Omeprazole

Description

The active ingredient in omeprazole delayed-release capsules, USP is a substituted benzimidazole, specifically 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl sulfinyl]-1H-benzimidazole. Its empirical formula is C17H19N3O3S, and it has a molecular weight of 345.42. Omeprazole USP appears as a white to off-white powder and melts between 150°C and 160°C with decomposition. It is soluble in dichloromethane, sparingly soluble in methanol and alcohol, and very slightly soluble in water. Omeprazole USP is supplied as delayed-release capsules for oral administration, with each capsule containing either 10 mg, 20 mg, or 40 mg of omeprazole in the form of enteric-coated granules. The inactive ingredients in the enteric-coated granules include glyceryl monostearate, hypromellose (5cps), meglumine, methacrylic acid copolymer, poloxamer, sugar globules, talc, titanium dioxide, and triethyl citrate. The capsule shells contain inactive ingredients such as black iron oxide, D & C Red 28, FD & C Blue 1, FD & C Red 40, gelatin, potassium hydroxide, propylene glycol, shellac, titanium dioxide, and yellow iron oxide.

Uses and Indications

This drug is indicated for the treatment of active duodenal ulcers in adults. It is also indicated for the eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults. Additionally, this drug is used for the treatment of active benign gastric ulcers in adults.

In pediatric patients aged 2 years and older, this drug is indicated for the treatment of symptomatic gastroesophageal reflux disease (GERD) and for the maintenance of healing of erosive esophagitis (EE) due to acid-mediated GERD. Furthermore, it is indicated for the treatment of pathologic hypersecretory conditions in adults.

There are no specific teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

For the treatment of active duodenal ulcer, the recommended dosage is 20 mg administered orally once daily for a duration of 4 weeks. In some cases, an additional 4 weeks may be necessary based on the patient's response.

For the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence, two therapeutic regimens are available:

Triple Therapy: This regimen consists of omeprazole delayed-release capsules 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, with each medication taken orally twice daily for 10 days.

Dual Therapy: This regimen includes omeprazole delayed-release capsules 40 mg administered orally once daily for 14 days, alongside clarithromycin 500 mg taken orally three times daily for the same duration.

In the case of active benign gastric ulcer, the recommended dosage is 40 mg orally once daily for a period of 4 to 8 weeks. For symptomatic gastroesophageal reflux disease (GERD), a dosage of 20 mg orally once daily for up to 4 weeks is advised. For eosinophilic esophagitis (EE) due to acid-mediated GERD, the dosage is also 20 mg orally once daily for 4 to 8 weeks. To maintain healing of EE due to acid-mediated GERD, a continuous dosage of 20 mg orally once daily is recommended.

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

All medications should be taken orally as prescribed.

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 rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider additional follow-up and diagnostic testing to ensure comprehensive patient evaluation.

Acute tubulointerstitial nephritis has been reported in some patients. If this condition is suspected, treatment should be discontinued immediately, and patients should be evaluated accordingly.

There is an association between proton pump inhibitor (PPI) therapy and an increased risk of Clostridium difficile-associated diarrhea. Clinicians should remain vigilant for this potential complication, particularly in patients with risk factors.

Long-term use of PPIs, especially at multiple daily doses, may increase the risk of osteoporosis-related fractures, particularly 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 have been observed. Treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity, and further evaluation should be considered.

Patients may experience new onset or exacerbation of cutaneous and systemic lupus erythematosus. In such cases, omeprazole should be discontinued, and referral to a specialist for evaluation is recommended.

Concomitant use of omeprazole with clopidogrel is contraindicated due to potential interactions that may diminish the effectiveness of clopidogrel. Additionally, the use of omeprazole alongside St. John’s Wort or rifampin should be avoided.

Long-term daily use of omeprazole (exceeding three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Monitoring for signs of deficiency is recommended in patients on prolonged therapy.

Hypomagnesemia and disturbances in mineral metabolism have been reported rarely with prolonged PPI treatment. Clinicians should monitor magnesium levels in patients receiving long-term therapy.

Increased levels of Chromogranin A (CgA) may interfere with diagnostic investigations for neuroendocrine tumors. It is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels to avoid false elevations.

Concomitant use of omeprazole with methotrexate may elevate and prolong serum concentrations of methotrexate and its metabolites, potentially leading to toxicity. In cases of high-dose methotrexate administration, a temporary withdrawal of omeprazole should be considered.

The risk of fundic gland polyps increases with long-term use of PPIs, particularly beyond one year. Therefore, it is advisable to use the shortest duration of therapy necessary to achieve treatment goals.

Side Effects

Most common adverse reactions reported in adults, with an incidence of 2% or greater, include headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. In pediatric patients aged 2 to 16 years, the safety profile is similar to that of adults; however, respiratory system events and fever were the most frequently reported reactions in pediatric studies.

Serious adverse reactions warranting caution include gastric malignancy, where a symptomatic response does not exclude the possibility of underlying gastric malignancy, necessitating further follow-up and diagnostic testing. Acute tubulointerstitial nephritis has been observed, and treatment should be discontinued and patients evaluated if this occurs. There is an increased risk of Clostridium difficile-associated diarrhea associated with PPI therapy. Long-term and multiple daily doses of PPIs may also be linked to an increased risk of osteoporosis-related fractures of the hip, wrist, or spine.

Severe cutaneous adverse reactions have been reported; treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity, with further evaluation considered. Additionally, new onset or exacerbation of cutaneous and systemic lupus erythematosus has been noted, necessitating discontinuation of omeprazole and referral to a specialist for evaluation. Long-term daily use of omeprazole (beyond three years) may lead to malabsorption or deficiency of cyanocobalamin (Vitamin B-12). Rarely, hypomagnesemia and disturbances in mineral metabolism have been reported with prolonged PPI treatment.

Interactions with other medications are significant; concomitant use of omeprazole with clopidogrel, St. John’s Wort, or rifampin should be avoided. Additionally, omeprazole may interfere with diagnostic investigations for neuroendocrine tumors by increasing Chromogranin A (CgA) levels, and it is recommended to temporarily discontinue omeprazole at least 14 days prior to assessing CgA levels. Caution is advised when using omeprazole with methotrexate, as it may elevate and prolong serum concentrations of methotrexate and its metabolite, potentially leading to toxicity. Long-term use of omeprazole may also increase the risk of fundic gland polyps, particularly beyond one year, thus the shortest duration of therapy is recommended.

Reports of overdosage with omeprazole have been received, with manifestations varying but including confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth. These symptoms were transient, and no serious clinical outcomes have been reported when omeprazole was taken alone.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary at this time.

Packaging & NDC

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

Pediatric Use

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

In the pediatric population, adverse reactions affecting the respiratory system were frequently reported 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, treatment of active benign gastric ulcers, or pathological hypersecretory conditions in pediatric patients.

Geriatric Use

Omeprazole has been administered to over 2,000 elderly individuals (≥ 65 years of age) in clinical trials conducted in the U.S. and Europe, 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 ruled out.

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 observed in young healthy volunteers.

Despite these pharmacokinetic changes, no dosage adjustment is necessary for elderly patients. However, healthcare providers should remain vigilant and monitor for any potential increased sensitivity or adverse effects in this population.

Pregnancy

There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. 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 oral esomeprazole magnesium administered during organogenesis at doses about 68 times and 42 times, respectively, the oral human dose of 40 mg. Changes in bone morphology were noted in offspring of rats dosed 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.

Epidemiological studies have compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with those of women exposed to H2-receptor antagonists or other controls. A population-based retrospective cohort study from the Swedish Medical Birth Registry reported on 955 infants whose mothers used omeprazole during pregnancy, finding that the number of infants exposed in utero to omeprazole with any malformation, low birth weight, low Apgar score, or hospitalization was similar to that observed in the general population.

In a separate cohort study covering all live births in Denmark, 1,800 live births were reported, with an overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole at 2.9%, compared to 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. Another retrospective cohort study indicated a malformation rate of 3.6% in offspring born to mothers with first trimester exposure to omeprazole. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy, reporting a rate of major congenital malformations of 4% in the omeprazole group, compared to 2% in controls exposed to non-teratogens and 2.8% in disease-paired controls.

Several studies have reported no apparent adverse short-term effects on the infant when single-dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Overall, omeprazole reproductive studies conducted in rats and rabbits during organogenesis did not disclose any evidence of teratogenic potential, although in rabbits, omeprazole produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at doses administered prior to mating through the lactation period. No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats or rabbits administered during organogenesis.

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 these patients to ensure safety and efficacy.

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

In cases of omeprazole overdosage, reports have indicated that doses as high as 2400 mg, which is approximately 120 times the usual recommended clinical dose, have been documented in humans. The manifestations associated with omeprazole overdosage may include a range of symptoms such as confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.

It is important to note that the symptoms of omeprazole overdosage are typically transient, and no serious clinical outcomes have been reported when omeprazole is taken in isolation. There is currently no specific antidote available for omeprazole overdosage; therefore, management should focus on symptomatic and supportive care.

Due to the extensive protein binding of omeprazole, it is not readily dialyzable, which limits the effectiveness of dialysis as a treatment option. In the event of an overdosage, healthcare professionals are advised to contact the Poison Control Center at 1-800-222-1222 for further management information and guidance.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. Omeprazole administered 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, did not affect fertility or reproductive performance.

In two 24-month carcinogenicity studies involving rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day, corresponding to about 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. 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. ECL cell hyperplasia was noted in all treated groups of both sexes. In one study, female rats treated with 13.8 mg/kg/day of omeprazole for one year, followed by an additional year without treatment, did not develop carcinoids. However, a notable increase in 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 between treated and control rats diminished (46% versus 26%), yet hyperplasia remained more prevalent in the treated group. Gastric adenocarcinoma was observed in one rat (2%), but no similar tumors were detected in male or female rats over the two-year period. Historically, this strain of rat has not shown similar tumors, 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 0.1 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 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were detected 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 reveal an increased occurrence of tumors, although the results were inconclusive. Additionally, a 26-week p53 (+/-) transgenic mouse carcinogenicity study yielded negative results.

Omeprazole demonstrated positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, one of two in vivo mouse micronucleus tests, and an in vivo bone marrow cell chromosomal aberration assay. Conversely, it was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay. The 24-month carcinogenicity studies in rats indicated a significant dose-related increase in gastric carcinoid tumors and ECL cell hyperplasia in 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

Postmarketing experience with omeprazole delayed-release capsules has identified several serious side effects reported voluntarily or through surveillance programs.

Acute tubulointerstitial nephritis, a type of kidney problem, has been observed in some patients taking proton pump inhibitors (PPIs), including omeprazole. This condition can occur at any time during treatment, and patients are advised to seek medical attention if they experience a decrease in urine output or blood in their urine.

There is an increased risk of severe diarrhea associated with omeprazole, potentially due to Clostridium difficile infection in the intestines. Patients should contact their healthcare provider if they experience watery stools, stomach pain, or persistent fever.

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

Certain types of lupus erythematosus have been reported in individuals taking PPIs, including omeprazole. Patients experiencing new or worsening joint pain or a rash that worsens with sun exposure should consult their healthcare provider.

Additional serious side effects include vitamin B-12 deficiency, which may arise from reduced stomach acid necessary for vitamin absorption, particularly in patients on omeprazole for over three years. Low magnesium levels have also been reported, typically after at least three months of treatment, with symptoms that may include seizures, muscle spasms, and abnormal heart rhythms. Patients should inform their doctor if they experience any of these symptoms.

Fundic gland polyps, a type of stomach growth, have been associated with long-term PPI use, especially after more than one year of treatment.

Rare but severe skin reactions have been documented, which may require hospitalization and can be life-threatening. Symptoms may include blistering, peeling, or bleeding skin, along with fever and chills. Patients should discontinue use and seek immediate medical attention if these symptoms occur.

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

Patient Counseling

Patients should be advised 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. It is important for patients to report any signs or symptoms that may indicate hypersensitivity reactions, acute tubulointerstitial nephritis, Clostridium difficile associated diarrhea, bone fractures, cutaneous and systemic lupus erythematosus, cyanocobalamin (Vitamin B-12) deficiency, or hypomagnesemia and mineral metabolism issues to their healthcare provider.

Patients should also inform their healthcare provider if they initiate treatment with clopidogrel, St. John’s Wort, or rifampin, or if they are taking high-dose methotrexate, as these may interact with their treatment. Omeprazole delayed-release capsules should be taken before meals, and patients may use antacids concurrently with the medication.

In the event of a missed dose, patients should take the missed dose as soon as possible. However, if the next scheduled dose is approaching, they should skip the missed dose and resume their regular dosing schedule without taking two doses at once. Patients must swallow the capsules whole and should not chew them. For those who have difficulty swallowing intact capsules, omeprazole delayed-release capsules can be opened and mixed with applesauce, as detailed in the Medication Guide.

Patients are encouraged to take omeprazole delayed-release capsules exactly as prescribed, at the lowest effective dose, and for the shortest duration necessary. They should consult their doctor if they experience serious stomach problems while on this medication. Immediate medical attention should be sought if there is a decrease in urination or the presence of blood in urine, as well as if they experience watery stools, stomach pain, and persistent fever.

Patients should discuss their risk of bone fractures with their doctor if they are taking omeprazole delayed-release capsules. They should also report any new or worsening joint pain or rashes on their cheeks or arms that worsen with sun exposure. If patients have been on omeprazole delayed-release capsules for an extended period (more than three years), they should talk to their doctor about the potential for vitamin B-12 deficiency.

Symptoms of low magnesium, such as seizures, jitteriness, muscle spasms, dizziness, tremors, cramps, abnormal heart rhythms, muscle weakness, or voice box spasms, should be reported to a healthcare provider immediately. Healthcare providers may monitor magnesium levels before starting treatment or during prolonged use of omeprazole delayed-release capsules. Patients should discontinue the medication and contact their doctor immediately if they experience severe skin reactions or serious allergic reactions.

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 discontinue omeprazole at least 14 days prior to assessing CgA levels and to consider repeating the test if initial levels are elevated. For serial testing, it is important to use the same commercial laboratory, as reference ranges may differ.

Patients should be counseled to use the lowest effective dose of proton pump inhibitor (PPI) therapy for the shortest duration necessary. If symptoms indicative of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) arise, omeprazole should be discontinued, and the patient referred for specialist evaluation, as most patients show improvement within 4 to 12 weeks after stopping the medication. For those on prolonged PPI therapy or concomitant medications that may lead to hypomagnesemia, such as diuretics, monitoring of magnesium levels is recommended prior to and during treatment.

Postmarketing reports have indicated severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) associated with PPI use. Additionally, acute tubulointerstitial nephritis (TIN) can occur at any time during therapy. Clostridium difficile-associated diarrhea (CDAD) has been noted with nearly all antibacterial agents, and hypomagnesemia, both symptomatic and asymptomatic, has been reported in patients on PPIs for three months or longer, particularly after one year of treatment. Furthermore, there is an increased risk of fundic gland polyps associated with long-term PPI use, especially beyond one year.

FDA Insert (PDF)

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

View full prescribing information (PDF)