Omeprazole

Description

The active ingredient in omeprazole delayed-release capsule, USP is a substituted benzimidazole, 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl sulfinyl]-1H-benzimidazole. Its molecular formula is C17H19N3O3S, with a molecular weight of 345.42. Omeprazole appears as a white to off-white crystalline powder that melts with decomposition at approximately 155°C. It is classified as a weak base, 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 media but maintains acceptable stability under alkaline conditions.

Omeprazole is supplied as delayed-release capsules for oral administration, available in strengths of 10 mg, 20 mg, or 40 mg, formulated as enteric-coated granules. The 10 mg and 20 mg capsules contain inactive ingredients including anhydrous lactose, low-substituted hydroxypropyl cellulose, magnesium oxide, magnesium stearate, microcrystalline cellulose, methacrylic acid copolymer dispersion type C, polysorbate 80, povidone, and talc. The capsule shells for the 10 mg formulation include black iron oxide, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide, while the 20 mg capsule shells consist of gelatin and titanium dioxide. The ink used for printing these capsules contains black iron oxide, propylene glycol, and shellac.

The 40 mg capsule contains 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. The capsule shells for the 40 mg formulation may include hypromellose, red iron oxide, titanium dioxide, and yellow iron oxide, and may also contain black iron oxide, carrageenan, and potassium chloride.

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

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

All dosages are to be taken 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. 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, along with referral to a specialist for further evaluation.

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 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.

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 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 recommended to use the shortest duration of therapy necessary to manage the patient's condition.

Side Effects

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

Serious adverse reactions warranting attention include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric malignancy, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued and patients evaluated accordingly. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term and multiple daily dose PPI therapy 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, cutaneous and systemic lupus erythematosus may occur, presenting as new onset or exacerbation of existing disease, necessitating discontinuation of omeprazole and referral to a specialist for evaluation.

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel should be avoided. Long-term daily use of omeprazole (beyond three years) may lead to cyanocobalamin (Vitamin B-12) deficiency due to malabsorption. Rarely, hypomagnesemia and mineral metabolism disturbances have been reported with prolonged PPI treatment. Concomitant use of omeprazole with St. John’s Wort or rifampin is also not recommended. Furthermore, increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors, and omeprazole should be temporarily stopped 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, 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

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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 for any indication in patients less than 1 month of age.

Geriatric Use

Clinical trials involving over 2000 elderly individuals (≥65 years of age) in the U.S. and Europe have demonstrated that omeprazole exhibits 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 geriatric patients, 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 changes, 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. In a population-based retrospective cohort study from the Swedish Medical Birth Registry, 955 infants whose mothers used omeprazole during pregnancy exhibited similar rates of malformations, low birth weight, low Apgar scores, or hospitalization compared to the general population. Additionally, a cohort study from Denmark reported an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole of 2.9%, which is comparable to the 2.6% rate in infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

Reproductive studies in rats and rabbits have shown dose-dependent embryo-lethality at omeprazole doses approximately 3.4 to 34 times an oral human dose of 40 mg, with teratogenicity not observed in animal studies with esomeprazole magnesium during organogenesis at doses about 68 times and 42 times, respectively, an oral human dose of 40 mg. However, changes in bone morphology were noted in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. When maternal administration was limited to gestation only, 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. A small prospective observational cohort study reported a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens.

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. Overall, while omeprazole has not been conclusively linked to teratogenic effects in humans, caution is advised when prescribing 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 of overdosage with omeprazole have been documented, with instances involving doses as high as 2400 mg, which is approximately 120 times the standard recommended clinical dose.

Clinical Manifestations

The symptoms associated with omeprazole overdosage may include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. It is noteworthy that these symptoms are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation.

Management of Overdosage

There is currently no specific antidote available for omeprazole overdosage. Therefore, the management of such cases should focus on symptomatic and supportive care. Given that omeprazole is extensively protein-bound, it is not readily dialyzable, which limits the effectiveness of dialysis as a treatment option.

In the event of an overdosage, it is imperative to contact the Poison Control Center at 1-800-222-1222 for further management information and guidance.

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. 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. Additionally, ECL cell hyperplasia was noted across 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 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 identified in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1 to 3.9 times the human dose). No astrocytomas were detected in female rats during this study. Conversely, a separate two-year carcinogenicity study in Sprague-Dawley rats did not reveal any astrocytomas 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 study involving p53 (+/-) transgenic mice did not yield positive results.

Omeprazole has shown clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay and in one of two in vivo mouse micronucleus tests, as well as in an in vivo bone marrow cell chromosomal aberration assay. 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 findings from the 24-month carcinogenicity studies in rats indicated a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia in both male and female animals. 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

Postmarketing experience with omeprazole delayed-release capsules has identified several adverse events reported voluntarily or through surveillance programs.

Acute tubulointerstitial nephritis has been observed in some patients, which can occur at any time during treatment. Patients are advised to seek medical attention if they experience a decrease in urine output or notice blood in their urine.

There is an increased risk of severe diarrhea associated with omeprazole, potentially due to Clostridium difficile infection. Symptoms such as watery stools, abdominal pain, and persistent fever warrant immediate consultation with a healthcare provider.

Long-term use of proton pump inhibitors (PPIs), including omeprazole, particularly at multiple daily doses for a year or longer, may elevate the risk of fractures in the hip, wrist, or spine. Patients should adhere to prescribed dosages and durations and discuss their individual risk of bone fractures with their healthcare provider.

Certain types of lupus erythematosus or exacerbation of pre-existing lupus have been reported in individuals taking PPIs. Patients experiencing new or worsening joint pain or a rash that worsens in sunlight should contact their doctor promptly.

Vitamin B-12 deficiency has been noted as a serious side effect, as omeprazole reduces stomach acid necessary for proper absorption of this vitamin. Patients on long-term therapy (exceeding three years) should discuss the potential for deficiency with their healthcare provider.

Low magnesium levels have been reported in some patients who have taken PPIs for at least three months, typically manifesting after a year of treatment. Symptoms of low magnesium may be subtle, but patients should inform their doctor if they experience seizures, dizziness, rapid heartbeat, or muscle spasms.

The development of fundic gland polyps has been associated with prolonged PPI use, particularly after more than one year of treatment.

Severe skin reactions, although rare, can occur and may require hospitalization. Symptoms may include blistering, peeling, or bleeding skin, accompanied by fever, chills, body aches, or respiratory distress. Patients should discontinue use and seek immediate medical attention if these symptoms arise.

Serious allergic reactions have also been reported. Patients should be vigilant for symptoms such as rash, throat tightness, facial swelling, or difficulty breathing, and should inform their healthcare provider if these occur, as discontinuation of omeprazole may be necessary.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, including the Medication Guide and Instructions for Use, to ensure they understand the proper use of omeprazole delayed-release capsules. Patients should be instructed to take the medication exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary to manage their condition.

It is important to inform patients that while omeprazole delayed-release capsules may alleviate acid-related symptoms, they could still experience serious stomach issues. Patients should be encouraged to communicate with their healthcare provider regarding any concerns about their symptoms.

Patients must be instructed to contact their doctor immediately if they notice a decrease in urination or observe blood in their urine. Additionally, they should seek medical attention if they experience watery stools, stomach pain, or persistent fever.

Healthcare providers should discuss the potential risk of bone fractures associated with long-term use of omeprazole delayed-release capsules and advise patients to take the medication only as directed. Patients should also be made aware of the possibility of vitamin B-12 deficiency if they have been on the medication for an extended period, specifically more than three years.

Patients should be informed to report any new or worsening joint pain, or the development of a rash on their cheeks or arms that worsens with sun exposure. They should also be instructed to notify their doctor if they experience symptoms such as seizures, dizziness, rapid heartbeat, jitteriness, tremors, muscle weakness, spasms, cramps, or any spasm of the voice box.

Instruct patients to report any signs of an allergic reaction, including rash, throat tightness, facial swelling, or difficulty breathing. They should be encouraged to communicate any side effects that are bothersome or persistent.

Patients should be advised to store omeprazole delayed-release capsules at room temperature, between 68°F to 77°F (20°C to 25°C), and to keep the medication out of the reach of children. It is crucial to emphasize that omeprazole delayed-release capsules should not be used for conditions for which they were not prescribed, nor should they be shared with others, as this could cause harm.

Finally, healthcare providers should remind patients that the Medication Guide contains essential information about omeprazole delayed-release capsules, and they should feel free to ask their doctor for further details.

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°C to 25°C (68°F 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 of proton pump inhibitors (PPIs) for the shortest duration necessary. Prolonged use beyond medical necessity should be avoided. If patients exhibit signs of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and referral to a specialist is recommended. Most patients show improvement within 4 to 12 weeks after stopping the PPI. Additionally, for those on long-term treatment or taking medications that may lead to hypomagnesemia, monitoring of magnesium levels is suggested prior to starting PPI therapy and periodically thereafter. Monitoring of calcium levels is also recommended for patients with a risk of hypocalcemia, with supplementation provided as needed. If hypocalcemia does not respond to treatment, discontinuation of the PPI should be considered.

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)