Omeprazole

Description

The active ingredient in omeprazole delayed-release capsule, USP is a substituted benzimidazole, specifically 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl)methyl sulfinyl]-1H-benzimidazole. Its molecular formula is C17H19N3O3S, and it has 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, with each capsule containing either 10 mg or 20 mg of omeprazole in the form of enteric-coated granules. The 10 mg and 20 mg capsules contain the following inactive ingredients: 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 include gelatin and titanium dioxide, while the 10 mg formulation contains 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 consists of 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 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. 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 taken orally 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 continuous dosage of 20 mg once daily is recommended.

For 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 varying from once daily to twice or three times daily, depending on the specific indication and therapy regimen.

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. Healthcare providers should assess the need for ongoing therapy and consider alternative treatments when appropriate.

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 for signs of deficiency is advised in patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported, albeit rarely, with prolonged PPI treatment. Clinicians should monitor magnesium levels in patients receiving long-term therapy.

The concomitant use of omeprazole with St. John’s Wort or rifampin should be avoided due to potential interactions that may affect the efficacy of omeprazole.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is important to note that increased levels of Chromogranin A (CgA) may interfere with test results. To ensure accurate assessment, omeprazole should be temporarily discontinued at least 14 days prior to measuring CgA levels.

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

Finally, the risk of fundic gland polyps increases with long-term 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, 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, and long-term or multiple daily doses of PPIs may elevate the risk of osteoporosis-related fractures of the hip, wrist, or spine.

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

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Long-term daily use of omeprazole (beyond three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rare reports of hypomagnesemia and mineral metabolism disturbances have been associated with prolonged PPI treatment. 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, especially 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 is no information available regarding 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) have demonstrated that omeprazole exhibits comparable safety and effectiveness profiles when administered to geriatric patients versus younger subjects. While other clinical experiences have not identified significant differences in response between these age groups, it is important to acknowledge that some elderly patients 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 noted in this population. 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 volunteers.

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. In animal reproduction studies, dose-dependent embryo-lethality was observed in rats and rabbits 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. However, teratogenicity was not observed in 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 in rats and rabbits, respectively.

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. 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; 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 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, showing 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. Additionally, 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 conducted with omeprazole in rats did not reveal any evidence of teratogenic potential, although in rabbits, omeprazole was associated with dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole prior to mating through the lactation period. Conversely, no effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium administered during organogenesis, although a pre- and postnatal developmental toxicity study in rats showed decreased neonatal survival and developmental delays at high doses. When maternal administration of esomeprazole was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.

Lactation

Limited data suggest that omeprazole may be present in human milk. However, there are no clinical data available regarding the effects of omeprazole on breastfed infants or on milk production.

When considering the use of omeprazole in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition should be taken into account.

Renal Impairment

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 patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring of these patients.

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 received 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 omeprazole overdosage can include a range of symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.

It is important to note that the symptoms associated with omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken alone. In the event of over-exposure, it is crucial to seek immediate assistance by contacting the Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

There is no specific antidote for omeprazole overdosage; therefore, treatment should focus on symptomatic and supportive care. Additionally, due to omeprazole's extensive protein binding, it is not readily dialyzable, which should be taken into consideration when managing cases of overdosage.

Nonclinical Toxicology

In nonclinical studies, omeprazole demonstrated no teratogenic effects. 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, omeprazole did not adversely affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed a dose-related increase in gastric ECL cell carcinoids at daily doses of 1.7, 3.4, 13.8, 44, 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. The incidence of carcinoids 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 for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a notable increase in 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 identified in one rat (2%), but no similar tumors were observed 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 of 40 mg/day based on body surface area). No astrocytomas were found in female rats in this study. In a separate two-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 of 40 mg/day on a body surface area basis). A 78-week carcinogenicity study in mice did not indicate 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 and in one of two in vivo mouse micronucleus tests, as well as in 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. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was consistent with findings from other studies involving fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

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

Acute tubulointerstitial nephritis has been observed in some patients, which can occur at any time during treatment. Additionally, there is an increased risk of severe diarrhea, potentially due to Clostridium difficile infection in the intestines. 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.

Certain patients have reported the development of lupus erythematosus or exacerbation of pre-existing lupus conditions while on PPI therapy. Serious side effects have also been noted, including vitamin B-12 deficiency, low magnesium levels, fundic gland polyps, and severe skin reactions. Furthermore, serious allergic reactions, such as rash, throat tightness, facial swelling, and difficulty breathing, have been documented.

Healthcare professionals and patients are encouraged to report any side effects to the FDA at 1-800-FDA-1088.

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 as prescribed, at the lowest effective dose, and for the shortest duration necessary to manage their condition.

It is important to communicate to patients that while omeprazole delayed-release capsules may alleviate acid-related symptoms, they could still experience serious stomach issues. Patients should be encouraged to discuss any concerns with their doctor. They should be informed to call their doctor immediately if they notice a decrease in urination or observe blood in their urine. Additionally, patients should seek medical attention if they experience watery stools, stomach pain, or persistent fever.

Patients must be reminded to adhere strictly to the prescribed dosage and duration of treatment. They should also be made aware of the potential risk of bone fractures associated with long-term use of omeprazole delayed-release capsules. It is advisable to discuss the possibility of vitamin B-12 deficiency with patients who have been on the medication for an extended period, specifically more than three years.

Healthcare providers should instruct patients to report any new or worsening joint pain or the development of a rash on their cheeks or arms that worsens with sun exposure. Patients should be informed to notify their doctor immediately if they experience symptoms such as seizures, dizziness, abnormal or rapid heartbeat, jitteriness, tremors, muscle weakness, spasms in the hands and feet, cramps, or voice box spasms.

Patients should also be advised to inform their doctor if they experience any allergic reactions, including rash, throat tightness, facial swelling, or difficulty breathing. They should be encouraged to report any side effects that are bothersome or persistent.

It is essential to instruct patients on the proper storage of omeprazole delayed-release capsules, which should be kept at room temperature between 68°F to 77°F (20°C to 25°C) and out of the reach of children. Patients must be cautioned against using omeprazole delayed-release capsules for any condition other than that for which it was prescribed and should not share their medication with others, as it may be harmful to them.

Finally, healthcare providers should remind patients that the Medication Guide contains crucial 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° 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 reductions in gastric acidity, potentially leading to false positive results in neuroendocrine tumor diagnostics. Clinicians are advised to discontinue omeprazole treatment at least 14 days prior to CgA level assessment 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.

Patients should be counseled to utilize the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy necessary for their condition. 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 experience improvement within 4 to 12 weeks after stopping the PPI, although serological test results may take longer to normalize. Additionally, postmarketing reports have indicated severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), as well as cases of CLE and SLE associated with PPI use. Rare instances of hypomagnesemia, which can lead to serious complications such as tetany, arrhythmias, and seizures, have also been documented in patients on PPIs for extended periods.

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)