Cox-E

• Cox-E tablet is indicated for the symptomatic relief of-
• Osteoarthritis (OA)
• Rheumatoid arthritis (RA)
• Ankylosing spondylitis, and

The pain and signs of inflammation associated with acute gouty arthritis.

For the short-term treatment of moderate pain associated with dental surgery.

Etoricoxib is a potent, orally active cyclooxygenase-2 (COX-2) specific inhibitor within, and significantly above, the clinical dose range. Two isoforms of cyclooxygenase have been identified: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is responsible for prostaglandin-mediated normal physiologic functions such as gastric cytoprotection and platelet aggregation. Inhibition of COX-1 by nonselective NSAIDs has been associated with gastric damage and inhibition of platelet aggregation. COX-2 has been shown to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. Selective inhibition of COX-2 by etoricoxib (within the clinical dose range) decreases these clinical signs and symptoms with decreased potential for Gl toxicity and effects on platelet aggregation. Etoricoxib produced dose-dependent inhibition of COX-2 without inhibition of COX-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric prostaglandin synthesis.

Adult and adolescent over 16 years:

Osteoarthritis : The recommended dose is 30 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 60 mg once daily may increase efficacy.

Rheumatoid arthritis : The recommended dose is 90 mg once daily.

Ankylosing spondylitis : The recommended dose is 90 mg once daily.

Acute gouty arthritis : The recommended dose is 120 mg once daily. In clinical trials for acute gouty arthritis, Etoricoxib was given for 8 days.

Postoperative dental surgery pain : The recommended dose is 90 mg once daily, limited to a maximum of 3 days.

Some patients may require additional postoperative analgesia. As the cardiovascular risks of Etoricoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis.

With medicine:

Oral anticoagulants : In subjects stabilized on chronic warfarin therapy, the administration of Cox-E was associated with an increase in prothrombin time.

Diuretics, ACE inhibitors and Angiotensin II Antagonists : NSAIDs may reduce the effect of diuretics and other antihypertensive drugs.

Acetylsalicylic Acid : Cox-E can be used concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose acetylsalicylic acid).

Ciclosporin and tacrolimus : Although this interaction has not been studied with Cox-E, coadministration of ciclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of ciclosporin or tacrolimus.

Lithium : NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels.

With food & others: Take without regards to meals.

Hypersensitivity to the active substance or to any of the excipients.

Active peptic ulceration or active gastro-intestinai (Gl) bleeding.

Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.

Pregnancy and lactation.

Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score 10).

Estimated renal creatinine clearance <30 ml/min.

Children and adolescents under 16 years of age.

Inflammatory bowel disease.

Congestive heart failure (NYHA ll-IV).

Patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg and has not been adequately controlled.

Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

Side-effects may include palpitation, fatigue, influenza-like symptoms, ecchymosis; less commonly dry mouth, taste disturbance, mouth ulcer, appetite and weight change, atrial fibrillation, transient ischaemic attack, chest pain, flushing, cough, dyspnoea, epistaxis, anxiety, mental acuity impaired, paraesthesia, electrolyte disturbance, myalgia and arthralgia; very rarely confusion and hallucinations.

The use of Etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in women attempting to conceive. It is not known whether Etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of lactating rats. Women who use Etoricoxib must not breastfeed.

Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or acetylsalicylic acid concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and Gl bleeding.

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with Cox-E after careful consideration.

Administration of Cox-E may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Monitoring of renal function in such patients should be considered.

Caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing edema from any other reason.

Any patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormalliver function test has occurred, should be monitored. If signs of hepatic insufficiency occur, or if persistently abnormal liver function tests (three times the upper limit of normal) are detected, Cox-E should be discontinued.

Cox-E should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Cox-E may mask fever and other signs of inflammation. Caution should be exercised when co-administering Cox-E with warfarin or other oral anticoagulants.

Administration of single doses of Cox-E up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity. In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the Gl tract, employ clinical monitoring, and institute supportive therapy, if required.

Store at a temperature of below 30°C, protect from light & moisture. Keep out of reach of children.