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, which functions as a gastric acid secretion inhibitor. The empirical formula of omeprazole is C17H19N3O3S, with a molecular weight of 345.42. The structural formula is provided in the accompanying documentation.

Omeprazole USP appears as a white to off-white powder that melts between 150°C and 160°C with decomposition. It exhibits solubility characteristics of being soluble in dichloromethane, sparingly soluble in methanol and alcohol, and very slightly soluble in water.

Omeprazole 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. The inactive ingredients in the granules include glyceryl monostearate, hypromellose (5cps), meglumine, methacrylic acid copolymer, poloxamer, sugar globules, talc, titanium dioxide, and triethyl citrate. The capsule shells consist of black iron oxide, D & C Red 28, FD & C Blue 1, FD & C Red 40, gelatin, potassium hydroxide, propylene glycol, shellac, titanium dioxide, and yellow iron oxide. Omeprazole delayed-release capsules comply with 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.

No teratogenic or nonteratogenic effects have been reported.

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 clinical response.

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

• Triple Therapy: Administer 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: Administer omeprazole delayed-release capsules 40 mg 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), a dosage of 20 mg orally once daily for up to 4 weeks is advised. For eosinophilic esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg orally once daily for 4 to 8 weeks. To maintain healing of EE due to acid-mediated GERD, a continuous dosage of 20 mg orally once daily is recommended.

For pathological hypersecretory conditions, the starting dose is 60 mg orally once daily; however, this may vary based on individual patient needs and should be adjusted as clinically indicated.

Contraindications

Use is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, the use of this product is contraindicated in patients receiving rilpivirine-containing products due to potential drug interactions. When administered in combination with omeprazole, refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin for further guidance.

Warnings and Precautions

In adults, the presence of gastric malignancy should be considered even if there is a symptomatic response to treatment. Additional follow-up and diagnostic testing are recommended to rule out this condition.

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

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

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. It is advisable to assess the need for ongoing therapy in patients at risk for bone fractures.

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. Further evaluation should be considered in these cases.

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

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

Long-term use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring for signs of deficiency is recommended in patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with prolonged PPI treatment. Regular monitoring of magnesium levels may be prudent in long-term users.

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

Concomitant use of omeprazole with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of omeprazole should be considered.

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

Side Effects

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

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of gastric cancer, 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. Long-term and multiple daily doses of PPIs may also 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 (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.

Important interactions include the avoidance of concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin. Additionally, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as this may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. The risk of fundic gland polyps increases with long-term use, 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. Symptoms were transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

Clinically significant drug interactions may occur with the use of this medication. It is essential to consult the full prescribing information for a comprehensive list of these interactions.

Pharmacodynamic interactions may lead to enhanced effects or increased toxicity when this medication is used concurrently with other agents. Careful monitoring of the patient's clinical status is advised to mitigate potential adverse effects.

Pharmacokinetic interactions may alter the absorption, distribution, metabolism, or excretion of this medication or co-administered drugs. Dosage adjustments may be necessary based on the specific interaction and the clinical context.

Healthcare professionals are encouraged to evaluate the patient's medication regimen thoroughly and to monitor for any signs of interaction, adjusting dosages as appropriate to ensure patient safety and therapeutic efficacy.

Packaging & NDC

The table below lists all NDC Code configurations of Omeprazole, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of omeprazole have been established in pediatric patients aged 2 to 16 years for the treatment of symptomatic gastroesophageal reflux disease (GERD), the treatment of erosive esophagitis (EE) due to acid-mediated GERD, and the maintenance of healing of EE due to acid-mediated GERD. The use of omeprazole in this age group is supported by adequate and well-controlled studies in adults, as well as uncontrolled safety, efficacy, and pharmacokinetic studies conducted in pediatric and adolescent patients.

In the pediatric population, adverse reactions affecting the respiratory system were frequently reported across the entire age range of 2 to 16 years. Additionally, accidental injuries were commonly 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, 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. 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 routine dose modifications are not warranted.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Reproduction studies in rats and rabbits have shown dose-dependent embryo-lethality at omeprazole doses approximately 3.4 to 34 times an oral human dose of 40 mg, based on a body surface area for a 60 kg person. However, teratogenicity was not observed in animal reproduction studies with the administration of oral esomeprazole magnesium during organogenesis at doses about 68 times and 42 times, respectively, an oral human dose of 40 mg.

Changes in bone morphology were noted in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. When maternal administration was limited to gestation only, there were no effects on bone physeal morphology in the offspring 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, finding that the number of infants exposed in utero to omeprazole with any malformation, low birth weight, low Apgar score, or hospitalization was similar to that observed in 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 a separate population-based retrospective cohort study covering all live births in Denmark, 1,800 live births were reported with mothers using omeprazole during the first trimester, revealing an overall rate of birth defects 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 involving 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester reported an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. Additionally, a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy, reporting 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 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. Omeprazole reproductive studies conducted with rats at oral doses up to 138 mg/kg/day during organogenesis 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/early postnatal survival at doses equal to or greater than 138 mg/kg/day. 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

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

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 and consider individual patient factors when treating patients with renal impairment, as the absence of detailed guidance necessitates careful clinical judgment.

Hepatic Impairment

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

Overdosage

Reports 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

Omeprazole has been evaluated for teratogenic effects, and no teratogenic effects were identified in the studies conducted. In terms of non-teratogenic effects, oral administration of omeprazole at doses up to 138 mg/kg/day in rats, which is approximately 34 times the human dose of 40 mg on a body surface area basis, did not adversely affect fertility or reproductive performance.

In carcinogenicity studies spanning 24 months in rats, omeprazole was administered at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day, resulting 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 infrequently observed in untreated rats. ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day 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 diminished (46% in treated versus 26% in controls), yet hyperplasia remained more prevalent in the treated group. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were detected in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were identified in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose of 40 mg/day based on body surface area). 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 of 40 mg/day on a body surface area basis). A 78-week carcinogenicity study in mice did not demonstrate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay 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 observed increase in gastric carcinoid tumors and ECL cell hyperplasia in the 24-month carcinogenicity studies in rats was significant and dose-related. It is noteworthy that 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

No postmarketing experience details are available in the provided text.

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. It is important for patients to be fully informed to ensure safe and effective treatment.

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 reductions in gastric acidity, potentially leading to false positive results in neuroendocrine tumor diagnostics. Clinicians are advised to discontinue omeprazole treatment at least 14 days prior to CgA level assessment and to consider retesting if initial levels are elevated. For serial monitoring, it is important to utilize 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. If symptoms indicative of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) arise, omeprazole should be discontinued, and the patient referred for specialist evaluation, with most patients showing improvement within 4 to 12 weeks post-discontinuation. For those on prolonged PPI therapy or concomitant medications that may induce hypomagnesemia, monitoring of magnesium levels is recommended prior to and during treatment. Postmarketing reports have indicated severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), as well as cases of hypomagnesemia, which can lead to serious complications such as tetany, arrhythmias, and seizures.

FDA Insert (PDF)

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

View full prescribing information (PDF)