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. The inactive ingredients consist of 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 taken orally 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 doses are to 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. It is advisable to assess the patient's bone health and consider alternative therapies when appropriate.

Severe cutaneous adverse reactions may occur. Treatment should be discontinued at the first signs or symptoms of such reactions or any other signs 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 warranted.

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 is recommended 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.

Concomitant use of PPIs 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.

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

Side Effects

Most common adverse reactions reported in adults, with an incidence of 2% or greater, include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 2 to 16 years, the safety profile is similar to that of adults; however, respiratory system events and fever were the most frequently reported reactions in pediatric studies.

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric malignancy, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued and patients evaluated if this occurs. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, and long-term or 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 reported; treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been noted, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Long-term daily use of omeprazole, particularly beyond 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.

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Furthermore, concomitant use with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity.

Long-term use of omeprazole is also associated with an increased risk of fundic gland polyps, particularly beyond one year of treatment.

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 are no known 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. 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 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 the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, active benign gastric ulcers, or pathological hypersecretory conditions in pediatric patients. 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 indicated no significant differences in safety and effectiveness between elderly patients and younger subjects. While other clinical experiences have not identified notable differences in response between these age groups, it is important to acknowledge that greater sensitivity in some older individuals cannot be entirely excluded.

Pharmacokinetic studies 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 variations, 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 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.

While teratogenicity was not observed in animal reproduction studies with oral esomeprazole magnesium 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. Importantly, 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.

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.

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 separate 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%.

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; however, in rabbits, omeprazole administered during organogenesis 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. Conversely, no effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium in rats or rabbits 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.

Healthcare professionals should weigh the potential risks and benefits of omeprazole use in pregnant patients, considering the available data and individual patient circumstances.

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 data in human subjects and the 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 renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution when prescribing to patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to 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 omeprazole is taken in isolation. In cases of overdosage, there is no specific antidote available; 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, healthcare professionals are advised to contact the Poison Control Center at 1-800-222-1222 for the most current information regarding the management of poisoning or overdosage.

Nonclinical Toxicology

In nonclinical studies, omeprazole demonstrated no teratogenic effects. 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, omeprazole did not affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed a dose-related increase in gastric ECL cell carcinoids 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 on a body surface area basis. The incidence of carcinoids 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 treated with 13.8 mg/kg/day for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a notable increase in 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 identified in one rat (2%), but no similar tumors were observed 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 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 of 40 mg/day on a body surface area basis). No astrocytomas were found in female rats in this study. Conversely, a 2-year carcinogenicity study in Sprague-Dawley rats at the high dose of 140.8 mg/kg/day (about 34 times the human dose) did not reveal any astrocytomas in either sex. A 78-week carcinogenicity study in mice did not indicate 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 and in one of two in vivo mouse micronucleus tests, as well as 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. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was consistent across both male and female animals. 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, including omeprazole, may elevate the risk of bone fractures, particularly in the hip, wrist, or spine. It is recommended that patients adhere to prescribed dosages and durations, and discuss their individual risk factors with their healthcare provider.

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

Vitamin B-12 deficiency has been noted in patients on prolonged therapy (greater than three years), as the medication reduces stomach acid necessary for vitamin absorption. Patients are encouraged to discuss this potential deficiency with their healthcare provider.

Low magnesium levels have been reported in individuals taking proton pump inhibitors for at least three months, typically after one year of treatment. Symptoms may not always be present, but patients should notify their doctor if they experience any related symptoms.

The development of fundic gland polyps has been associated with long-term use of proton pump inhibitors, particularly after one year of treatment.

Severe skin reactions, although rare, can occur and may involve blistering, peeling, or bleeding skin, as well as systemic symptoms such as fever and chills. Patients experiencing these symptoms should discontinue use and seek immediate medical attention, as these reactions can be life-threatening.

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 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, or hypomagnesemia and mineral metabolism issues to their healthcare provider.

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 antacids may be used concurrently. In the event of a missed dose, patients should take the missed dose as soon as possible unless the next scheduled dose is due; in that case, they should skip the missed dose and resume their regular dosing schedule without taking two doses at once.

Patients must swallow the omeprazole delayed-release capsules whole and should not chew them. For those who have difficulty swallowing intact capsules, the capsules can be opened and the contents mixed with applesauce, as detailed in the Medication Guide. It is essential for patients to read the Medication Guide before starting treatment and with each refill, as new information may be available. Patients should take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary.

Patients are encouraged to discuss their risk of bone fracture with their healthcare provider if they are prescribed omeprazole delayed-release capsules. They should contact their doctor immediately if they notice a decrease in urine output or blood in their urine, experience watery stools accompanied by stomach pain and persistent fever, or develop new or worsening joint pain or a rash that worsens in sunlight. Additionally, patients should talk to their doctor about the potential for vitamin B-12 deficiency if they have been on omeprazole delayed-release capsules for more than three years. Symptoms of low magnesium should be reported to a healthcare provider without delay, and patients should discontinue the medication and seek immediate medical attention if they experience severe skin reactions.

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). Temporary excursions outside this range are permissible, provided the temperature does not exceed 30°C (86°F) or drop below 15°C (59°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 levels are elevated. For serial testing, it is important to use the same commercial laboratory, as reference ranges may differ.

Patients should be counseled to use the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy suitable for their condition. If symptoms indicative of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) arise, the medication should be discontinued, and the patient referred for specialist evaluation, as most patients show improvement within 4 to 12 weeks after stopping the PPI. For those on prolonged treatment or taking medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels is recommended before starting PPI therapy and periodically thereafter. Additionally, in patients with a preexisting risk of hypocalcemia, monitoring of magnesium and calcium levels should be considered, with supplementation as needed, and discontinuation of the PPI if hypocalcemia remains unresponsive to treatment.

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)