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 an inhibitor of gastric acid secretion. The molecular 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 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 under alkaline conditions. The dissolution test for omeprazole should be conducted in accordance with USP Test 2.

Omeprazole is formulated as delayed-release capsules for oral administration, with each capsule containing either 10 mg or 20 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients for the 10 mg and 20 mg capsules include hypromellose, magnesium oxide, methacrylic acid copolymer dispersion type C, povidone, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide, and triethyl citrate. The capsule shells for the 20 mg formulation consist of gelatin and titanium dioxide, while the 10 mg formulation includes gelatin, iron oxide black, iron oxide red, iron oxide yellow, and titanium dioxide. The black ink used for printing on both the 10 mg and 20 mg capsules contains black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. The sugar spheres incorporated in the formulation are composed of maize starch and sucrose.

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 treatment of erosive esophagitis (EE) due to acid-mediated GERD. It is also indicated for the maintenance of healing of EE due to acid-mediated GERD in this age group.

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

In patients with pathological hypersecretory conditions, the starting dose is 60 mg orally once daily. This dosage may vary based on individual patient needs and should be adjusted as clinically indicated.

All medications should be administered orally, with the frequency of dosage varying according to the specific condition being treated, as outlined above.

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 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 signs of this infection in patients undergoing PPI treatment.

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

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 evaluation should be considered.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel.

Long-term daily use of omeprazole, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin B-12 levels is recommended 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. Omeprazole should be temporarily discontinued at least 14 days prior to assessing 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 use of PPIs, particularly beyond one year. It is recommended to use the shortest duration of therapy necessary to manage the patient's condition effectively.

Side Effects

Most common adverse reactions reported in adults, occurring with an incidence of 2% or greater, include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 2 to 16 years, the safety profile is similar to that observed in 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 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, and long-term use of PPIs may elevate the risk of osteoporosis-related fractures of the hip, wrist, or spine.

Severe cutaneous adverse reactions have been reported; treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been noted, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Cyanocobalamin (Vitamin B-12) deficiency may occur with daily long-term use exceeding three years, leading to malabsorption or deficiency. Rare cases of hypomagnesemia and mineral metabolism disturbances have been reported with prolonged PPI treatment. Caution is advised regarding interactions with clopidogrel, St. John’s Wort, rifampin, and methotrexate, as these may elevate serum concentrations and potentially lead to toxicity. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing Chromogranin A levels due to potential interference with diagnostic investigations for neuroendocrine tumors.

Long-term use of omeprazole, particularly beyond one year, may increase the risk of fundic gland polyps, and the shortest duration of therapy should be utilized.

Reports of overdosage with omeprazole have included symptoms such as 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, which could enhance therapeutic outcomes or increase the risk of adverse effects. Monitoring for signs of increased effects or toxicity is recommended when combining drugs with similar mechanisms of action.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of a drug, potentially necessitating dosage adjustments. Healthcare providers should evaluate the need for dose modifications based on the specific interactions identified in the prescribing information.

For comprehensive guidance on managing drug interactions, including specific recommendations for dosage adjustments and monitoring parameters, refer to the full prescribing information.

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

In the pediatric population, adverse reactions affecting the respiratory system were frequently reported among patients aged 2 to 16 years. Additionally, accidental injuries were commonly noted in this age group.

The safety and effectiveness of omeprazole have not been established in patients younger than 1 year of age for the treatment of symptomatic GERD or for 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. It is also contraindicated in patients less than 1 month of age for any indication.

Geriatric Use

Clinical trials involving over 2000 elderly individuals (≥65 years of age) in the U.S. and Europe have demonstrated that there are no significant differences in the safety and effectiveness of omeprazole 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 differences, no dosage adjustment is necessary for elderly patients. However, healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant patients. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with 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 studies with esomeprazole magnesium, an enantiomer of omeprazole, administered during organogenesis at doses about 68 times and 42 times 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. Importantly, 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; 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 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 involving 955 infants whose mothers used omeprazole during pregnancy reported similar rates of malformations, low birth weight, low Apgar scores, or hospitalization compared to the general population. Another study from Denmark indicated an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%, comparable to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported a malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole, while a small prospective observational cohort study found a rate of major congenital malformations of 4% in the omeprazole group.

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 section under general anesthesia. Reproductive studies with omeprazole in rats did not reveal any evidence of teratogenic potential; however, in rabbits, omeprazole administered during organogenesis resulted in 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 from parents treated with omeprazole prior to mating through the lactation period. Conversely, no effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium in rats or rabbits during organogenesis, although a pre- and postnatal developmental toxicity study in rats indicated decreased neonatal survival at doses equal to or greater than 138 mg/kg/day. When maternal administration of esomeprazole was confined to gestation only, no effects on bone physeal morphology in the offspring were observed 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

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 individuals with reduced kidney function, as the lack of information necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

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 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 use of the medication.

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 two 24-month carcinogenicity studies conducted in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day (approximately 0.4 to 34 times the human dose of 40 mg/day, based on body surface area) 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 infrequently observed in untreated rats. ECL cell hyperplasia was noted in all treated groups across both sexes. In one study, female rats receiving 13.8 mg omeprazole/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 the treated group still exhibited a higher incidence of hyperplasia. Gastric adenocarcinoma was identified in one rat (2%), with no similar tumors observed in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, although the interpretation of a single tumor finding is 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). No astrocytomas were found in female rats in this study. In a separate 2-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 reveal an increased incidence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study did not yield positive results.

Omeprazole demonstrated 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. 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.

At oral doses up to 138 mg/kg/day in rats (approximately 34 times the oral human dose of 40 mg based on body surface area), omeprazole did not adversely affect fertility or reproductive performance.

In the aforementioned 24-month carcinogenicity studies in rats, a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals. 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 specific postmarketing experience details are available in the extracted data. 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. It is important for patients to be fully informed to ensure safe and effective treatment.

Storage and Handling

Omeprazole delayed-release capsules, USP are supplied in a tight container that is designed to protect the contents from light and moisture. It is essential to store the capsules at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are crucial to maintain the integrity and efficacy of the product.

Additional Clinical Information

Serum chromogranin A (CgA) levels may increase due to drug-induced decreases in gastric acidity, potentially leading to false positive results in neuroendocrine tumor diagnostics. Healthcare providers are advised to discontinue omeprazole treatment at least 14 days prior to assessing CgA levels and to consider repeating the test if initial levels are elevated. For serial testing, it is recommended to use the same commercial laboratory to ensure consistency in reference ranges.

Patients should utilize the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy necessary for their condition, avoiding prolonged use beyond medical indications. If patients exhibit signs of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and referral to a specialist is warranted. For those on extended treatment or concomitant medications that may induce hypomagnesemia, such as diuretics, monitoring of magnesium levels is advisable prior to and during PPI therapy. Postmarketing reports have indicated severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), as well as cases of hypomagnesemia and increased risk of fundic gland polyps with long-term PPI use. Additionally, the concomitant use of PPIs with high-dose methotrexate may elevate serum levels of the drug, increasing the risk of toxicity.

FDA Insert (PDF)

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

View full prescribing information (PDF)