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 g/mol. 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, USP is provided in delayed-release capsules intended for oral administration, with each capsule containing either 10 mg, 20 mg, or 40 mg of omeprazole in the form of enteric-coated granules. Inactive ingredients include anhydrous lactose, cetyl alcohol, di-sodium hydrogen phosphate dihydrate, hypromellose, hypromellose phthalate, mannitol, simethicone emulsion 30%, sodium lauryl sulfate, and sugar sphere.

Uses and Indications

Omeprazole delayed-release capsules are a proton pump inhibitor (PPI) indicated for the treatment of active duodenal ulcer in adults. This drug is also indicated for the eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults. Additionally, it is indicated for the treatment of active benign gastric ulcer in adults.

In pediatric patients aged 2 years and older, omeprazole 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, this drug is indicated for the management of pathologic hypersecretory conditions in adults.

Limitations of use have not been specified in the provided information. There are no teratogenic or nonteratogenic effects mentioned.

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 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: 20 mg

• Amoxicillin: 1000 mg

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

Dual Therapy:

• 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 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. In patients with erosive esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg once daily for 4 to 8 weeks. For the maintenance of healing of EE due to acid-mediated GERD, a continuous dosage of 20 mg once daily is recommended.

In patients with pathological hypersecretory conditions, the starting dose is 60 mg orally once daily. This dosage may vary based on individual patient needs and should be adjusted 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, the presence of gastric malignancy should be considered even if there is a symptomatic response to treatment. Additional follow-up and diagnostic testing are recommended to rule out this condition.

Acute tubulointerstitial nephritis has been reported; therefore, treatment should be discontinued, and patients should be evaluated promptly if symptoms arise.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Healthcare professionals should be vigilant for this potential complication.

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. Monitoring for signs of bone health deterioration is advised.

Severe cutaneous adverse reactions may occur; treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation should be considered in these cases.

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

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions. Additionally, the use of omeprazole alongside St. John’s Wort or rifampin should be avoided.

Long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin levels may be necessary in patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with extended PPI treatment. Regular monitoring of magnesium levels is advisable for patients on long-term therapy.

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 results.

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.

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

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 have also been identified. Gastric malignancy should be considered in adults, as symptomatic response does not preclude 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. Long-term and multiple daily dose PPI therapy may elevate the risk of osteoporosis-related fractures 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 other signs of hypersensitivity, with further evaluation considered. 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 (e.g., longer than 3 years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia and mineral metabolism disturbances have been reported with prolonged treatment with PPIs.

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 recommended to temporarily stop omeprazole at least 14 days prior to assessing CgA levels. The concomitant use of omeprazole with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration. The risk of fundic gland polyps increases with long-term use, particularly beyond one year.

In cases of overdosage, reports indicate variable manifestations, including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms are generally transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary 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 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 range of 2 to 16 years. Additionally, accidental injuries were commonly reported 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 or the maintenance of healing of EE due to acid-mediated GERD. Furthermore, omeprazole is not indicated for 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. 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, demonstrating no significant differences in safety and effectiveness when compared to younger subjects. While other clinical experiences have not identified notable differences in response between elderly and younger patients, it is important to acknowledge that some older individuals may exhibit greater sensitivity to the medication.

Pharmacokinetic studies indicate 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 variations, no dosage adjustment is necessary for elderly patients. Healthcare providers should remain vigilant in monitoring for any potential increased sensitivity in this population, although current evidence does not necessitate changes in dosing regimens.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. 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 oral esomeprazole magnesium administered 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 in the offspring were observed at any age.

The estimated background risks of major birth defects and miscarriage for the indicated population are unknown, although 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 epidemiological studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those of women exposed to H2-receptor antagonists or other controls. A population-based retrospective cohort study from the Swedish Medical Birth Registry reported on 955 infants whose mothers used omeprazole during pregnancy, revealing similar rates of malformations, low birth weight, low Apgar scores, or hospitalization compared to the general population. However, the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed group than expected.

A population-based retrospective cohort study in Denmark reported an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. Another retrospective cohort study indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. A small prospective observational cohort study following 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group.

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 did not reveal any evidence of teratogenic potential, although in rabbits, omeprazole 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. Conversely, no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal survival and developmental delays at high doses, but when maternal administration was confined to gestation only, no effects on bone physeal morphology in the offspring were noted at any age.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. Reproductive studies conducted with omeprazole in rats during the lactation period have shown dose-related embryo/fetal toxicity and postnatal developmental toxicity. Additionally, effects on maternal bone were observed in pregnant and lactating rats when esomeprazole magnesium was administered. However, when maternal administration of esomeprazole was limited to the gestation period, there were no observed effects on bone physeal morphology in the offspring at any age. Given the lack of human data and potential risks observed in animal studies, caution is advised when considering the use of omeprazole or esomeprazole in lactating mothers.

Renal Impairment

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

Hepatic Impairment

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

Overdosage

Reports of overdosage with omeprazole have been documented, with instances involving doses as high as 2400 mg, which is approximately 120 times the standard recommended clinical dose.

Clinical Manifestations

The symptoms associated with omeprazole overdosage may include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. It is noteworthy that these symptoms are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation.

Management of Overdosage

Currently, there is no specific antidote available for omeprazole overdosage. Therefore, management 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 cases of overdosage.

In the event of an overdosage, it is imperative 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 increase in the incidence of gastric ECL cell carcinoids in both male and female rats, with a notably higher incidence in females, who exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day of omeprazole for one year, followed by an additional year without treatment, did not develop carcinoids. However, a significant 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 solitary 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, which is approximately 0.1 to 3.9 times the human dose of 40 mg/day based on body surface area. No astrocytomas were detected in female rats during this study. 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, equivalent to 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. 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. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was dose-related and consistent across both male and female subjects. Carcinoid tumors have also been reported in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

Postmarketing experience has identified several adverse 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 medical attention if they experience a decrease in urine output or notice 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 (PPIs), including omeprazole, has been associated with an elevated risk of bone fractures, particularly in the hip, wrist, or spine. It is recommended that patients use omeprazole at the lowest effective dose for the shortest duration necessary and discuss their individual risk of fractures with their doctor.

Certain types of lupus erythematosus have been reported in patients taking PPIs, including omeprazole. Patients experiencing new or worsening joint pain or a rash that worsens in sunlight should consult their healthcare provider.

Vitamin B-12 deficiency may occur with prolonged use of omeprazole, as the medication reduces stomach acid necessary for vitamin B-12 absorption. Patients on long-term therapy (more than three years) should discuss the potential for deficiency with their doctor.

Low magnesium levels have been noted in some individuals taking PPIs for at least three months, typically after a year of treatment. Symptoms may not always be present, but patients should inform their healthcare provider if they develop any concerning symptoms.

The development of fundic gland polyps has been associated with long-term PPI use, particularly after more than one year of treatment.

Severe skin reactions, although rare, can occur with omeprazole delayed-release capsules. These reactions may present as skin rashes with blistering, peeling, or bleeding, and may require hospitalization. Patients should discontinue use and seek immediate medical attention if they experience symptoms such as fever, chills, body aches, shortness of breath, or swollen lymph nodes, as these may indicate a serious skin reaction.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, including the Medication Guide and Instructions for Use, prior to starting treatment with omeprazole delayed-release capsules. It is important for patients to report any signs or symptoms that may indicate serious adverse reactions, such as hypersensitivity reactions, acute tubulointerstitial nephritis, Clostridium difficile-associated diarrhea, bone fractures, severe cutaneous adverse reactions, cutaneous and systemic lupus erythematosus, cyanocobalamin (Vitamin B-12) deficiency, hypomagnesemia, and mineral metabolism issues.

Patients should also inform their healthcare provider if they initiate treatment with clopidogrel, St. John’s Wort, or rifampin, or if they are taking high-dose methotrexate. Omeprazole delayed-release capsules should be taken before meals, and patients may use antacids concurrently with the medication.

In the event of a missed dose, patients should take the missed dose as soon as possible. However, if the next scheduled dose is approaching, they should skip the missed dose and resume their regular dosing schedule without taking two doses at once. Patients must swallow the capsules whole and should not chew them. For those who have difficulty swallowing intact capsules, omeprazole delayed-release capsules can be opened and mixed with applesauce, as detailed in the Medication Guide.

Patients are encouraged to read the Medication Guide each time they receive a refill, as it may contain new information. They should take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary. It is advisable for patients to discuss their risk of bone fractures with their healthcare provider if they are on this medication.

Patients should contact their doctor immediately if they notice a decrease in urine output or blood in their urine. They should also seek medical attention if they experience watery stools, stomach pain, and persistent fever, or if they develop new or worsening joint pain or a rash that worsens in sunlight. Long-term users of omeprazole delayed-release capsules (more than three years) should discuss the potential for vitamin B-12 deficiency with their doctor. Additionally, patients should inform their healthcare provider right away if they experience symptoms of low magnesium. If severe skin reactions occur, patients must stop taking the medication and contact their doctor immediately.

Storage and Handling

Omeprazole Delayed-Release Capsules are supplied in a tight container that is designed to protect the contents from light and moisture. The recommended storage temperature for these capsules is between 20°C to 25°C (68°F to 77°F), with permissible excursions ranging from 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential 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 symptoms indicative of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) arise, the drug should be discontinued, and the patient referred for specialist evaluation. Most patients experience 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, such as diuretics, monitoring of magnesium levels is recommended before and during treatment. In patients with a risk of hypocalcemia, monitoring of calcium levels is also advised, with supplementation provided as 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)