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. Its empirical formula is C17H19N3O3S, and it has a molecular weight of 345.42. Omeprazole appears as a white to off-white crystalline powder that melts with decomposition at approximately 155°C. It is classified as a weak base, 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 media but maintains acceptable stability in alkaline conditions.

Omeprazole Delayed-Release Capsules, USP are formulated as delayed-release capsules intended for oral administration. Each capsule contains 10 mg of omeprazole in the form of enteric-coated microtablets. Inactive ingredients in the formulation include crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, silicon dioxide, talc, titanium dioxide, and triethyl citrate. The capsule shells are made of gelatin and may also contain sodium lauryl sulfate. The imprinting ink used on the capsules consists of ammonium hydroxide, butyl alcohol, black iron oxide, isopropyl alcohol, propylene glycol, and shellac glaze, and may additionally contain dehydrated alcohol.

Uses and Indications

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

In pediatric patients aged 1 year 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.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

Omeprazole Delayed-Release Capsules are administered orally.

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg once daily for a duration of 4 weeks. In some cases, an additional 4 weeks may be necessary based on the patient's 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, administered twice daily for 10 days.

• Amoxicillin: 1000 mg, administered as directed.

• Clarithromycin: 500 mg, administered as directed.

Dual Therapy:

• Omeprazole Delayed-Release Capsules: 40 mg, administered once daily for 14 days.

• Clarithromycin: 500 mg, administered three times daily for 14 days.

For the treatment of active benign gastric ulcer, the recommended dosage is 40 mg once daily for a period of 4 to 8 weeks.

In cases of symptomatic gastroesophageal reflux disease (GERD), the dosage is 20 mg once daily for up to 4 weeks. For erosive esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg once daily for 4 to 8 weeks. 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 response.

Contraindications

Use of this product is contraindicated in the following situations:

Patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation should not use this product due to the risk of severe allergic reactions. Additionally, the use of this product is contraindicated in patients receiving rilpivirine-containing products, as potential drug interactions may occur.

When administered in combination with Omeprazole Delayed-Release Capsules, refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin to ensure safe use.

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 imperative to discontinue the medication and evaluate the patient accordingly.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should be vigilant for signs of this infection, particularly in patients receiving long-term PPI therapy.

Long-term use of PPIs, especially at multiple daily doses, may increase the risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. It is advisable to assess the patient's bone health and consider alternative therapies when appropriate.

Severe cutaneous adverse reactions may occur in some patients. Treatment should be discontinued 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, it is recommended to discontinue Omeprazole Delayed-Release Capsules and refer the patient to a specialist for further evaluation.

Concomitant use of Omeprazole Delayed-Release Capsules with clopidogrel is contraindicated 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 is recommended for patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported, albeit rarely, with prolonged PPI treatment. Clinicians should monitor magnesium levels in patients receiving long-term therapy.

The concomitant use of Omeprazole Delayed-Release Capsules with St. John’s Wort or rifampin should be avoided due to potential interactions that may affect the efficacy of the medication.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is crucial to note that increased levels of Chromogranin A (CgA) may interfere with test results. It is recommended to temporarily discontinue Omeprazole Delayed-Release Capsules at least 14 days prior to assessing CgA levels.

When used in conjunction with methotrexate, PPIs may elevate and prolong serum concentrations of methotrexate and/or its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of Omeprazole Delayed-Release Capsules should be considered.

Finally, the risk of developing 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

Patients receiving Omeprazole Delayed-Release Capsules may experience a range of adverse reactions. Common adverse reactions reported include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence.

In pediatric patients aged 1 to 16 years, the safety profile 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; 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 Delayed-Release Capsules may be associated with an increased risk of osteoporosis-related bone fractures, particularly of the hip, wrist, or spine. Patients should be advised of this risk, especially those on multiple daily doses. Severe cutaneous adverse reactions have been reported; treatment should be discontinued at the first signs or symptoms of such reactions, and further evaluation should be considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been observed, warranting discontinuation of the medication and referral to a specialist.

Cyanocobalamin (Vitamin B-12) deficiency may occur with daily long-term use exceeding three years, leading to malabsorption. Rare cases of hypomagnesemia and disturbances in mineral metabolism have been reported with prolonged PPI treatment. Interactions with other medications, such as clopidogrel, St. John’s Wort, rifampin, and methotrexate, necessitate caution; concomitant use should be avoided or monitored closely. Specifically, with high-dose methotrexate, a temporary withdrawal of Omeprazole Delayed-Release Capsules may be advisable to prevent elevated serum concentrations and potential toxicity.

In terms of diagnostic considerations, increased levels of Chromogranin A (CgA) may interfere with investigations for neuroendocrine tumors; it is recommended to temporarily discontinue Omeprazole Delayed-Release Capsules at least 14 days prior to assessing CgA levels. Long-term use beyond one year may also increase the risk of fundic gland polyps, and the shortest duration of therapy should be utilized.

In cases of overdosage, reports have indicated variable manifestations 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 Delayed-Release Capsules were taken alone.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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 1 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 range of 1 to 16 years. Specifically, fever was commonly reported in patients aged 1 to less than 2 years, while accidental injuries were frequently noted in those aged 2 to 16 years.

It is important to note that the safety and effectiveness of Omeprazole Delayed-Release Capsules have not been established in patients under 1 year of age for any indication. Additionally, the safety and effectiveness of this medication have not been established in pediatric patients for the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcers, or pathological hypersecretory conditions. 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 results 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 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 Delayed-Release Capsules in pregnant women. 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.

Reproductive studies in rats and rabbits have shown dose-dependent embryo-lethality at doses of omeprazole that were approximately 3.4 to 34 times the oral human dose of 40 mg, based on body surface area for a 60 kg person. However, teratogenicity was not observed in animal reproduction studies with the administration of oral esomeprazole, an enantiomer of omeprazole, during organogenesis at doses approximately 68 times and 42 times the oral human dose of 40 mg for rats and rabbits, respectively.

Changes in bone morphology were noted in the 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 esomeprazole or omeprazole. Importantly, when maternal administration was limited to gestation only, there were no observed effects on bone physeal morphology in the offspring at any age.

The estimated background risks of major birth defects and miscarriage for the indicated population remain unknown. 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. Additionally, 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.

Healthcare professionals should weigh the potential benefits against the risks when considering the use of omeprazole in pregnant patients.

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 Delayed-Release Capsules in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Reports of overdosage with omeprazole in humans have documented doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations associated with omeprazole overdosage can include a range of symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.

It is important to note that the symptoms of omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when the drug is taken alone. In cases of suspected overdosage, there is no specific antidote available; therefore, treatment should focus on symptomatic and supportive care.

Given that omeprazole is extensively protein-bound, it is not readily dialyzable, which limits the effectiveness of dialysis in managing overdosage. In the event of an overdosage, healthcare professionals are advised to contact the Poison Control Center at 1-800-222-1222 for further management information and guidance.

Nonclinical Toxicology

In two 24-month carcinogenicity studies conducted in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44.0, 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 a dose-related increase in gastric ECL cell carcinoids in both male and female rats. The incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently observed in untreated rats. ECL cell hyperplasia was noted in all treated groups across both sexes. In one study, female rats receiving 13.8 mg omeprazole/kg/day (about 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 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%), with no similar tumors identified in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, although the interpretation of a single tumor finding is challenging. In a separate 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were detected in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose). No astrocytomas were found in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were observed in either sex at the high dose of 140.8 mg/kg/day (about 34 times the human dose). A 78-week carcinogenicity study in mice did not reveal an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole demonstrated positive 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. Conversely, 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.

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), omeprazole did not adversely affect fertility or reproductive performance.

In the aforementioned 24-month carcinogenicity studies in rats, a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals. Similar carcinoid tumors have 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 events associated with the use of Omeprazole Delayed-Release Capsules, reported voluntarily or through surveillance programs.

Acute tubulointerstitial nephritis has been observed in some patients, which can occur at any time during treatment. Patients are advised to seek immediate medical attention if they experience a decrease in urine output or blood in their urine.

There is an increased risk of severe diarrhea, potentially due to Clostridium difficile infection in the intestines. Patients should contact their healthcare provider if they experience watery stools, abdominal pain, or persistent fever.

Long-term use of proton pump inhibitors, including Omeprazole, may elevate the risk of bone fractures, particularly in the hip, wrist, or spine. It is recommended that patients use the medication as prescribed, at the lowest effective dose, and for the shortest duration necessary, while discussing fracture risk with their healthcare provider.

Certain types of lupus erythematosus have been reported in patients taking proton pump inhibitors. Individuals may experience new or worsening joint pain or a rash that exacerbates with sun exposure, necessitating prompt medical consultation.

Vitamin B-12 deficiency has been noted in patients who have been on Omeprazole Delayed-Release Capsules for extended periods (more than three years), as the medication reduces stomach acid necessary for vitamin B-12 absorption.

Low magnesium levels can occur in some patients after at least three months of treatment, typically manifesting after one year. This condition can be serious and requires monitoring.

The development of fundic gland polyps has been associated with prolonged use of proton pump inhibitors, particularly after more than one year of treatment.

Severe skin reactions, although rare, may occur and can affect any part of the body. Symptoms may include skin rash with blistering, peeling, or bleeding, accompanied by fever, chills, body aches, shortness of breath, or swollen lymph nodes. Patients experiencing these symptoms should discontinue use and seek immediate medical attention, as these reactions may be life-threatening.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, including the Medication Guide and Instructions for Use, to ensure they understand the proper use of Omeprazole Delayed-Release Capsules. It is important to take the medication exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary.

While Omeprazole Delayed-Release Capsules may alleviate acid-related symptoms, patients should be informed that serious stomach problems could still occur. They should be encouraged to communicate with their healthcare provider regarding any concerns. Immediate medical attention should be sought if patients experience a decrease in urination or notice blood in their urine. Additionally, they should contact their doctor promptly if they develop watery stools, stomach pain, or a persistent fever.

Patients should be made aware of the potential risk of bone fractures associated with long-term use of Omeprazole Delayed-Release Capsules and should discuss this risk with their healthcare provider. New or worsening joint pain, as well as a rash on the cheeks or arms that worsens in sunlight, should also be reported to their doctor without delay.

For those who have been on Omeprazole Delayed-Release Capsules for an extended period (more than three years), it is advisable to discuss the possibility of vitamin B-12 deficiency with their healthcare provider. Furthermore, healthcare providers may monitor magnesium levels before initiating treatment or during prolonged use of the medication.

Patients should be instructed to report any symptoms such as rash, throat tightness, facial swelling, or difficulty breathing, as these may indicate an allergic reaction. They should also inform their healthcare provider of any side effects that are bothersome or persistent.

It is crucial that patients do not alter their dosage or discontinue the medication without consulting their healthcare provider. If a patient has difficulty swallowing a whole capsule, they may open it and mix the contents with applesauce, but they should not chew or crush the capsules.

In the event of a missed dose, patients should take the dose as soon as they remember, unless it is nearly time for the next scheduled dose. In such cases, they should skip the missed dose and resume their regular dosing schedule, avoiding the temptation to take two doses simultaneously. If an overdose occurs, patients should seek immediate medical assistance by calling their doctor or contacting a poison control center at 1-800-222-1222, or by going to the nearest emergency room.

Storage and Handling

Omeprazole Delayed-Release Capsules are supplied in a tight container that is protected from light and moisture. It is essential to store the capsules at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. For dispensing, the capsules should be placed in a tight and light-resistant container, as specified by USP standards.

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 Chartwell RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)