奥美拉唑说明书

_______________________________________________________________________________________________________________________________________ _______________________________________________________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets safely and effectively. See full prescribing information for Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets. Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets Initial U.S. Approval: 2006 ----------------------------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: Sodium content should be taken into consideration when administering to patients on a sodium-restricted diet or at risk of developing congestive heart failure (CHF). (5.3) • Buffer Content: Magnesium content increases risk of hypermagnesemia and magnesium toxicity in the elderly and in patients with renal impairment or renal disease (5.3) • Buffer Content: Use 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) ------------------------------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): 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) -----------------------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) See 17 for PATIENT COUNSELING INFORMATION. Revised: 12/2009 FULL PRESCRIBING INFORMATION: CONTENTS* 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 Gastric Ulcer 2.4 Gastroesophageal Reflux Disease (GERD) 2.5 Maintenance of Healing of Erosive Esophagitis 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Concomitant Gastric Malignancy 5.2 Atrophic Gastritis 5.3 Buffer Content 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Post-marketing 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 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION: 1 INDICATIONS AND USAGE 1.1 Duodenal Ulcer Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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 Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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 Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for the treatment of heartburn and other symptoms associated with GERD. [See Clinical Studies (14.3)] Erosive Esophagitis Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for the short-term treatment (4-8 weeks) of erosive esophagitis that has been diagnosed by endoscopy. The efficacy of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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 omeprazole may be considered. [See Clinical Studies (14.3)] 1.4 Maintenance of Healing of Erosive Esophagitis Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months. [See Clinical Studies (14.4)] 2 DOSAGE AND ADMINISTRATION 2.1 Instructions for Use Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide is available as tablets in 20 mg and 40 mg strengths of omeprazole for oral administration in adult patients 18 years and older. All recommended doses throughout the labeling are based upon omeprazole. Since both the 20 mg and 40 mg tablets contain the same amount of sodium bicarbonate (750 mg) and magnesium hydroxide (343 mg), two 20 mg tablets are not equivalent to one 40 mg tablet; therefore, two 20 mg tablets should not be substituted for one 40 mg tablet. Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contain magnesium hydroxide, the tablets should not be substituted for ZEGERID products (e.g., ZEGERID Powder for Oral Suspension or ZEGERID Capsules). Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets should be taken on an empty stomach with water at least one hour before a meal. Do not use other liquids. 2.2 Short-Term Treatment of Active Duodenal Ulcer The recommended adult oral dose of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is 20 mg once daily. Most patients heal within 4 weeks. Some patients may require an additional 4 weeks of therapy. 2.3 Benign Gastric Ulcer The recommended adult oral dose of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is 40 mg once daily for 4-8 weeks. 2.4 Gastroesophageal Reflux Disease (GERD) The recommended adult oral dose for the treatment of patients with symptomatic GERD and no esophageal erosions is 20 mg once daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis is 20 mg once daily for 4-8 weeks. 2.5 Maintenance of Healing of Erosive Esophagitis The recommended adult oral dose of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is 20 mg once daily. 3 DOSAGE FORMS AND STRENGTHS Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets, 20 mg, are white oval-shaped tablets. One side of each tablet is embossed with “ZM 20.” Each tablet contains 20 mg omeprazole and 750 mg sodium bicarbonate plus 343 mg magnesium hydroxide. Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets, 40 mg, are white oval-shaped tablets. One side of each tablet is embossed with “ZM 40.” Each tablet contains 40 mg omeprazole and 750 mg sodium bicarbonate plus 343 mg magnesium hydroxide. 4 CONTRAINDICATIONS Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets 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. Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is contraindicated in patients who cannot take magnesium. [See Warnings and Precautions (5.3)] 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 20 mg and 40 mg Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablet contains 750 mg (9 mEq) of sodium bicarbonate (equivalent to 209 mg of Na+) and 343 mg (12 mEq) of magnesium hydroxide (equivalent to 143 mg of Mg2+). Sodium Bicarbonate Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains sodium bicarbonate, it should be used with caution in patients with Bartter’s syndrome, hypokalemia, hypocalcemia, respiratory and metabolic alkalosis, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome. The sodium content of this product should be taken into consideration when administering to patients on a sodium-restricted diet or at risk of developing congestive heart failure (CHF). Chronic use of sodium bicarbonate may lead to systemic alkalosis and increased sodium intake can produce edema and weight increase. Magnesium Hydroxide Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains magnesium hydroxide, it should be used with caution in 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. Hypermagnesemia has been reported in infants whose mothers were using magnesium-containing antacid products chronically in high doses. 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 1 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 1: Adverse Reactions Occurring in 1% or More of Patients on Omeprazole Therapy from U.S. Studies Omeprazole Placebo Ranitidine (n = 465) (n = 64) (n = 195) Headache 6.9 (2.4) 6.3 7.7 (2.6) Diarrhea 3.0 (1.9) 3.1 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 The international clinical trials were double-blind and open-label in design. Table 2: Incidence of Adverse Reactions ≥ 1% Causal Relationship Not Assessed from International Studies Omeprazole Placebo (n = 2631) (n = 120) Body as a whole, site unspecified Abdominal Pain 5.2 3.3 Asthenia 1.3 0.8 Digestive System Constipation 1.5 0.8 Diarrhea 3.7 2.5 Flatulence 2.7 5.8 Nausea 4.0 6.7 Vomiting 3.2 10.0 Acid Regurgitation 1.9 3.3 Nervous System / Psychiatric Headache 2.9 2.5 The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from omeprazole-treated patients enrolled in these studies included headache (6.9%), abdominal pain (5.2%), nausea (4.0%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%). Additional adverse reactions that were reported with an incidence of ≥ 1% included acid regurgitation (1.9%), upper respiratory infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), asthenia (1.3%), back pain (1.1%), and cough (1.1%). The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less. 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of omeprazole. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure. Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria (see also Skin below); fever; pain; fatigue; malaise Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema Endocrine: Gynecomastia Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth. 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: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy, hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests (ALT, AST, GGT, alkaline phosphatase, and bilirubin) Metabolic/Nutritional: Hypoglycemia, hyponatremia, weight gain Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia, vertigo Respiratory: Epistaxis, pharyngeal pain Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal). Stevens-Johnson syndrome, and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis Special Senses: Tinnitus, taste perversion Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thromobocytopenia, leukopenia, leucocytosis 7 DRUG INTERACTIONS Drugs metabolized by cytochrome P450 (CYP) 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 P450 system (e.g., cyclosporine, disulfiram, benzodiazepines). Patients should be monitored