Omeprazole

Description

The active ingredient in omeprazole delayed-release capsules 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 powder and melts between 150°C and 160°C with decomposition. It is soluble in dichloromethane, sparingly soluble in methanol and alcohol, and very slightly soluble in water.

Omeprazole USP is provided as delayed-release capsules for oral administration. Each delayed-release capsule contains 20 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the delayed-release capsules include crospovidone, hypromellose, magnesium stearate, mannitol, meglumine, methacrylic acid copolymer, poloxamer, povidone, and triethyl citrate. The capsule shells are composed of D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, yellow iron oxide, gelatin, silicon dioxide, sodium lauryl sulfate, and titanium dioxide. The imprinting ink contains D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, n-butyl alcohol, pharmaceutical glaze, propylene glycol, SDA-3A alcohol, and synthetic black iron oxide.

Uses and Indications

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

In pediatric patients aged 2 years and older, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) and for the maintenance of healing of erosive esophagitis (EE) due to acid-mediated GERD. Furthermore, it is indicated for the treatment of pathologic hypersecretory conditions in adults.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

The recommended dosage for the treatment of active duodenal ulcer is 20 mg administered orally once daily for a duration of 4 weeks. In certain patients, an additional 4 weeks of treatment may be necessary.

For the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

• Triple Therapy: This regimen consists of omeprazole delayed-release capsules 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, with each medication taken orally twice daily for 10 days.

• Dual Therapy: This regimen includes omeprazole delayed-release capsules 40 mg administered orally once daily for 14 days, alongside clarithromycin 500 mg taken orally three times daily for the same duration.

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 initial dosage is 20 mg orally once daily for 4 to 8 weeks. If there is no response, an additional 4 weeks of treatment may be warranted. In instances of recurrence, further courses of 4 to 8 weeks may be considered.

To maintain healing of EE due to acid-mediated GERD, a dosage of 20 mg orally once daily is recommended. For patients with hepatic impairment (Child-Pugh Class A, B, or C) and Asian patients, the dosage should be reduced to 10 mg once daily.

For pathological hypersecretory conditions, the starting dose is 60 mg orally once daily, with adjustments made based on individual patient needs 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 rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to ensure comprehensive patient evaluation.

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 remain vigilant for this potential complication, particularly in patients with risk factors.

Long-term use of PPIs, especially at multiple daily doses, may elevate 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; 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 further evaluation is advised.

Concomitant use of omeprazole with clopidogrel should be avoided due to potential interactions that may diminish the effectiveness of clopidogrel.

Long-term daily use of omeprazole, particularly beyond 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 prolonged PPI treatment. Clinicians should monitor magnesium levels in patients receiving long-term therapy.

Concomitant use of omeprazole with St. John’s Wort or rifampin is not recommended due to potential interactions that may affect drug efficacy.

Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors. It is advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels to ensure accurate diagnostic results.

Caution is warranted when using omeprazole in conjunction with methotrexate, as this combination 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 recommended to use the shortest duration of therapy necessary to manage the patient's condition effectively.

Side Effects

Most common adverse reactions reported in adults, occurring 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 studies involving this population.

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric cancer, necessitating further diagnostic evaluation. 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 use of PPIs 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 any 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. Additionally, omeprazole may interfere with diagnostic investigations for neuroendocrine tumors by increasing Chromogranin A (CgA) levels, and it is recommended to temporarily discontinue omeprazole 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. Long-term use of omeprazole may also increase the risk of fundic gland polyps, particularly beyond one year, thus the shortest duration of therapy is recommended.

Reports of overdosage with omeprazole have been received, with manifestations varying but including 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 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, treatment of active benign gastric ulcers, or pathological hypersecretory conditions in pediatric patients.

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 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 greater sensitivity in some older individuals cannot be entirely excluded.

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 young 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 or adverse effects in this population.

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 omeprazole use during the first trimester. 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. However, teratogenicity was not observed in animal studies with the enantiomer esomeprazole administered during organogenesis at doses about 68 times and 42 times the oral human dose of 40 mg, respectively.

Changes in bone morphology were noted in offspring of rats dosed throughout most of pregnancy and lactation at doses equal to or greater than approximately 34 times the oral human dose of 40 mg. When maternal administration was limited to gestation only, no effects on bone physeal morphology in the offspring were observed at any age. The estimated background risks of major birth defects and miscarriage for the general population remain 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 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. A population-based retrospective cohort study from the Swedish Medical Birth Registry involving 955 infants whose mothers used omeprazole during pregnancy found that the incidence of malformations, low birth weight, low Apgar scores, or hospitalization was similar to that observed in the general population. Additionally, a cohort study covering all live births in Denmark reported a birth defect rate of 2.9% in infants born to mothers with first trimester exposure to omeprazole, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the same period.

A retrospective cohort study involving 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. Furthermore, a small prospective observational cohort study of 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. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups.

In summary, while animal studies have shown some evidence of embryo-lethality and fetal toxicity at high doses, omeprazole has not demonstrated teratogenic potential in rats and rabbits during organogenesis. Caution is advised when prescribing omeprazole to pregnant patients, and the potential risks should be weighed against the benefits of treatment.

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 in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition should be taken into account.

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

Reports of overdosage with omeprazole have been documented in humans, with instances of doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose.

Symptoms of Overdosage

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

Management of Overdosage

There is currently no specific antidote for omeprazole overdosage. Therefore, treatment should focus on symptomatic and supportive care. Given that omeprazole is extensively protein-bound and not readily dialyzable, standard detoxification methods may not be effective.

In the event of an overdosage, it is crucial to contact the Poison Control Center at 1-800-222-1222 for further management information and guidance.

Nonclinical Toxicology

In nonclinical studies, omeprazole has been evaluated for its potential teratogenic and non-teratogenic effects, as well as its carcinogenicity and mutagenicity.

No information is available regarding teratogenic effects. However, in studies assessing non-teratogenic effects, 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, demonstrated no adverse effects on fertility and reproductive performance.

In two 24-month carcinogenicity studies conducted in rats, omeprazole was 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). 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 observed in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently observed in untreated rats. Additionally, ECL cell hyperplasia was noted in all treated groups of both sexes.

In one of the carcinogenicity studies, female rats received 13.8 mg omeprazole/kg/day (about 3.4 times the human dose of 40 mg/day, based on body surface area) for one year, followed by an additional year without treatment. No carcinoids were detected in these rats. An increased incidence of 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%), although the treated group still exhibited a higher incidence of hyperplasia. Gastric adenocarcinoma was observed in one rat (2%), with no similar tumors identified in male or female rats treated for two years. 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 (approximately 0.1 to 3.9 times the human dose of 40 mg/day, based on body surface area). No astrocytomas were observed in female rats during this study. Conversely, in a separate 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were detected in either males or females at the high dose of 140.8 mg/kg/day (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 reveal an increased occurrence of tumors; however, the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study did not yield positive results.

Postmarketing Experience

Postmarketing experience with omeprazole delayed-release capsules has identified several serious side effects reported voluntarily or through surveillance programs.

Acute tubulointerstitial nephritis, a type of kidney problem, has been observed in some patients taking proton pump inhibitors (PPIs), including omeprazole. This condition can occur at any time during treatment, and patients are advised to seek medical attention if they experience a decrease in urine output or blood in their urine.

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

Long-term use of PPIs, particularly at multiple daily doses for a year or longer, may elevate the risk of fractures in the hip, wrist, or spine. Patients are encouraged to use omeprazole as prescribed and discuss their individual risk of bone fractures with their healthcare provider.

Certain types of lupus erythematosus have been reported in patients taking PPIs, including omeprazole. This autoimmune disorder may manifest as new or worsening joint pain or a rash that exacerbates in sunlight, prompting patients to consult their doctor if such symptoms arise.

Additional serious side effects include vitamin B-12 deficiency, which may occur after prolonged use (more than three years), and low magnesium levels, which can develop in some individuals after at least three months of treatment. Symptoms of low magnesium may include seizures, muscle spasms, dizziness, and abnormal heart rhythms, necessitating immediate medical attention.

Patients taking omeprazole for extended periods may also be at risk for developing fundic gland polyps, particularly after one year of use.

Severe skin reactions, although rare, can occur and may present as blistering, peeling, or bleeding rashes, potentially requiring hospitalization. Symptoms such as fever, chills, and shortness of breath should prompt immediate discontinuation of the medication and consultation with a healthcare provider.

Lastly, serious allergic reactions have been reported, characterized by rash, facial swelling, throat tightness, and difficulty breathing. Patients experiencing these symptoms should inform their doctor, who may consider discontinuing omeprazole.

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 report any signs or symptoms that may indicate serious conditions, such as hypersensitivity reactions, acute tubulointerstitial nephritis, Clostridium difficile associated diarrhea, bone fractures, 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, as these may interact with their treatment. 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 take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary. They should consult their healthcare provider if they experience serious stomach problems while on this medication. Immediate medical attention is warranted if there is a decrease in urine output or the presence of blood in the urine. Patients should also seek prompt medical advice if they experience watery stools, stomach pain, and persistent fever.

It is advisable for patients to discuss their risk of bone fractures with their healthcare provider if they are taking omeprazole delayed-release capsules. They should report any new or worsening joint pain or rashes that worsen in sunlight. Long-term users (more than three years) should talk to their doctor about the potential for vitamin B-12 deficiency. Symptoms of low magnesium, such as seizures, jitteriness, muscle spasms, dizziness, abnormal heart rhythms, or muscle weakness, should be reported immediately.

Patients must stop taking omeprazole delayed-release capsules and contact their healthcare provider right away if they experience severe skin reactions, including rash, blistering, peeling, or bleeding, along with fever, chills, body aches, shortness of breath, or swollen lymph nodes. Additionally, any signs of serious allergic reactions, such as rash, facial swelling, throat tightness, or difficulty breathing, should be communicated to their doctor without delay.

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° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are crucial to maintain the integrity and efficacy of the product.

Additional Clinical Information

Serum chromogranin A (CgA) levels may increase due to drug-induced decreases in gastric acidity when patients are treated with omeprazole. This elevation can lead to false positive results in diagnostic tests for neuroendocrine tumors. Clinicians are advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider repeating the test if initial levels 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 of proton pump inhibitors (PPIs) for the shortest duration necessary. Prolonged use beyond medical necessity should be avoided. If patients exhibit signs of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and referral to a specialist is recommended. Most patients show improvement within 4 to 12 weeks after stopping the PPI. For those on long-term treatment or taking medications that may lead to hypomagnesemia, monitoring of magnesium levels is advisable before starting PPI therapy and periodically thereafter. Additionally, monitoring of magnesium and calcium levels should be considered in patients with a risk of hypocalcemia, with supplementation provided as needed. If hypocalcemia does not respond to treatment, discontinuation of the PPI may be warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)