additionally, ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats receiving 13.8 mg omeprazole/kg/day (approximately 3.4 times the human dose) for one year, followed by 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 singular finding challenging.

In a 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). No astrocytomas were detected in female rats during this study. Conversely, a 2-year carcinogenicity study in Sprague-Dawley rats did not reveal any astrocytomas 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 incidence 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, in one of two in vivo mouse micronucleus tests, and in 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.

Postmarketing Experience

Patients are advised 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 and potential risks associated with the medication.

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, USP 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), 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 of proton pump inhibitors (PPIs) for the shortest duration necessary. Prolonged use beyond medical necessity should be avoided. 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 PPI therapy or taking medications that may lead to hypomagnesemia, monitoring of magnesium levels is advisable before and during treatment. Calcium levels should also be monitored in patients with a risk of hypocalcemia, and supplementation may be necessary. If hypocalcemia does not respond to treatment, discontinuation of the PPI should be considered.

FDA Insert (PDF)

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

View full prescribing information (PDF)