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. 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 supplied as delayed-release capsules for oral administration. Each delayed-release capsule contains either 10 mg, 20 mg, or 40 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the enteric-coated granules include glyceryl monostearate, hypromellose (5cps), meglumine, methacrylic acid copolymer, poloxamer, sugar globules, talc, titanium dioxide, and triethyl citrate. The capsule shells contain 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, this drug 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

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: This regimen consists of omeprazole delayed-release capsules 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 delayed-release capsules 40 mg administered orally once daily for 14 days, alongside clarithromycin 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), a dosage of 20 mg orally once daily for up to 4 weeks is advised. For erosive esophagitis (EE) due to acid-mediated GERD, the dosage is 20 mg orally once daily for 4 to 8 weeks. To maintain healing of EE due to acid-mediated GERD, a continuous dosage of 20 mg orally once daily is recommended.

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

All medications should 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 due to potential drug interactions. When used in combination with clarithromycin and amoxicillin, please 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 rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to ensure comprehensive patient evaluation.

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 remain vigilant for this potential complication in patients undergoing PPI treatment.

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically in the hip, wrist, or spine. It is advisable to assess the need for ongoing 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 while on omeprazole. In such cases, discontinuation of the medication is recommended, and referral to a specialist for further evaluation is warranted.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel. Healthcare providers should avoid this combination.

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 extended therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported, albeit rarely, with prolonged PPI treatment. Clinicians should consider monitoring 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.

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 diagnostic results.

Caution is advised when administering methotrexate alongside PPIs, as this combination 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. 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. Long-term and multiple daily doses of PPIs 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, 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 metabolite, potentially leading to toxicity. The risk of fundic gland polyps increases with long-term use, particularly beyond one year, thus the shortest duration of therapy is recommended.

Reports of overdosage with omeprazole have been received, with manifestations varying but including 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 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 across the entire age range of 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 (≥ 65 years of age) 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 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 or adverse effects 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. Reproduction studies in rats and rabbits have shown dose-dependent embryo-lethality at omeprazole 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 animal reproduction studies with the administration of oral esomeprazole, an enantiomer of omeprazole, 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. 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, finding that the number of infants exposed in utero to omeprazole with any malformation, low birth weight, low Apgar score, or hospitalization was similar to that observed in the general population. Another study covering all live births in Denmark reported an overall rate of birth defects of 2.9% in infants born to mothers with first trimester exposure to omeprazole, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

A retrospective cohort study involving 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester reported an overall malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. Additionally, a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy, reporting a rate of major congenital malformations of 4% in the omeprazole group.

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. Omeprazole 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 produced 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.

No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal/early postnatal survival at doses equal to or greater than 138 mg/kg/day. 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, 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

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.

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 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 in humans have documented instances involving doses as high as 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations associated with 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 of omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. In cases of suspected overdosage, there is no specific antidote available; 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

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, observed in both male and female rats. The incidence of these tumors was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely seen 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 of omeprazole for one year, followed by 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 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 of 40 mg/day based on body surface area). No astrocytomas were detected in female rats during this study. Conversely, a 2-year carcinogenicity study in Sprague-Dawley rats at the high dose of 140.8 mg/kg/day (about 34 times the human dose) did not reveal any astrocytomas in either sex. 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. 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.

In summary, the findings from the carcinogenicity studies indicate a significant increase in gastric carcinoid tumors and ECL cell hyperplasia in rats, with similar observations noted in studies involving other proton pump inhibitors or high doses of H2-receptor antagonists.

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

Certain types of lupus erythematosus have been reported in patients taking PPIs, including omeprazole. This autoimmune disorder may manifest as new or worsening joint pain or a rash that exacerbates in sunlight. Patients should inform their doctor if they experience these symptoms.

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 patients taking PPIs for at least three months, with symptoms potentially developing after a year of treatment. Symptoms may include seizures, muscle spasms, dizziness, and abnormal heart rhythms, necessitating immediate medical consultation.

The development of fundic gland polyps, a type of stomach growth, has been noted in patients using PPIs long-term, especially 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, along with fever and body aches. Patients should discontinue use and seek medical attention if these symptoms arise.

Serious allergic reactions have also been reported, characterized by rash, facial swelling, throat tightness, and difficulty breathing. Patients experiencing these symptoms should inform their healthcare provider, who may consider discontinuing omeprazole.

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 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.

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

In the event of a missed dose, patients should be advised to 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 should swallow the capsules whole and not chew them. For those who have difficulty swallowing intact capsules, they may open the capsules and mix the contents with applesauce, as detailed in the Medication Guide.

Patients should be counseled to take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary. While the medication may alleviate acid-related symptoms, patients should be made aware that serious stomach problems could still occur, and they should consult their doctor if they experience a decrease in urination or notice blood in their urine.

Patients should seek immediate medical attention if they develop watery stools, stomach pain, and persistent fever. They should also contact their healthcare provider if they experience new or worsening joint pain or a rash that worsens in sunlight. It is advisable for patients to discuss the risk of vitamin B-12 deficiency with their doctor if they have been on omeprazole delayed-release capsules for an extended period, particularly longer than three years.

Patients should be informed to report any symptoms such as seizures, jitteriness, spasms of the hands and feet, dizziness, jerking movements or shaking (tremors), cramps or muscle aches, abnormal or rapid heartbeat, or muscle weakness to their healthcare provider. Additionally, healthcare providers may monitor magnesium levels before and during treatment if patients are on omeprazole delayed-release capsules for a prolonged period.

Patients should be instructed to discontinue the medication and contact their doctor immediately if they experience a skin rash that may blister, peel, or bleed on any part of their body, including the lips, eyes, mouth, nose, genitals, hands, or feet. They should also inform their healthcare provider if they experience any symptoms such as rash, facial swelling, throat tightness, or difficulty breathing. Lastly, patients should be encouraged to report any side effects that are bothersome or persistent.

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 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 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 suggestive of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE), omeprazole should be discontinued, and a specialist referral is recommended. For those on long-term treatment or concomitant medications that may lead to hypomagnesemia, such as diuretics or digoxin, monitoring of magnesium levels prior to and during PPI therapy may be warranted.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Omeprazole as submitted by Dr. Reddy's Laboratories Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)