- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- Company information
- More information about this medicine
AdultsThe recommended daily dose is 10 ml suspension (1 g) taken as a single dose at bedtime. For severe or persistent symptoms, or during acute exacerbations, an additional 5 or 10 ml suspension (500 mg-1 g) may be given as a morning dose.
ElderlyIn common with many drugs, blood levels may be higher in elderly patients. The recommended daily dose of 10 ml (1 g) should not be exceeded in this age group and in some cases 5 ml (500 mg) may give satisfactory relief. The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored for gastrointestinal bleeding during NSAID therapy.
ChildrenThere are no clinical data to recommend use of Relifex in children.
ElderlyThe elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).Respiratory Disorders:Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Cardiovascular Renal and Hepatic Impairment:The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. In patients with severe renal impairment (creatinine clearance less than 30 ml/minute): laboratory tests should be performed at baseline and within some weeks of starting therapy. Further tests should be carried out as necessary; if the impairment worsens, discontinuation of therapy may be warranted. In moderate renal impairment (creatinine clearance 30 to 49 ml/min) there is a 50 % increase in unbound plasma 6-MNA and dose reduction may be warranted (see section 4.5).As with other NSAIDs, abnormalities of liver function tests, rare cases of jaundice and hepatic failure (some of them with fatal outcomes), have been reported. A patient with signs/symptoms suggesting liver dysfunction or who has experienced an abnormal liver function test while on nabumetone therapy should be evaluated for evidence of development of a more serious hepatic reaction. Nabumetone should be discontinued if such a reaction occurs.
Cardiovascular and cerebrovascular effects:Appropriate monitoring and therapy should be instigated if warranted 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.Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are 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. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
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. The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients required concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).Patients with a history of GI peptic disease, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.Caution should be advised in patients received concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anti-coagulants such as warfarin, NSAIDs, selective serotonin re-uptake inhibitors or anti-platelet agents such as aspirin and clopidogrel (see section 4.5).When GI bleeding or ulceration occurs in patients receiving nabumetone, the treatment should be withdrawn.NSAIDS should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8). In patients with active peptic ulcer, physicians must wheigh the benefits of therapy with nabumetone against possible hazards, institute an appropriate ulcer treatment regimen and monitor the patients' progress carefully.Nabumetone is better tolerated than most other NSAIDs, primarily because it results in fewer effects on the gastrointestinal (GI) system. In a review of both pre- and post-registration data from clinical trials with nabumetone, the mean cumulative frequencies of GI perforations, ulcers or bleeds (PUBs) in patients treated from 3 to 6 months, 1 year and 2 years were respectively 0.3 %, 0.5 % and 0.8 %; although these figures are lower than those ascribed to other NSAIDs, the prescribing physician should be aware that these ADR can occur even in the absence of previous peptic disease.Despite the relative gastrointestinal and renal safety of nabumetone, caution should be used when administering to patients with:- active upper GI ulceration. Appropriate treatment should be instigated prior to initiating nabumetone therapy.- previous aspirin- or other NSAID-induced asthma, urticaria or other allergic type reactions. Since fatal asthma attacks have been reported in such patients receiving other NSAIDs, the first administration of nabumetone should be medically supervised.
SLE and mixed connective tissue disease:In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders, there may be an increased risk of aseptic meningitis (see section 4.8).
Dermatological: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 (see section 4.8). 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. Relifex should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Impaired female fertilityThe use of Relifex may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Relifex should be considered.NSAIDs could hide signs of infectious disease.Cases of blurred vision or reduced visual activity have been reported with NSAID use, including nabumetone. Patients presenting with these events must be submitted to ophtalmological examination.
|Blood and lymphatic system disorders|
|Not known:||Neutropenia, agranulocytosis, leucopenia, aplastic anaemia and haemolytic anaemia.|
|Immune system disorders|
|Very rare:||Anaphylaxis, anaphylactoid reaction|
|Uncommon:||Confusion, nervousness, insomnia|
|Not known:||Depression, hallucinations|
|Nervous system disorders|
|Uncommon:||Somnolence, dizziness, headache, paraesthesia|
|Not known:||Aseptic meningitis (especially in patients with existing autoimmune disorders such as systemic lupus erythematosus, mixed connective tissue disease, with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4)), vertigo, drowsiness|
|Uncommon:||Abnormal vision, eye disorder|
|Not known:||Optic neuritis|
|Ear and labyrinth disorders|
|Common:||Tinnitus, ear disorder|
|Common:||Increases in blood pressure|
|Respiratory, thoracic and mediastinal disorders|
|Uncommon:||Dyspnoea, respiratory disorder, epistaxis|
|Very rare:||Interstitial pneumonitis|
|Not known:||Asthma, aggravated asthma, bronchospasm|
|Common:||Diarrhoea, constipation, dyspepsia, gastritis, nausea, abdominal pain, flatulence|
|Uncommon:||Duodenal ulcer, Gl bleeding, gastric ulcer, Gl disorder, melena, vomiting, stomatitis, dry mouth|
|Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration. Less frequently, gastritis has been observed.|
|Very rare:||Hepatic failure, jaundice|
|Skin and subcutaneous tissue disorders|
|Uncommon:||Photosensitivity, urticaria, sweating|
|Very rare:||Bullous reactions induding toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiforme, angioedema, pseudoporphyria, alopecia|
|Musculoskeletal and connective tissue disorders|
|Renal and urinary disorders|
|Uncommon:||Urinary tract disorder|
|Very rare:||Renal failure, nephrotic syndrome|
|Not known:||Interstitial nephritis|
|Reproductive system and breast disorders|
|General disorders and administration site conditions|
|Uncommon:||Elevated liver function tests|
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