SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Orbis Ibuprofen For Children 100mg/5ml Oral Suspension Ibuprofen 100mg/5ml Oral Suspension

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Ibuprofen 100 mg / 5ml For excipients- see section 6.1

3    PHARMACEUTICAL FORM

Oral Suspension

4.1    Therapeutic indications Children under 12 years:

Rheumatic or muscular pain, headache, dental pain, feverishness, symptoms of colds and influenza

4.2    Posology and method of administration

For oral administration and for short term use only

For OTC use

Children under12 years of age:

Not recommended for children weighing less than 5 kg.

The minimum effective dose should be used for the shortest time necessary to relieve symptoms.

For pain and fever - 20mg/kg/day in divided doses.

Maximum dose 200mg, maximum daily dose 800mg divided as follows:

Age	Dosage
Infants from 3 months up to 6 months weighing more than 5kg	2.5ml three times a day. Do not use for more than 24 hours
Infants from 6 months up to12 months	2.5ml three times a day
Children from 1 year up to 4 years	5ml three times a day
Children from 4 years up to 7 years	7.5ml three times a day
Children from 7 years up to 12 years	10ml three times a day

Doses should be given approximately every 6 to 8 hours, (or with a minimum of 4 hours between each dose if required).

For children aged 6 months and over: If the child's symptoms persist for more than 3 days, consult a doctor.

For children aged 3 - 6 months: if the child's symptoms persist for more than 24 hours, consult a doctor.

For post immunisation pyrexia: One 2.5 ml dose followed by one further 2.5 ml dose 6 hours later if necessary. No more than two 2.5ml doses in 24 hours. If the fever is not reduced, consult your doctor.

Not suitable for children under 3 months of age unless advised by your doctor.

4.3. Contraindications

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 heart failure, renal failure or hepatic failure (see section 4.4) Last trimester of pregnancy (see section 4.6).

4.4 Special warnings and precautions for use

Undesirable effects may be minimized 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 cyclooxygenase-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 sections 4.3 and 4.8)

Hepatic:

Hepatic dysfunction (see sections 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 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 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 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).

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.

For OTC use

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 ingredient of the product, aspirin or other related painkillers

•    are taking other NSAID painkillers, or aspirin with a daily dose above 75mg

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

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

•    are a smoker

•    are pregnant

If symptoms persist or worsen, consult your doctor.

This product contains Maltitol liquid. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

It also contains sodium methyl parahydroxybenzoate (E219) and sodium propyl parahydroxybenzoate (E217). These may cause allergic reactions (possibly delayed).

Interaction with other medicinal products and other forms of interaction

Ibuprofen should be avoided 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: Increased 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 GIycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma GIycoside 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

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

During the 3 trimester, ibuprofen is contraindicated as there is 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 mother and child. (See section 4.3 Contraindications).

In limited studies, ibuprofen appears in the breast milk in 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

None expected at recommended doses and duration of therapy.

4.8. Undesirable effects

Hypersensitivity reactions have been reported and these may consist of:

(a)    Non-specific allergic reactions and anaphylaxis

(b)    Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, dyspnoea

(c)    Various skin reactions, e.g. pruritus, 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 long-term 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, 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 colitis and Crohn's disease (see section 4.4).

Nervous System: Uncommon: Headache

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

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, agranulocytosis). 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 - Johnson syndrome, erythema multiforme and toxic 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 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 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).

Overdose

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

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans 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 within 30 minutes after immediate release aspirin dosing (81 mg), 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 like for occasional ibuprofen use.

5.2 Pharmacokinetic properties

buprofen 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 the breast milk in very low concentrations.

5.3    Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Glycerol

xanthan gum

maltitol liquid

polysorbate 80

saccharin sodium

citric acid monohydrate

sodium methyl parahydroxybenzoate

sodium propyl parahydroxybenzoate

purified water strawberry flavour.

6.2    Incompatibilities

Not Applicable.

6.3    Shelf life

24 months.

6.4    Special precautions for storage

Do not store above 25°C.

6.5    Nature and contents of container

Amber Type III glass bottle.

Child resistant, tamper-evident polypropylene cap. 2.5ml/5ml double ended measuring spoon is supplied Pack sizes available:100ml

6.6    Special precautions for disposal

None

7    MARKETING AUTHORISATION HOLDER

Orbis Consumer Products Limited Cunard Road London NW10 6PN

8    MARKETING AUTHORISATION NUMBER(S)

PL 17862/0010

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 07/06/2011

10 DATE OF REVISION OF THE TEXT

20/12/2012