NABUMETONE

Posology Adults:

The usual starting dose is 1g (two tablets) per day taken as a single daily dose at bedtime. For severe or persistent symptoms, or during acute exacerbations an additional 500mg- 1g may be given as a morning dose.

Elderly:

Blood levels may be higher in elderly patients because of accumulation of the drug as a result of reduced metabolism and elimination by the liver and kidneys. The recommended daily dose of 1g should not be exceeded in this age group and in some cases 500mg may give satisfactory relief.

The risk of serious consequences of adverse effects is increased in the elderly. The lowest dose possible should be used and patients should be monitored for gastrointestinal bleeding for 4 weeks following initiation of therapy with nabumetone.

Children:

Not recommended as there is no clinical data. Method of Administration For oral administration. Nabumetone should be administered with or after food to minimise the risk of gastrointestinal adverse effects. 4).

4). Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports.

Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo and comparator groups has not been taken into account in estimation of these frequencies. Rare and very rare events were generally determined from spontaneous data.

Blood and lymphatic system disorders Very Rare:

Not known: Thrombocytopenia Anaemia (incl. 4)) Eye disorders Uncommon: Abnormal vision, eye disorder Ear and labyrinth disorders Common: Tinnitus, ear disorder Vascular disorders Common: Increases in blood pressure Respiratory, thoracic and mediastinal disorders Uncommon: Dyspnoea, respiratory disorder, epistaxis Very rare: Interstitial pneumonitis Gastrointestinal disorders Common: Diarrhoea, constipation, dyspepsia, gastritis, nausea, abdominal pain, flatulence Uncommon: Duodenal ulcer, GI bleeding, gastric ulcer GI disorder, melena, vomiting, stomatitis, dry mouth Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature.

4). 4) have been reported following administration. Less frequently, gastritis has been observed.

Hepatobiliary disorders Very rare:

Hepatic failure, jaundice Skin and subcutaneous tissue disorders Common: Rash, pruritus Uncommon: Photosensitivity, urticaria, sweating Very rare: Bullous reactions including toxic epidermal necrolysis, Stevens Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, angioedema, pseudoporphyria, alopecia Musculoskeletal and connective tissue disorders Uncommon: Myopathy Renal and urinary disorders Uncommon: Urinary tract disorder Very rare: Renal failure, nephrotic syndrome Reproductive system and breast disorders Very rare: Menorrhagia General disorders and administration site conditions Common: Oedema Uncommon: Asthenia, fatigue Investigations Uncommon: Elevated liver function tests Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

The use of nabumetone with concomitant NSAIDs, including cyclooxygenase- 2 selective inhibitors, should be avoided. Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms.

2). Gastrointestinal bleeding, ulceration and perforation GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

3) and in the elderly. These patients should commence treatment on the lowest dose available. g. 5). Patients with a history of GI peptic disease, particularly when elderly, should be alerted to report any unusual abdominal symptoms indicative for ulceration (especially GI bleeding), particularly in the initial stages of treatment.

5). When GI bleeding or ulceration occurs in patients receiving nabumetone, the treatment should be withdrawn. 8). 8%. Although these figures seem low, the prescribing physician should be aware that these ADR can occur even in the absence of previous peptic disease.

Cardiovascular and cerebrovascular effects Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure, as fluid retention and oedema have been reported in association with NSAID therapy.

g. myocardial infarction or stroke). There is insufficient data to exclude such a risk for nabumetone. Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with nabumetone after careful consideration.

g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). 8). At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, nabumetone should be withdrawn immediately and an alternative treatment considered (as appropriate).

1. • Nabumetone must not be given to patients who have experienced asthma, urticaria, or allergictype reactions after taking acetylsalicylic acid or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

• Nabumetone is contraindicated in patients with severe hepatic failure. • Nabumetone is contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. • Nabumetone is contraindicated in patients with active, or history of recurrent, peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

• Nabumetone is contraindicated in the third trimester of pregnancy and in nursing mothers. • Nabumetone is contraindicated in patients with severe heart failure, and in patients with current cerebrovascular or other haemorrhage.