SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Ibuprofen Tablets BP 400mg Ibucalm 400mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains: Ibuprofen 400mg

3 PHARMACEUTICAL FORM

A pink biconvex round film coated tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

POM

Mild to moderate pain such as dysmenorrhoea, dental and post-operative pain and for the symptomatic relief of headache, including migraine headache.

Rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease)

Ankylosing spondylitis

Osteoarthritis

Sero-negative arthropathies

Pain relief of peri-articular disorders such as frozen shoulder (capsulitis), bursitis, tendinitis, tenosynovitis, low-back pain, and soft tissue injuries such as sprains and strains

P

Rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.

4.2 Posology and method of administration

POM

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

For oral administration - To be taken preferably with or after food.

Adults: 1200 to 1800mg daily in divided doses. Some patients can be maintained on 600 - 1200mg daily. Total dosage must not exceed 2400mg even in divided doses.

Children: 20mg/kg body weight in divided doses. For juvenile rheumatoid arthritis up to 40mg/kg body weight daily in divided doses. Children under 30kg must not receive more than 500mg daily even in divided doses. Not recommended for children weighing less than 7kg.

Elderly: 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 regularly for GI bleeding during NSAID therapy.

P

For oral administration and short-term use only.

Adults, the elderly and children over 12 years:

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

200mg - 400mg up to twice a day as required.

Leave at least four hours between doses and do not take more than 1200mg in any 24 hour period.

4.3 Contraindications

POM

Hypersensitivity to ibuprofen or to any of the constituents.

NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to Ibuprofen, Aspirin, or other non-steroidal anti-inflammatory drugs.

Severe hepatic, renal and cardiac failure (See section 4.4 - Special warnings and precautions for use).

During the last trimester of pregnancy (See section 4.6 - pregnancy and lactation).

Active or previous peptic ulcer.

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

Use with concomitant NSAIDs including cyclo-oxygenase 2 specific inhibitors (see section 4.5 - Interactions)

P

Hypersensitivity to Ibuprofen or any of the excipients in the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.

Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

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

Severe hepatic failure, renal failure or heart failure (See section 4.4)

Last trimester of pregnancy (See Section 4.6).

4.4 Special warnings and precautions for use

POM

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

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 administration).

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. Renal function should be monitored in these patients (See section 4.3 - Contraindications).

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

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 serous GI events.

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 or anti-platelet agents such as aspirin (See section 4.5 Interactions).

When GI bleeding or ulceration occurs in patients receiving ibuprofen, 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 - Undesirable effects).

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 -Undesirable effects).

Female fertility:

The use of Ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In woman who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Ibuprofen should be considered.

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 (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.

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).

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. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

P

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

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:

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

Other NSAIDs:

The use of Ibuprofen with concomitant NSAIDs including cyclo-oxygenase-2 selective inhibitors should be avoided (see section 4.5).

SLE and mixed connective tissue disease:

Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (see section 4.8).

Renal:

Renal impairment as renal function may further deteriorate (see section 4.3 and 4.8)

Hepatic:

Hepatic dysfunction (see section 4.3 and 4.8)

Cardiovascular and cerebrovascular effects:

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (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.

Impaired female fertility:

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

Gastrointestinal:

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).

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), 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 or anti-platelet agents such as aspirin (See Section 4.5 Interactions).

When GI bleeding or ulceration occurs in patients receiving Ibuprofen, the treatment should be withdrawn.

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. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The label will include:

Read the enclosed leaflet before taking this product. Do not take if you

□    Have (or have had two or more episodes of ) a stomach ulcer, perforation or bleeding

□    Are allergic to Ibuprofen or any other ingredients of the product, aspirin or other related painkillers

□    Are taking other NSAIDs painkillers, or aspirin with a daily dose above 75mg

Speak to a pharmacist or your doctor before taking this product if you:

□    Have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, liver, heart, kidney, or bowel problems

□    Are a smoker

□    Are pregnant

If symptoms persist or worsen, consult your doctor.

4.5 Interaction with other medicinal products and other forms of interaction

POM

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

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 (see section 5.1).

Anti-hypertensives: Reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

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

Lithium: Decreased elimination of lithium.

Methotrexate: Decreased elimination 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.

Corticosteroids: Increased risk of GI bleeding (See section 4.4 - Special warnings and precautions for use).

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4 - Special warnings and precautions for use).

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.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4)

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

Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and Ibuprofen.

P

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 (See Section 4.4).

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 (see section 5.1).

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

Ibuprofen should be used with caution in combination with:

Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See Section 4.4).

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

Corticosteroids: Increase the risk of gastrointestinal ulceration or bleeding (see section 4.4)

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4)

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

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

Methotrexate: There is a potential for an increase in plasma 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 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.

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.

4.6 Pregnancy and lactation

POM

Pregnancy:

Congenital abnormalities have been reported in association with NSAID 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 (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (See section 4.3 Contraindications). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

Lactation:

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

See section 4.4 Special warnings and precautions for use, regarding female fertility.

P

Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Ibuprofen in pregnancy should, if possible, be avoided during the first 6 months of pregnancy.

During the 3^rd trimester, Ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both the mother and child. (See Section 4.3).

In limited studies, Ibuprofen appears in breast milk in a very low concentration and is unlikely to affect the breast-fed infant adversely.

See Section 4.4 regarding female fertility.

4.7 Effects on ability to drive and use machines

POM

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

P

None expected at recommended doses and duration of therapy.

4.8 Undesirable effects

POM

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 Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions 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, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular: Oedema has been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (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) (see section 4.4).

Other adverse events reported less commonly include:

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic: Abnormal liver function, hepatitis and jaundice.

Neurological and Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis: (especially in patients with existing auto-immune 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), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: Bullous reactions including Steven Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.

P

Hypersensitivity reactions have been reported and these may consist of: -

-    Non specific allergic reaction and anaphylaxis

-    Respiratory tract reactivity, eg asthma, aggravated asthma, bronchospasm or dyspnoea

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

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

Hypersensitivity reactions:

Uncommon: hypersensitivity reactions with urticaria and pruritus.

Very rare: Severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).

Exacerbation of asthma and bronchospasm.

Gastrointestinal:

The most commonly-observed adverse events are gastrointestinal in nature. Uncommon: Abdominal pain, nausea and dyspepsia.

Rare: Diarrhoea, flatulence, constipation and vomiting.

Very Rare: Peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly. Ulcerative stomatitis, gastritis.

Exacerbation of ulcerative colitis and Crohn’s disease (See Section 4.4)

Nervous system:

Uncommon: Headache

Very rare: Aseptic meningitis - single cases have been reported very rarely.

Renal:

Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Hepatic:

Very rare: Liver disorders.

Haematological:

Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, granulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Dermatological:

Uncommon: Various skin rashes.

Very rare: Severe forms of skin reactions such as bullous reactions, including stevens-Johnsons Syndrome, erythema multiforme epidermal necrolysis can occur.

Immune System:

In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with Ibuprofen, single cases of symptoms of aseptic meningitis, such as a stiff neck, headache. Nausea. Vomiting, fever or disorientation have been observed (See Section 4.4)

Cardiovascular and Cerebrovascular:

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 doses 240mg 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).

4.9 Overdose

In children ingestion of more than 400mg/kg may cause symptoms. In adults the dose response effect is les clear cut. The half life in overdose 1.5-3 hours.

Symptoms:

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache, and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time / INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Management:

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

POM

Ibuprofen is a propionic acid derivative which has analgesic, anti-inflammatory and anti-pyretic actions. It acts by inhibiting the cyclo-oxygenase responsible for the biosynthesis of prostaglandins.

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 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of aspirin 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.

P

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In human ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

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 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of aspirin 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.

5.2 Pharmacokinetic properties

POM

Ibuprofen is absorbed from the gastrointestinal tract, and peak plasma concentrations occur about one to two hours after ingestion. It is extensively bound to plasma proteins and has a half-life of about two hours. It is rapidly excreted in the urine as metabolites and their conjugates.

About 1% is excreted in the urine unchanged and about 14% as conjugated ibuprofen.

P

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1 to 2 hours. These times may vary with different dosage forms.

The half-life of Ibuprofen is about 2 hours.

In limited studies, Ibuprofen appears in breast milk in very low concentrations.

5.3 Preclinical safety data

There is no clinically relevant preclinical safety data.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica, potato starch, povidone, microcrystalline cellulose, alginic acid, magnesium stearate, sodium lauryl sulphate, sodium starch glycollate, croscarmellose sodium, hypromellose, glycerol and Mastercote Pink FA 2481 (titanium dioxide E171, carmine E120, hydroxypropylmethyl cellulose E464).

6.2 Incompatibilities

None Known

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Do not store above 25°C. Store in the original package (blisters) or keep the container tightly closed (plastic containers).

6.5 Nature and contents of container For POM and Pharmacy only sales

Securitainers or Tampertainers or opaque plastic screw capped containers of polyethylene or polypropylene containing 28, 50, 84, 100, 250 or 500 tablets.

For Pharmacy Only Sales

Cartons of 6, 12, 24 or 48 tablets in blister packs of aluminium foil/pvc.

10