Esomeprazole and Naproxen

Naproxen and esomeprazole magnesium delayed-release tablets, a combination of naproxen and esomeprazole magnesium, is indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric ulcers. The naproxen component of naproxen and esomeprazole magnesium delayed-release tablet is indicated for relief of signs and symptoms of: osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults. juvenile idiopathic arthritis (JIA) in adolescent patients. The esomeprazole magnesium component of naproxen and esomeprazole magnesium delayed-release tablet is indicated to decrease the risk of developing naproxen-associated gastric ulcers.

Naproxen and esomeprazole magnesium delayed-release tablets consist of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but inhibition of cyclooxygenase (COX-1 and COX-2). Naproxen and esomeprazole magnesium delayed-release tablets have analgesic, anti-inflammatory, and antipyretic properties contributed by the naproxen component. Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen concentrations reached during therapy have produced in vivo effects.

Administration Use the lowest naproxen dose for the shortest duration consistent with individual patient treatment goals. If a total daily dose of less than 40 mg esomeprazole is more appropriate, a different treatment should be considered. Swallow naproxen and esomeprazole magnesium delayed-release tablets whole with liquid at least 30 minutes before meals. Recommended Dosage. Adolescents 12 years of age and older weighing 38 kg to less than 50 kg: One naproxen and esomeprazole magnesium delayed-release tablet twice daily of 375 mg naproxen/20 mg of esomeprazole Adults and adolescents 12 years of age and older greater than 50 kg: One naproxen and esomeprazole magnesium delayed-release tablet twice daily of either: 375 mg naproxen/20 mg of esomeprazole, or 500 mg of naproxen/20 mg of esomeprazole Renal or Hepatic Impairment.

Naproxen and esomeprazole magnesium delayed-release tablet is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. Hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria. History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients.

Boxed warning (risk of serious cardiovascular and gastrointestinal events): Cardiovascular Thrombotic Events Non-Steroidal Anti-inflammatory Drugs (NSAIDs), a component of naproxen and esomeprazole magnesium delayed-release tablets, cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events GI Bleeding, Ulceration and Perforations Hepatotoxicity Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylactic Reactions Serious or Severe Skin Reactions Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Fetal Toxicity Hematologic Toxicity Active Bleeding Acute Tubulointerstitial Nephritis Clostridium difficile -Associated Diarrhea Bone Fracture Cutaneous and Systemic Lupus Erythematosus Cyanocobalamin (Vitamin B-12) Deficiency Hypomagnesemia and Mineral Metabolism Fundic Gland Polyps Most common adverse reactions in clinical trials (greater than 5%) are gastritis and diarrhea.

See Table 3 and Table 4 for clinically significant drug interactions and interactions with diagnostics with naproxen and esomeprazole magnesium. Table 3: Clinically Significant Drug Interactions with Naproxen and Esomeprazole Magnesium – Affecting Drugs Co-Administered with Naproxen and Esomeprazole Magnesium Delayed-Release Tablets and Interactions with Diagnostics Clinical Impact: Naproxen Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of naproxen and anticoagulants have increased the risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store in the original container and keep the bottle tightly closed to protect from moisture.