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 molecular formula is C17H19N3O3S, and it has a molecular weight of 345.42. Omeprazole, USP 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.

Each omeprazole delayed-release capsule, intended for oral administration, contains either 10 mg, 20 mg, or 40 mg of omeprazole. The capsules include several inactive ingredients: acetone, di-sodium hydrogen phosphate dihydrate, FD&C blue 1, gelatin, hydroxypropyl cellulose, hypromellose, hypromellose phthalate, polyethylene glycol, sodium lauryl sulfate, sugar spheres, talc, titanium dioxide, and triethyl citrate. The shell of each 10 mg and 40 mg capsule contains FD&C red 3 and FD&C green 3, while the 20 mg capsule shell contains iron oxide red and iron oxide yellow. The capsule is printed with black pharmaceutical ink, which consists of black iron oxide, potassium hydroxide, propylene glycol, and shellac.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcer 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 ulcer in adults.

In pediatric populations, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) in patients aged 1 year and older, as well as for the treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients aged 1 month and older. Furthermore, it is indicated for the maintenance of healing of EE due to acid-mediated GERD in patients aged 1 year and older.

This drug is also 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 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:

• Omeprazole: 20 mg taken twice daily for 10 days.

• Amoxicillin: 1000 mg taken twice daily for 10 days.

• Clarithromycin: 500 mg taken twice daily for 10 days.

Dual Therapy:

• Omeprazole: 40 mg administered once daily for 14 days.

• Clarithromycin: 500 mg taken three times daily for 14 days.

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

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

For pathological hypersecretory conditions, the starting dose is 60 mg once daily; however, this may vary based on individual patient needs, and healthcare professionals should refer to the full prescribing information for further guidance.

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 omeprazole, refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin for further guidance.

Warnings and Precautions

In adults, it is important to note that a symptomatic response to treatment does not exclude the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to rule out this condition.

Acute tubulointerstitial nephritis has been reported in patients receiving treatment. If this condition is suspected, it is imperative to discontinue the medication and evaluate the patient accordingly.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should be vigilant for signs of this infection in patients undergoing PPI treatment.

Long-term use of PPIs, particularly at multiple daily doses, may elevate the risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. It is advisable to assess the need for continued therapy in patients at risk for bone fractures.

Severe cutaneous adverse reactions 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 assessment.

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 may be necessary in patients on prolonged therapy.

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

The concomitant use of omeprazole with St. John's Wort or rifampin is contraindicated due to potential interactions that may affect the efficacy of omeprazole.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is crucial to note that increased levels of Chromogranin A (CgA) may interfere with test results. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels.

When administering high doses of methotrexate, caution is advised as the 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 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 1 to 16 years, the safety profile is similar to that observed in 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 while evaluating affected patients. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy, and long-term use of PPIs may elevate the risk of osteoporosis-related fractures 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 any 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, particularly 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.

Concomitant use of omeprazole with clopidogrel, St. John's Wort, or rifampin is not recommended due to potential interactions. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors; therefore, it is advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is also warranted when using omeprazole alongside methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity; a temporary withdrawal of omeprazole should be considered during high-dose methotrexate administration.

Long-term use of omeprazole may increase the risk of fundic gland polyps, particularly beyond one year, and it is recommended to use the shortest duration of therapy necessary.

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 have been established in pediatric patients aged 1 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. In patients aged 1 month to less than 1 year, omeprazole is indicated for the treatment of EE due to acid-mediated GERD.

Adverse reactions have been frequently reported in the pediatric population, particularly respiratory system events across the entire age range of 1 month to 16 years. In the 1 month to less than 1 year age group, otitis media was commonly reported, while fever was frequently noted in children aged 1 to less than 2 years. Additionally, accidental injuries were frequently reported in the 2 to 16 year age group.

It is important to note that the safety and effectiveness of omeprazole have not been established in patients less than 1 year of age for the treatment of symptomatic GERD or for the maintenance of healing of EE due to acid-mediated GERD. Furthermore, omeprazole has not been studied in pediatric patients 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. The safety and effectiveness of omeprazole have not been established in patients less than 1 month of age for any indication.

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 differences, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. Healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population, although the overall safety profile appears consistent with that of younger patients.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant patients. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with the use of omeprazole during the first trimester. However, reproduction studies in rats and rabbits have shown dose-dependent embryo-lethality at doses approximately 3.4 to 34 times the oral human dose of 40 mg, based on body surface area for a 60 kg person.

Teratogenicity was not observed in animal reproduction studies with esomeprazole magnesium, an enantiomer of omeprazole, when administered during organogenesis at doses about 68 times and 42 times the oral human dose of 40 mg for 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. However, when maternal administration was limited to gestation only, no effects on bone physeal morphology in the offspring were observed at any age.

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

Several studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those exposed to H2-receptor antagonists or other controls. A population-based retrospective cohort study from the Swedish Medical Birth Registry reported on 955 infants whose mothers used omeprazole during pregnancy, revealing similar rates of malformations, low birth weight, low Apgar scores, 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%. A retrospective cohort study indicated an overall malformation rate of 3.6% in the omeprazole group among 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester. Additionally, a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy, reporting a rate of major congenital malformations of 4%.

Furthermore, 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 sections under general anesthesia. Reproductive studies conducted with omeprazole in rats did not reveal any evidence of teratogenic potential; however, 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 from parents treated with omeprazole. Conversely, no effects on embryo-fetal development were noted in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis, although a pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal survival and developmental delays at high doses.

Healthcare professionals should weigh the potential benefits and risks of omeprazole use in pregnant patients, considering the available data and individual patient circumstances.

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 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 for omeprazole overdosage. 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 suspected overdosage, it is imperative to contact the Poison Control Center at 1-800-222-1222 for further management 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 marked increase in treatment-related ECL cell hyperplasia was recorded at the end of the first year (94% in treated rats versus 10% in controls). By the second year, the difference diminished (46% in treated versus 26% in controls), yet hyperplasia remained more prevalent in the treated group. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were identified in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were 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, in a separate two-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found 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 indicate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week study involving p53 (+/-) transgenic mice did not yield positive results.

Animal pharmacology and toxicology assessments indicated that omeprazole exhibited clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, as well as in one of two in vivo mouse micronucleus tests and an in vivo bone marrow cell chromosomal aberration assay. However, 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. Furthermore, the significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies aligns with findings from other studies involving 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 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 contact their healthcare provider if they experience a decrease in urine output or blood in their urine.

There is an increased risk of severe diarrhea associated with omeprazole, which may be linked to Clostridium difficile infection in the intestines. Patients should seek medical attention if they develop watery stools, stomach pain, and 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 use omeprazole as prescribed and discuss their individual risk of bone 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 with sun exposure, prompting patients to consult their doctor if such symptoms arise.

Additional serious side effects include vitamin B-12 deficiency, which may occur due to 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, typically after at least three months of treatment, with symptoms that may or may not be present.

Fundic gland polyps, a type of stomach growth, have been noted in patients using PPIs for over one year. Severe skin reactions, although rare, can occur and may require hospitalization. Symptoms may include blistering, peeling, or bleeding skin, along with fever, chills, body aches, shortness of breath, or swollen lymph nodes.

Patients are advised to report any of the following symptoms to their healthcare provider immediately: seizures, dizziness, abnormal or rapid heartbeat, jitteriness, tremors, muscle weakness, spasms of the hands and feet, cramps, muscle aches, or voice box spasms.

Healthcare providers may monitor magnesium levels before initiating treatment with omeprazole delayed-release capsules or during prolonged therapy.

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 for patients to be aware that while omeprazole may alleviate acid-related symptoms, they could still experience serious stomach issues. Therefore, they should be encouraged to discuss any ongoing or worsening symptoms with their healthcare provider. Patients should be instructed to contact their doctor if they notice a decrease in urination or observe blood in their urine.

Additionally, patients should seek immediate medical attention if they experience watery stools, stomach pain, and persistent fever. They should also be informed about the potential risk of bone fractures associated with long-term use of omeprazole and should discuss this risk with their healthcare provider.

Patients should be vigilant for new or worsening joint pain or the development of a rash on their cheeks or arms that worsens with sun exposure, and they should report these symptoms to their doctor promptly. If patients have been on omeprazole for an extended period (more than three years), they should discuss the possibility of vitamin B-12 deficiency with their healthcare provider.

Healthcare providers may need to monitor magnesium levels in patients who will be on omeprazole for a prolonged duration. Patients should be instructed to report any symptoms such as rash, facial swelling, throat tightness, or difficulty breathing, as these may indicate an allergic reaction.

Patients should be encouraged to report any side effects that are bothersome or persistent. Proper storage of omeprazole delayed-release capsules is essential; they should be kept at room temperature between 59°F to 86°F (15°C to 30°C) and out of the reach of children.

Finally, patients should be cautioned against using omeprazole for any condition other than that for which it was prescribed and should not share the medication with others, as it may be harmful to them.

Storage and Handling

The product is supplied in a tightly closed container to ensure integrity and stability. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the product from light and moisture to maintain its efficacy. For dispensing, a tight, light-resistant container is recommended to further safeguard the product from environmental factors.

Additional Clinical Information

Standardized susceptibility test procedures necessitate the use of laboratory control microorganisms to ensure the technical accuracy of laboratory procedures.

For the administration of therapies, dual therapy consists of omeprazole 40 mg once daily and clarithromycin 500 mg three times daily for 14 days, followed by omeprazole 20 mg once daily for an additional 14 days. In contrast, triple therapy involves omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily for 10 days, followed by omeprazole 20 mg once daily for another 18 days.

Clinicians should counsel patients that those who do not achieve eradication of H. pylori after either the omeprazole/clarithromycin/amoxicillin triple therapy or the omeprazole/clarithromycin dual therapy may have clarithromycin-resistant H. pylori isolates. It is advisable to conduct clarithromycin susceptibility testing when possible, as patients with such resistance should not be treated with regimens that include clarithromycin as the sole antimicrobial agent.

FDA Insert (PDF)

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

View full prescribing information (PDF)