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 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 in alkaline conditions. The dissolution test for omeprazole is to be conducted in accordance with USP Test 2.

Omeprazole is formulated as delayed-release capsules for oral administration, available in strengths of 10 mg, 20 mg, and 40 mg, each containing enteric-coated granules of omeprazole. The 10 mg and 20 mg capsules include inactive ingredients such as anhydrous lactose, low-substituted hydroxypropyl cellulose, magnesium oxide, magnesium stearate, microcrystalline cellulose, methacrylic acid copolymer dispersion type C, polysorbate 80, povidone, and talc, along with triethyl citrate. The capsule shells for the 10 mg formulation contain black iron oxide, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide, while the 20 mg formulation's capsule shells consist of gelatin and titanium dioxide.

The 40 mg capsule formulation incorporates inactive ingredients such as acetone, anhydrous lactose, croscarmellose sodium, dehydrated alcohol, dibutyl sebacate, hypromellose phthalate, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, polysorbate 80, povidone, and talc, with its capsule shells containing hypromellose, red iron oxide, titanium dioxide, and yellow iron oxide. Additionally, the capsule shells may also include black iron oxide, carrageenan, and potassium chloride. The ink used for printing on the capsules contains black iron oxide, propylene glycol, and shellac.

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 management 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. Some patients may require an additional 4 weeks of treatment based on clinical response.

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

Triple Therapy: This regimen includes omeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, with each medication taken orally twice daily for 10 days.

Dual Therapy: This regimen consists of omeprazole 40 mg administered orally once daily for 14 days, alongside clarithromycin 500 mg taken three times daily for the same duration.

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

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

For 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 dosages are to be administered orally, with frequency typically ranging from once to twice daily, depending on the specific indication.

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 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 imperative 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 elevate 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 have been observed in some patients. Treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity, and further evaluation should be considered.

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 is warranted.

Concomitant use of omeprazole with clopidogrel should be avoided 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 for signs of deficiency 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 crucial to be aware that increased levels of Chromogranin A (CgA) may interfere with test results. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels.

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

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

Side Effects

Most common adverse reactions reported in adults, 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 of adults; however, respiratory system events and fever were the most frequently reported reactions in studies involving this population.

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying malignancy, necessitating further diagnostic evaluation. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued if this condition is suspected. 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, particularly in the hip, wrist, or spine.

Severe cutaneous adverse reactions have been reported; treatment should be discontinued at the first signs of such reactions or any other signs of hypersensitivity, with further evaluation recommended. 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. 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 to avoid 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, necessitating careful monitoring of therapeutic outcomes and potential adverse effects. In cases where such interactions are identified, dosage adjustments may be warranted to mitigate risks.

Pharmacokinetic interactions can alter the absorption, distribution, metabolism, or excretion of concomitantly administered drugs. These interactions may require 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 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 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) have demonstrated that omeprazole exhibits comparable safety and effectiveness profiles when administered to geriatric patients versus younger subjects. While no significant differences in response have been identified between these age groups, it is important to acknowledge that some elderly patients may exhibit greater sensitivity to the drug, although this has not been definitively established.

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

Despite these pharmacokinetic differences, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. 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 women. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. However, reproduction studies in rats and rabbits have shown dose-dependent embryo-lethality at doses approximately 3.4 to 34 times the oral human dose of 40 mg, based on a body surface area for a 60 kg person.

Teratogenicity was not observed in animal reproduction studies with oral esomeprazole magnesium administered during organogenesis at doses about 68 times and 42 times, respectively, the oral human dose of 40 mg. Changes in bone morphology were noted in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times the oral human dose of 40 mg. However, when maternal administration was limited to gestation only, no effects on bone physeal morphology in the offspring were observed at any age.

The estimated background risks of major birth defects and miscarriage for the indicated population are unknown, but all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Several epidemiological studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those of women exposed to H2-receptor antagonists or other controls. A population-based retrospective cohort study from the Swedish Medical Birth Registry reported on 955 infants whose mothers used omeprazole during pregnancy, revealing similar rates of malformations, low birth weight, low Apgar score, 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%, comparable to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

A retrospective cohort study indicated an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole, compared to 5.5% for H2-blockers and 4.1% for unexposed mothers. A small prospective observational cohort study involving 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens and 2.8% in disease-paired controls.

Additionally, several studies have reported no apparent adverse short-term effects on the infant when single doses of oral or intravenous omeprazole were administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Reproductive studies conducted with omeprazole in rats did not reveal any evidence of teratogenic potential, although in rabbits, omeprazole administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions.

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 omeprazole use. Caution is advised when prescribing omeprazole to pregnant patients, and the benefits should be weighed against potential risks.

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, the developmental and health benefits of breastfeeding should be weighed 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 available 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 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 indicated instances of 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, with symptoms including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions that are consistent with those observed in normal clinical use.

It is noteworthy that the symptoms associated with omeprazole overdosage are generally 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. Therefore, in the event of an overdosage, treatment should focus on symptomatic and supportive care.

Healthcare professionals are advised that in cases of over-exposure, it is essential 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

No teratogenic effects were observed in the studies conducted. In terms of non-teratogenic effects, 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 impact fertility or reproductive performance.

In two separate 24-month carcinogenicity studies involving rats, omeprazole was administered at daily doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day, corresponding to about 0.4 to 34 times the human dose of 40 mg/day based on body surface area. These studies revealed a dose-related increase in the incidence of gastric ECL cell carcinoids in both male and female rats, with a notably higher incidence in females, who exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. Additionally, ECL cell hyperplasia was noted across all treated groups of both sexes. In one study, female rats receiving 13.8 mg omeprazole/kg/day (approximately 3.4 times the human dose) for one year, followed by an additional year without treatment, did not develop carcinoids. However, a significant 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 identified in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were detected in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose). No astrocytomas were found in female rats during this study. Conversely, in a 2-year carcinogenicity study with 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 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, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, it was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was dose-related and consistent across both male and female subjects. 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 specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

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

Storage and Handling

Omeprazole delayed-release capsules, 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 when patients are treated with omeprazole. This elevation can lead to false positive results in diagnostic tests for neuroendocrine tumors. Clinicians are advised to discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider retesting if initial levels are elevated. For serial testing, it is important to use the same commercial laboratory, as reference ranges may differ.

Omeprazole delayed-release capsules should be taken before meals, and antacids can be used concurrently. Patients must swallow the capsules whole and not chew them; however, those unable to swallow intact capsules may open them and mix the contents with applesauce. It is recommended that patients use the lowest effective dose for the shortest duration necessary. Clinicians should monitor for signs of cutaneous lupus erythematosus or systemic lupus erythematosus and discontinue treatment if these occur. Additionally, monitoring of magnesium and calcium levels is advisable in patients at risk for hypocalcemia.

Postmarketing reports have indicated severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as acute tubulointerstitial nephritis, which can occur at any time during therapy. Clostridium difficile-associated diarrhea has been associated with PPI use, and observational studies suggest a potential link between PPI therapy and an increased risk of osteoporosis-related fractures. Rare cases of cyanocobalamin deficiency and hypomagnesemia have also been documented in patients receiving prolonged PPI treatment.

FDA Insert (PDF)

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

View full prescribing information (PDF)