Omeprazole

Description

Omeprazole delayed-release capsules, USP contain the active ingredient omeprazole, a substituted benzimidazole with the chemical structure 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl)methylsulfinyl]-1H-benzimidazole, which functions as a gastric acid secretion inhibitor. The molecular formula of omeprazole is C17H19N3O3S, and it has a molecular weight of 345.42.

Omeprazole appears as a white to off-white powder that decomposes between 150°C and 160°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, with rapid degradation occurring in acidic environments, while it maintains acceptable stability under alkaline conditions.

The drug is formulated as delayed-release capsules for oral administration, with each capsule containing either 10 mg, 20 mg, or 40 mg of omeprazole in the form of enteric-coated granules. Inactive ingredients in the capsules include disodium hydrogen phosphate dihydrate, hydroxypropyl cellulose, hypromellose, lactose monohydrate, mannitol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, mono and di-glycerides, polysorbate, sodium lauryl sulfate, talc, titanium dioxide, and triethyl citrate. The empty hard gelatin capsule shells are composed of gelatin and iron oxide red, and the capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution. Omeprazole meets the USP Dissolution Test 2.

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

No teratogenic or nonteratogenic effects have been reported with the use of this drug.

Dosage and Administration

For the treatment of active duodenal ulcer, the recommended dosage of omeprazole delayed-release capsules 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 Helicobacter pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

Triple Therapy:

• Omeprazole delayed-release capsules: 20 mg

• Amoxicillin: 1000 mg

• Clarithromycin: 500 mg Each medication should be taken orally twice daily for 10 days.

Dual Therapy:

• Omeprazole delayed-release capsules: 40 mg administered orally once daily for 14 days.

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

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

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

In patients with pathological hypersecretory conditions, the starting dose of omeprazole is 60 mg administered orally once daily; this may vary based on individual patient needs.

All medications should be taken orally, and healthcare professionals should ensure that patients are informed about the proper administration techniques.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. Additionally, it should not be administered to patients receiving rilpivirine-containing products due to potential drug interactions. When used in combination with clarithromycin and amoxicillin, refer to the Contraindications section of their respective prescribing information for further guidance.

Warnings and Precautions

In adults, 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 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 be vigilant for signs of this infection in patients undergoing PPI treatment.

Long-term use of PPIs, particularly at multiple daily doses, may increase the risk of osteoporosis-related fractures, specifically of the hip, wrist, or spine. It is advisable to assess the patient's bone health and consider alternative therapies when appropriate.

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, and referral to a specialist for evaluation should be considered.

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 PPIs, particularly beyond three years, may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring of vitamin B-12 levels is recommended for patients on extended therapy.

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

In patients undergoing diagnostic investigations for neuroendocrine tumors, it is important to note that increased levels of Chromogranin A (CgA) may interfere with test results. To ensure accurate assessment, omeprazole should be temporarily discontinued at least 14 days prior to measuring CgA levels.

When used alongside methotrexate, PPIs 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.

Finally, the risk of fundic gland polyps increases with long-term PPI use, 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 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 gastric cancer, 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 elevate the risk of osteoporosis-related fractures of the hip, wrist, or spine.

Severe cutaneous adverse reactions have been reported; treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been noted, necessitating discontinuation of omeprazole and referral to a specialist for evaluation. Long-term daily use (exceeding 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. Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. 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, particularly beyond one year.

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. Symptoms were generally transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

Clinically significant drug interactions may occur with the use of this medication. It is essential to consult the full prescribing information for a comprehensive list of these interactions.

Pharmacodynamic interactions may lead to enhanced effects or increased toxicity when this medication is used concurrently with other agents. Careful monitoring of the patient's clinical status is advised to mitigate potential adverse effects.

Pharmacokinetic interactions may alter the absorption, distribution, metabolism, or excretion of this medication or the concomitant drugs. Dosage adjustments may be necessary based on the specific interaction and the clinical scenario.

Healthcare professionals should remain vigilant and consider both the pharmacodynamic and pharmacokinetic profiles of all medications prescribed to ensure patient safety and therapeutic efficacy.

Packaging & NDC

The table below lists all NDC Code configurations of Omeprazole, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of omeprazole have been established in pediatric patients aged 2 to 16 years for the treatment of symptomatic gastroesophageal reflux disease (GERD), the treatment of erosive esophagitis (EE) due to acid-mediated GERD, and the maintenance of healing of EE due to acid-mediated GERD. The use of omeprazole in this age group is supported by adequate and well-controlled studies in adults, as well as uncontrolled safety, efficacy, and pharmacokinetic studies conducted in pediatric and adolescent patients.

In the pediatric population, adverse reactions affecting the respiratory system were frequently reported among patients aged 2 to 16 years. Additionally, accidental injuries were commonly noted in this age group.

The safety and effectiveness of omeprazole have not been established in patients younger than 1 year of age for the treatment of symptomatic GERD or the maintenance of healing of EE due to acid-mediated GERD. Furthermore, omeprazole is not indicated for the treatment of active duodenal ulcers, H. pylori eradication to reduce the risk of duodenal ulcer recurrence, 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 that there are 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 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 differences, no dosage adjustment is necessary for elderly patients when prescribing omeprazole. However, healthcare providers should remain vigilant and monitor for any potential increased sensitivity in this population.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant 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, 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 reported no apparent adverse short-term effects on infants when single doses of oral or intravenous omeprazole were administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. A population-based retrospective cohort study from the Swedish Medical Birth Registry indicated that the incidence of malformations, low birth weight, low Apgar scores, or hospitalization in infants exposed in utero to omeprazole was similar to that observed in the general population.

However, a slight increase in the number of infants born with ventricular septal defects and stillbirths was noted among omeprazole-exposed infants compared to expected rates. A retrospective cohort study covering all live births in Denmark reported an overall birth defect rate 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. Additionally, a retrospective cohort study indicated a malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole, compared to 5.5% for H2-blockers and 4.1% for unexposed mothers.

A small prospective observational cohort study involving 113 women exposed to omeprazole during pregnancy reported a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens and 2.8% in disease-paired controls. No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis. However, a pre- and postnatal developmental toxicity study in rats with esomeprazole magnesium showed decreased neonatal survival at doses equal to or greater than 138 mg/kg/day (about 34 times the oral human dose of 40 mg). Physeal dysplasia in the femur was also observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day.

Lactation

Effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses ranging from 14 to 280 mg/kg/day, which is approximately 3.4 to 68 times the oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis.

When rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (compared to placebo treatment) was noted at doses equal to or greater than 138 mg/kg/day, approximately 34 times the oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis.

The effects of esomeprazole on breastfed infants have not been established, and caution is advised when administering this medication to lactating mothers.

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 indicated 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 experience.

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. Currently, there is 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 are advised to contact the Poison Control Center at 1-800-222-1222 for the most current information regarding the management of poisoning or overdosage.

Nonclinical Toxicology

In nonclinical studies, omeprazole demonstrated no teratogenic effects. At oral doses up to 138 mg/kg/day in rats, approximately 34 times the human dose of 40 mg on a body surface area basis, omeprazole did not affect fertility or reproductive performance.

Carcinogenicity studies conducted over 24 months in rats revealed a dose-related increase in gastric ECL cell carcinoids at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day, which corresponds to about 0.4 to 34 times the human dose of 40 mg/day on a body surface area basis. The incidence of carcinoids was significantly higher in female rats, which exhibited elevated blood levels of omeprazole. Gastric carcinoids are rarely observed in untreated rats. ECL cell hyperplasia was noted in all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day for one year and subsequently observed for an additional year without treatment did not develop carcinoids. However, a 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 identified in one rat (2%), but no similar tumors were observed in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, making the interpretation of this solitary finding challenging.

In a 52-week toxicity study involving Sprague-Dawley rats, brain astrocytomas were detected in a small number of males receiving omeprazole at doses of 0.4, 2, and 16 mg/kg/day, approximately 0.1 to 3.9 times the human dose of 40 mg/day based on body surface area. No astrocytomas were found in female rats in this study. In a separate two-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were observed in either sex at the high dose of 140.8 mg/kg/day, about 34 times the human dose of 40 mg/day on a body surface area basis. A 78-week carcinogenicity study in mice did not indicate an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Animal pharmacology and toxicology assessments indicated that omeprazole was 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. The significant increase in gastric carcinoid tumors and ECL cell hyperplasia observed in the 24-month carcinogenicity studies in rats was consistent across both male and female subjects. Carcinoid tumors have also been reported in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Postmarketing Experience

No specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Medication Guide and Instructions for Use. This information is essential for understanding the proper use of the medication, potential side effects, and any necessary precautions. Emphasizing the importance of this material can help ensure that patients are well-informed and can engage in their treatment plan effectively.

Storage and Handling

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

Additional Clinical Information

Serum chromogranin A (CgA) levels may increase due to drug-induced decreases in gastric acidity when patients are treated with omeprazole. This elevation can lead to false positive results in diagnostic tests for neuroendocrine tumors. Clinicians are advised to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider repeating the test if initial results are elevated. For serial 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 of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) while on omeprazole, the medication should be discontinued, and a specialist referral is recommended. Most patients will see improvement within 4 to 12 weeks after stopping the PPI. Additionally, for those on long-term treatment or taking medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels before and during PPI therapy may be warranted.

FDA Insert (PDF)

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

View full prescribing information (PDF)