ETX Tablet

Indication:

- Symptomatic relief of rheumatoid arthritis, osteoarthritis (OA) and acute gouty arthritis.

Dosage and administration:

- In osteoarthritis, etoricoxib is given orally in a usual dose of 30 once daily, increased to 60 mg once daily if necessary. The recommended dose in rheumatoid arthritis is 90mg once daily, higher doses of 120mg once daily are used in gouty arthritis although such doses should only be used for the acute symptomatic period and for a maximum of 8 days.

Etoricoxib is contraindicated in patients with:

- Hypersensitivity to any component of this product. A history of asthma, urticaria, or other allergic reactions after taking aspirin or other NSAID's.

- Congestive heart failure (NY HA II-IV).

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

- Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty).

- Severe hepatic dysfunction (serum albumin <25 g/1 or Child-Pugh score ≥ 10, see footnote) active peptic ulceration or gastrointestinal (GI) bleeding

- Estimated creatinine clearance < 30mL/min

Etoricoxib should not be used as adjunctive therapy with other NSAID's due to the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions.

Hypersensitivity reactions including anaphylaxis and angioedema have occurred in patients receiving etoricoxib; it should be stopped at the first signs of hypersensitivity. Etoricoxib should be avoided in patients with severe hepatic impairment (Child-Pugh score of 10 or more).

The following are some of the side effects that are known to be associated with this medicine. Common (affect between 1 in 11 and 1 in 100people)

Excessive fluid retention in the body tissues, resulting in swelling (oedema). dizziness, Headache, High blood pressure (hypertension). Awareness of your heartbeat (palpitations). Disturbances of the gut such as diarrhoea, nausea, Uncommon (affect between 1 in 100 and 1 in 1000 people)

Change in appetite, weight gain, Anxiety or depression, Difficulty sleeping (insomnia), Change in taste, Changes in sensation, eg pins and needles or

Tingling sensations, Blurred vision, Nosebleeds (epistaxis). Very rare (affect less than 1 in 10,000 people) Ulceration or bleeding in the stomach or intestine (see warning section above for more information). Liver or kidney disorders, Confusion.

Diuretics, Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin II Antagonists (AIIAs): Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the antihypertensive effect of diuretics, ACE inhibitors and AIIAs. This interaction should be given consideration in patients taking etoricoxib concomitantly with these products.

Aspirin: Etoricoxib can be used concomitantly with low-dose aspirin at doses for

cardiovascular prophylaxis. At steady state, etoricoxib 120mg once daily had no effect on the anti-platelet activity of low-dose aspirin (81 mg once daily)

Digoxin: Etoricoxib 120mg once daily for IO days did not alter the steady state plasma AUC0- 24hr or renal elimination of digoxin. Therefore, digoxin and etoricoxib may be co-administered without dose adjustment

Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400mg once a day increased the AUC of etoricoxib by 43%. The clinical significance of this increase is not known. Oral Contraceptives: Etoricoxib 60mg given concomitantly with an oral contraceptive containing 35mcg ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC 0-24hr of EE by 37%. Etoricoxib 120mggiven with the same oral contraceptive, concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib.

Caution should be exercised in patients with history-of heart, liver, kidney disease, high blood pressure, blood clotting disorder, any allergy, children, elderly, during pregnancy and breast feeding. Drink adequate fluid to avoid dehydration. Stop the medication immediately if gastrointestinal lesions occur. Monitor blood pressure regularly while taking this medication. When using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction, medically appropriate supervision should be maintained. If these patients deteriorate during treatment, appropriate measures should be taken, including discontinuation of therapy.

Etoricoxib is a member of a new class of agents called Coxibs. 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 GI toxicity and effects on platelet aggregation.