Omeprazole: Package Insert and Label Information
OMEPRAZOLE- omeprazole capsule, delayed release
Lake Erie Medical DBA Quality Care Products LLC
1 INDICATIONS AND USAGE
1.1 Duodenal Ulcer (adults)
Omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.
Omeprazole delayed-release capsules, in combination with clarithromycin and amoxicillin, are indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults.
Omeprazole delayed-release capsules, in combination with clarithromycin are indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults.
Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.1) and Dosage and Administration (2)].
Among patients who fail therapy, Omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [See Microbiology section (12.4)], and the clarithromycin package insert, Microbiology section.)
1.2 Gastric Ulcer (adults)
Omeprazole delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults for upto 4 weeks [See Clinical Studies (14.2)].
1.3 Treatment of Gastroesophageal Reflux Disease (GERD) (adults and pediatric patients)
Omeprazole delayed-release capsules are indicated for the treatment of heartburn and other symptoms associated with GERD in pediatric patients and adults.
Omeprazole delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) of erosive esophagitis that has been diagnosed by endoscopy in pediatric patients and adults [See Clinical Studies (14.4)].
The efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of erosive esophagitis or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole may be considered.
1.4 Maintenance of Healing of Erosive Esophagitis (adults and pediatric patients)
Omeprazole delayed-release capsules are indicated to maintain healing of erosive esophagitis in pediatric patients and adults.
Controlled studies do not extend beyond 12 months [See Clinical Studies (14.4)].
1.5 Pathological Hypersecretory Conditions (adults)
Omeprazole delayed-release capsules are indicated for the long-term treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.
2 DOSAGE AND ADMINISTRATION
Omeprazole delayed-release capsules should be taken before eating. In the clinical trials, antacids were used concomitantly with omeprazole.
Patients should be informed that the omeprazole delayed-release capsule should be swallowed whole.
For patients unable to swallow an intact capsule, alternative administration options are available [See Dosage and Administration (2.8)].
2.1 Short-Term Treatment of Active Duodenal Ulcer
The recommended adult oral dose of omeprazole delayed-release capsules is 20 mg once daily. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.
2.2 H. pylori Eradication for the Reduction of the Risk of Duodenal Ulcer Recurrence
Triple Therapy (omeprazole/clarithromycin/amoxicillin) — The recommended adult oral regimen is omeprazole delayed-release capsules 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg each given twice daily for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief.
Dual Therapy (omeprazole/clarithromycin) — The recommended adult oral regimen is omeprazole delayed-release capsuels 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days. In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of omeprazole delayed-release capsules 20 mg once daily is recommended for ulcer healing and symptom relief.
2.3 Gastric Ulcer
The recommended adult oral dose is 40 mg once daily for 4 to 8 weeks.
2.4 Gastroesophageal Reflux Disease (GERD)
The recommended adult oral dose for the treatment of patients with symptomatic GERD and no esophageal lesions is 20 mg daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis and accompanying symptoms due to GERD is 20 mg daily for 4 to 8 weeks.
2.5 Maintenance of Healing of Erosive Esophagitis
The recommended adult oral dose is 20 mg daily. Controlled studies do not extend beyond 12 months [See Clinical Studies (14.4)].
2.6 Pathological Hypersecretory Conditions
The dosage of omeprazole delayed-release capsules in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 120 mg three times daily have been administered. Daily dosages of greater than 80 mg should be administered in divided doses. Some patients with Zollinger-Ellison syndrome have been treated continuously with omeprazole delayed-release capsules for more than 5 years.
2.7 Pediatric Patients
For the treatment of GERD and maintenance of healing of erosive esophagitis, the recommended daily dose for pediatric patients 2 to 16 years of age is as follows:
|Patient Weight||Omeprazole Daily Dose|
|10 < 20 kg||10 mg|
|≥ 20 kg||20 mg|
On a per kg basis, the doses of omeprazole required to heal erosive esophagitis in pediatric patients are greater than those for adults.
Alternative administrative options can be used for pediatric patients unable to swallow an intact capsule [See Dosage and Administration (2.8)].
2.8 Alternative Administration Options
Omeprazole is available as a delayed-release capsule.
For patients who have difficulty swallowing capsules, the contents of an omeprazole delayed-release capsule can be added to applesauce. One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.
3 DOSAGE FORMS AND STRENGTHS
Omeprazole delayed-release capsules USP, 10 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size ‘4’ hard gelatin capsule shells with opaque purple colored cap and opaque yellow colored body imprinted, ‘OMERPAZOLE’
on cap and ‘R643’ on body with black ink.
Omeprazole delayed-release capsules USP, 20 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size ‘2’ hard gelatin capsule shells with opaque purple colored cap and opaque grey colored body,imprinted ‘OMEPRAZOLE’
on cap and ‘R644’ on body with black
ink. Omeprazole delayed-release capsules USP, 40 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size ‘1’ hard gelatin capsule shells with opaque yellow colored cap and opaque purple colored body, imprinted ‘OMEPRAZOLE’
on cap and ‘R645’ on body with black ink.
Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6) ].
For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with omeprazole, refer to the CONTRAINDICATIONS section of their package inserts.
5 WARNINGS AND PRECAUTIONS
5.1 Concomitant Gastric Malignancy
Symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.
5.2 Atrophic Gastritis
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.
5.3 Acute Interstitial Nephritis
Acute interstitial nephritis has been observed in patients taking PPIs including omeprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue omeperazole if acute interstitial nephritis develops [see Contraindications (4)].
5.4 Cyanocobalamin (vitamin B-12) Deficiency
Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo-or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acidsuppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.
5.5 Clostridium difficile associated diarrhea
Published observational studies suggest that PPI therapy like omeprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2) ].
Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with omeprazole, refer to WARNINGS and PRECAUTIONS sections of those package inserts.
5.6 Interaction with Clopidogrel
Avoid concomitant use of omeprazole with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using omeprazole, consider alternative anti-platelet therapy [see Drug Interactions (7.3) and Pharmacokinetics (12.3)].
5.7 Bone Fracture
Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) and Adverse Reactions (6.3)].
Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [See Adverse Reactions (6.3)].
5.9 Comcomitant Use of Omeprazole with St. John’s Wort or rifampin
Drugs which induce CYP2C19 or CYP3A4 (such as St John’s Wort or rifampin) can substantially decrease omeprazole concentrations [See Drug Interactions (7.3)]. Avoid concomitant use of omeprazole with St John’s Wort or rifampin.
5.10 Interactions with Diagnostic Investigations for Neuroendocrine Tumors
Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors.Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.
5.11 Concomitant use of NEXIUM with Methotrexate
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7.6)].
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience with Omeprazole Monotherapy
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described below reflects exposure to omeprazole delayed-release capsules in 3096 patients from worldwide clinical trials (465 patients from US studies and 2,631 patients from international studies). Indications clinically studied in US trials included duodenal ulcer, resistant ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from omeprazole-treated patients enrolled in these studies included headache (6.9%), abdominal pain (5.2%), nausea (4%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%).
Additional adverse reactions that were reported with an incidence ≥1% included acid regurgitation (1.9%), upper respiratory infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), asthenia (1.3%), back pain (1.1%), and cough (1.1%).
The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less.
The clinical trial safety profile in pediatric patients who received omeprazole delayed-release capsules was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of the respiratory system were most frequently reported in the 2 to 16 year age group (18.5%). Similarly, accidental injuries were reported frequently in the 2 to 16 year age group (3.8%) [See Use in Specific Populations (8.4)].
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