Esomeprazole

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. • Maintenance of healing of EE in adults. • Short-term treatment of heartburn and other symptoms associated GERD in adults and pediatric patients 12 years to 17 years of age. • 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. • Helicobacter pylori eradication in adult patients to reduce the risk of duodenal ulcer recurrence in combination with amoxicillin and clarithromycin.

Esomeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, esomeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Population Recommended Adult and Pediatric Dosage. Healing of EE (1 year and older) EE due to Acid-Mediated GERD (1 month to less than 1 year) Adults 20 mg or 40 mg A maximum dosage of 20 mg once daily is recommended for patients with severe liver impairment (Child-Pugh Class C). once daily for 4 to 8 weeks, some patients may require an additional 4 to 8 weeks 12 years to 17 years 20 mg or 40 mg once daily for 4 to 8 weeks 1 month to 11 years see full prescribing information for weight-based dosing and duration of treatment. Maintenance of Healing of EE Adults 20 mg once daily.

• NEXIUM is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria. • For information about contraindications of amoxicillin and clarithromycin, indicated in combination with NEXIUM for H. pylori eradication to reduce the risk of duodenal ulcer recurrence, refer to the Contraindications section of the respective prescribing information. • Proton pump inhibitors (PPIs), including NEXIUM, are contraindicated in patients receiving rilpivirine-containing products.

• Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. • Acute Tubulointerstitial Nephritis: Discontinue treatment and evaluate patients. • Clostridium difficile- Associated Diarrhea: PPI therapy may be associated with increased risk. • 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. • Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. • Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous, new onset or exacerbation of existing disease, discontinue NEXIUM and refer to specialist for evaluation.

The following serious adverse reactions are described below and elsewhere in labeling: • Acute Tubulointerstitial Nephritis • Clostridium difficile-Associated Diarrhea • Bone Fracture • Severe Cutaneous Adverse Reactions • Cutaneous and Systemic Lupus Erythematosus • Cyanocobalamin (Vitamin B-12) Deficiency • Hypomagnesemia and Mineral Metabolism • Fundic Gland Polyps Most common adverse reactions: • 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.

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with esomeprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Esomeprazole and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. • Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with esomeprazole may reduce antiviral effect and promote the development of drug resistance.

Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F).