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)methylsulfinyl]-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 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, available in strengths of 10 mg, 20 mg, or 40 mg, each containing enteric-coated granules. The inactive ingredients in the 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. Omeprazole delayed-release capsules comply with USP Dissolution Test 2.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcer 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 ulcer 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

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: 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), a dosage of 20 mg orally once daily is advised for up to 4 weeks. In patients with erosive esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg orally once daily for a duration of 4 to 8 weeks. For the maintenance of 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.

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 (5.1).

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 (5.2).

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 (5.3).

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically in the hip, wrist, or spine. It is advisable to assess the need for continued therapy in patients at risk for bone fractures (5.4).

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 should be considered in these cases (5.5).

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such instances, discontinuation of omeprazole is recommended, and referral to a specialist for evaluation is warranted (5.6).

Concomitant use of omeprazole with clopidogrel should be avoided due to potential interactions that may diminish the effectiveness of clopidogrel (5.7). Additionally, long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12) (5.8).

Hypomagnesemia and disturbances in mineral metabolism have been reported, albeit rarely, with prolonged PPI treatment. Monitoring of magnesium levels may be necessary in patients on long-term therapy (5.9).

Healthcare professionals should also avoid concomitant use of omeprazole with St. John’s Wort or rifampin due to potential interactions (5.10).

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 diagnostic results (5.11).

Concomitant use of PPIs with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of omeprazole should be considered (5.12).

The risk of fundic gland polyps increases with long-term use of PPIs, particularly beyond one year. Therefore, it is advisable to use the shortest duration of therapy necessary (5.13).

Side Effects

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

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric malignancy, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued and patients evaluated if this occurs. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term and multiple daily doses of PPIs may also be linked to an increased 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 (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia and disturbances in mineral metabolism have been reported with prolonged PPI treatment.

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Increased levels of Chromogranin A (CgA) due to omeprazole may interfere with diagnostic investigations for neuroendocrine tumors, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. 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; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration. 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 of overdosage 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 a drug, which may necessitate modifications in dosing regimens or increased frequency of monitoring for 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 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 related to the respiratory system were frequently reported, as were incidents 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 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.

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 when 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 some older individuals may exhibit greater sensitivity to the medication.

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 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. Healthcare providers should remain vigilant in monitoring for any potential increased sensitivity in this population, although current evidence does not necessitate changes in dosing regimens.

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. 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 the administration of oral esomeprazole, an enantiomer of omeprazole, 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 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. 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.

In a separate population-based retrospective cohort study covering all live births in Denmark, 1,800 live births were analyzed, revealing 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. Additionally, a retrospective cohort study reported a malformation rate of 3.6% in offspring born to mothers exposed to omeprazole in the first trimester, compared to other groups.

A small prospective observational cohort study involving 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group, 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 indicate potential risks at high doses, the available human data do not suggest a significant increase in major congenital malformations with first trimester use of omeprazole. Caution is advised when prescribing omeprazole to pregnant patients, particularly during the first trimester.

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 prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 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 120 times the usual recommended clinical dose. The manifestations of overdosage are variable and may include symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are similar to 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 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. Notably, 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. 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 higher 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 in hyperplasia incidence between treated and control rats diminished (46% versus 26%), yet the treated group still exhibited a higher prevalence. 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 solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were identified 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 detected in female rats during this study. Conversely, in a separate two-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found 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.

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 has 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 data.

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 testing, it is important to use the same commercial laboratory, as reference ranges may differ.

Patients should be counseled to use the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy suitable for their condition. If any signs or symptoms indicative of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) arise, the medication should be discontinued, and the patient referred for specialist evaluation. Most patients experience improvement within 4 to 12 weeks after stopping the PPI. Additionally, for those on prolonged PPI therapy or concomitant medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels prior to and during treatment may be warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)