Danilo

• Rheumatoid arthritis

Etoricoxib 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.

N/A

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.

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.

With medicine: Oral anticoagulants: In subjects stabilized on chronic warfarin therapy, the administration of Etoricoxib 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: Etoricoxib 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 Etoricoxib, 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.

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.

Administration of single doses of Etoricoxib 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.

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 Etoricoxib after careful consideration. Administration of Etoricoxib 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, Etoricoxib should be discontinued. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Etoricoxib may mask fever and other signs of inflammation. Caution should be exercised when co-administering Etoricoxib with warfarin or other oral anticoagulants.