SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Calprofen 100mg/5ml Oral Suspension Ibuprofen

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

3    PHARMACEUTICAL FORM

Oral Suspension

Sugar Free, Colour Free and Strawberry Flavour

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Children aged 3 months to 12 years:

Mild to moderate pain, post-immunisation pyrexia, rheumatic or muscular pain, headache, reduction of fever, sore throat, teething pain, toothache, minor aches and pains, symptoms of cold and influenza.

4.2 Posology and method of administration

To be taken orally. For short term use only.

Children aged 3 months to 12 years:

Not recommended for children weighing less than 5 kg. For pain and fever - 20mg/kg/day in divided doses.

2.5    ml three times a day. Do not use for more than 24 hours.

2.5    ml three times a day.

2.5    ml three to four times a day 5 ml three to four times a day 10 ml three to four times a day

Doses should be taken every 6 - 8 hours when required, and at least 4 hours should be left between doses.

Post-immunisation fever:

2.5 ml (50 mg) followed by one further dose of 2.5 ml (50mg) six hours later if necessary. No more than 2 doses in 24 hours. If fever is not reduced, consult a doctor.

Do not give to children under 3 months of age.

For children aged >3 months to <5 months: if the child’s symptoms worsen or if the symptoms persist for more than 24 hours, consult a doctor

For children aged 6 months and over: if symptoms worsen or if the symptoms persist for more than 3 days, consult a 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 minimised by using the lowest effective dose for the shortest possible 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.

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. The use of Ibuprofen is therefore not recommended in women attempting to conceive.

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, or 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.

Dehydration:

There is a risk of renal impairment in dehydrated children.

The label will include:

Read the enclosed leaflet before taking this product.

Do not give this product if your baby or child

•    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

•    Is taking other NSAIDs painkillers, or aspirin with a daily dose above 75 mg

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

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

If you are an adult taking this product you should not take this product in the last 3 months of pregnancy and you should contact your doctor or pharmacist before taking it in the first 6 months of pregnancy, if trying to get pregnant, if you are elderly or if you are a smoker.

Do not give to babies aged from 3to under 6 months for more than 24 hours.

Do not give to children aged 6 months and older for more than 3 days.

If symptoms persist or worsen, consult your doctor promptly.

Do not exceed the stated dose.

Not recommended for children under 3 months.

4.5 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:

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4)

Anti-hypertensives 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 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 Fertility, 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 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).

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

It is not expected that Calprofen 100mg/5ml Oral Suspension would interfere with the ability to drive or operate machinery at the recommended dose 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 or dyspnoea,

c)    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 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 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.

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).

4.9 Overdose

In children, ingestion of more than 400mg/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 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 400 mg 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 likely for occasional ibuprofen use.

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed from the gastro-intestinal tract and rapidly distributed throughout the whole body. Peak plasma concentrations occur about 1 to 2 hours after ingestion with food or in 45 minutes if taken on an empty stomach. These times may vary with different dosage forms.

The excretion is rapid and complete via the kidneys.

The elimination half-life is about 2 hours.

It is metabolized to two inactive metabolites and these are rapidly excreted in urine. About 1 percent is excreted in urine as unchanged Ibuprofen and about 14 percent as conjugated Ibuprofen.

Ibuprofen is extensively bound to plasma proteins.

5.3 Preclinical safety data

No relevant information additional to that contained elsewhere in the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycerol (E422), xanthan gum, maltitol syrup (Lycasin 80/55 (E965)), polysorbate 80, saccharin sodium (E954), citric acid monohydrate, sodium methylhydroxybenzoate, sodium propylhydroxybenzoate, purified water and strawberry flavour.

6.2 Incompatibilities

Not applicable.

6.3    Shelf life

36 months.

6.4    Special precautions for storage

Do not store above 25°C.

Keep out of reach and sight of children.

6.5 Nature and contents of container

Amber glass bottle sealed with a child resistant, tamper evident cap. Pack sizes: 50ml and 100ml

6.6 Special precautions for disposal

Shake well before use. Return any left over medicine to the Pharmacist.

7    MARKETING AUTHORISATION HOLDER

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire

SL6 3UG

UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 15513/0147

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

21/07/2006

DATE OF REVISION OF THE TEXT

10/03/2014