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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Abfen 600 mg Effervescent Granules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One sachet contains 600 mg ibuprofen.

Excipients with known effect:

Sodium (197 mg/sachet)

Sucrose (3333 mg/sachet)

3 PHARMACEUTICAL FORM

Effervescent granules

Abfen 600 mg Effervescent Granules are white granules with an orange flavour.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Abfen 600 mg Effervescent Granules are indicated for their analgesic and antiinflammatory effects in the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.

In the treatment of non-articular rheumatic Abfen 600 mg Effervescent Granules are indicated in peri-articular conditions such as frozen shoulder (capsulitis), bursitis, tendinitis, tenosynovitis and low back pain; Abfen 600 mg Effervescent Granules can also be used in soft-tissue injuries such as sprains and strains.

Abfen 600 mg Effervescent Granules are also indicated for their analgesic effect in the relief of moderate pain such as dysmenorrhoea, dental and post-operative pain and for symptomatic relief of headache including migraine headache.

4.2 Posology and method of administration Posology

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 dosage of ibuprofen is 1,200-1,800 mg daily in divided doses. Some patients can be maintained on 600-1,200 mg daily. Total daily dose should not exceed 2,400 mg.

Paediatric population:

Abfen 600 mg Effervescent Granules are not suitable for use in children and adolescents below the age of 18 years.

Elderly:

The elderly are at increased risk of 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.

Renal impairment:

Caution should be taken with ibuprofen dosage in patients with renal impairment. The dosage should be assessed individually. The dose should be kept as low as possible and renal function should be monitored (see sections 4.3, 4.4 and 5.2).

Hepatic impairment:

Caution should be taken with dosage in patients with hepatic impairment. The dosage should be assessed individually and the dose should be kept as low as possible (see sections 4.3, 4.4 and 5.2).

Method of Administration

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

Abfen 600 mg Effervescent Granules should be constituted in water and consumed as an oral suspension, once effervescence subsides. The minimum amount of water required to disperse one sachet is 125 ml.

After reconstitution, the suspension has a white, translucent appearance, free from foreign substances, with an orange odour.

A transient sensation of burning in the mouth or throat may occur with Abfen 600 mg Effervescent Granules; ensure they are dissolved in plenty of water.

4.3    Contraindications

•    Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

•    Ibuprofen should not be used in patients who have previously shown hypersensitivity reactions (e.g. asthma, urticaria, angioedema or rhinitis) after taking ibuprofen, acetylsalicylic acid (e.g. Aspirin) or other NSAIDs.

•    Ibuprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAID therapy. Ibuprofen should not be used in patients with active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

•    Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding.

•    Ibuprofen is contraindicated in patients with severe heart failure (NYHA Class IV), hepatic failure or renal failure (see section 4.4).

•    Ibuprofen is contraindicated during the last trimester of pregnancy (see section 4.6).

4.4    Special warnings and precautions for use

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).

Each Abfen 600 mg Effervescent Granules sachet contains 3333 mg of sucrose per dose. This should be taken into account in patients with diabetes mellitus. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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

Each Abfen 600 mg Effervescent granules sachet contains 8.6 mmol (197 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

The use of ibuprofen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the increased risk of ulceration or bleeding (see section 4.5).

Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

The habitual intake of painkillers, particularly the combination of several painkillers, may lead to permanent renal damage with the risk of renal failure. This risk may be increased by salt loss and dehydration.

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).

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 requiring concomitant low dose acetylsalicylic acid (e.g. Aspirin), or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

Patients with a history of gastrointestinal disease, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal 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 acetylsalicylic acid (e.g. Aspirin) (see section 4.5).

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 ulcerative colitis or Crohn’s disease as these conditions may be exacerbated (see section 4.8).

Respiratory disorders

Caution is required if ibuprofen is 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).

Ibuprofen should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with ibuprofen administration.

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 studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) 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. < 1200 mg/ day) is associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided. Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.

Renal effects

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

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin 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 taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

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 below and section 4.8).

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 section 4.8). Patients appear to be at highest

risk of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

Aseptic meningitis

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

Impaired female fertility

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.

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.

Antihypertensives, beta-blockers and diuretics:	NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors, beta-blockers, angiotensin-II receptor antagonists and diuretics. 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.
Cholestyramine:	The concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.
Lithium:	Decreased elimination of lithium.
Probenecid:	Medicinal products that contain probenecid may delay the excretion of NSAIDs.
Methotrexate:	NSAIDs may inhibit the tubular secretion of methotrexate and reduce clearance of methotrexate.
Ciclosporin:	Increased risk of nephrotoxicity.
Mifepristone:	A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that coadministration of NSAIDs on the day of prostaglandin administration does not adversely

	influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy.
Other analgesics and cyclooxygenase-2 selective inhibitors:	Avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4).
Acetylsalicylic acid (e.g. Aspirin):	Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects. Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
Corticosteroids:	Increased risk of gastrointestinal ulceration or bleeding with NSAIDs (see section 4.4).
Anticoagulants:	NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
Phenytoin:	Concomitant use of ibuprofen with phenytoin may increase serum levels of phenytoin.
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.
Sulfonylureas:	NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):	Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).
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.
Aminoglycosides:	NSAIDs may decrease the excretion of aminoglycosides.
Herbal extracts:	Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

4.6 Fertility, Pregnancy and lactation

Fertility

The use of ibuprofen may impair 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 (see section 4.4).

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformation was increased from less than 1% up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals the administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have also been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimesters of pregnancy, Abfen 600 mg Effervescent Granules should not be given unless clearly necessary. If Abfen 600 mg Effervescent Granules are used by a woman attempting to conceive or during the first and second trimester, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester, all prostaglandin synthesis inhibitors may expose the foetus to:

-    cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension),

-    renal dysfunction, which may progress to renal failure with oligohydramnios.

At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to:

-    possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses,

- inhibition of uterine contractions, resulting in delayed or prolonged labour.

Consequently, ibuprofen is contraindicated during the last trimester of pregnancy.

Breastfeeding

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

4.7 Effects on ability to drive and use machines

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery. This applies to a greater extent in combination with alcohol.

4.8 Undesirable effects

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 ibuprofen administration. Less frequently, gastritis has been observed.

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, angioedema and, more rarely, exfoliative and bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

Adverse events at least possibly related to ibuprofen are displayed by MedDRA frequency convention and system organ class database. The following frequency groupings are used: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1000 to <1/100), Rare (>1/10,000 to <1/1000), Very rare (<1/10,000) and Not known (cannot be estimated from the available data).

System organ class	Frequency	Adverse reaction
Infections and infestations	Uncommon	Rhinitis

	Rare	Meningitis aseptic
Blood and lymphatic system disorders	Uncommon	Leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia , haemolytic anaemia
Immune system disorders	Rare	Anaphylactic reaction
Psychiatric disorders	Uncommon	Insomnia, anxiety
	Rare	Depression, confusional state
Nervous system disorders	Common	Headache, dizziness
	Uncommon	Paraesthesia, somnolence
	Rare	Optic neuritis
Eye disorders	Uncommon	Visual impairment
	Rare	Toxic optic neuropathy
Ear and labyrinth disorders	Uncommon	Hearing impaired
	Rare	Tinnitus, vertigo
Respiratory, thoracic and mediastinal disorders	Uncommon	Asthma, bronchospasm, dyspnoea
Gastrointestinal disorders	Common	Dyspepsia, diarrhoea, nausea, vomiting, abdominal pain, flatulence, constipation, melaena, haematemesis, gastrointestinal haemorrhage
	Uncommon	Gastritis, duodenal ulcer, gastric ulcer, mouth ulceration, gastrointestinal perforation
	Very rare	Pancreatitis
	Not known	Colitis and Crohn's disease
Hepatobiliary disorders	Uncommon	Hepatitis, jaundice, hepatic function abnormal
	Rare	Liver injury
	Very rare	Hepatic failure
Skin and subcutaneous tissue disorders	Common	Rash
	Uncommon	Urticaria, pruritus, purpura, angioedema, photosensitivity reaction
	Very rare	Bullous dermatoses, including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme
Renal and urinary disorders	Uncommon	Tubulointerstitial nephritis, nephrotic syndrome and renal failure
General disorders and administration site conditions	Common	Fatigue
	Rare	Oedema

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day ) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Ibuprofen can cause prolongation of bleeding time through reversible inhibition of platelet aggregation.

In the majority of cases where aseptic meningitis has been reported, there has been some form of underlying autoimmune disease (in particular, systemic lupus erythematosus and related connective tissue diseases).

Oedema, hypertension and heart failure as well as deterioration of ulcerative colitis and Crohn’s disease have been reported in connection with NSAID treatment.

A transient sensation of burning in the mouth or throat may occur with Abfen 600 mg Effervescent Granules.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose Toxicity

Signs and symptoms of toxicity have generally not been observed at doses below 100 mg/kg in the paediatric population or in adults. However, supportive care may be needed in some cases. Paediatric populations have been observed to manifest signs and symptoms of toxicity after ingestion of 400 mg/kg or greater.

Symptoms

Most patients who have ingested significant amounts of ibuprofen will manifest symptoms within 4 to 6 hours.

The most frequently reported symptoms of overdose include nausea, vomiting, abdominal pain, lethargy and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, convulsion, and loss of consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnoea, diarrhoea and depression of the CNS and respiratory system have also been rarely reported. Disorientation, excitation, fainting and cardiovascular toxicity, including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and liver damage are possible. Large overdoses are generally well tolerated when no other drugs are being taken.

Therapeutic measures

Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient’s clinical condition.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic classification: Anti-inflammatory and antirheumatic products, nonsteroids; propionic acid derivatives.

ATC code: M01AE01

Ibuprofen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). It contains the propionic acid derivative p-isobutyl-hydratropic acid with the generic name ibuprofen. Ibuprofen has anti-inflammatory, analgesic and antipyretic effects. The antiphlogistic effect is comparable with that of acetylsalicylic acid (e.g. Aspirin) and indometacin. The pharmacological effect of ibuprofen is probably associated with its ability to inhibit prostaglandin synthesis. Ibuprofen prolongs bleeding time through reversible inhibition of platelet aggregation.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic studies show that when single doses of ibuprofen 400 mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic acid dosing (81 mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).

Ibuprofen inhibits renal prostaglandin synthesis. In patients with normal renal function this effect is of no particular significance. In patients with chronic renal insufficiency, decompensated heart or liver insufficiency as well as conditions

involving changes in plasma volume, the inhibited prostaglandin synthesis can lead to acute renal insufficiency, fluid retention and heart failure (see section 4.3).

5.2 Pharmacokinetic properties Absorption

Ibuprofen is rapidly absorbed from the gastrointestinal tract with a bioavailability of 80-90%. Peak serum concentrations occur one to two hours after administration. If administered with food, peak serum concentrations are lower and achieved more slowly than when taken on an empty stomach Food does not affect markedly total bioavailability.

Distribution

Ibuprofen is extensively bound to plasma proteins (99%). Ibuprofen has a small volume of distribution being about 0.12-0.2 L/kg in adults.

Biotransformation

Ibuprofen is rapidly metabolized in the liver through cytochrome P450, preferentially CYP2C9, to two primary inactive metabolites, 2-hydroxyibuprofen and 3-carboxyibuprofen. Following oral ingestion of the drug, slightly less than 90% of an oral dose of ibuprofen can be accounted for in the urine as oxidative metabolites and their glucuronic conjugates. Very little ibuprofen is excreted unchanged in the urine.

Elimination

Excretion by the kidney is both rapid and complete. The elimination half-life is approximately 2 hours. The excretion of ibuprofen is virtually complete 24 hours after the last dose.

Special populations Elderly

Given that no renal impairment exists, there are only small, clinically insignificant differences in the pharmacokinetic profile and urinary excretion between young and elderly.

Paediatric population

The systemic exposure of ibuprofen following weight adjusted therapeutic dosage (5 mg/kg to 10 mg/kg bodyweight) in children aged 1 year or over, appears similar to that in adults.

Children 3 months to 2.5 years appeared to have a higher volume of distribution (L/kg) and clearance (L/kg/h) of ibuprofen than did children >2.5 to 12 years of age.

Renal impairment

For patients with mild renal impairment, increased unbound (S)-ibuprofen, higher AUC values for (S)-ibuprofen and increased enantiomeric AUC (S/R) ratios as compared with healthy controls have been reported.

In end-stage renal disease patients receiving dialysis the mean free fraction of ibuprofen was about 3% compared with about1% in healthy volunteers. Severe impairment of renal function may result in accumulation of ibuprofen metabolites. The significance of this effect is unknown. The metabolites can be removed by haemodialysis (see sections 4.2, 4.3 and 4.4).

Hepatic impairment

Alcoholic liver disease with mild to moderate hepatic impairment did not result in substantially altered pharmacokinetic parameters.

In cirrhotic patients with moderate hepatic impairment (Child Pugh’s score 6-10) treated with racemic ibuprofen an average 2-fold prolongation of the half-life was observed and the enantiomeric AUC ratio (S/R) was significantly lower compared to healthy controls suggesting an impairment of metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer (see sections 4.2, 4.3 and 4.4).

5.3 Preclinical safety data

There are no preclinical data of relevance for the safety assessment, apart from what has already been taken into account in this summary of product characteristics.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Croscarmellose sodium Malic acid

Microcrystalline cellulose

Saccharin sodium

Sucrose

Povidone

Orange flavour

Sodium laurilsulfate

Sodium hydrogen carbonate Sodium carbonate, anhydrous

6.2 Incompatibilities

Not applicable.

6.3 Shelf life 3 years

6.4 Special precautions for storage

Do not store above 25 °C. Store in the original package in order to protect from light and moisture.

6.5 Nature and contents of container

A heat-sealed sachet consisting of a paper/polythene/aluminium foil/polythene laminate.

Pack sizes: 10, 20, 30, 40, 50 sachets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.

7    MARKETING AUTHORISATION HOLDER

BGP Products Ltd.

Abbott House

Vanwall Business Park

Vanwall Road

Maidenhead

Berkshire

SL6 4XE

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 43900/0008

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

09/05/2013

10    DATE OF REVISION OF THE TEXT

18/02/2016