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, which functions as an inhibitor of gastric acid secretion. The molecular formula of omeprazole is C17H19N3O3S, with a molecular weight of 345.42. The structural formula is represented as follows:

Omeprazole, USP appears as a white to off-white crystalline powder that decomposes at approximately 155°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; it is rapidly degraded in acidic environments but maintains acceptable stability in alkaline conditions.

Each omeprazole delayed-release capsule is designed for oral administration and contains either 10 mg, 20 mg, or 40 mg of omeprazole. The capsules also include several inactive ingredients: acetone, di-sodium hydrogen phosphate dihydrate, FD&C blue 1, gelatin, hydroxypropyl cellulose, hypromellose, hypromellose phthalate, polyethylene glycol, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide, and triethyl citrate. The 10 mg and 40 mg capsule shells contain FD&C red 3 and FD&C green 3, while the 20 mg capsule shell includes iron oxide red and iron oxide yellow. The capsule is printed with black pharmaceutical ink, which consists of black iron oxide, potassium hydroxide, propylene glycol, and shellac. Omeprazole Delayed-Release Capsules USP 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 populations, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) in patients aged 1 year and older, as well as for the treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients aged 1 month and older. Furthermore, it is indicated for the maintenance of healing of EE due to acid-mediated GERD in patients aged 1 year and older.

This drug is also indicated for the management of pathologic hypersecretory conditions in adults. There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg administered orally once daily for a duration of 4 weeks. In some cases, an additional 4 weeks may be necessary based on the patient's response.

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

Triple Therapy:

• Omeprazole: 20 mg

• Amoxicillin: 1000 mg

• Clarithromycin: 500 mg Each medication should be taken orally twice daily for 10 days.

Dual Therapy:

• Omeprazole: 40 mg once daily for 14 days

• Clarithromycin: 500 mg three times daily for 14 days

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

For symptomatic gastroesophageal reflux disease (GERD), a dosage of 20 mg orally once daily for up to 4 weeks is advised. In patients with erosive esophagitis (EE) due to acid-mediated GERD, the dosage is 20 mg once daily for 4 to 8 weeks. For the maintenance of healing of EE due to acid-mediated GERD, a continuous dosage of 20 mg 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 healthcare professionals should refer to the full prescribing information for further guidance.

All dosages are to be administered orally.

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, please refer to the Contraindications section of their respective prescribing information for further guidance.

Warnings and Precautions

In adults, it is important to note that a symptomatic response to treatment does not exclude the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to rule out this condition.

Acute tubulointerstitial nephritis has been reported in patients receiving treatment. If this condition is suspected, it is crucial to discontinue the medication and evaluate the patient accordingly.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should be vigilant for this potential complication, particularly in patients with risk factors.

Long-term use of PPIs, especially at multiple daily doses, may increase the risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. Healthcare providers should assess the need for ongoing therapy and consider alternative treatments in patients at risk for fractures.

Severe cutaneous adverse reactions have been observed in some patients. It is essential to discontinue treatment at the first signs or symptoms of such reactions or any other signs of hypersensitivity, and to consider further evaluation by a specialist.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such cases, discontinuation of omeprazole is recommended, and referral to a specialist for evaluation should be considered.

Concomitant use of omeprazole with clopidogrel is not advised due to potential interactions that may diminish the effectiveness of clopidogrel.

Long-term daily use of PPIs, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin B-12 levels may be warranted 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. To ensure accurate assessment, omeprazole should be temporarily discontinued at least 14 days prior to measuring CgA levels.

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

Finally, the risk of fundic gland polyps increases with long-term 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

Common adverse reactions reported in clinical trials include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence in adult patients. In pediatric patients aged 1 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 associated with the use of this medication include gastric malignancy, where a symptomatic response does not exclude the possibility of gastric malignancy, necessitating additional follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued while evaluating affected patients. There is an increased risk of Clostridium difficile-associated diarrhea with PPI therapy, and long-term or multiple daily doses 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 other signs of hypersensitivity, with further evaluation considered. Additionally, cutaneous and systemic lupus erythematosus may occur, presenting as new onset or exacerbation of existing disease, warranting discontinuation of omeprazole and referral to a specialist for evaluation. Long-term daily use (exceeding three years) may lead to cyanocobalamin (Vitamin B-12) deficiency due to malabsorption. 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. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; therefore, omeprazole should be temporarily discontinued 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 metabolite, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

Long-term use of omeprazole may increase the risk of fundic gland polyps, particularly beyond one year, thus the shortest duration of therapy is recommended. Reports of overdosage with omeprazole have been received, with manifestations 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

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 lead to additive or synergistic effects, necessitating careful monitoring of therapeutic outcomes and potential adverse effects. In cases where such interactions are identified, dosage adjustments may be required to mitigate risks.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of concomitantly administered drugs. These interactions may necessitate modifications in dosing regimens or increased frequency of monitoring to ensure therapeutic efficacy and safety.

Healthcare providers are advised 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 1 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 infants aged 1 month to less than 1 year, omeprazole is indicated for the treatment of EE due to acid-mediated GERD.

Adverse reactions in the pediatric population, particularly in the age group of 1 month to 16 years, frequently include respiratory system events. In infants aged 1 month to less than 1 year, otitis media was commonly reported, while fever was frequently observed in children aged 1 to less than 2 years. Accidental injuries were notably reported in the 2 to 16 year age group.

It is important to note that the safety and effectiveness of omeprazole have not been established in patients less than 1 year of age for the treatment of symptomatic GERD or for 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. Furthermore, 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 from these studies indicate that there are 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 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 observed in young healthy volunteers.

Despite these pharmacokinetic differences, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. 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 patients.

Pregnancy

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

While teratogenicity was not observed in animal reproduction studies with esomeprazole magnesium, an enantiomer of omeprazole, doses about 68 times and 42 times the oral human dose of 40 mg were administered to rats and rabbits, respectively, during organogenesis. 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 general 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 studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those 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. Another study from Denmark reported an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%. A retrospective cohort study indicated an overall malformation rate of 3.6% in the omeprazole group among 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester. Additionally, a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy, reporting a rate of major congenital malformations of 4%.

Furthermore, 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 sections under general anesthesia. Reproductive studies conducted with omeprazole in rats did not reveal any evidence of teratogenic potential; however, in rabbits, omeprazole was associated with 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 prior to mating through the lactation period.

In contrast, 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 at high doses and developmental delays in the immediate post-weaning timeframe. 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 dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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

Omeprazole has been evaluated for its potential teratogenic effects, but no specific information is available regarding such effects.

In terms of non-teratogenic effects, studies have demonstrated that 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, did not adversely affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed that omeprazole, at daily doses ranging from 1.7 to 140.8 mg/kg/day (approximately 0.4 to 34 times the human dose of 40 mg/day based on body surface area), resulted in a dose-related increase in gastric ECL cell carcinoids in both male and female rats. The incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. Additionally, ECL cell hyperplasia was noted in all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day (about 3.4 times the human dose) for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a notable increase in treatment-related ECL cell hyperplasia was recorded at the end of the first year (94% in treated rats versus 10% in controls). By the second year, the difference between treated and control rats diminished (46% versus 26%), yet hyperplasia remained more prevalent in the treated group. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were identified in male or female rats over the two-year study period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this singular finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were detected in a small number of male rats receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose). No astrocytomas were found in female rats in this study. Conversely, a two-year carcinogenicity study in Sprague-Dawley rats at the high dose of 140.8 mg/kg/day did not reveal any astrocytomas in either sex. A 78-week carcinogenicity study in mice did not demonstrate an increased incidence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Animal pharmacology and toxicology assessments indicated that omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, 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. Furthermore, the significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was consistent with findings from other studies involving 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. 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

The product is supplied in a tightly closed container to ensure its integrity. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the product from light and moisture to maintain its efficacy. For dispensing, a tight, light-resistant container is recommended to further safeguard the product from environmental factors.

Additional Clinical Information

Standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical accuracy of laboratory procedures.

For the administration of therapies, dual therapy consists of omeprazole 40 mg once daily and clarithromycin 500 mg three times daily for 14 days, followed by omeprazole 20 mg once daily for an additional 14 days. In contrast, triple therapy involves omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily for 10 days, followed by omeprazole 20 mg once daily for another 18 days. Clinicians should counsel patients that those who do not achieve eradication of H. pylori after either the triple or dual therapy may have clarithromycin-resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing is recommended when feasible, and patients with such resistance should not be treated with regimens that include clarithromycin as the sole antimicrobial agent.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Omeprazole as submitted by Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)