This combination tablet is used for the relief of signs and symptoms of:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• It is also indicated to reduce the risk of developing gastric ulcers in patients who are at risk of NSAID-associated gastric ulcers.

This formulation contains an immediate-release Esomeprazole Magnesium layer and an enteric-coated Naproxen core. Esomeprazole is released first in the stomach, while Naproxen is released later in the small intestine after dissolution of the coating.

Naproxen is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. It works by inhibiting prostaglandin synthesis. Esomeprazole is a proton pump inhibitor that reduces gastric acid secretion by selectively inhibiting the H⁺/K⁺-ATPase enzyme in gastric parietal cells. By blocking the final step of acid production, it lowers gastric acidity and helps protect the stomach.

Carefully consider the potential benefits & risks of this tablet & other treatment options before deciding to use this tablet. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. If a dose of Esomeprazole lower than a total daily dose of 40 mg is more appropriate, a different treatment should be considered.

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis

• Adults: One tablet twice daily of either: 375 mg naproxen/20 mg of esomeprazole; or 500 mg naproxen/20 mg of esomeprazole.

Juvenile Idiopathic Arthritis in Adolescent Patients 12 Years of Age & Older

• Weight greater than 50 kg: 375 mg naproxen/20 mg of esomeprazole; or 500 mg naproxen/20 mg of esomeprazole.
• Weight 38 kg to less than 50 kg: One tablet twice daily of 375 mg naproxen/20 mg of esomeprazole.

Do not split, chew, crush or dissolve the tablet. This tablet is to be taken at least 30 minutes before meals.

With medicines:

• Concomitant use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors, diuretics, and beta-blockers.
• Co-administration of this tablet with warfarin may increase the risk of bleeding complications.
• Esomeprazole reduces gastric acid secretion and may affect the absorption of drugs whose bioavailability depends on gastric pH, such as ketoconazole, iron salts, and digoxin.

With food & others: Administration of Naproxen and Esomeprazole together with high-fat meals in healthy individuals does not significantly affect the extent of naproxen absorption, but it prolongs time to peak concentration (tmax) by about 10 hours and reduces peak plasma concentration (Cmax) by approximately 12%.

• Hypersensitivity to any component of this tablet or substituted benzimidazoles.
• History of asthma, urticaria, or other allergic reactions after aspirin or other NSAID use.
• Use during the peri-operative period of coronary artery bypass graft (CABG) surgery.

The inclusion of immediate-release esomeprazole reduces gastrointestinal adverse effects associated with naproxen. Compared to naproxen alone, this combination significantly lowers the incidence of gastric ulcers and NSAID-related upper GI complications. Naproxen: Clinical and epidemiological data indicate that coxibs and some NSAIDs (especially at high doses or long-term use) may slightly increase the risk of arterial thrombotic events such as myocardial infarction or stroke. Although naproxen (1000 mg daily) may have a comparatively lower risk, it cannot be completely excluded. Edema, hypertension, and cardiac failure have also been reported with NSAID use. The most common adverse effects are gastrointestinal, including peptic ulcer, perforation, or GI bleeding, which may sometimes be fatal, particularly in elderly patients. Reported symptoms include nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of ulcerative colitis or Crohn’s disease. Gastritis has also been reported occasionally.

Pregnancy: In women planning pregnancy or during the first and second trimesters, this combination should be used only if the potential benefit outweighs the risk to the fetus. It is contraindicated in the third trimester of pregnancy.

Breast-feeding: Naproxen is excreted in small amounts in breast milk. It is unknown whether esomeprazole is excreted in human milk. Therefore, this medicine should not be used during breastfeeding.

Fertility: NSAIDs such as naproxen may impair female fertility. Therefore, this combination is not recommended for women trying to conceive.

General: The use of Naproxen and Esomeprazole tablet together with other NSAIDs, including COX-2 selective inhibitors, should be avoided due to the increased risk of serious NSAID-related adverse effects. This combination may be used with low-dose acetylsalicylic acid when necessary. Adverse effects can be reduced by using the lowest effective dose for the shortest possible duration. Risk factors for NSAID-related gastrointestinal complications include advanced age, concurrent use of anticoagulants, corticosteroids, other NSAIDs (including low-dose aspirin), cardiovascular disease, Helicobacter pylori infection, and a history of peptic ulcer or upper GI bleeding. In conditions such as inducible porphyria, systemic lupus erythematosus, and mixed connective tissue disease, Naproxen should be used only after careful benefit-risk assessment. Long-term users, especially beyond one year, require regular monitoring.

Older people: Elderly patients have a higher risk of adverse effects, particularly gastrointestinal bleeding and perforation, which may be fatal. The esomeprazole component reduces the incidence of ulcers in this group.

Gastrointestinal effects: Serious GI bleeding, ulceration, or perforation may occur at any time during NSAID therapy, with or without warning symptoms. The risk increases with higher doses, history of ulcers (especially with complications), and in elderly patients. Treatment should start with the lowest effective dose. Protective therapy (e.g., proton pump inhibitors or misoprostol) should be considered in high-risk patients, including those taking low-dose aspirin or other drugs that increase GI risk. Patients with prior gastrointestinal disease (ulcerative colitis, Crohn’s disease) should be monitored as NSAIDs may worsen these conditions. Esomeprazole may still allow dyspepsia to occur and may slightly increase the risk of gastrointestinal infections such as Salmonella and Campylobacter. Long-term acid suppression may reduce absorption of vitamin B12. If GI bleeding occurs, treatment should be discontinued immediately.

Cardiovascular and cerebrovascular effects: NSAIDs may cause fluid retention, edema, and may worsen hypertension or heart failure. Caution is required in patients with hypertension, heart failure, ischemic heart disease, peripheral arterial disease, or cerebrovascular disease. Long-term use in patients with cardiovascular risk factors (e.g. smoking, diabetes, hyperlipidemia) requires careful evaluation.

Renal effects: Long-term NSAID use may cause renal papillary necrosis and other kidney damage.

Elderly: Total plasma levels of naproxen may remain unchanged, but free drug levels may increase. Use the lowest effective dose and adjust if necessary.

Renal impairment: Not recommended in moderate to severe renal impairment (creatinine clearance <30 ml/min).

Hepatic impairment: Use with caution in mild to moderate liver impairment with possible dose adjustment. Not recommended in severe hepatic impairment.

Naproxen overdose symptoms: Lethargy, dizziness, drowsiness, abdominal pain, nausea, vomiting, heartburn, indigestion, liver function changes, metabolic acidosis, renal dysfunction, apnea, confusion, and gastrointestinal bleeding. Severe cases may lead to hypertension, acute renal failure, respiratory depression, or coma.

Esomeprazole overdose symptoms: Usually mild and transient; even high doses (up to 80 mg single dose or >240 mg/day) have shown limited toxicity.

Management: Treatment is mainly supportive and symptomatic. No specific antidote exists. Naproxen is not effectively removed by dialysis due to high protein binding. Activated charcoal may be useful if taken within 4 hours. Forced diuresis or urine alkalinization is not effective. Esomeprazole overdose is also managed symptomatically.

Drugs for Osteoarthritis ,Drugs for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Store below 30°C, protect from light and moisture. Keep out of reach of children.