Nosmen Special Precautions

Cardiovascular: NSAIDs are associated with an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events including MI and stroke. Risk may be increased with long-term use or preexisting cardiac risk factors (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). Carefully evaluate individual cardiovascular profiles prior to prescribing and periodically reevaluate the need for symptomatic relief and response to therapy.
The cardiovascular safety of etoricoxib has been assessed in the MEDAL program which pooled data from 3 studies involving over 30,000 patients with either osteoarthritis or rheumatoid arthritis. Patients with osteoarthritis were given etoricoxib 60 or 90 mg daily; those with rheumatoid arthritis received 90 mg daily. In all studies, diclofenac 150 mg daily was given as the comparator. After an average treatment duration of 18 months, the rate of thrombotic events such as myocardial infarction, stroke, and sudden or unexplained death with etoricoxib were similar to those for diclofenac. One of the 3 studies showed that there was a non-significant increase in the rate of heart failure with etoricoxib 90 mg daily compared to diclofenac.
In another study that pooled pre-licensing data, the risk of thrombotic events with etoricoxib, given at a dose of at least 60 mg daily, was also found to be similar to that for placebo treatment, ibuprofen 2.4 g daily, diclofenac 150 mg daily and naproxen 1 g daily, although there was a trend towards more events with etoricoxib than with naproxen. The EMEA's Committee for Medicinal Product for Human Use (CHMP) has recommended the inclusion of a warning in the labelling of etoricoxib that it must not be given to patients whose blood pressure is persistently above 140/90 mmHg and inadequately controlled; in addition, high blood pressure should be controlled before starting treatment and monitored for 2 weeks afterwards then regularly thereafter. Etoricoxib should be used the shortest duration possible and lowest effective daily dose. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically.
New onset or worsening edema and heart failure may occur. Use caution with preexisting edema (any cause), left ventricular dysfunction, or NYHA class I heart failure. Use is contraindicated with NYHA class II-IV heart failure. Discontinue use if worsening heart failure, edema, or uncontrolled/severe hypertension occurs.
Hepatic: Elevations in transaminases (three or more times the upper limit of normal) may occur; monitor hepatic function closely in patients with previous abnormal hepatic function test or signs/symptoms of hepatic dysfunction. Severe hepatic reactions (e.g. hepatitis, jaundice, liver failure) have (rarely) occurred with use, discontinue if signs or symptoms of hepatic disease develop, if systemic manifestations occur, or with persistent or worsening abnormal hepatic function test.
Renal: Long-term administration of NSAIDs has resulted in renal papillary necrosis. NSAIDs use may compromise existing renal function through a dose-dependent decrease in prostaglandin synthesis, resulting in a reduction in renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, ACE inhibitors, angiotensin II receptor blockers and elderly are at greater risk for renal toxicity.
Etoricoxib should be used with caution in patients with renal impairment; the lowest effective dose should be used for the shortest possible duration, and renal function should be monitored. Sodium and water retention may occur and renal function may deteriorate, possibly leading to renal failure; deterioration in renal function has also been reported after topical use. Avoid if eGFR less than 30 ml/minute/1.73 m².
Gastro-intestinal: It is generally accepted that the inhibition of cyclo-oxygenase-1 (COX-1) plays a role in the adverse gastrointestinal effects of the NSAIDs, and COX-2 by NSAIDs such as etoricoxib may cause less gastrotoxicity than that seen with the non-selective inhibition of the traditional NSAIDs. In addition, etoricoxib should not be used in patients with active gastrointestinal ulceration or bleeding. In a study of the pooled data from 3 randomised clinical studies, etoricoxib (in doses of 60 or 90 mg daily) was associated with significantly less frequent upper gastrointestinal clinical events than diclofenac (150 mg daily).
Use caution with history of GI disease (bleeding or ulcer), concurrent therapy with aspirin or other NSAIDs, anticoagulants and/or corticosteroids, smoking, alcohol, and the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; consider alternate therapies for high-risk patients. When used concomitantly with aspirin (even at low doses), gastroprotective therapy (e.g. proton pump inhibitors, misoprostol) is recommended.
Skin: Serious hypersensitivity reactions, including anaphylaxis, angioedema, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been (rarely) reported with etoricoxib; discontinue use at first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticarial with NSAIDs or aspirin therapy.
Use in Patients with Infection: Etoricoxib may mask the signs and symptoms of infection resulting in delayed diagnosis.