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, USP 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), the dosage is 20 mg orally once daily for up to 4 weeks. In patients with erosive esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg once daily for a duration of 4 to 8 weeks. For the maintenance of healing of EE due to acid-mediated GERD, a 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 dosages 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 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 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 increase the risk of osteoporosis-related fractures, particularly 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; 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.

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 should be considered.

Concomitant use of omeprazole with clopidogrel is not advised 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 necessary in 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 with St. John’s Wort or rifampin should be avoided 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 used in conjunction with methotrexate, PPIs 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.

Finally, 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 achieve treatment goals.

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 accordingly. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term and multiple daily dose PPI therapy 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, cutaneous and systemic lupus erythematosus may occur, presenting as new onset or exacerbation of existing disease, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Long-term daily use of omeprazole, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rare cases of hypomagnesemia and mineral metabolism disturbances have been reported with prolonged PPI treatment.

Concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided due to potential interactions. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; therefore, omeprazole should be temporarily stopped 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 metabolites, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

Long-term use of omeprazole may increase the risk of fundic gland polyps, particularly beyond one year, and the shortest duration of therapy should be utilized.

Reports of overdosage with omeprazole have included symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were 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 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 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.

In this age group, adverse reactions affecting the respiratory system were frequently reported, along with a notable incidence of accidental injuries.

However, the safety and effectiveness of omeprazole delayed-release capsules have not been established in patients under 1 year of age for the treatment of symptomatic GERD or the maintenance of healing of EE due to acid-mediated GERD. Additionally, 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. Furthermore, omeprazole is not recommended for patients under 1 month of age for any indication.

Geriatric Use

Omeprazole has been administered to over 2000 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 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.

While teratogenicity was not observed in animal studies with esomeprazole magnesium, an enantiomer of omeprazole, administered during organogenesis at doses about 68 times and 42 times 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. 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; 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 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 among omeprazole-exposed infants than expected in this population.

Another population-based retrospective cohort study from 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. A retrospective cohort study indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole, compared to 5.5% for H2-blockers and 4.1% for unexposed mothers. 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, compared to 2% in controls exposed to non-teratogens and 2.8% in disease-paired controls.

Additionally, several studies have reported 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. However, in rabbits, omeprazole administered during organogenesis 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 resulting from parents treated with omeprazole at doses administered prior to mating through the lactation period. Conversely, no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis, although a pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal survival and developmental delays at high doses.

Lactation

There are no adequate and well-controlled studies with omeprazole in nursing mothers. 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 on a body surface area basis) during lactation demonstrated 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 at oral doses ranging from 14 to 280 mg/kg/day (about 3.4 to 68 times the oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). However, when maternal administration of esomeprazole was limited to gestation only, there were no observed effects on bone physeal morphology in the offspring at any age.

Given the lack of human data and the findings in animal studies, caution is advised when considering the use of omeprazole or esomeprazole 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 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

In cases of omeprazole overdosage, reports have indicated that doses as high as 2400 mg, which is approximately 120 times the usual recommended clinical dose, have been documented in humans.

Symptoms of Overdosage The clinical manifestations of 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 as a treatment option.

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

In two 24-month carcinogenicity studies conducted in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day (approximately 0.4 to 34 times the human dose of 40 mg/day, based on body surface area) resulted in 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 rarely observed in untreated rats. ECL cell hyperplasia was noted in all treated groups of both sexes. In one study, female rats receiving 13.8 mg omeprazole/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 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 identified in one rat (2%), with no similar tumors observed 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 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. Conversely, in a separate 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 incidence of tumors, although the results were inconclusive. Additionally, a 26-week study involving p53 (+/-) transgenic mice did not yield positive results.

Omeprazole demonstrated clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, it was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay.

Omeprazole, at oral doses up to 138 mg/kg/day in rats (approximately 34 times the oral human dose of 40 mg based on body surface area), did not adversely affect fertility or reproductive performance. In the aforementioned 24-month carcinogenicity studies, a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female rats. 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 contact their healthcare provider 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 seek medical attention if they develop watery stools, abdominal pain, or persistent fever.

Long-term use of proton pump inhibitors (PPIs), including omeprazole, may elevate the risk of bone fractures, particularly in the hip, wrist, or spine, for those taking multiple daily doses for a year or longer. Patients are encouraged to discuss their individual risk of fractures with their healthcare provider.

Certain types of lupus erythematosus have been reported in individuals taking PPIs, with some experiencing worsening symptoms. Patients should notify their doctor if they develop new or worsening joint pain or a rash that exacerbates with sun exposure.

Vitamin B-12 deficiency has been noted in patients who have been on omeprazole delayed-release capsules for an extended period (more than three years), as the medication reduces stomach acid necessary for vitamin B-12 absorption. Patients should consult their healthcare provider regarding this potential deficiency.

Low magnesium levels can occur in some individuals after at least three months of PPI therapy, typically manifesting after a year of treatment. Symptoms may not always be present, but patients should inform their doctor if they experience any related 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 and may require hospitalization. Symptoms may include skin rash with blistering, peeling, or bleeding, and may be accompanied by fever, chills, body aches, shortness of breath, or swollen lymph nodes.

Serious allergic reactions have also been reported, and patients are advised to inform their healthcare provider if they experience any concerning symptoms while taking omeprazole delayed-release capsules.

Patients are encouraged to report side effects to the FDA at 1-800-FDA-1088.

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 for patients to take omeprazole exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary for their treatment.

While omeprazole may alleviate acid-related symptoms, patients should be informed that serious stomach problems could still occur, and they should consult their doctor if they experience a decrease in urination or notice blood in their urine. Additionally, patients should seek immediate medical attention if they develop watery stools, stomach pain, or a persistent fever.

Healthcare providers should discuss the potential risk of bone fractures associated with long-term use of omeprazole delayed-release capsules. Patients should be instructed to report any new or worsening joint pain or rashes, particularly those that worsen in sunlight. It is also essential to address the possibility of vitamin B-12 deficiency for patients who have been on omeprazole for an extended period, specifically more than three years.

Patients should be made aware of the symptoms of low magnesium and instructed to inform their doctor if they experience any. They should stop taking omeprazole and contact their healthcare provider immediately if they develop a skin rash that may blister, peel, or bleed.

Before initiating treatment, healthcare providers may check magnesium levels in patients who will be on omeprazole for a prolonged period. Patients must adhere to the prescribed dosage and should not alter their dose or discontinue the medication without consulting their doctor.

Omeprazole is typically taken once daily, and the timing should be based on the patient's medical condition. Patients should take the capsules before meals and may use antacids concurrently. If a patient has difficulty swallowing the capsule, they can open it and mix the contents with applesauce.

In the event of a missed dose, patients should take it as soon as they remember, unless it is close to the time for their next dose; in that case, they should skip the missed dose and resume their regular schedule. Patients should be cautioned against taking two doses simultaneously to compensate for a missed dose.

If a patient suspects an overdose of omeprazole, they should contact their doctor or call the poison control center at 1-800-222-1222 immediately, or go to the nearest emergency room. Lastly, it is crucial to keep omeprazole delayed-release capsules and all medications out of the reach of children.

Storage and Handling

Omeprazole Delayed-Release Capsules are supplied in a tight container that is designed to protect the contents from light and moisture. It is essential to store the capsules at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°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 monitoring, 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, monitoring of magnesium levels prior to and during PPI therapy is advisable. 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 Glenmark Pharmaceuticals Inc. , USA. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)