Abbott Healthcare Products Limited

Brufen Paediatric 100mg/5ml oral suspension.

Each 5ml contains 100mg Ibuprofen

Excipients: Each 5ml also contains:

5mg methyl parahydroxybenzoate (E218)

2.5mg propyl parahydroxybenzoate (E216)

500mg sorbitol solution non-crystallising (E420)

3.3 g sucrose

0.5mg sunset yellow FC edicol (E110)

For full list of excipients, see section 6.1.

Oral suspension

Orange-coloured and flavoured syrup-like suspension.

Brufen Paediatric Oral Suspension is indicated in the management of various arthroses such as rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's Disease) and osteoarthritis, fibrositis, ankylosing and other muscular syndromes such as low back pain, soft tissue trauma and various inflammations of tendon, joint capsules and ligaments.

As an analgesic in the relief of mild to moderate pain.

For the treatment of pyrexia in children.

For oral administration.

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

Adults: The recommended dosage of Brufen is 1200-1800 mg daily in divided doses. Some patients can be maintained on 600-1200 mg daily. Total daily dose should not exceed 2400 mg.

Children: The recommended dose of Brufen is 20 mg per kg of bodyweight daily in divided doses. This can be achieved as follows:

1-2 years: 2.5 ml (50 mg) three to four times a day.

3-7 years: one 5 ml spoonful (100 mg) three to four times a day.

8-12 years: two 5 ml spoonfuls (200 mg) three to four times a day.

In juvenile rheumatoid arthritis, the daily dosage may be increased to 40 mg/kg bodyweight daily in severe cases. In children weighing less than 30 kg, the total daily dose of Brufen should not exceed 500 mg.

Elderly: no special dosage modifications are required, unless renal or hepatic function is impaired, in which case dosage should be assessed individually.

Brufen is contraindicated in patients with known hypersensitivity to the active substance or to any of the inactive ingredients.

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

Brufen is contraindicated in patients with severe heart failure.

Brufen should not be used in patients with known hypersensitivity or who have experienced asthma, urticaria or allergic-type reactions after taking Brufen, aspirin or other NSAIDs.

General Precautions

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, Posology and method of administration, and GI and cardiovascular risks below). Patients treated with NSAIDs long-term should undergo regular medical supervision to monitor for adverse events.

Caution is required if Brufen Paediatric Oral Suspension is administered to patients suffering from, or with a previous history of, bronchial asthma since ibuprofen has been reported to cause bronchospasm in such patients.

Caution is required in patients with renal, hepatic or cardiac impairment since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and assessment of renal function should be monitored prior to the initiation of therapy and regularly thereafter.

Caution is required in patients with a history of heart failure and/or hypertension as fluid retention and oedema has been reported in association with NSAID therapy.

The use of ibuprofen 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 ibuprofen should be considered.

Elderly: the elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2, Posology and method of administration).

As with other NSAIDs, ibuprofen may mask the signs of infection.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malaabsorption or sucrase-isomaltase insufficinency should not take this medicine.

Brufen contains 3.3 g of sucrose per 5ml dose. This should be taken into account in patients with diabetes mellitus. May be harmful to the teeth.

The excipients methyl parahydroxybenzoate (E218), propylparahydroxybenzoate (E216) and sunset yellow FC edicol (E110) may cause allergic reactions (possibly delayed).

The use of Brufen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the potential for additive effects.

Gastrointestinal bleeding, ulceration and perforation:

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 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, Contraindications), 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 requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (See below and 4.5, Interaction with other medicinal products and other forms of interactions).

Patients with a history of GI 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 receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (See section 4.5, Interaction with other medicinal products and other forms of interactions).

When GI bleeding or ulceration occurs in patients receiving Brufen, 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 their condition may be exacerbated (See section 4.8, Undesirable effects).

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 data suggest that use of ibuprofen, particularly at a high dose (2400 mg/ 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.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Renal Effects

Caution should be used when initiating treatment with Brufen in patients with considerable dehydration.

As with other NSAIDs, long-term administration of Brufen has resulted in renal papillary necrosis and other renal pathological changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependant reduction in prostaglandins formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those who are taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

Haematological Effects

As NSAIDs can interfere with platelet function and may prolong bleeding time, Brufen should be used with caution in patients with intracranial haemorrhage and bleeding diathesis.

Dermatological Effects

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 4.8, Undesirable effects). Patients appear to be at the highest risk of 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. Brufen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Aseptic Meningitis

Aseptic meningitis has been observed on rare occasions in patients with Brufen therapy. Although it is probably more likely to occur in patients with systematic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision.

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

Antihypertensives: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors.

Diuretics: NSAIDs may reduce the diuretic effect. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

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

Lithium: NSAIDs may decrease elimination of lithium.

Methotrexate: NSAIDs may decrease elimination of methotrexate.

Cyclosporin: increased risk of nephrotoxicity with NSAIDs.

Other analgesics including cyclooxygenase-2 selective inhibitors: avoid concomitant use of two or more NSAIDs, (including aspirin) as this may increase the risk of adverse effects (see section 4.4).

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding with NSAIDs (See section 4.4, Special warnings and precautions for use)

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (See section 4.4, Special warnings and precautions for use).

Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.

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 use (see section 5.1).

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding with NSAIDs (See section 4.4, Special warnings and precautions for use).

Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

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

Probenacid: there have been no reports of interactions between probenacid and ibuprofen. However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites.

Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.

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

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

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy should be avoided except under compelling circumstances. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (closure of the ductus arteriosus), ibuprofen should not be used in the third trimester of pregnancy.

Labour and delivery: Administration of ibuprofen is not recommended during labour and delivery. The onset of labour may be delayed and the duration increased with a greater bleeding tendency in both mother and child.

In limited studies to date, ibuprofen appears in breast milk in very low concentrations. Brufen is not recommended for use in nursing mothers.

No adverse effects known.

Immune system disorders:

Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely , bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

Gastrointestinal disorders:

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, Special warnings and precautions for use). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (See section 4.4 - Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Other adverse events reported include:

Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (2400 mg/ daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4, Special warnings and precautions for use)).

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and haemolytic anemia.

Psychiatric disorders: depression, confusion, hallucinations

Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness

Eye disorders: disturbances of vision, optic neuritis

Ear and labyrinth disorders: vertigo, tinnitus

Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis, jaundice

Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare).

General disorders and administration site conditions: malaise, fatigue.

Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Symptoms include nausea, vomiting, dizziness, convulsion, loss of consciousness and depression of the CNS and respiratory system. Large overdoses are generally well tolerated when no other drugs are involved.

Treatment consists of gastric lavage and, if necessary, correction of serum electrolytes and appropriate supportive measures.

There is no specific antidote to ibuprofen.

Ibuprofen is a propionic acid derivative, having analgesic, anti-inflammatory and anti-pyretic activity. The drug's therapeutic effect as a non-steroidal anti-inflammatory drug is thought to result from its inhibitory activity on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. 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.

Ibuprofen is rapidly absorbed from the gastrointestinal tract, peak serum concentrations occurring 1-2 hours after administration. The elimination half-life is approximately 2 hours.

Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney either as such or as conjugates. Excretion by the kidney is both rapid and complete.

Ibuprofen is extensively bound to plasma proteins.

Not applicable.

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Sucrose

Citric Acid Monohydrate

Sodium Benzoate (E211)

Agar BPC '54 Pdr

Glycerol (E422)

Sorbitol Solution Non-Crystallising (E420)

Irradiated Light Kaolin

Polysorbate 80

Sunset Yellow FC Edicol (E110)

Orange Flavour D717

Purified Water

Not applicable

3 years.

Once opened, the contents of the bottle should be used within 12 months.

No special storage conditions

A 200 ml amber-coloured polyethylene terepthalate (PET) bottle with a pilfer-proof neck finish, fitted with an aluminium cap fitted with a LDPE liner.

No special requirements.

Abbott Laboratories Ireland Limited

4051 Kingswood Drive

Citywest Business Campus

Dublin 24

PA 38/80/6

Date of first authorisation: 02 March 1981

Date of last renewal of authorisation: 02 March 2011

November 2011