Zegerid Information
Zegerid (Omeprazole; sodium bicarbonate) Description
Zegerid (Omeprazole; sodium bicarbonate) ® with Magnesium Hydroxide (omeprazole/sodium bicarbonate/magnesium hydroxide) is a combination of omeprazole, a proton-pump inhibitor, and sodium bicarbonate plus magnesium hydroxide, both of which are antacids. Omeprazole is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1-benzimidazole, a racemic mixture of two enantiomers that inhibits gastric acid secretion. Its empirical formula is CHNOS, with a molecular weight of 345.42. The structural formula is:
Omeprazole is a white to off-white crystalline powder which melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.
Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide is available in two strengths, 40 mg and 20 mg of omeprazole, and is formulated as an immediate-release chewable tablet. Each chewable tablet contains either 40 mg or 20 mg of omeprazole and 600 mg of sodium bicarbonate plus 700 mg of magnesium hydroxide with the following inactive ingredients: hydroxypropyl cellulose, croscarmellose sodium, xylitol, sucralose, flavoring, magnesium stearate, and FD&C Red #40 Aluminum Lake.
Zegerid (Omeprazole; sodium bicarbonate) Clinical Pharmacology
Omeprazole is acid labile and thus rapidly degraded by gastric acid. Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide is an immediate-release chewable tablet formulation that contains an antacid component (sodium bicarbonate plus magnesium hydroxide) which raises the gastric pH and thus protects omeprazole from acid degradation.
Zegerid (Omeprazole; sodium bicarbonate) Contraindications
Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide is contraindicated in patients with known hypersensitivity to any components of the formulation.
Zegerid (Omeprazole; sodium bicarbonate) Precautions
Symptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.
Each 20 mg and 40 mg Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide chewable tablet contains 600 mg (7 mEq) of sodium bicarbonate (equivalent to 164 mg of Na+) and 700 mg (24 mEq) of magnesium hydroxide (equivalent to 292 mg of Mg++).
The sodium content of this product should be taken into consideration when administering to patients on a sodium-restricted diet.
Magnesium hydroxide should be used with caution in neonates, elderly, and in patients with renal impairment or renal disease due to increased risk of developing hypermagnesemia and magnesium toxicity. Magnesium hydroxide should not be used in patients with renal failure unless serum magnesium levels are being closely monitored.
Sodium bicarbonate is contraindicated in patients with metabolic alkalosis and hypocalcemia. Sodium bicarbonate should be used with caution in patients with Bartter's syndrome, hypokalemia, respiratory alkalosis, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome.
Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide should be taken on an empty stomach at least one hour prior to a meal. Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide chewable tablets are available in 40 mg and 20 mg dosage strengths of omeprazole with 600 mg sodium bicarbonate plus 700 mg magnesium hydroxide per tablet.
Directions for Use: Chew the tablet and swallow with water. DO NOT USE OTHER LIQUIDS.
Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin may need to be monitored for increases in INR and prothrombin time. Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system (eg, cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with Zegerid (Omeprazole; sodium bicarbonate) .
Because of its profound and long-lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (eg, ketoconazole, ampicillin esters, and iron salts). In the clinical efficacy trials antacids were used concomitantly with the administration of omeprazole.
Concomitant administration of omeprazole and atazanavir has been reported to reduce the plasma levels of atazanavir.
Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.
Co-administration of omeprazole and clarithromycin have resulted in increases of plasma levels of omeprazole, clarithromycin, and 14-hydroxy-clarithromycin (see also ).
In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (approximately 0.5 to 28.5 times the human dose of 40 mg/day, based on body surface area) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (approximately 2.8 times the human dose of 40 mg/day, based on body surface area) for one year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of one year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for two years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4, 2, and 16 mg/kg/day (about 0.1 to 3.3 times the human dose of 40 mg/day, based on body surface area). No astrocytomas were observed in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in males and females at the high dose of 140.8 mg/kg/day (about 28.5 times the human dose of 40 mg/day, based on body surface area). A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive. Omeprazole was positive for clastogenic effects in an human lymphocyte chromosomal aberration assay, in one of two mouse micronucleus tests, and in an bone marrow cell chromosomal aberration assay. Omeprazole was negative in the Ames Test, an mouse lymphoma cell forward mutation assay and an rat liver DNA damage assay.
Omeprazole at oral doses up to 138 mg/kg/day (about 28 times the human dose of 40 mg/day, based on body surface area) was found to have no effect on the fertility and general reproductive performance in rats.
Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.
Pharmacokinetic studies with buffered omeprazole have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young subjects). The plasma half-life averaged one hour, about the same as that in nonelderly, healthy subjects taking Zegerid (Omeprazole; sodium bicarbonate) . However, no dosage adjustment is necessary in the elderly. (See )
Zegerid (Omeprazole; sodium bicarbonate) Adverse Reactions
Omeprazole was generally well tolerated during domestic and international clinical trials in 3096 patients.
In the U.S. clinical trial population of 465 patients, the adverse experiences summarized in were reported to occur in 1% or more of patients on therapy with omeprazole. Numbers in parentheses indicate percentages of the adverse experiences considered by investigators as possibly, probably or definitely related to the drug.
Additional adverse experiences occurring in < 1% of patients or subjects in domestic and/or international trials conducted with omeprazole, or occurring since the drug was marketed, are shown below within each body system. In many instances, the relationship to omeprazole was unclear.
Allergic reactions, including, rarely, anaphylaxis (see also Skin below), fever, pain, fatigue, malaise, abdominal swelling.
Chest pain or angina, tachycardia, bradycardia, palpitation, elevated blood pressure, and peripheral edema.
Pancreatitis (some fatal), anorexia, irritable colon, flatulence, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, dry mouth, stomatitis. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued.
Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.
Mild and, rarely, marked elevations of liver function tests [ALT (SGPT), AST (SGOT), γ-glutamyl transpeptidase, alkaline phosphatase, and bilirubin (jaundice)]. In rare instances, overt liver disease has occurred, including hepatocellular, cholestatic, or mixed hepatitis, liver necrosis (some fatal), hepatic failure (some fatal), and hepatic encephalopathy.
Hyponatremia, hypoglycemia, and weight gain.
Muscle cramps, myalgia, muscle weakness, joint pain, and leg pain.
Psychic disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, dream abnormalities; vertigo; paresthesia; and hemifacial dysesthesia.
Epistaxis, pharyngeal pain.
Rash and rarely, cases of severe generalized skin reactions including toxic epidermal necrolysis (TEN; some fatal), Stevens-Johnson syndrome, and erythema multiforme (some severe); purpura and/or petechiae (some with rechallenge); skin inflammation, urticaria, angioedema, pruritus, photosensitivity, alopecia, dry skin, and hyperhidrosis.
Tinnitus, taste perversion.
Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis and double vision.
Interstitial nephritis (some with positive rechallenge), urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine, proteinuria, hematuria, glycosuria, testicular pain, and gynecomastia.
Rare instances of pancytopenia, agranulocytosis (some fatal), thrombocytopenia, neutropenia, leukopenia, anemia, leucocytosis, and hemolytic anemia have been reported.
The incidence of clinical adverse experiences in patients greater than 65 years of age was similar to that in patients 65 years of age or less.
Additional adverse reactions that could be caused by sodium bicarbonate include metabolic alkalosis, seizures, and tetany.
The use of magnesium hydroxide is associated with diarrhea, abdominal cramping, chalky taste, diuresis, dehydration, nausea, and vomiting.
Zegerid (Omeprazole; sodium bicarbonate) Overdosage
Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience. (See ) Symptoms were transient, and no serious clinical outcome has been reported when omeprazole was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.
As with the management of any overdose, the possibility of multiple drug ingestion should be considered. For current information on treatment of any drug overdose, a certified Regional Poison Control Center should be contacted. Telephone numbers are listed in the Physicians' Desk Reference (PDR) or local telephone book.
Single oral doses of omeprazole at 1350, 1339, and 1200 mg/kg were lethal to mice, rats, and dogs, respectively. Animals given these doses showed sedation, ptosis, tremors, convulsions, and decreased activity, body temperature, and respiratory rate and increased depth of respiration.
In addition, a sodium bicarbonate overdose may cause hypocalcemia, hypokalemia, hypernatremia, and seizures.
Similarly, a magnesium overdose may lead to hypermagnesemia. Hypermagnesemia results in a depressant effect on the central nervous system, causing anorexia and nausea, and neuromuscular system. Magnesium toxicity causes hypotension, muscle weakness, and electrographic changes.
Zegerid (Omeprazole; sodium bicarbonate) Dosage And Administration
Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide (omeprazole/sodium bicarbonate/magnesium hydroxide) is available as chewable tablets in 20 mg and 40 mg strengths for adult use. Directions for use for each indication are summarized in .
Because Zegerid (Omeprazole; sodium bicarbonate) chewable tablets contain magnesium hydroxide, the chewable tablets should not be substituted for other dosage forms (eg, Zegerid (Omeprazole; sodium bicarbonate) Powder for Oral Suspension or Zegerid (Omeprazole; sodium bicarbonate) Capsules).
Since both the 20-mg and 40-mg chewable tablets contain the same amount of sodium bicarbonate (600 mg) and magnesium hydroxide (700 mg), two 20-mg chewable tablets are not equivalent to one 40-mg chewable tablet; therefore, two 20-mg chewable tablets should not be substituted for one 40-mg chewable tablet.
Zegerid (Omeprazole; sodium bicarbonate) with Magnesium Hydroxide should be taken on an empty stomach at least one hour before a meal.
Zegerid (Omeprazole; sodium bicarbonate) How Supplied
NDC 68012-152-30 Bottles of 30 chewable tablets
NDC 68012-154-30 Bottles of 30 chewable tablets
Zegerid (Omeprazole; sodium bicarbonate) References
Zegerid (Omeprazole; sodium bicarbonate) ® with Magnesium Hydroxide Chewable Tablets are manufactured for Santarus, Inc., San Diego, CA 92130
by: Patheon Pharmaceuticals, Inc. Cincinnati, OH 45237
For more information call 1-888-778-0887
Revised: March 2006
Zegerid (Omeprazole; sodium bicarbonate) ® is a registered trademark of Santarus, Inc.
© 2006 Santarus, Inc.
