Omeprazole

Description

The active ingredient in omeprazole delayed-release capsules is a substituted benzimidazole, specifically 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl)methyl sulfinyl]-1H-benzimidazole. Its empirical formula is C17H19N3O3S, and it has a molecular weight of 345.42. Omeprazole appears as a white to off-white powder and melts between 150°C and 160°C with decomposition. It is soluble in dichloromethane, sparingly soluble in methanol and alcohol, and very slightly soluble in water.

Omeprazole USP is provided as delayed-release capsules for oral administration. Each delayed-release capsule contains 40 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the delayed-release capsules include glyceryl monostearate, hypromellose (5cps), meglumine, methacrylic acid copolymer, poloxamer, sugar globules, talc, titanium dioxide, and triethyl citrate. The capsule shells are composed of black iron oxide, D & C Red 28, FD & C Blue 1, FD & C Red 40, gelatin, potassium hydroxide, propylene glycol, shellac, titanium dioxide, and yellow iron oxide.

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 maintenance of healing of erosive esophagitis (EE) due to acid-mediated GERD. Furthermore, it is indicated for the treatment of pathologic hypersecretory conditions in adults.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

The recommended dosage and administration of the medication are as follows:

For the treatment of active duodenal ulcer, the standard dosage is 20 mg administered orally once daily for a duration of 4 weeks. In some cases, an additional 4 weeks of treatment may be necessary based on clinical response.

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

• Triple Therapy: Administer omeprazole delayed-release capsules at a dosage of 20 mg, amoxicillin at 1000 mg, and clarithromycin at 500 mg, with each medication taken orally twice daily for 10 days.

• Dual Therapy: Administer omeprazole delayed-release capsules at a dosage of 40 mg once daily for 14 days, alongside clarithromycin at 500 mg taken orally three times daily for the same duration.

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

For symptomatic gastroesophageal reflux disease (GERD), the dosage is 20 mg orally once daily for up to 4 weeks.

For erosive esophagitis (EE) due to acid-mediated GERD, the initial dosage is 20 mg orally once daily for 4 to 8 weeks. If there is no response, an additional 4 weeks of treatment may be warranted. In instances of recurrence, further courses of 4 to 8 weeks may be considered.

To maintain healing of EE due to acid-mediated GERD, a dosage of 20 mg orally once daily is recommended. For patients with hepatic impairment (Child-Pugh Class A, B, or C) and Asian patients, the dosage may be reduced to 10 mg once daily.

For pathological hypersecretory conditions, the starting dose is 60 mg orally once daily, with adjustments made based on individual patient needs as clinically indicated.

All dosages should be administered 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 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, the presence of gastric malignancy should be considered even if there is a symptomatic response to treatment. Additional follow-up and diagnostic testing are recommended to rule out this condition.

Acute tubulointerstitial nephritis has been reported; therefore, treatment should be discontinued and patients evaluated if symptoms arise. There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea, necessitating caution in patients with a history of this infection.

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 professionals should monitor patients for signs of bone fractures and consider alternative therapies when appropriate.

Severe cutaneous adverse reactions may occur; treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity, with further evaluation recommended. Additionally, there is a risk of new onset or exacerbation of cutaneous and systemic lupus erythematosus; in these cases, omeprazole should be discontinued, and referral to a specialist is advised.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions. Long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12), necessitating monitoring of vitamin levels in long-term users.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with prolonged PPI treatment. Caution is advised when using omeprazole alongside St. John’s Wort or rifampin, as these interactions may reduce the efficacy of the medication.

Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels to ensure accurate results.

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

The risk of fundic gland polyps increases with long-term use of omeprazole, particularly beyond one year. Therefore, it is advisable to use the shortest duration of therapy necessary to achieve treatment goals.

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 pediatric studies.

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

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Additionally, omeprazole may interfere with diagnostic investigations for neuroendocrine tumors by increasing Chromogranin A (CgA) levels, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. The risk of fundic gland polyps increases with long-term use, particularly beyond one year.

Reports of overdosage with omeprazole have been received, with manifestations including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. Symptoms of overdosage were transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

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 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, treatment of active benign gastric ulcers, or pathological hypersecretory conditions in pediatric patients.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals aged 65 years and older in clinical trials conducted in the U.S. and Europe. The results from these studies indicate no significant differences in safety and effectiveness between elderly patients and younger subjects. While other clinical experiences have not identified notable differences in response between these age groups, it is important to acknowledge that greater sensitivity in some older individuals cannot be entirely excluded.

Pharmacokinetic studies reveal 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 seen 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. 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. While teratogenicity was not observed in animal studies with esomeprazole magnesium during organogenesis at doses about 68 times and 42 times the human dose, 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 human dose.

When maternal administration of omeprazole 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.

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, finding similar rates of malformations, low birth weight, low Apgar scores, and hospitalization compared to the general population. However, a slight increase in the number of infants born with ventricular septal defects and stillborn infants was observed among omeprazole-exposed infants.

Another retrospective cohort study covering all live births in Denmark reported a birth defect rate of 2.9% in infants born to mothers with first trimester exposure to omeprazole, compared to 2.6% in those not exposed to any proton pump inhibitor. A separate study involving 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester reported an overall malformation rate of 3.6%. A small prospective observational cohort study of 113 women exposed to omeprazole during pregnancy indicated a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens.

Several studies have reported no apparent adverse short-term effects on infants when single doses of oral or intravenous omeprazole were administered to over 200 pregnant women as premedication for cesarean sections under general anesthesia. Reproductive studies conducted with rats at oral doses up to 138 mg/kg/day during organogenesis 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. No effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium in rats or rabbits during organogenesis.

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

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 these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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

In cases of omeprazole overdosage, reports indicate that doses as high as 2400 mg have been documented, which is approximately 120 times the standard recommended clinical dose. The clinical manifestations associated with omeprazole overdosage may include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.

It is important to note that the symptoms of 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. Therefore, management 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, healthcare professionals are advised 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 nonclinical toxicology profile through various studies assessing its teratogenic and non-teratogenic effects, as well as its potential for carcinogenicity and mutagenicity.

No teratogenic effects have been reported. 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 adversely affect fertility or reproductive performance.

In carcinogenicity studies conducted over 24 months in rats, omeprazole was administered 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. 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 observed in females, who exhibited elevated blood levels of omeprazole. Gastric carcinoids are infrequently observed in untreated rats. ECL cell hyperplasia was noted across 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 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 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 during 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 demonstrate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Postmarketing Experience

Postmarketing experience with omeprazole delayed-release capsules has identified several serious side effects reported voluntarily or through surveillance programs.

Acute tubulointerstitial nephritis, a type of kidney problem, has been observed in some patients taking proton pump inhibitors (PPIs), including omeprazole. This condition can occur at any time during treatment, and patients are advised to seek medical attention if they experience a decrease in urine output or blood in their urine.

There is an increased risk of severe diarrhea associated with omeprazole, potentially due to Clostridium difficile infection in the intestines. Patients should contact their healthcare provider if they develop watery stools, stomach pain, or persistent fever.

Long-term use of PPIs, such as omeprazole, particularly at multiple daily doses for a year or longer, may elevate the risk of fractures in the hip, wrist, or spine. Patients are encouraged to discuss their individual risk of bone fractures with their healthcare provider.

Certain types of lupus erythematosus have been reported in individuals taking PPIs, including omeprazole. Patients experiencing new or worsening joint pain or a rash that worsens with sun exposure should consult their doctor.

Additional serious side effects include vitamin B-12 deficiency, which may arise from reduced stomach acid necessary for vitamin absorption, particularly in patients on omeprazole for extended periods (more than three years).

Low magnesium levels have also been reported in some patients taking PPIs for at least three months, with symptoms potentially manifesting after a year of treatment. Symptoms may include seizures, muscle spasms, dizziness, and abnormal heart rhythms, necessitating immediate medical attention.

The development of fundic gland polyps has been noted in patients using PPIs long-term, especially after more than one year of treatment.

Severe skin reactions, although rare, can occur with omeprazole, presenting as skin rashes that may blister, peel, or bleed. These reactions can be life-threatening and may require hospitalization. Patients should discontinue use and seek immediate medical care if they experience such symptoms, which may be accompanied by fever, chills, or respiratory distress.

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 medication's proper use and potential risks. Patients should be instructed to report any signs or symptoms indicative of hypersensitivity reactions, acute tubulointerstitial nephritis, Clostridium difficile associated diarrhea, bone fractures, cutaneous and systemic lupus erythematosus, cyanocobalamin (Vitamin B-12) deficiency, hypomagnesemia, and mineral metabolism issues to their healthcare provider promptly.

It is important for patients to inform their healthcare provider if they initiate treatment with clopidogrel, St. John’s Wort, or rifampin, or if they are taking high-dose methotrexate, as these may interact with their treatment. Patients should be advised to take omeprazole delayed-release capsules before meals and that antacids may be used concurrently with these capsules.

In the event of a missed dose, patients should take the missed dose as soon as possible. However, if the next scheduled dose is approaching, they should skip the missed dose and resume their regular dosing schedule without taking two doses at once. Patients must swallow the omeprazole delayed-release capsules whole and should not chew them. For those who have difficulty swallowing intact capsules, it is permissible to open the capsules and mix the contents with applesauce, as detailed in the Medication Guide.

Patients should take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary. While these capsules may alleviate acid-related symptoms, patients should be made aware that serious stomach problems could still occur, and they should consult their doctor regarding any concerns.

Patients should be instructed to contact their healthcare provider immediately if they notice a decrease in urination or observe blood in their urine. They should also seek medical attention if they experience watery stools, stomach pain, or persistent fever. Additionally, patients should discuss the risk of bone fractures with their doctor if they are prescribed omeprazole delayed-release capsules.

Patients must report any new or worsening joint pain or rashes on their cheeks or arms that worsen with sun exposure. If patients have been on omeprazole delayed-release capsules for an extended period (more than three years), they should discuss the potential for vitamin B-12 deficiency with their healthcare provider. Symptoms of low magnesium, such as seizures, jitteriness, muscle spasms, dizziness, tremors, cramps, abnormal heart rhythms, muscle weakness, or voice box spasms, should prompt immediate communication with their doctor.

Finally, patients should be instructed to discontinue omeprazole delayed-release capsules and contact their healthcare provider immediately if they experience severe skin reactions, including rashes that may blister, peel, or bleed.

Storage and Handling

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

Additional Clinical Information

Serum chromogranin A (CgA) levels may increase due to drug-induced decreases in gastric acidity when patients are treated with omeprazole. This elevation can lead to false positive results in diagnostic tests for neuroendocrine tumors. Clinicians are advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider repeating the test if initial results are elevated. For serial monitoring, it is important to use the same commercial laboratory, as reference ranges may differ.

Patients should be counseled to use the lowest effective dose and shortest duration of proton pump inhibitor (PPI) therapy necessary for their condition. Prolonged use of PPIs should be avoided unless medically indicated. If patients exhibit signs or symptoms consistent with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and referral to a specialist is recommended. Most patients will see improvement within 4 to 12 weeks after stopping the PPI. For those on long-term treatment or taking medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels prior to and during PPI therapy is advisable. Additionally, monitoring of magnesium and calcium levels should be considered in patients with a preexisting risk of hypocalcemia, and supplementation may be necessary. 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 Quallent Pharmaceuticals Health LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)