Omeprazole

Description

Omeprazole delayed-release capsules, USP, contain the active ingredient omeprazole, a substituted benzimidazole with the chemical structure 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl)methylsulfinyl]-1H-benzimidazole, which functions as a gastric acid secretion inhibitor. The molecular formula of omeprazole is C17H19N3O3S, and it has a molecular weight of 345.42.

Omeprazole appears as a white to off-white powder that decomposes between 150°C and 160°C. It is classified as a weak base, exhibiting solubility characteristics that include 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, with rapid degradation occurring in acidic environments, while it maintains acceptable stability under alkaline conditions.

The drug is formulated as delayed-release capsules 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 in the capsules include disodium hydrogen phosphate dihydrate, hydroxypropyl cellulose, hypromellose, lactose monohydrate, mannitol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, mono and di-glycerides, polysorbate, sodium lauryl sulfate, talc, titanium dioxide, and triethyl citrate. The empty hard gelatin capsule shells are composed of gelatin and iron oxide red, and the capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. Omeprazole meets the USP Dissolution Test 2.

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, this drug 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

Omeprazole delayed-release capsules are administered orally. The dosage and administration guidelines are as follows:

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg once daily for a duration of 4 weeks. Some patients may require an additional 4 weeks of treatment based on clinical response.

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

• Triple Therapy: Administer omeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, with each medication taken twice daily for 10 days.

• Dual Therapy: Administer omeprazole 40 mg once daily for 14 days, alongside clarithromycin 500 mg taken three times daily for the same duration.

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

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

In patients with pathological hypersecretory conditions, the starting dose is 60 mg once daily, with adjustments made based on individual patient response.

The frequency of administration typically varies by indication, generally being once daily or as specified in combination therapies.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, it should not be administered to patients receiving rilpivirine-containing products due to potential drug interactions. When used in combination with clarithromycin and amoxicillin, refer to the respective contraindications outlined in their prescribing information.

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 conduct a thorough evaluation of the patient.

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. 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 indications 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 should be considered.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel. Healthcare professionals should avoid this combination to ensure optimal patient outcomes.

Long-term daily use of omeprazole, 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 extended 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 the medication.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is essential to be aware that increased levels of Chromogranin A (CgA) may interfere with test results. To mitigate this, omeprazole should be temporarily discontinued at least 14 days prior to assessing CgA levels.

When administering high doses of methotrexate, caution is advised as the concomitant use of PPIs may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. A temporary withdrawal of omeprazole should be considered in these cases.

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 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 clinical studies involving this age group. Additionally, accidental injuries were commonly reported among pediatric participants.

Serious adverse reactions warranting caution include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying malignancy, 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, as well as a potential for long-term use to lead to osteoporosis-related fractures of the hip, wrist, or spine.

Severe cutaneous adverse reactions may occur, and treatment should be discontinued at the first signs of such reactions or other hypersensitivity symptoms. New onset or exacerbation of cutaneous and systemic lupus erythematosus has been reported, requiring discontinuation of omeprazole and referral to a specialist for evaluation. Long-term daily use of omeprazole may also lead to cyanocobalamin (Vitamin B-12) deficiency due to malabsorption.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with prolonged PPI treatment. Caution is advised regarding drug interactions; 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, necessitating a temporary cessation of omeprazole at least 14 days prior to assessment. When used with high-dose methotrexate, a temporary withdrawal of omeprazole may be considered due to the potential for elevated serum concentrations and toxicity.

Long-term use of omeprazole may increase the risk of fundic gland polyps, particularly beyond one year, thus it is recommended to use the shortest duration of therapy necessary.

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 is taken alone.

Drug Interactions

Clinically important drug interactions should be reviewed in the full prescribing information. It is essential for healthcare professionals to consider the potential for both pharmacodynamic and pharmacokinetic interactions when prescribing medications.

Pharmacodynamic interactions may occur when two drugs with similar effects are used concurrently, potentially leading to enhanced therapeutic effects or increased risk of adverse reactions. Monitoring for increased effects or side effects is advised in such cases.

Pharmacokinetic interactions can arise from alterations in drug absorption, distribution, metabolism, or excretion. These interactions may necessitate dosage adjustments or increased monitoring of drug levels to ensure therapeutic efficacy while minimizing toxicity.

Healthcare providers are encouraged to consult the complete prescribing information for a comprehensive list of drug interactions and specific recommendations regarding dosage adjustments and monitoring protocols.

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 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. Additionally, omeprazole has not been studied in pediatric patients for the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, treatment of active benign gastric ulcers, or pathological hypersecretory conditions.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals (≥ 65 years of age) in clinical trials conducted in the U.S. and Europe. The results from these studies indicate that there are no significant differences in safety and effectiveness between elderly patients and younger subjects. However, it is important to note that while clinical experience has not identified distinct differences in response, a greater sensitivity in some older individuals cannot be entirely ruled out.

Pharmacokinetic studies reveal that the elimination rate of omeprazole is somewhat decreased in the elderly, with an increased bioavailability observed. Specifically, the plasma clearance of omeprazole in elderly patients is approximately 250 mL/min, which is about half that of younger volunteers. Additionally, the plasma half-life of omeprazole in this population averages one hour, which is roughly twice that seen in young healthy volunteers.

Despite these pharmacokinetic differences, no dosage adjustment is necessary for elderly patients. Healthcare providers should remain vigilant in monitoring for any potential increased sensitivity in this population, although the overall safety profile appears consistent with that of younger individuals.

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, but 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, showing similar rates of malformations, low birth weight, low Apgar score, 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 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.

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 and rabbits during organogenesis did not disclose any evidence of teratogenic potential. However, 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 resulting from parents treated with omeprazole at doses administered prior to mating through the lactation period.

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 of esomeprazole was confined to gestation only, there were no effects on bone physeal morphology in the offspring 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 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

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 have been documented regarding overdosage with omeprazole in humans, with doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations of overdosage have been variable, but commonly reported symptoms include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are consistent with those observed in normal clinical experience.

It is noteworthy that the symptoms associated with omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. Currently, there is no specific antidote available for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable.

In the event of an overdosage, treatment should focus on symptomatic and supportive care. 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, with a notably higher incidence in female rats, who exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently 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 significant 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). No astrocytomas were found in female rats in this study. In a separate two-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 indicate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week study involving p53 (+/-) transgenic mice did not yield positive 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. 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 aligns with findings from other studies involving rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

No specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Medication Guide and Instructions for Use. This information is essential for understanding the proper use of the medication, potential side effects, and any necessary precautions. Emphasizing the importance of this material can help ensure that patients are well-informed and can engage in their treatment plan effectively.

Storage and Handling

Omeprazole delayed-release capsules are supplied in a tight container to ensure protection 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 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 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. Additionally, for those on long-term PPI therapy or taking medications that may lead to hypomagnesemia, monitoring of magnesium levels is suggested prior to starting treatment and periodically thereafter. Monitoring of calcium levels is also recommended for patients at risk of hypocalcemia, with supplementation provided as needed. 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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)