SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Fenpaed Ibuprofen 100 mg/5 ml Oral Suspension Numark Ibuprofen 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

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 due to sore throat, teething pain, toothache, headache, minor aches and pains, symptoms of cold and influenza, post-immunisation pyrexia and reduction of fever.

4.2 Posology and method of administration

For oral administration and short-term use only.

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

Children aged 3 months to 12 years:

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

One 2.5 ml dose may be given 3 times in 24 hours. Do not use for more than 24 hours 2.5ml three to four times a day.

5ml three times a day 7.5ml three times a day

Doses should be given every 6 to 8 hours if required. Leave as least 4 hours between doses.

Post-immunisation fever: 2.5ml (50mg) followed by one further dose of 2.5ml (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 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 and in adolescents 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 previous peptic ulcer/ haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

History of gastrointestinal bleeding or perforation, related to NSAID’s 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).

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

Significant dehydration (caused by vomiting, diarrhoea or insufficient fluid intake).

4.4. Special warnings and precautions for use

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

The use of Fenpaed Ibuprofen 100 mg/5 ml Oral Suspension with concomitant NSAIDs including cylooxygenase-2 selective inhibitors should be avoided (see section 4.5)

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

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

Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration.

Renal impairment as renal function may further deteriorate (see sections 4.3 and 4.8)

Hepatic dysfunction (see section 4.3 and 4.8)

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.

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.

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 gastrotoxicity or bleeding, such as 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.

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

Administration of NSAID’S such as Ibuprofen may cause dose dependent renal toxicity in patients with reduced renal blood flow or blood volume where renal prostaglandins support the maintenance of renal perfusion. Patients at risk of this reaction include those with impaired renal function, heart failure or liver dysfunction. This is of particular importance in hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur. Caution is therefore required in the use of Ibuprofen in such patients.

There is a risk of renal impairment in dehydrated children and adolescents.

Ibuprofen should be used with caution in patients with bronchial asthma or allergic disease, since such patients may have NSAID - sensitive asthma which has been associated with severe bronchospasm.

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 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.

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 100mg/5ml Oral Suspension should be discontinued at the first appearance of skin rash, mucosal lesion, or any other sign of hypersensitivity.

Exceptionally, varicella can be at the origin of serious cutaneous and soft tissues infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of ibuprofen in case of varicella (chickenpox).

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, liver, heart, kidney or bowel problems

If you are an adult taking this product:

Do not take it; if you are pregnant.

Consult your doctor or pharmacist before taking if; you are trying to get

pregnant; are elderly; are a smoker.

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

Do not give to children aged 6 months and older for more than 3 days. Consult your doctor promptly if symptoms persist or worsen.

Do not exceed the stated dose.

Do not give to babies under 3 months of age.

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

Ibuprofen should be avoided in combination with:

Acetylsalicylic acid (Aspirin): Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects (see section 4.4).

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)

Ticlopidine: NSAIDs should not be combined with ticlopidine due to a risk of an additive effect in the inhibition of the platelet function.

Methotrexate: There is a potential for an increase in plasma methotrexate.

Ibuprofen should be used with caution in combination with:

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).

Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Diuretic can increase risk of nephrotoxicity of NSAIDs.

Corticosteroids: increase the risk gastrointestinal ulceration or bleeding (see section 4.4).

Anti-platelets 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 increased plasma glycoside levels.

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.

Lithium: There is evidence for potential increase in plasma levels of lithium.

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 quinolone may have increased risk of developing convulsions.

4.6 Pregnancy and lactation

Whilst no teratogenic effects have been demonstrated in animal experiments the use of Ibuprofen 100 mg/5ml Oral Suspension, 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 arteriosis 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 breast-fed infants 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

The following frequencies are taken as a basis when evaluating undesirable effects: Very common: > 1/10

>    1/100 to < 1/10

>    1/1,000 to < 1/100

>    1/10,000 to < 1/1,000 < 1/10,000

cannot be estimated from the available data

Hypersensitivity reactions have been reported and these may consist of: (a) Non-specific allergic reactions and anaphylaxis

Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, 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 longterm treatment, additional adverse effects may occur.

Hypersensitivity reactions:

Uncommon: Hypersensitivity reactions with urticaria and pruritis.

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, panytopenia, 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 reaction, 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 studies suggest that use of ibuprofen (particularly at high doses 2400mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction 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

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swelling and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid (aspirin) 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).

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed following administration and is 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 half-life of ibuprofen is about 2 hours.

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

It is metabolised 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 liquid (E965), polysorbate 80, saccharin sodium (E954), citric acid monohydrate, sodium methylhydroxybenzoate (E219), sodium propylhydroxybenzoate (E217), purified water and strawberry flavour.

6.2 Incompatibilities

None stated except as in ‘Interactions with other medicaments’.

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

An amber glass bottle sealed with child resistant, tamper evident cap. Pack sizes available: 100 ml.

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

6.6 Special precautions for disposal

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

7    MARKETING AUTHORISATION HOLDER

Pinewood Laboratories Limited Ballymacarbry,

Clonmel,

Co. Tipperary,

Ireland.

8    MARKETING AUTHORISATION NUMBER(S)

PL 04917/0082

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12^th November 2007

DATE OF REVISION OF THE TEXT

03/01/2016