SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Flurbiprofen Tablets BP 50 mg.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 50 mg of Flurbiprofen PhEur.

3    PHARMACEUTICAL FORM

Tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Flurbiprofen is a non-steroidal anti-inflammatory agent which has significant anti-inflammatory, analgesic and antipyretic properties and is indicated in the treatment of rheumatoid disease, osteoarthritis and ankylosing spondylitis.

4.2    Posology and method of administration

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Adults: The recommended daily dose is 150mg to 200 mg in divided doses. In patients with severe symptoms or disease of recent origin, or during acute exacerbations, the total daily dosage may be increased to 300 mg in divided doses.

Elderly: Although flurbiprofen is generally well tolerated in the elderly, some patients, especially with impaired renal function, may eliminate non-steroidal anti-inflammatory drugs more slowly than normal. In these cases flurbiprofen

should be used with caution and the dosage should be assessed individually. Therapy should start at the lowest recommended dose.

Children: Flurbiprofen is not indicated for use in children.

Method of administration: Oral; the tablets should be swallowed with a drink of water.

4.3 Contraindications

As with other non-steroidal anti-inflammatory drugs (NSAIDs) flurbiprofen should be avoided in patients with peptic ulceration or a history of peptic ulcer disease, gastrointestinal haemorrhage and ulcerative colitis.

Flurbiprofen should not be given to patients who have experienced bronchospasm, anaphylactoid reactions, angioedema or other hypersensitivity type reactions from the use of aspirin or other non-steroidal anti-inflammatory drugs.

Flurbiprofen is not indicated for use in children.

Severe heart failure.

4.4 Special warnings and precautions for use

Fluid retention and oedema have been reported in common with other nonsteroidal anti-inflammatory agents. Flurbiprofen should be used with caution in patients with a history of cardiac decompensation and hypertension.

Caution is necessary if given to patients with non-allergic asthma.

As it has been shown that flurbiprofen may prolong bleeding time, it should be used with caution in patients with a potential for abnormal bleeding.

Flurbiprofen should be used with caution in patients with renal or hepatic impairment.

The concomitant use of more than one NSAID is not recommended.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

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.

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 flurbiprofen.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with flurbiprofen 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).

4.5 Interaction with other medicinal products and other forms of interaction

Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.

Frusemide: Special clinical studies have shown that the diuretic response to frusemide can occasionally be reduced by flurbiprofen.

Anticoagulants: Interference with the action of anticoagulants has occasionally been reported.

Cyclosporin: Increased risk of nephrotoxicity with non-steroidal antiinflammatory drugs.

Corticosteroids: Increased risk of gastrointestinal bleeding.

Methotrexate: Decreased elimination of methotrexate. Mifepristone: NSAIDs should not be used for 8 - 12 days after administration of mifepristone as NSAIDs can reduce the effects of mifepristone.

Quinolone antibiotics: Studies have indicated that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. There may be an increased risk of developing convulsions in patients taking quinolone antibiotics and NSAIDs.

Antihypertensives: Reduced antihypertensive effect.

Lithium: Decreased elimination of lithium.

Other studies have failed to show any interaction between flurbiprofen and digoxin, tolbutamide or antacids.

4.6 Pregnancy and lactation

The safety of flurbiprofen during pregnancy or lactation has not been established. Pre-clinical studies have not revealed any teratogenic effects but parturition was delayed and prolonged.

4.7 Effects on ability to drive and use machines

No adverse effects known.

4.8 Undesirable effects

Side effects that have been reported include dyspepsia, nausea, vomiting, gastrointestinal haemorrhage, diarrhoea and ulcers of the mouth. Exacerbation of peptic ulceration and perforation have been reported. Urticaria, angioedema and rashes of varying descriptions have been reported.

Very rarely cholestatic jaundice has been reported, which is reversible on withdrawal of the drug. Thrombocytopenia has been reported. It is usually reversible on withdrawal of the drug. Very rarely aplastic anaemia and agranulocytosis have been reported in association with the use of flurbiprofen but causality has not been established.

Toxic nephropathies have been associated with the use of non-steroidal anti inflammatory agents in general and have rarely been reported in patients who have received flurbiprofen.

Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

4.9 Overdose

Treatment of overdosage includes gastric lavage and, if necessary, correction of serum electrolytes. There is no specific antidote to flurbiprofen.

5.1 Pharmacodynamic properties

Flurbiprofen has analgesic, anti-inflammatory and antipyretic properties. It is an inhibitor of the enzyme cyclo-oxygenase responsible for the biosynthesis of prostaglandins. Flurbiprofen produces gastrointestinal side effects in man, although these are usually less severe than with aspirin.

5.2 Pharmacokinetic properties

Flurbiprofen is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 90 minutes after ingestion. It is reported to be about 99% bound to plasma proteins and to have an elimination half life of about three to four hours. It is metabolised mainly by hydroxylation and conjugation and excreted in the urine.

5.3 Preclinical safety data

Not available.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose, maize starch, polyvidone, ethanol 96%*, colloidal silicon dioxide, stearic acid, magnesium stearate, polyvinylacetate phthalate, purified water*, ethyl acetate*, calcium carbonate, acacia, titanium dioxide E171, sucrose, sodium benzoate E211, polyvinylpyrrolidone, quinoline yellow aluminium lake E104, sunset yellow aluminium lake E110, purified talc, yellow carnauba wax, white beeswax and shellac. The printing ink contains industrial methylated spirits*, shellac, soya lecithin, n-butyl alcohol*, polydimethyl siloxane and the colour black iron oxide E172.

* Not detected in the finished product.

6.2 Incompatibilities

None known.

Shelf life

3 years.

6.4    Special precautions for storage

Store below 25 °C.

6.5    Nature and contents of container

1.    Blister strips composed of 250 pm transparent PVC and 20 pm hard temper aluminium foil, contained in a carton.

2.    Polypropylene tubes fitted with polyethylene caps. High density polyethylene film may be used as packing material.

Pack sizes: 50, 84, 100, 250, 500 and 1000 tablets.

6.6    Special precautions for disposal

None stated.

7    MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Limited T/A Genus Pharmaceuticals Park View House 65 London Road Newbury

Berkshire RG14 1JN, UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 06831/0235

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/03/2009

10    DATE OF REVISION OF THE TEXT

22/06/2009