These highlights do not include all the information needed to use ZEGERID (omeprazole/sodium bicarbonate) Powder for Oral Suspension and Capsules safely and effectively. See full prescribing information for ZEGERID Powder for Oral Suspension and Capsules.
ZEGERID (omeprazole/sodium bicarbonate) Powder for Oral Suspension and Capsules
Initial U.S. Approval: 2004
RECENT MAJOR CHANGES
Warnings and Precautions 05/2011
Hypomagnesemia (5.5)
Warnings and Precautions 06/2011
Diminished anti-platelet activity of clopidogrel (5.6)
INDICATIONS AND USAGE
ZEGERID Powder for Oral Suspension and Capsules is a proton pump inhibitor indicated for:
Short-term treatment of active duodenal ulcer (1.1)
Short-term treatment of active benign gastric ulcer (1.2)
Treatment of gastroesophageal reflux disease (GERD) (1.3)
Maintenance of healing of erosive esophagitis (1.4)
Reduction of risk of upperGI bleeding in critically ill patients (1.5)
The safety and effectiveness of ZEGERID Powder for Oral Suspension and Capsules in pediatric patients (<18 years of age) have not been established. (8.4)
DOSAGE AND ADMINISTRATION
Short-Term Treatment of Active Duodenal Ulcer: 20 mg once daily for 4 weeks (some patients may require an additional 4 weeks of therapy (14.1)) (2)
Gastric Ulcer: 40 mg once daily for 4-8 weeks (2)
Gastroesophageal Reflux Disease (GERD) (2)
-
Symptomatic GERD (with no esophageal erosions): 20mg once daily for up to 4 weeks
-
Erosive Esophagitis: 20 mg once daily for 4-8 weeks
Maintenance of Healing of Erosive Esophagitis: 20 mg once daily (2)
Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients: (40mg oral suspension only) 40 mg initially followed by 40 mg 6-8 hours later and 40 mg daily thereafter for 14 days (2)
DOSAGE FORMS AND STRENGTHS
ZEGERID (omeprazole/sodium bicarbonate) is available as a capsule and as a powder for oral suspension in 20 mg and 40 mg strengths (3)
CONTRAINDICATIONS
Known hypersensitivity to any components of the formulation (4)
WARNINGS AND PRECAUTIONS
Concomitant Gastric Malignancy: Symptomatic response to therapy with ZEGERID Powder for Oral Suspension and Capsules does not preclude the presence of gastric malignancy (5.1)
Atrophic Gastritis: Has been observed in gastric corpus biopsies from patients treated long-term with omeprazole (5.2)
Buffer Content: Sodium content to be taken into consideration when administering to patients on a sodium-restricted diet. To be used with caution in patients with Bartter's syndrome, hypokalemia, respiratory alkalosis, and problems with acid-base balance because of its sodium bicarbonate content; long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome (5.3)
Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. (5.4)
Hypomagnesemia has been reported rarely with prolonged treatment with PPIs (5.5)
Diminished anti-platelet activity of clopidogrel due to impaired CYP2C19 function by 80 mg omeprazole (5.6)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 2%) are:
Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence (6)
To report SUSPECTED ADVERSE REACTIONS, contact Santarus Inc. at 1-888-778-0887 or http://www.santarus.com/contact/, or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.
DRUG INTERACTIONS
Drugs metabolized by cytochrome P450 (e.g., diazepam, warfarin, phenytoin, cyclosporine, disulfiram, benzodiazepines): ZEGERID can prolong their elimination. Monitor to determine the need for possible dose adjustments when taken with ZEGERID (7)
Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time (7)
Drugs for which gastric pH can affect bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, and digoxin): ZEGERID may interfere with absorption due to inhibition of gastric acid secretion (7)
Voriconazole: May increase plasma levels of omeprazole (7)
ZEGERID may reduce plasma levels of atazanavir and nelfinavir (7)
ZEGERID may increase serum levels of tacrolimus, voriconazole, saquinavir, and clarithromycin (7)
Co-administration of clopidogrel with 80 mg omeprazole may reduce the pharmacological activity of clopidogrel if given concomitantly or if given 12 hours apart (7)
USE IN SPECIFIC POPULATIONS
Pregnancy: Based upon animal data, may cause fetal harm (8.1)
The safety and effectiveness of ZEGERID in pediatric patients less than 18 years of age have not been established. (8.4)
Hepatic Impairment: Consider dose reduction, particularly for maintenance of healing of erosive esophagitis (12.3)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling
Revised: 09/2011
Back to Highlights and Tabs
FULL PRESCRIBING INFORMATION: CONTENTS*
* Sections or subsections omitted from the full prescribing information are not listed
1 INDICATIONS AND USAGE
1.1 Duodenal Ulcer
1.2 Gastric Ulcer
1.3 Treatment of Gastroesophageal Reflux Disease (GERD)
1.4 Maintenance of Healing of Erosive Esophagitis
1.5 Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients (40mg oral suspension only)
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Concomitant Gastric Malignancy
5.2 Atrophic gastritis
5.3 Buffer Content
5.4 Bone Fracture
5.5 Hypomagnesemia
5.6 Diminished Anti-platelet Activity of clopidogrel due to Impaired CYP2C19 Function by Omeprazole
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Impairment
8.7 Renal Impairment
8.8 Asian Population
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Duodenal Ulcer Disease
14.2 Gastric Ulcer
14.3 Gastroesophageal Reflux Disease (GERD)
14.4 Long Term Maintenance Treatment of Erosive Esophagitis
14.5 Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Duodenal Ulcer
ZEGERID (omeprazole/sodium bicarbonate) is indicated for short-term treatment of active duodenal ulcer. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. [See Clinical Studies (14.1)]
1.2 Gastric Ulcer
ZEGERID is indicated for short-term treatment (4-8 weeks) of active benign gastric ulcer. [See Clinical Studies (14.2)]
1.3 Treatment of Gastroesophageal Reflux Disease (GERD)
Symptomatic GERD
ZEGERID is indicated for the treatment of heartburn and other symptoms associated with GERD. [See Clinical Studies (14.3)]
Erosive Esophagitis
ZEGERID is indicated for the short-term treatment (4-8weeks) of erosive esophagitis which has been diagnosed by endoscopy.
The efficacy of ZEGERID used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is recurrence of erosive esophagitis or GERD symptoms (e.g., heartburn), additional 4-8 week courses of ZEGERID may be considered. [See Clinical Studies (14.3)]
1.4 Maintenance of Healing of Erosive Esophagitis
ZEGERID is indicated to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months. [See Clinical Studies (14.4)]
1.5 Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients (40mg oral suspension only)
ZEGERID Powder for Oral Suspension 40 mg/1680mg is indicated for the reduction of risk of upperGI bleeding in critically ill patients. [SeeCLINICAL STUDIES, Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients (14.5)]
2 DOSAGE AND ADMINISTRATION
ZEGERID (omeprazole/sodium bicarbonate) is available as a capsule and as a powder for oral suspension in 20 mg and 40mg strengths of omeprazole for adult use. Directions for use for each indication are summarized in Table 1. All recommended doses throughout the labeling are based upon omeprazole
Since both the 20 mg and 40 mg oral suspension packets contain the same amount of sodium bicarbonate (1680 mg), two packets of 20 mg are not equivalent to one packet of ZEGERID 40 mg; therefore, two 20 mg packets of ZEGERID should not be substituted for one packet of ZEGERID40mg.
Since both the 20 mg and 40 mg capsules contain the same amount of sodium bicarbonate (1100mg), two capsules of 20 mg are not equivalent to one capsule of ZEGERID 40 mg; therefore, two 20 mg capsules of ZEGERID should not be substituted for one capsule of ZEGERID 40mg.
ZEGERID should be taken on an empty stomach at least one hour before a meal.
For patients receiving continuous Nasogastric (NG)/ Orogastric (OG) tube feeding, enteral feeding should be suspended approximately 3 hours before and 1 hour after administration of ZEGERID Powder for Oral Suspension.
Table 1: Recommended Doses of ZEGERID by Indication for Adults 18 Years and Older
* Most patients heal within 4 weeks. Some patients may require an additional 4 weeks of therapy. [See Clinical Studies (14.1)]
** For additional information, [See Clinical Studies (14)]
+ For additional information, [See Indications and Usage (1)]
Indication
Recommended Dose
Frequency
Short-Term Treatment of Active Duodenal Ulcer
20 mg
Once daily for 4 weeks*,+
Benign Gastric Ulcer
40 mg
Once daily for 4-8 weeks**,+
Gastroesophageal Reflux Disease (GERD)
Symptomatic GERD (with no esophageal erosions)
20 mg
Once daily for up to 4 weeks+
Erosive Esophagitis
20 mg
Once daily for 4-8 weeks+
Maintenance of Healing of Erosive Esophagitis
20 mg
Once daily**
Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients
(40 mg oral suspension only)
40 mg
40 mg initially followed by 40mg 6-8 hours later and 40mg daily thereafter for 14days**
Special Populations
Hepatic Insufficiency
Consider dose reduction, particularly for maintenance of healing of erosive esophagitis. [See Clinical Pharmacology (12.3)]
Administration of Capsules
ZEGERID Capsules should be swallowed intact with water. DO NOT USE OTHER LIQUIDS. DO NOT OPEN CAPSULE AND SPRINKLE CONTENTS INTO FOOD.
Preparation and Administration of Suspension
Directions for use: Empty packet contents into a small cup containing 1-2 tablespoons of water. DO NOT USE OTHER LIQUIDS OR FOODS. Stir well and drink immediately. Refill cup with water and drink.
If ZEGERID is to be administered through a nasogastric (NG) or orogastric (OG) tube, the suspension should be constituted with approximately 20 mL of water. DO NOT USE OTHER LIQUIDS OR FOODS. Stir well and administer immediately. An appropriately-sized syringe should be used to instill the suspension in the tube. The suspension should be washed through the tube with 20 mL of water.
Use with clopidogrel
Avoid concomitant use of clopidogrel and omeprazole. Coadministration of clopidogrel with 80 mg omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12 hours apart [see Warnings and Precautions (5.6) and Drug Interactions (7)].
3 DOSAGE FORMS AND STRENGTHS
ZEGERID 20-mg Capsules: Each opaque, hard gelatin, white capsule, imprinted with the Santarus logo and “20”, contains 20mg omeprazole and 1100mg sodium bicarbonate.
ZEGERID 40-mg Capsules: Each opaque, hard gelatin, colored dark blue and white capsule, imprinted with the Santarus logo and “40”, contains 40mg omeprazole and 1100mg sodium bicarbonate.
ZEGERID Powder for Oral Suspension is a white, flavored powder packaged in unit-dose packets. Each packet contains either 20 mg or 40mg omeprazole and 1680 mg sodium bicarbonate.
4 CONTRAINDICATIONS
ZEGERID is contraindicated in patients with known hypersensitivity to any components of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, and urticaria.
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 Buffer Content
Each ZEGERID Capsule contains 1100 mg (13mEq) of sodium bicarbonate. The total content of sodium in each capsule is 304 mg.
Each packet of ZEGERID Powder for Oral Suspension contains 1680 mg (20mEq) of sodium bicarbonate (equivalent to 460 mg of Na+).
The sodium content of ZEGERID products should be taken into consideration when administering to patients on a sodium restricted diet.
Because ZEGERID products contain sodium bicarbonate, they should be used with caution in patients with Bartter's syndrome, hypokalemia, hypocalcemia, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome.
Chronic use of sodium bicarbonate may lead to systemic alkalosis and increased sodium intake can produce edema and weight increase.
5.4 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 the established treatment guidelines. [See Dosage and Administration (2) and Adverse Reactions (6.2)]
5.5 Hypomagnesemia
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 (6.2)]
5.6 Diminished Anti-platelet Activity of clopidogrel due to Impaired CYP2C19 Function by Omeprazole
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 interfere with CYP2C19 activity. Avoid concomitant use of clopidogrel and omeprazole. Co-administration of clopidogrel with 80 mg omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12 hours apart [see Drug Interactions (7)].
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
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 clinical practice.
In the U.S. clinical trial population of 465 patients, the adverse reactions summarized in Table 2 were reported to occur in 1% or more of patients on therapy with omeprazole. Numbers in parentheses indicate percentages of the adverse reactions considered by investigators as possibly, probably or definitely related to the drug.
Table 2: Adverse Reactions Occurring In 1% or More of Patients on Omeprazole Therapy
Omeprazole (n = 465)
Placebo (n = 64)
Ranitidine (n = 195)
Headache
6.9 (2.4)
6.3
7.7 (2.6)
Diarrhea
3.0 (1.9)
3.1 (1.6)
2.1 (0.5)
Abdominal Pain
2.4 (0.4)
3.1
2.1
Nausea
2.2 (0.9)
3.1
4.1 (0.5)
URI
1.9
1.6
2.6
Dizziness
1.5 (0.6)
0.0
2.6 (1.0)
Vomiting
1.5 (0.4)
4.7
1.5 (0.5)
Rash
1.5 (1.1)
0.0
0.0
Constipation
1.1 (0.9)
0.0
0.0
Cough
1.1
0.0
1.5
Asthenia
1.1 (0.2)
1.6 (1.6)
1.5 (1.0)
Back Pain
1.1
0.0
0.5
Table 3 summarizes the adverse reactions that occurred in 1% or more of omeprazole-treated patients from international double-blind, and open-label clinical trials in which 2,631 patients and subjects received omeprazole.
Table 3: Incidence of Adverse Reactions ≥ 1% Causal Relationship not Assessed
