1 INDICATIONS AND USAGE NEXIUM is a proton pump inhibitor (PPI).

NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the: • Short-term treatment in the healing of erosive esophagitis (EE) in adults and pediatric patients 12 years to 17 years of age.

( 1.1 ) • Maintenance of healing of EE in adults.

( 1.2 ) • Short-term treatment of heartburn and other symptoms associated GERD in adults and pediatric patients 12 years to 17 years of age.

( 1.3 ) • Risk reduction of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults at risk for developing gastric ulcers due to age (60 years and older) and/or documented history of gastric ulcers.

( 1.4 ) • Helicobacter pylori eradication in adult patients to reduce the risk of duodenal ulcer recurrence in combination with amoxicillin and clarithromycin.

( 1.5 ) • Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome in adults.

( 1.6 ) NEXIUM for delayed-release oral suspension is indicated for the: • Short-term treatment in the healing of EE in pediatric patients 1 year to 11 years of age and of EE due to acid-mediated GERD in pediatric patients 1 month to less than 1 year of age.

( 1.1 ) • Short-term treatment of heartburn and other symptoms associated with GERD in pediatric patients 1 year to 11 years of age.

( 1.3 ) 1.1 Healing of Erosive Esophagitis (EE) Adults NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed EE in adults.

For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4- to 8- week course of NEXIUM may be considered.

Pediatric Patients 12 Years to 17 Years of Age NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the short-term treatment (4 to 8 weeks) for the healing of EE in pediatric patients 12 years to 17 years of age.

Pediatric Patients 1 Year to 11 Years of Age NEXIUM for delayed-release oral suspension is indicated for the short-term treatment (8 weeks) for the healing of EE in pediatric patients 1 year to 11 years of age.

Pediatric Patients 1 Month to Less Than 1 Year of Age NEXIUM for delayed-release oral suspension is indicated for short-term treatment (up to 6 weeks) of EE due to acid-mediated GERD in pediatric patients 1 month to less than 1 year of age.

1.2 Maintenance of Healing of EE NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the maintenance of healing of EE in adults.

Controlled studies do not extend beyond 6 months.

1.3 Treatment of Symptomatic GERD Adults NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults.

Pediatric Patients 12 Years to 17 Years of Age NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for short-term treatment (4 weeks) of heartburn and other symptoms associated with GERD in pediatric patients 12 years to 17 years of age.

Pediatric Patients 1 Year to 11 Years of Age NEXIUM for delayed-release oral suspension is indicated for short-term treatment (up to 8 weeks) of heartburn and other symptoms associated with GERD in pediatric patients 1 year to 11 years of age.

1.4 Risk Reduction of Nonsteroidal Anti-Inflammatory Drugs (NSAID)-Associated Gastric Ulcer NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in adult patients at risk for developing gastric ulcers.

Patients are considered to be at risk due to their age (60 years and older) and/or documented history of gastric ulcers.

Controlled studies do not extend beyond 6 months.

1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Eradication of H.

pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Triple Therapy NEXIUM delayed-release capsules or NEXIUM for delayed-release oral suspension in combination with amoxicillin and clarithromycin is indicated for the treatment of adult patients with H.

pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H.

pylori .

In patients who fail therapy, susceptibility testing should be done.

If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see Clinical Pharmacology (12.4) and the prescribing information for clarithromycin].

1.6 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome, in adults.

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: • Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3) ] • Bone Fracture [see Warnings and Precautions (5.4) ] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] • Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6) ] • Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8) ] • Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9) ] • Fundic Gland Polyps [see Warnings and Precautions (5.13) ] Most common adverse reactions (6.1) : • Adults (≥ 18 years) ( > 1%) are: headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth.

• Pediatrics (1 to 17 years) ( > 2%) are: headache, diarrhea, abdominal pain, nausea, and somnolence.

• Pediatrics (1 month to less than 1 year) (>1%) are: abdominal pain, regurgitation, tachypnea, and increased ALT.

To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 practice.

Adults The safety of NEXIUM delayed-release capsules was evaluated in over 15,000 patients (aged 18 to 84 years) in clinical trials worldwide including over 8,500 patients in the United States and over 6,500 patients in Europe and Canada.

Over 2,900 patients were treated in long-term studies for up to 6 to 12 months.

The safety in the treatment of healing of EE in adults was assessed in four randomized comparative clinical trials, which included 1,240 patients who received NEXIUM 20 mg once daily, 2,434 patients on NEXIUM 40 mg once daily, and 3,008 patients on omeprazole 20 mg once daily.

The most frequently occurring adverse reactions (at least 1%) in all three groups were headache (5.5%, 5%, and 3.8%, respectively) and diarrhea (no difference among the three groups).

Nausea, flatulence, abdominal pain, constipation, and dry mouth occurred at similar rates among patients taking NEXIUM or omeprazole.

Less common adverse reactions with an incidence of less than 1% are listed below by body system: Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors; Cardiovascular: flushing, hypertension, tachycardia; Endocrine: goiter; Gastrointestinal: bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting; Hearing: earache, tinnitus; Hematologic: anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia; Hepatic: bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased; Metabolic/Nutritional: glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease; Musculoskeletal: arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica; Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, dizziness, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect; Reproductive: dysmenorrhea, menstrual disorder, vaginitis; Respiratory: asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis; Skin and Appendages: acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria; Special Senses: otitis media, parosmia, taste loss, taste perversion; Urogenital: abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria; Visual: conjunctivitis, vision abnormal.

The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to NEXIUM, were reported in 1% or less of patients: increased creatinine, uric acid, total bilirubin, alkaline phosphatase, ALT, AST, hemoglobin, white blood cell count, platelets, serum gastrin, potassium, sodium, thyroxine and thyroid stimulating hormone [see Clinical Pharmacology (12.2) ] .

Decreases were seen in hemoglobin, white blood cell count, platelets, potassium, sodium, and thyroxine.

Endoscopic findings that were reported as adverse reactions include: duodenitis, esophagitis, esophageal stricture, esophageal ulceration, esophageal varices, gastric ulcer, gastritis, hernia, benign polyps or nodules, Barrett’s esophagus, and mucosal discoloration.

The incidence of adverse reactions during 6-month trials for the maintenance of healing of EE with NEXIUM 20 mg once daily was similar to placebo.

There were no differences in types of adverse reactions seen during maintenance treatment up to 12 months compared to short-term treatment.

Two placebo-controlled studies were conducted in 710 adult patients for the treatment of symptomatic GERD.

The most common adverse reactions that were reported were: diarrhea (4%), headache (4%), and abdominal pain (4%).

Combination Treatment with NEXIUM, Amoxicillin and Clarithromycin In clinical trials of H.

pylori eradication of to reduce duodenal ulcer recurrence, no additional adverse reactions specific to the combination of NEXIUM delayed-release capsules, amoxicillin and clarithromycin were observed and were similar to those observed with NEXIUM, amoxicillin, or clarithromycin alone.

The most frequently reported adverse reactions for patients who received NEXIUM, amoxicillin and clarithromycin for 10 days were diarrhea (9%), taste perversion (4%), and abdominal pain (4%).

No adverse reactions were observed at higher rates with NEXIUM, amoxicillin and clarithromycin than were observed with NEXIUM alone.

In clinical trials using of NEXIUM, amoxicillin and clarithromycin, no additional increased laboratory abnormalities particular to these drug combinations were observed.

For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to Adverse Reactions section of the respective prescribing information.

Pediatrics 1 Year to 17 Years of Age The safety of NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension was evaluated in 316 pediatric and adolescent patients aged 1 year to 17 years in four clinical trials for the treatment of symptomatic GERD [see Clinical Studies (14.3) ] .

In 109 pediatric patients aged 1 year to 11 years, the most frequently reported (at least 1%) treatment-related adverse reactions in these patients were diarrhea (3%), headache (2%) and somnolence (2%).

In 149 pediatric patients aged 12 years to 17 years the most frequently reported adverse reactions (at least 2%) were headache (8%), abdominal pain (3%), diarrhea (2%), and nausea (2%).

1 Month to Less Than 1 Year of Age The safety of esomeprazole magnesium was evaluated in 167 infants from 1 month to less than 1 year of age with GERD in three clinical trials [see Use in Specific Populations (8.4) ] .

In a study that included 43 pediatric patients, the most frequently reported adverse reactions (at least 5%) with esomeprazole magnesium were irritability and vomiting.

In a study that included 98 pediatric patients, administered esomeprazole magnesium for up to 6 weeks (including 39 patients randomized to the withdrawal phase), reported adverse reactions were: abdominal pain (1%), regurgitation (1%), tachypnea (1%), and increased ALT (1%).

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of esomeprazole.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These reports are listed below by body system: Blood and Lymphatic: agranulocytosis, pancytopenia; Eye: blurred vision; Gastrointestinal: pancreatitis; stomatitis; microscopic colitis; fundic gland polyps; Hepatobiliary: hepatic failure, hepatitis with or without jaundice; Immune System: anaphylactic reaction/shock; systemic lupus erythematosus; Infections and Infestations: GI candidiasis; Clostridium difficile- associated diarrhea; Metabolism and nutritional disorders: hypomagnesemia (may lead to hypocalcemia and/or hypokalemia) [see Warnings and Precautions (5.9) ] ; Musculoskeletal and Connective Tissue: muscular weakness, myalgia, bone fracture; Nervous System: hepatic encephalopathy, taste disturbance; Psychiatric: aggression, agitation, depression, hallucination; Renal and Urinary: interstitial nephritis; Reproductive System and Breast: gynecomastia, erectile dysfunction; Respiratory, Thoracic, and Mediastinal: bronchospasm; Skin and Subcutaneous Tissue: alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), cutaneous lupus erythematosus.

Adverse reactions associated with omeprazole may also be expected to occur with esomeprazole.

See the full prescribing information for omeprazole for complete safety information.