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)methylsulfinyl]-1H-benzimidazole, which functions as a gastric acid secretion inhibitor. The empirical formula 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, showing rapid degradation in acidic environments while maintaining acceptable stability in alkaline conditions.

Omeprazole delayed-release capsules are formulated to meet USP Drug Release Test 2 standards and are intended for oral administration. Each capsule contains enteric-coated granules of omeprazole in dosages of 10 mg, 20 mg, or 40 mg, combined with inactive ingredients such as crospovidone, hypromellose, magnesium stearate, mannitol, meglumine, methacrylic acid copolymer, poloxamer, povidone, and triethyl citrate. The capsule shells are composed of D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, yellow iron oxide, gelatin, silicon dioxide, sodium lauryl sulfate, and titanium dioxide. The imprinting ink includes D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, n-butyl alcohol, pharmaceutical glaze, propylene glycol, SDA-3A alcohol, and synthetic black iron oxide.

Uses and Indications

This drug 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 pediatric patients and adults. Additionally, this drug is indicated for the maintenance of healing of erosive esophagitis in pediatric patients and adults, as well as for the treatment of pathological hypersecretory conditions in adults.

Limitations of Use: The safety and effectiveness of this drug in pediatric patients under 1 year of age have not been established.

Dosage and Administration

For the short-term 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:

• Omeprazole: 20 mg, administered twice daily for 10 days.

• Amoxicillin: 1000 mg, administered twice daily for 10 days.

• Clarithromycin: 500 mg, administered twice daily for 10 days.

Dual Therapy:

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

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

In the treatment of gastric ulcers, the recommended dosage is 40 mg once daily for a period of 4 to 8 weeks. For gastroesophageal reflux disease (GERD), the dosage is 20 mg once daily 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 is 60 mg once daily, although this may vary based on individual patient needs.

In 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 less than 20 kg, a dosage of 10 mg once daily is indicated.

• For those weighing more than 20 kg, a dosage of 20 mg once daily is recommended.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to any component of the formulation. This is due to the potential for severe allergic reactions, which may pose significant health risks.

Warnings and Precautions

Symptomatic response to therapy with omeprazole does not exclude the possibility of concomitant gastric malignancy. Healthcare professionals should remain vigilant and consider further diagnostic evaluation in patients presenting with symptoms suggestive of gastric cancer, even if they exhibit improvement with omeprazole treatment.

Long-term use of omeprazole has been associated with the development of atrophic gastritis, as evidenced by gastric corpus biopsies from patients undergoing extended therapy. Clinicians should monitor patients receiving prolonged treatment for any signs or symptoms indicative of gastric mucosal changes.

When prescribing omeprazole in combination with clarithromycin and/or amoxicillin, it is essential to consult the full prescribing information for each medication. This ensures that potential drug interactions and contraindications are adequately addressed, optimizing patient safety and therapeutic efficacy.

Side Effects

Patients may experience a range of adverse reactions while using the medication. Common adverse reactions 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 reported as the most frequently occurring reactions in clinical studies involving this population.

Additional adverse reactions of note include known hypersensitivity to any component of the formulation. In cases of overdosage, reports have indicated a variety of manifestations, including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were generally transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

Omeprazole may interact with various medications, influencing their pharmacokinetics and pharmacodynamics.

Drugs Affected by Gastric pH:Omeprazole can interfere with the absorption of drugs whose bioavailability is dependent on gastric pH, such as ketoconazole, ampicillin esters, and iron salts. This is due to its inhibition of gastric acid secretion, which may necessitate monitoring for therapeutic effectiveness and potential dose adjustments of these medications.

Cytochrome P450 Metabolized Drugs:Omeprazole has the potential to prolong the elimination of drugs metabolized by the cytochrome P450 system, including diazepam, warfarin, phenytoin, cyclosporine, disulfiram, and other benzodiazepines. It is advisable to monitor these patients closely to determine if dose adjustments are required, particularly for warfarin, as concomitant use may lead to increased INR and prothrombin time.

Specific Drug Interactions:

• Voriconazole: May increase plasma levels of omeprazole, which could enhance its effects and side effects.

• Atazanavir and Nelfinavir: Omeprazole may reduce the plasma levels of these antiretroviral agents, potentially diminishing their therapeutic efficacy.

• Tacrolimus: Omeprazole may increase serum levels of tacrolimus, necessitating careful monitoring of tacrolimus levels to avoid toxicity.

• Saquinavir: Similar to tacrolimus, omeprazole may increase plasma levels of saquinavir, warranting monitoring for adverse effects.

Healthcare professionals should consider these interactions when prescribing omeprazole and adjust dosages or monitor patients accordingly to ensure safe and effective therapy.

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 use of omeprazole in pediatric patients aged 2 to 16 years for the treatment of gastroesophageal reflux disease (GERD) is supported by extrapolation from adequate and well-controlled studies conducted in adults, along with safety and pharmacokinetic studies performed specifically in pediatric and adolescent populations. However, 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 2000 elderly individuals (≥ 65 years of age) in clinical trials conducted in the U.S. and Europe. The results indicated 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 ruled out.

Pharmacokinetic studies reveal that the elimination rate of omeprazole is somewhat decreased in elderly patients, with an increased bioavailability observed. Specifically, the plasma clearance of omeprazole in this population is approximately 250 mL/min, which is about half that of younger volunteers. Additionally, the plasma half-life of omeprazole in elderly patients averages one hour, which is approximately twice that observed in young healthy volunteers. Despite these pharmacokinetic changes, no dosage adjustment is necessary for elderly patients when prescribing omeprazole.

Healthcare providers should remain vigilant in monitoring elderly patients for any potential increased sensitivity to the medication, even though clinical data do not indicate a need for dosage modifications.

Pregnancy

Pregnancy Category C. Reproductive studies in rats and rabbits, as well as multiple cohort studies involving pregnant women, have not demonstrated an increased risk of congenital anomalies or adverse pregnancy outcomes associated with omeprazole use during the first trimester. 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 0.50–1.34), low birth weight, or low Apgar scores. While the overall malformation rate was reported at 4.4% (95% CI 3.6–5.3), the rate for first trimester exposure was 3.6% (95% CI 1.5–8.1). The relative risk of malformations associated with first trimester exposure compared to non-exposed women was 0.9 (95% CI 0.3–2.2). 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 rats at doses up to 56 times the human dose and in rabbits at doses up to 56 times the human dose did not show evidence of teratogenicity. In pregnant rabbits, doses between 5.5 to 56 times the human dose resulted in dose-related increases in embryo lethality, fetal resorptions, and pregnancy loss. Additionally, in rats treated with omeprazole at similar high doses, there were instances of dose-related embryo/fetal toxicity and postnatal developmental toxicity in offspring.

Lactation

Omeprazole concentrations have been measured in the breast milk of a lactating mother 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 breastfed infants, as well as the potential for tumorigenicity demonstrated in rat carcinogenicity studies, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue the drug, taking 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.

Hepatic Impairment

There is no information available regarding the use of this medication in patients with hepatic impairment. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions specified for individuals with compromised liver function. Healthcare professionals should exercise caution and consider the overall clinical context when prescribing this medication to patients with liver problems, as the absence of specific guidance necessitates careful evaluation of potential risks and benefits.

Overdosage

Reports have indicated instances of overdosage with omeprazole in humans, with doses reaching up to 2400 mg, which is approximately 120 times the usual recommended clinical dose. The manifestations of overdosage have been variable, including symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms are consistent with adverse reactions observed in normal clinical use. Importantly, the symptoms reported were transient, and no serious clinical outcomes have been documented when omeprazole was taken in isolation.

Currently, there is no specific antidote available for omeprazole overdosage. Given that omeprazole is extensively protein-bound, it is not readily dialyzable. Therefore, 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 when managing any overdose situation. For the most current information regarding the treatment of drug overdoses, it is advisable to contact the local Poison Control Center.

In animal studies, single oral doses of omeprazole at 1350 mg/kg in mice, 1339 mg/kg in rats, and 1200 mg/kg in dogs have been found to be lethal. Observed effects in these animals included sedation, ptosis, tremors, convulsions, decreased activity, reduced body temperature, and alterations in respiratory rate and depth.

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).

Omeprazole at oral doses up to 138 mg/kg/day in rats (approximately 56 times the human dose on a body surface area basis) was found to have no effect on fertility and reproductive performance.

In two 24-month carcinogenicity studies in rats, omeprazole administered at daily doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day (about 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 (approximately 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%), with no similar tumors noted in male or female rats treated for two years. Historically, no similar tumors have been reported in this strain of rat, although the interpretation of a single tumor finding is 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), while no astrocytomas were observed in female rats. In a 2-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 57 times the human dose on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not demonstrate increased tumor occurrence, although the study was inconclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was also not positive.

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 reactions reported voluntarily or through surveillance programs. These include Clostridium difficile-associated diarrhea, acute interstitial nephritis, hypomagnesemia, bone fractures, cutaneous and systemic lupus erythematosus, acute liver injury, anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and other hypersensitivity reactions.

Additionally, gastrointestinal infections, respiratory infections, cardiovascular events, and renal events have also been reported in the postmarketing experience. The frequency of these adverse reactions is not known.

Patient Counseling

Healthcare providers should advise patients that omeprazole delayed-release capsules are to be taken before meals to ensure optimal effectiveness. It is important to inform patients that these capsules must be swallowed whole and should not be chewed or crushed, as this may affect the medication's action.

For patients who experience difficulty swallowing capsules, healthcare providers can recommend an alternative method. Patients may open the capsule and mix the contents with one tablespoon of applesauce. Providers should instruct patients to place the applesauce in an empty bowl, carefully open the capsule, and empty all the pellets onto the applesauce. The mixture should be thoroughly combined and swallowed immediately with a glass of cool water to ensure complete ingestion of the pellets.

Healthcare providers should emphasize that the applesauce used should not be hot and must be soft enough to swallow without chewing. Additionally, it is crucial to inform patients that the pellets/applesauce mixture should not be stored for future use, as this may compromise the medication's effectiveness.

Storage and Handling

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

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)