RECENT MAJOR CHANGES

Warnings and Precautions, Hypomagnesemia (5.7)     05/2011

Warnings and Precautions,      11/2011

Diminished anti-platelet activity of clopidogrel (5.6)

Warnings and Precautions,     01/2012

Clostridium difjicile associated diarrhea (5.4)

Warnings and Precautions,     01/2012

Comcomitant Use of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets with St John's Wort or Rifampin (5.8)

Warnings and Precautions,     01/2012

Investigations for Neuroendocrine Tumors (5.9)

INDICATIONS AND USAGE

Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is a proton pump inhibitor indicated for:

• Treatment of duodenal ulcer (1.1)
• Treatment of gastric ulcer (1.2)
• Treatment of gastroesophageal reflux disease (GERD) (1.3)
• Maintenance of healing of erosive esophagitis (1.4)

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)) (2.2)
• Gastric Ulcer: 40 mg once daily for 4-8 weeks (2.3)
• Gastroesophageal Reflux Disease (GERD) (2.4)

  -

  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 (2.5)

DOSAGE FORMS AND STRENGTHS

• Tablets 20 mg omeprazole, 750 mg sodium bicarbonate, and 343 mg magnesium hydroxide (3)
• Tablets 40 mg omeprazole, 750 mg sodium bicarbonate, and 343 mg magnesium hydroxide (3)

CONTRAINDICATIONS

• Known hypersensitivity to Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets or any components in the formulation (4)
• Patients who cannot take magnesium (4)

WARNINGS AND PRECAUTIONS

• Concomitant Gastric Malignancy: Symptomatic response to therapy with Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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: Contains sodium bicarbonate. (5.3)
• PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. (5.4)
• 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. (5.5)
• Diminished anti-platelet activity of clopidogrel due to impaired CYP2C19 function by 80 mg omeprazole (5.6)
• Hypomagnesemia has been reported rarely with prolonged treatment with PPIs (5.7)
• Avoid concomitant use of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets with St John's Wort or rifampin due to the potential reduction in omeprazole concentrations (5.8, 7.2)
• Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased Choromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. (5.9, 12.2)

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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Drugs metabolized by cytochrome P450 (e.g., diazepam, warfarin, phenytoin, cyclosporine, disulfiram, benzodiazepines): Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets can prolong their elimination. Monitor to determine the need for possible dose adjustments when taken with Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets (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): Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets may interfere with absorption due to inhibition of gastric acid secretion (7)
• Voriconazole: May increase plasma levels of omeprazole (7)
• Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets may reduce plasma levels of atazanavir and nelfinavir (7)
• Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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 Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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 (8.6)

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

2 DOSAGE AND ADMINISTRATION

2.1 Instructions for Use

2.2 Short-Term Treatment of Active Duodenal Ulcer

2.3 Benign Gastric Ulcer

2.4 Gastroesophageal Reflux Disease (GERD)

2.5 Maintenance of Healing of Erosive Esophagitis

2.6 Use with clopidogrel

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 Clostridium difficile associated diarrhea

5.5 Bone Fracture

5.6 Diminished Anti-platelet Activity of clopidogrel due to Impaired CYP2C19 Function by Omeprazole

5.7 Hypomagnesemia

5.8 Concomitant use of omeprazole with St John's Wort or rifampin

5.9 Interactions with Investigations for Neuroendocrine Tumors

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-marketing Experience

7 DRUG INTERACTIONS

7.1 Drugs metabolized by cytochrome P450 (CYP)

7.2 Drugs for which gastric pH can affect bioavailability

7.3 Antiretroviral Agents

7.4 Antimicrobials

7.5 Clopidogrel

7.6 Tacrolimus

7.7 Interactions With Investigations of Neuroendocrine Tumors

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

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION