Zegerid with Magnesium Hydroxide

• Santarus, Incorporated

Rx Only

Chewable Tablets

ZEGERID® 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]-1H-benzimidazole, a racemic mixture of two enantiomers that inhibits gastric acid secretion. Its empirical formula is C17H19N3O3S, 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 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 with Magnesium Hydroxide is contraindicated in patients with known hypersensitivity to any components of the formulation.

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 Table 11 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.

Table 12 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.

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.

Body As a Whole

Allergic reactions, including, rarely, anaphylaxis (see also Skin below), fever, pain, fatigue, malaise, abdominal swelling.

Cardiovascular

Chest pain or angina, tachycardia, bradycardia, palpitation, elevated blood pressure, and peripheral edema.

Gastrointestinal

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.

Hepatic

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.

Metabolic/Nutritional

Hyponatremia, hypoglycemia, and weight gain.

Musculoskeletal

Muscle cramps, myalgia, muscle weakness, joint pain, and leg pain.

Nervous System/Psychiatric

Psychic disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, dream abnormalities; vertigo; paresthesia; and hemifacial dysesthesia.

Respiratory

Epistaxis, pharyngeal pain.

Skin

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.

Special Senses

Tinnitus, taste perversion.

Ocular

Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis and double vision.

Urogenital

Interstitial nephritis (some with positive rechallenge), urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine, proteinuria, hematuria, glycosuria, testicular pain, and gynecomastia.

Hematologic

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.

The most frequently reported adverse events with Zegerid are headache, diarrhea, and abdominal pain. In critically ill patients treated with Zegerid, adverse events generally reflected the serious, underlying medical condition of the patients, and were similar for patients treated with Zegerid and with the comparator (acid-controlling) drug. Symptomatic response to therapy 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.

Zegerid Capsules contain 300 mg of sodium per dose in the form of sodium bicarbonate (1100 mg/13 mEq), and Zegerid Powder for Oral Suspension contains 460 mg of sodium per dose in the form of sodium bicarbonate (1680 mg/20 mEq). The chewable tablet dosage form contains 600 mg (7 mEq) of sodium bicarbonate. This should be taken into consideration for patients on a sodium-restricted diet. Sodium bicarbonate is contraindicated in patients with metabolic alkalosis and hypocalcemia. The chewable tablet dosage form also contains 700 mg (24 mEq) of magnesium hydroxide. The use of magnesium hydroxide is associated with diarrhea, abdominal cramping, chalky taste, diuresis, dehydration, nausea and vomiting. Zegerid is contraindicated in patients with known hypersensitivity to any component of the formulation.