SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Paramed Ibuprofen for Children 100 mg/5 ml Oral Suspension Sachets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient: Ibuprofen 100 mg/5 ml (equivalent to 2.0% w/v). This product also contains the excipient maltitol liquid, see section 4.3. For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral suspension.

Opaque, white to off-white viscous suspension.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

For the fast and effective reduction of fever, including post immunisation pyrexia, cold and flu symptoms, and the fast and effective relief of mild to moderate pain, such as sore throat, teething pain, toothache, headache, minor aches and sprains.

4.2 Posology and method of administration

For oral administration and short term use only.

Squeeze the sachet to aid mixing.

For pain and fever:

For children weighing 5 kg or more, the daily dosage of the suspension is 20 mg/kg bodyweight in divided doses. Using the spoon provided this can be achieved as follows:

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

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

Children 1 - 4 years: One 5 ml dose may be taken 3 times in 24 hours.

Children 4 -7 years: 7.5 ml dose (5 ml + 2.5 ml spoonful) may be taken 3 times in 24 hours. Children 7 - 12 years: 10 ml dose. Two 5 ml spoonfuls may be taken 3 times in 24 hours.

For infants aged 3 - 5 months medical advice should be sought if symptoms worsen or not later than 24 hours if symptoms persist.

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

Not suitable for children under 3 months of age or for children weighing less than 5 kg.

Leave at least 4 hours between 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 2.5 ml doses in 24 hours. If the fever is not reduced, consult your doctor.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

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

4.3 Contraindications

Hypersensitivity to ibuprofen or any of the constituents of the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) associated with 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 (NYHA Class IV) (See Section 4.4 Special warnings and precautions for use).

Last trimester of pregnancy (See Section 4.6 Pregnancy and lactation).

Each 5ml spoonful contains 2g of maltitol liquid. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

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).

There is a risk of renal impairment in dehydrated children.

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

The elderly are at increased risk of the serious consequences of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal..

Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (See Section 4.8 Undesirable effects).

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.

Other NSAIDs:

The use of ibuprofen tablets with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

Chronic inflammatory intestinal disease (ulcerative colitis, Crohn’s disease) - as these conditions may be exacerbated (See Section 4.8 Undesirable effects).

Caution 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 with NSAID therapy.

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

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

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 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 gastrointestinal 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 hemorrhage 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 gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

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

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 Interaction with other medicinal products and other forms of interaction).

When gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Cardiovascular and cerebrovascular effects

Clinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg daily) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infraction or stroke) Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g.< 1200mg daily) is associated with an increased risk of myocardial infraction.

The label will include:

Please read the enclosed leaflet carefully.

Do not let your child take this medicine if they:

•    are under 3 months old, or weigh less than 5 kg

•    are allergic to ibuprofen or any of the other ingredients, aspirin or other related painkillers

•    are intolerant to some sugars

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

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

Consult your doctor or pharmacist if your child has or has had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems, or is receiving any regular treatment.

Pregnant women or smokers considering taking this medicinal product should consult their doctor before use.

If the child’s symptoms persist for more than 3 days or worsen, consult your doctor.

For children under 6 months, if the symptoms persist for more than 24 hours (3 doses) or worsen, consult your doctor.

Warning - Do not exceed the stated dose.

Keep all medicines out of the reach and sight of children.

Not suitable for children under 3 months of age or weighing less than 5 kg.

4.5 Interaction with other medicinal products and other forms of interaction

Ibuprofen should not be used in combination with:

Aspirin (Acetylsalicylic acid):

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).

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).

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 Special warnings and precautions for use).

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 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:

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

Children under 12 are unlikely to become pregnant or breast feed, however, whilst no teratogenic effects have been demonstrated in animal studies, the use of the suspension should be avoided if possible during the first six months of pregnancy.

During the third 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 dose (2400 mg daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infraction or stroke) (see section 4.4).

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

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.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Propionic acid derivatives ATC code: M01AE01

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. It has analgesic, antipyretic and anti-inflammatory properties.

Furthermore, ibuprofen reversibly inhibits platelet aggregation.

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

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 lowdose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is both 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 - 2 hours. These times may vary with different dosage forms.

The half life of ibuprofen is about two hours.

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

5.3 Preclinical safety data

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

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maltitol Liquid Glycerol Xanthan Gum Sodium Benzoate Sodium Cyclamate Citric Acid Orange Flavour Acesulfame Potassium Polysorbate 80 Di sodium Edetate

Purified Water

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years.

6.4    Special precautions for storage

Do not store above 25°C.

6.5    Nature and contents of container

The suspension is packed in laminate sachets consisting of:

Surlyn® ionomer (product contact material)/low density polyethylene/8 micron aluminium/paper Or

Surlyn® ionomer (product contact material), 9 micron aluminium, low density polyethylene, PET.

Each sachet contains 5 ml of the suspension.

Pack sizes of 8 or 16 sachets in a cardboard carton.

A double-ended spoon with measures of 2.5 ml and 5 ml is provided.

6.6    Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Wrafton Laboratories Limited

Wrafton

Braunton

North Devon

EX33 2DL

MARKETING AUTHORISATION NUMBER(S)

PL 12063/0061.

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

07/09/2006

10    DATE OF REVISION OF THE TEXT

11/12/2015