Non-steroidal anti-inflammatory drugs (NSAIDs).

Generic

Each tablet contains 200mg Ibuprofen.

Coated tablet. White, sugar coated tablets smooth in texture with a polished surface. 'Anadin I' printed on one side.

GSL For the relief of mild to moderate pain including rheumatic and muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness and for the relief of the symptoms of cold and influenza.

For oral administration and short-term use only.

Adults, the elderly and young persons over 12 years of age:

The minimum effective dose should be used for the shortest time necessary to relieve symptoms. If the product is required for more than 10 days or if the symptoms worsen, the patient should consult a doctor.

1 or 2 tablets to be taken up to three times a day, as required. The tablets should be taken with water.

Leave at least 4 hours between doses and do not take more than 1200mg (6 tablets) in any 24 hour period.

Not to be given to children under 12 years of age.

20mg/kg/day in divided doses. In children weighing less than 30kg, maximum daily dose should not exceed 500mg. Not recommended in children weighing less than 7kg.

Hypersensitivity to ibuprofen or any of the constituents in the product.

Ibuprofen is contra-indicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angiodema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.

Active or previous peptic ulcer (two or more episodes of proven ulceration or bleeding).

History of upper gastrointestinal bleeding or perforation, related to previous NSAID therapy.

Patients with severe hepatic failure, renal failure or heart failure.

Use in last trimester of pregnancy.

Caution is required in patients with certain conditions:

• Systemic lupus erythematosus as well as those with mixed connective tissue disease due to increased risk of aseptic meningitis.

• Gastrointestinal disorders and chronic inflammatory intestinal disease as these conditions may be exacerbated (ulcerative colitis, Crohn's disease.

• Caution is required prior to starting treatment in patients with a history of hypertension and or heart/failure. Oedema, hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur.

• Renal impairment as renal function may deteriorate.

• Hepatic dysfunction.

Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration to control symptoms (see GI and cardiovascular risks below).

The elderly are at increased risk of the serious consequences of adverse reactions.

Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease.

Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors.

SLE and mixed connective tissue disease

Systemic lupus erythematosus and mixed connective tissue disease due to increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. 1200mg daily) is associated with an increased risk of myocardial infarction.

There is some evidence that drugs, which inhibit cyclo-oxygenase/prostaglandin synthesis, may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

Gastro-intestinal (GI) bleeding, ulceration, or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI effects (including ulcerative colitis, Crohn's disease).

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, and in the elderly . These patients should commence treatment on the lowest dose available.

Patients with a history of GI toxicity, 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 receiving concomitant medications which could increase the risk of gastrotoxicity or bleeding, such as corticosteroids, or anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

Where GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn immediately.

Dermatological

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. 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. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Patients with rare hereditary problems of fructose intolerance should not take this medicine as this product contains sucrose.

Each tablet contains 67mg of sucrose. This should be taken into account in patients with diabetes mellitus.

The label will include:

Do not take if: You have or have ever had a stomach ulcer, or stomach bleeding or a perforation due to NSAIDs. You are allergic to ibuprofen or aspirin, any other NSAID or any of the ingredients listed on the enclosed leaflet.

Talk to a pharmacist or your doctor before taking this medicine if you are pregnant, breast-feeding, asthmatic, or if you suffer from kidney, heart or liver problems.

Ibuprofen should not be used in combination with:

Aspirin: unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex-vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Other NSAIDs including cyclooxygenase-2 selective inhibitors: as these may increase the risk of adverse effects.

Ibuprofen should be used with caution in combination with:

Corticosteroids: may increase the risk of adverse reactions, especially of the gastrointestinal tract.

Antihypertensives and diuretics: NSAIDs may diminish the effects of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Anticoagulants: NSAIDS may enhance the effects of anticoagulants, such as warfarin.

Anti-platelet agents and selective serotonin-reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: There is evidence for potential increase in plasma levels of lithium.

Methotrexate: There is the potential for increased plasma levels of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Tacrolimus: Possible increase risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV positive haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Hypersensitivity reactions have been reported and these may consist of

a) Non specific allergic reactions and anaphylaxis,

b) Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea or

c) Various skin reactions, e.g. pruritus, urticaria, angioedema, and more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis, and erythema multiforme).

The list of the following adverse effects relates to those experienced with ibuprofen at OTC doses, from short-term use. In chronic conditions, under long-term treatment, additional adverse effects may occur.

Clinical trial and epidemiological data suggest that use of ibuprofen (particularly at high doses 2400mg daily) and in long-term treatment may be associated with a small increases risk of arterial thrombotic events (for example myocardial infarction or stroke).

Wyeth Consumer Healthcare

GSL

21 November 2011