Arcoxia Special Precautions

Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with an increased risk of thrombotic events (especially MI and stroke), relative to placebo and some NSAIDs (naproxen). As the cardiovascular risks of selective COX-2 inhibitors 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.
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with etoricoxib after careful consideration.
Selective COX-2 inhibitors are not a substitute for aspirin for cardiovascular prophylaxis because of their lack of effect on platelets. Because etoricoxib, a member of this class, does not inhibit platelet aggregation, antiplatelet therapies should not be discontinued.
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) for etoricoxib, other selective COX-2 inhibitors and NSAIDs, when taken concomitantly with acetylsalicylic acid (even at low doses). The relative difference in gastrointestinal safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been adequately evaluated in long-term clinical trials.
In patients with advanced renal disease, treatment with ARCOXIA is not recommended. Clinical experience in patients with estimated creatinine clearance of <30 mL/min is very limited. If therapy with ARCOXIA must be initiated in such patients, close monitoring of the patient's renal function is advisable.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of ARCOXIA may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Patients at greatest risk of this response are those with pre-existing significantly impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients should be considered.
Caution should be used when initiating treatment with ARCOXIA in patients with considerable dehydration. It is advisable to rehydrate patients prior to starting therapy with ARCOXIA.
As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and hypertension have been observed in some patients taking ARCOXIA. The possibility of fluid retention, edema or hypertension should be taken into consideration when ARCOXIA is used in patients with pre-existing edema, hypertension, or heart failure. All Nonsteroidal Anti-inflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent congestive heart failure (see SIDE EFFECTS). Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, special attention should be paid to blood pressure monitoring during treatment with etoricoxib. If blood pressure rises significantly, alternative treatment should be considered.
Physicians should be aware that individual patients may develop upper gastrointestinal (GI) ulcers/ulcer complications irrespective of treatment. Although the risk of GI toxicity is not eliminated with ARCOXIA, the results of the MEDAL Program demonstrate that in patients treated with ARCOXIA, the risk of GI toxicity with ARCOXIA 60 mg or 90 mg once daily is significantly less than with diclofenac 150 mg daily. In clinical studies with ibuprofen and naproxen, the risk of endoscopically detected upper GI ulcers was lower in patients treated with ARCOXIA 120 mg once daily than in patients treated with the non-selective NSAIDs. While the risk of endoscopically detected ulcers was low in patients treated with ARCOXIA 120 mg it was higher than in patients treated with placebo. Upper GI ulcers/ulcer complications have occurred in patients treated with ARCOXIA. These events can occur at any time during use and without warning symptoms. Independent of treatment, patients with a prior history of GI perforation, ulcers and bleeding (PUB) and patients greater than 65 years of age are known to be at a higher risk for a PUB.
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials treated for up to one year with ARCOXIA 30, 60 and 90 mg daily. In active comparator portions of clinical trials, the incidence of elevated AST and/or ALT in patients treated with ARCOXIA 60 and 90 mg daily was similar to that of patients treated with naproxen 1000 mg daily, but notably less than the incidence in the diclofenac 150 mg daily group. These elevations resolved in patients treated with ARCOXIA, with approximately half resolving while patients remained on therapy. In controlled clinical trials of ARCOXIA 30 mg daily versus ibuprofen 2400 mg daily or celecoxib 200 mg daily, the incidence of elevations of ALT or AST was similar.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for persistently abnormal liver function tests. If persistently abnormal liver function tests (three times the upper limit of normal) are detected, ARCOXIA should be discontinued.
ARCOXIA should be used with caution in patients who have previously experienced acute asthmatic attacks, urticaria, or rhinitis, which were precipitated by salicylates or non-selective cyclooxygenase inhibitors. Since the pathophysiology of these reactions is unknown, physicians should weigh the potential benefits of prescribing ARCOXIA versus the potential risks.
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.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see SIDE EFFECTS). These serious events may occur without warning. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see SIDE EFFECTS). Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
ARCOXIA may mask fever, which is a sign of infection. The physician should be aware of this when using ARCOXIA in patients being treated for infection.
Use in Children: Safety and effectiveness of etoricoxib in pediatric patients have not been established.
Use in the Elderly: Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young. In clinical studies, a higher incidence of adverse experiences was seen in older patients compared to younger patients; the relative differences between etoricoxib and control groups were similar in the elderly and the young. Greater sensitivity of some older individuals cannot be ruled out.