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, which functions as a gastric acid secretion inhibitor. The empirical formula of omeprazole is C17H19N3O3S, with a molecular weight of 345.42.

Omeprazole appears as a white to off-white crystalline powder that decomposes at approximately 155°C. It is classified as a weak base, exhibiting solubility characteristics that include 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 environments but maintains acceptable stability in alkaline conditions.

Omeprazole delayed-release capsules are formulated to meet USP Dissolution Test 2 and are available for oral administration in dosages of 10 mg, 20 mg, or 40 mg. Each capsule contains enteric-coated granules of omeprazole along with inactive ingredients such as magnesium hydroxide, mannitol, methacrylic acid copolymer dispersion, povidone, and triethyl citrate. The capsule shells consist of gelatin, red iron oxide, and titanium dioxide. The imprinting ink used on the capsules includes ammonium hydroxide, black iron oxide, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, potassium hydroxide, propylene glycol, and shellac.

Uses and Indications

Omeprazole is indicated for the treatment of duodenal ulcers and gastric ulcers in adults. It is also indicated for the treatment of gastroesophageal reflux disease (GERD) in both adults and children, as well as for the maintenance of healing of erosive esophagitis.

The safety and effectiveness of omeprazole in pediatric patients under 1 year of age have not been established. There are no teratogenic effects associated with the use of 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. 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 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, with each medication taken twice daily for 10 days.

Dual Therapy: This regimen includes omeprazole 40 mg and clarithromycin 500 mg. Omeprazole should be taken once daily for 14 days, followed by clarithromycin taken three times daily for an additional 14 days.

In the case of gastric ulcers, the recommended dosage is 40 mg once daily for a treatment period of 4 to 8 weeks. For gastroesophageal reflux disease (GERD), a dosage of 20 mg once daily is advised for 4 to 8 weeks.

To maintain healing of erosive esophagitis, a dosage of 20 mg once daily is recommended. For patients with pathological hypersecretory conditions, the dosage may vary with individual patient needs, typically starting at 60 mg once daily.

For pediatric patients aged 2 to 16 years with GERD and for the maintenance of healing of erosive esophagitis, the following dosages are recommended based on weight: for those weighing between 10 kg and 20 kg, a dosage of 10 mg once daily is appropriate; for those weighing over 20 kg, a dosage of 20 mg once daily is indicated.

Contraindications

Use of this product is contraindicated in individuals with known hypersensitivity to any component of the formulation or to substituted benzimidazoles. This is due to the potential risk of severe allergic reactions, including angioedema and anaphylaxis, which have been reported in such cases.

Warnings and Precautions

Symptomatic response to treatment does not exclude the possibility of underlying gastric malignancy. Therefore, healthcare professionals should remain vigilant and consider further diagnostic evaluation in patients presenting with symptoms suggestive of gastric conditions.

Long-term therapy with proton pump inhibitors (PPIs) has been associated with the development of atrophic gastritis. Clinicians should monitor patients on extended PPI therapy for signs of this condition and consider periodic reassessment of the need for continued treatment.

There is an increased risk of Clostridium difficile-associated diarrhea in patients receiving PPI therapy. Healthcare providers should be aware of this risk and monitor patients for symptoms of diarrhea, particularly in those with a history of gastrointestinal infections.

Concomitant use of omeprazole with clopidogrel is not recommended due to the potential for reduced effectiveness of clopidogrel, which may increase the risk of cardiovascular events. Clinicians should evaluate alternative therapies when considering treatment regimens that include these medications.

Long-term and multiple daily doses of PPI therapy may elevate the risk of osteoporosis-related fractures, particularly of the hip, wrist, or spine. It is advisable to assess bone health in patients on prolonged PPI therapy and to implement preventive measures as necessary.

Rare cases of hypomagnesemia have been reported in patients undergoing prolonged treatment with PPIs. Monitoring of serum magnesium levels may be warranted in patients at risk for magnesium deficiency or those exhibiting symptoms suggestive of hypomagnesemia.

The concomitant use of omeprazole with St. John’s Wort or rifampin should be avoided, as these agents may significantly reduce omeprazole concentrations, potentially compromising its therapeutic efficacy.

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is important to note that increases in intragastric pH due to PPI therapy may lead to hypergastrinemia and enterochromaffin-like cell hyperplasia, resulting in elevated Chromogranin A levels. These changes can interfere with the accuracy of diagnostic assessments for neuroendocrine tumors, necessitating careful consideration of PPI use prior to such evaluations.

Side Effects

Patients may experience a range of adverse reactions while using this medication. The 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 observed in adults; however, respiratory system events and fever were noted as the most frequently reported reactions in clinical studies involving this population.

Serious hypersensitivity reactions have been documented, including angioedema and anaphylaxis, which require immediate medical attention.

In cases of overdosage, patients may present with confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. Other adverse reactions may resemble those typically observed in normal clinical experience.

Long-term therapy with this medication may lead to additional adverse effects, such as atrophic gastritis and an increased risk of Clostridium difficile-associated diarrhea. Furthermore, prolonged use of proton pump inhibitors (PPIs) has been associated with an elevated risk of osteoporosis-related fractures of the hip, wrist, or spine. Rare instances of hypomagnesemia have also been reported with extended treatment.

It is important to note that a symptomatic response to treatment does not exclude the possibility of gastric malignancy. Additionally, patients should avoid concomitant use of omeprazole with clopidogrel, St John’s Wort, or rifampin due to potential drug interactions. There may also be interactions with diagnostic investigations for neuroendocrine tumors, as increases in intragastric pH can lead to hypergastrinemia, enterochromaffin-like cell hyperplasia, and elevated Chromogranin A levels, which may interfere with diagnostic assessments.

Drug Interactions

Concomitant use of omeprazole with certain antiretroviral agents is not recommended due to significant interactions. Specifically, omeprazole reduces plasma levels of atazanavir and nelfinavir, which may compromise their efficacy. In contrast, omeprazole increases plasma levels of saquinavir; therefore, monitoring for toxicity is advised, and a dose reduction of saquinavir should be considered.

Omeprazole may also interfere with the bioavailability of drugs that are sensitive to gastric pH changes, including ketoconazole, iron salts, erlotinib, ampicillin esters, and digoxin. Patients receiving both omeprazole and digoxin should be monitored for potential increases in digoxin toxicity.

The interaction between omeprazole and clopidogrel is clinically significant, as omeprazole decreases exposure to the active metabolite of clopidogrel, potentially reducing its antiplatelet effect.

For cilostazol, omeprazole increases systemic exposure to cilostazol and one of its active metabolites, warranting consideration of a dose reduction of cilostazol.

Omeprazole can prolong the elimination of drugs metabolized by cytochrome P450 enzymes, such as diazepam, warfarin, phenytoin, cyclosporine, disulfiram, and benzodiazepines. Patients on warfarin should be closely monitored for increases in INR and prothrombin time, and dose adjustments may be necessary based on clinical response.

Additionally, the use of combined inhibitors of CYP 2C19 and 3A4, such as voriconazole, may elevate omeprazole levels.

Omeprazole may also increase serum levels of tacrolimus and methotrexate, necessitating careful monitoring and potential dose adjustments for these medications.

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

Omeprazole is indicated for the treatment of gastroesophageal reflux disease (GERD) in pediatric and adolescent patients aged 2 to 16 years. This indication is supported by the extrapolation of results from adequate and well-controlled studies conducted in adults, along with safety and pharmacokinetic studies specifically performed in the pediatric population.

The safety and effectiveness of omeprazole for the treatment of GERD in patients younger than 1 year of age have not been established. Additionally, the safety and effectiveness of omeprazole for other pediatric indications remain unproven.

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, demonstrating no significant differences in safety and effectiveness when compared to younger subjects. While other clinical experiences have not identified notable differences in response between elderly and younger patients, it is important to acknowledge that greater sensitivity in some older individuals cannot be entirely excluded.

Pharmacokinetic studies indicate 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 variations, no dosage adjustment is necessary for elderly patients. However, healthcare providers should remain vigilant and consider the potential for increased sensitivity in some older individuals when prescribing omeprazole. Regular monitoring and assessment of therapeutic response may be warranted to ensure optimal treatment outcomes in this population.

Pregnancy

Pregnancy Category C. Reproductive studies in rats and rabbits, as well as multiple cohort studies involving pregnant women who used omeprazole during the first trimester, have not demonstrated an increased risk of congenital anomalies or adverse pregnancy outcomes. However, there are no adequate and well-controlled studies on the use of omeprazole in pregnant women. Due to the limitations of animal reproduction studies in predicting human response, omeprazole should be used during pregnancy only if clearly needed.

The majority of reported experiences with omeprazole during human pregnancy involve first trimester exposure, with the duration of use often unspecified, such as whether it was intermittent or chronic. An expert review by the Teratogen Information System (TERIS) concluded that therapeutic doses of omeprazole during pregnancy are unlikely to pose a substantial teratogenic risk, although the quantity and quality of data were assessed as fair.

In utero exposure to omeprazole has not been associated with an increased risk of malformations (odds ratio 0.82, 95% CI 0.50 to 1.34), low birth weight, or low Apgar scores. While the overall malformation rate was reported at 4.4% (95% CI 3.6 to 5.3), the rate for first trimester exposure was 3.6% (95% CI 1.5 to 8.1). The relative risk of malformations associated with first trimester exposure compared to non-exposed women was 0.9 (95% CI 0.3 to 2.2). Rates of preterm delivery and growth retardation did not differ between groups, and there were no significant differences in rates of spontaneous or elective abortions, gestational age at delivery, or mean birth weight.

Notably, several studies have indicated 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. However, reproductive studies in rabbits at doses approximately 5.5 to 56 times the human dose indicated dose-related increases in embryo lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 5.6 to 56 times the human dose, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring.

Given these findings, healthcare professionals should carefully weigh the benefits and risks of omeprazole use in pregnant patients.

Lactation

Omeprazole concentrations have been measured in breast milk following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was found to be less than 7% of the peak serum concentration, corresponding to approximately 0.004 mg of omeprazole in 200 mL of milk.

Due to the excretion of omeprazole in human milk and the potential for serious adverse reactions in nursing infants, as well as the potential for tumorigenicity demonstrated in rat carcinogenicity studies, lactating mothers should carefully consider whether to discontinue breastfeeding or to discontinue the drug. This decision should take into account the importance of omeprazole to the mother’s health.

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 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 documented regarding 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 overdosage have been variable, but commonly reported symptoms include confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These adverse reactions are consistent with those observed in normal clinical use of the medication.

It is noteworthy that the symptoms associated with omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. There is currently no specific antidote available for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable.

In the event of an overdosage, treatment should focus on symptomatic and supportive care. Healthcare professionals should also consider the possibility of multiple drug ingestion, as is standard in the management of any overdose situation. For the most current information regarding the treatment of any drug overdose, it is advisable to contact a Poison Control Center at 1-800-222-1222.

Animal studies have indicated that single oral doses of omeprazole at 1350 mg/kg in mice, 1339 mg/kg in rats, and 1200 mg/kg in dogs were lethal. Observed effects in these animals included sedation, ptosis, tremors, convulsions, decreased activity, reduced body temperature, and alterations in respiratory rate, including increased depth of respiration.

Nonclinical Toxicology

Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (approximately 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (also about 56 times the human dose on a body surface area basis) did not reveal any evidence of teratogenic potential. However, in rabbits, omeprazole administered at doses ranging from 6.9 to 69.1 mg/kg/day (approximately 5.5 to 56 times the human dose on a body surface area basis) 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 at doses of 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis). Notably, omeprazole at oral doses up to 138 mg/kg/day in rats did not affect fertility or reproductive performance.

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day (approximately 0.7 to 57 times a human dose of 20 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats, with a markedly higher incidence observed in female rats, which exhibited higher blood levels of omeprazole. Gastric carcinoids are rarely seen in untreated rats. ECL cell hyperplasia was present in all treated groups of both sexes. In one study, female rats treated with 13.8 mg omeprazole/kg/day (about 6 times a human dose of 20 mg/day, based on body surface area) for one year and followed for an additional year without the drug did not show carcinoids. An increased incidence of treatment-related ECL cell hyperplasia was noted at the end of one year (94% in treated rats vs 10% in controls). By the second year, the difference between treated and control rats was smaller (46% vs 26%) but still indicated more hyperplasia in the treated group. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were noted in male or female rats treated for two years. Historically, no similar tumors have been reported in this strain of rat, making the interpretation of a single tumor finding challenging. In a 52-week toxicity study in 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 0.2 to 6.5 times the human dose on a body surface area basis), with no astrocytomas observed in female rats. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in males or females at the high dose of 140.8 mg/kg/day (about 57 times the human dose on a body surface area basis). A 78-week carcinogenicity study in mice did not demonstrate increased tumor occurrence, although the study was inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole was found to be positive for clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and 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.

Postmarketing Experience

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

There is an increased risk of severe diarrhea, which may be attributed to an infection with Clostridium difficile in the intestines. Additionally, long-term use of omeprazole has been associated with chronic inflammation of the stomach lining, known as atrophic gastritis.

Furthermore, low magnesium levels have been reported in some individuals taking proton pump inhibitors for an extended duration, typically after at least three months of treatment, with a higher incidence observed after one year. This condition can be serious and warrants monitoring in patients receiving prolonged therapy.

Patient Counseling

Healthcare providers should advise patients to take the omeprazole delayed-release capsule before eating to ensure optimal effectiveness. It is important to inform patients that the capsule must be swallowed whole and should not be chewed or crushed.

For patients who experience difficulty swallowing capsules, healthcare providers can recommend an alternative method. Patients may open the capsule and add the contents to one tablespoon of applesauce in an empty bowl. All pellets from the capsule should be carefully emptied onto the applesauce, mixed thoroughly, and swallowed immediately with a glass of cool water to ensure complete ingestion of the pellets. It is crucial to emphasize that the applesauce should not be hot and must be soft enough to swallow without chewing. Additionally, the mixture of pellets and applesauce should not be stored for future use.

Healthcare providers should also counsel patients to be vigilant for certain side effects. Patients should be instructed to immediately report and seek medical attention for diarrhea that does not improve, as this may indicate Clostridium difficile associated diarrhea. Furthermore, patients should be advised to report any cardiovascular or neurological symptoms, such as palpitations, dizziness, seizures, or tetany, as these may be indicative of hypomagnesemia and require prompt evaluation and care.

Storage and Handling

Omeprazole delayed-release capsules are supplied in a tight container that is designed to protect the contents from light and moisture. The recommended storage temperature for these capsules is between 20° to 25°C (68° to 77°F), with permissible excursions allowed between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)