1 NAME OF THE MEDICINAL PRODUCT

Nurofen for Children Orange

Nurofen for Children Orange Baby

Nurofen for Children 3 months to 9 years Orange

Nurofen for Children Cold, Pain and Fever Orange Flavour 100mg/5mL Oral Suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 100 mg/5ml (equivalent to 2.0% w/v).

For excipients, see 6.1.

3 PHARMACEUTICAL FORM

Oral suspension.

An off-white, orange-flavoured, syrupy suspension.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Prescription and OTC: For the fast and effective reduction of fever, including post immunisation pyrexia and the fast and effective relief of the symptoms of colds and influenza and mild to moderate pain, such as a sore throat, teething pain, toothache, headache, minor aches and sprains.

4.2    Posology and method of administration

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

For pain, fever and symptoms of cold and infuenza: The daily dosage of Nurofen For Children is 20-30 mg/kg bodyweight in divided doses. Using the spoon or syringe dosing device provided this can be achieved as follows:

Infants 3 - 6 months weighing more than 5kg: One 2.5ml dose may be taken 3 times in 24 hours.

Infants 6 - 12 months: One 2.5ml dose may be taken 3 to 4 times in 24 hours.

Children 1 - 3 years: One 5ml dose may be taken 3 times in 24 hours.

Children 4 - 6 years: 7.5ml (5ml +2.5ml spoonful) may be taken 3 times in 24 hours. Children 7 - 9 years: Two 5ml doses may be taken 3 times in 24 hours.

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

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

For Juvenile Rheumatoid Arthritis: The usual daily dosage is 30 to 40 mg/kg/day in three to four divided doses.

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.

For oral administration.

For short term use only.

For infants aged 3-6 months medical advice should be sought if symptoms worsen or not later than 24 hours if symptoms persist.

If in children aged from 6months this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

4.3 Contraindications

Hypersensitivity to ibuprofen or any of the constituents 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 antiinflammatory drugs.

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

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

Severe hepatic failure, renal failure or heart failure (See section 4.4, Special warnings and precautions for use)

Last trimester of pregnancy (See section 4.6 Pregnancy and lactation)

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 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 Undesirable effects)

Renal:

Renal impairment as renal function may further deteriorate (See section 4.3 Contraindications and Section 4.8 Undesirable effects)

There is a risk of renal impairment in dehydrated children

Hepatic:

Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects)

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.

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 ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or antiplatelet 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.

Patients with a rare hereditary problems of fructose intolerance should not take this medicine.

The label will state:

Read the leaflet carefully before use.

Do not give this product if your baby or child:

•    Is under 3 months old

•    has (or has had two or more episodes of ) a stomach ulcer, perforation or bleeding

•    is allergic to ibuprofen or any other ingredient of the product, aspirin or other related painkillers

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

Speak to your doctor or pharmacist before giving this product if baby or child:

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

This product is intended for children aged between 3 months and 12 years. If you are an adult taking this product:

Speak to a pharmacist or your doctor before taking if:

•    You are a pregnant

•    You are trying to get pregnant

•    Are elderly

•    Are a smoker

Do not exceed the stated dose.

Keep out of the reach and sight of children.

For short term use.

If symptoms persist or worsen, consult your doctor.

4.5 Interaction with other medicinal products and other forms of interaction

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: as these may 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 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 studies, the use of this product 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 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, eg 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 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, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Skin:

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).

4.9 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 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

Ibuprofen is a proprionic acid derivative NSAID which has analgesic, antipyretic and anti-inflammatory properties. Ibuprofen inhibits prostaglandin synthesis, furthermore, ibuprofen reversibly inhibits platelet aggregation

Ibuprofen has been shown to an have onset of both analgesic and antipyretic action within 30 minutes.

ATC Code, M01A E01

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 with 8 h before or within 30 min 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 relevant effect is considered to be likely for occasional use.

5.2 Pharmacokinetic properties

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 the breast milk in very low concentrations.

Preclinical safety data

There are no preclinical safety data of relevance to the consumer.

PHARMACEUTICAL PARTICULARS

List of excipients

Citric acid Sodium citrate Sodium chloride Sodium saccharin Domiphen bromide Purified water Polysorbate 80 Maltitol liquid Xanthan gum Orange flavour Glycerol.

100 ml - 3 years.

6.4 Special precautions for storage

Do not store above 25°C.

6.5    Nature and contents of container

Amber-coloured polyethylene terephthalate (PET) bottle with a child-resistant closure fitted with a low density polyethylene liner. The bottle contains 100 ml of product. A double-ended spoon with measures of 2.5 ml and 5 ml will be provided.

OR

Amber-coloured polyethylene terephthalate (PET) bottle with a child-resistant closure fitted with a low density polyethylene liner. The bottle contains 100 ml of product. A syringe composed of a polypropylene barrel and a PE piston with measures of 2.5 ml and 5 ml will be provided.

Not all pack sizes will be marketed.

6.6    Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Reckitt Benckiser Healthcare (UK) Ltd

Slough

SL1 4AQ

8 MARKETING AUTHORISATION NUMBER(S)

PL 00063/0668

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

5 August 2004

05/09/2014