Zegerid with Magnesium Hydroxide (Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

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.

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 CLINICAL PHARMACOLOGY, Pharmacokinetics).

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 ADVERSE REACTIONS.) 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.

CONTRAINDICATIONS

ZEGERID with Magnesium Hydroxide is contraindicated in patients with known hypersensitivity to any components of the formulation.

REFERENCES

1. Friedman JM and Polifka JE. Omeprazole. In: Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). 2nd ed. Baltimore, MD: The Johns Hopkins University Press 2000; p. 516.
2. Kallen BAJ. Use of omeprazole during pregnancy – no hazard demonstrated in 955 infants exposed during pregnancy. Eur Obstet Gynecol Reprod Biol 2001; 96(1):63-8.
3. Ruigómez A, Rodriguez LUG, Cattaruzzi C, et al. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 1999; 150:476-81.
4. Lalkin A, Loebstein, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 1998; 179:727-30.

SANTARUS, INC. ^®

ZEGERID® 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® is a registered trademark of Santarus, Inc.

© 2006 Santarus, Inc.