Ibuprofen

Care Ibuprofen for Children Oral Suspension

Ibuprofen 100 mg / 5ml

Excipients with known effect:

Each 5ml contains:

- 8.6mg Sodium Methyl Parahydroxybenzoate(E219)

- 2.25mg Sodium Propyl Parahydroxybenzoate(E217)

- 1375mg Maltitol Liquid (Contains Maltitol & Sorbitol (80:20))

For the full list of excipients, see section 6.1.

Oral Suspension

A white, opaque smooth suspension.

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

Posology

Children 8 to 12 years: 10ml three to four times daily.

Children 3 to 7 years: 5ml three to four times daily.

Children 1 to 2 years: 2.5ml three to four times daily.

Infants 6 to 12 months: 2.5ml three times daily.

If this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

Not to be given to children under six months of age except on the advice of a doctor.

For post immunisation fever: 2.5ml followed by one further 2.5ml 6 hours later, if necessary. No more than 2 doses in 24 hours. If fever is not reduced, consult your doctor.

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

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4).

Method of administration

To be taken with or after food.

For oral administration and short term use only.

Hypersensitivity to the active substance (ibuprofen) or to any of the excipients listed in section 6.1.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, bronchospasm, rhinitis, angioedema or urticaria) particularly associated with therapy with aspirin or other 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 (NYHA Class IV), renal failure or hepatic failure (see section 4.4).

Last trimester of pregnancy (see section 4.6).

Children under 6 months.

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).

Should be used with care in patients with renal, hepatic or cardiac impairment as the use of non-steroidal anti-inflammatory drugs may result in the deterioration of renal function. The dose should be kept as low as possible.

For short term use only.

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

Respiratory:

In patients suffering from or with a previous history of bronchial asthma or allergic disease, bronchospasm may be precipitated.

Other NSAIDS:

The use of this medicine 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). There is a risk of renal impairment in dehydrated children.

Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

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 studies 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 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.

Cases of Kounis syndrome have been reported in patients treated with Ibuprofen. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction-associated with constriction of coronary arteries and potentially leading to 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 any time 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 at the initial stages of treatment.

Caution should be advised in patients with conditions involving an increased tendency to bleed or who are 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 bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Severe cutaneous adverse reactions (SCARs):

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (Dress syndrome), and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with the use of ibuprofen (see section 4.8). Most of these reactions occurred within the first month.

If signs and symptoms of these reactions appear ibuprofen should be withdrawn immediately and an alternative treatment considered (as appropriate).

In exceptional cases, 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 this medicine in cases of varicella.

Masking of symptoms of underlying infections:

Care Ibuprofen for Children Oral Suspension can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Care Ibuprofen for Children Oral Suspension is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

Excipient warnings:

• Sodium Methyl Parahydroxybenzoate (E219) and Sodium Propyl Parahydroxybenzoate (E217) may cause allergic reactions (possibly delayed).

• Sodium Benzoate (E 211): This medicine contains 5mg Sodium Benzoate in each 5ml dose.

• Sodium: This medicine contains less than 1mmol sodium (23mg) per dosage unit, that is to say essentially 'sodium-free'.

• Maltitol Liquid (contains Maltitol and Sorbitol): Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product. - Maltitol: Calorific value 2.3kcal/5ml maltitol, may have a mild laxative effect Sorbitol: This medicine contains 275mg sorbitol in each 5ml dose. Sorbitol may cause gastrointestinal discomfort and mild laxative effect”.

The label will include:

Read the enclosed leaflet before taking this product.

Do not give to your child if they:

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

• are allergic to ibuprofen or any other ingredients 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 the person taking the product:

• Has or has 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 is intended for children aged between 6 months and 12 years.

If you are an adult taking this product:

Speak to your doctor or pharmacist before taking if;

You are pregnant; you are trying to get pregnant; are elderly; are a smoker

Do not exceed the stated dose.

Ibuprofen should be avoided in combination with:

Acetylsalicylic acid (Aspirin): Unless low-dose acetylsalicylic acid (not above 75mg daily) has been advised by a doctor, 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 ex-vivo 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).

Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs and may cause hyperkalemia in patients under these treatments. 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: 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.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. From the 20th week of pregnancy onward, ibuprofen use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, during the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to ibuprofen for several days from gestational week 20 onward. Ibuprofen should be discontinued if oligohydramnios or ductus arteriosus constriction are found.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

- cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction (see above), which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

- inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, ibuprofen is contraindicated during the third trimester of pregnancy.

Breast-feeding

In limited studies, ibuprofen appears in the breast milk in very low concentration and is unlikely to affect the breast-fed infant adversely.

Fertility

See section 4.4 regarding female fertility

Dizziness and headache have been reported rarely with Ibuprofen, which will affect the ability to drive and operate machinery; patients should be warned not to drive or operate machinery if these side effects are experienced. Not applicable in children under 12 years.

Hypersensitivity reactions have been reported following treatment with Ibuprofen. These may consist of:

a) non-specific allergic reactions and anaphylaxis,

b) respiratory tract reactivity comprising of asthma, aggravated asthma, bronchospasm or dyspnoea, or

c) various skin reactions, e.g., pruritis, urticaria, angiodema 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. In this section, frequencies of undesirable effects are defined as follows: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).

Infections and infestations:

Not known: Exacerbation of infections related inflammation has been described, in exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection.

Skin and subcutaneous tissue disorders:

Very rare: Severe cutaneous adverse reactions (SCARs) (including Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis).

Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalised exanthematous pustulosis (AGEP).

Blood and lymphatic system disorders:

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, bruising and purpura.

Immune System disorders:

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.

Not known: 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).

Nervous System disorders:

Uncommon: Headache and dizziness

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

Ear & Labyrinth disorders:

Rare: Hearing disturbance

Cardiac disorders:

Not known: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

Not known: Kounis syndrome

Vascular disorders:

Not known: Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) 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).

Gastrointestinal disorders:

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).

Hepatobiliary disorders:

Very rare: liver disorders.

Skin and subcutaneous tissue disorders:

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.

Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalised exanthematous pustulosis (AGEP), Photosensitivity reactions.

Renal and urinary disorders:

Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Not Known: Ureteric colic, dysuria, renal tubular acidosis*

Metabolism and Nutrition Disorders

Not Known: Decreased appetite, Hypokalaemia*

*Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses.

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 or search for 'MHRA Yellow Card' in the Google Play or Apple App Store.

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, hypokalaemia* and/or 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.

In serious poisoning metabolic acidosis may occur and 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.

Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8).

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.

Pharmacotherapeutic group: Anti-Inflammatory and antirheumatic products, non-steroids - Propionic acid derivatives, ATC code: M01AE

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 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 400mg were taken within 8 hours before or within 30 minutes after immediate release acetylsalicylic acid dosing (81mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. Although there are uncertainties regarding extrapolation of these ex-vivo 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).

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.

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

Sodium Methyl Parahydroxybenzoate(E219)

Sodium Propyl Parahydroxybenzoate(E217)

Citric Acid (E330)

Saccharin Sodium(E954)

Sodium Benzoate(E211)

Dispersible Cellulose

Juicy Orange Flavour

Polysorbate 80(E433)

Maltitol Liquid(Contains Maltitol & Sorbitol (80:20))

Xanthan Gum(E415)

Purified Water

None

2 years.

Do not store above 25°C.

100ml amber PET bottle with polypropylene child-resistant cap with tamper evident band and Saranex faced EPE liner.

A measuring spoon is provided.

Not applicable.

Thornton & Ross Limited

Linthwaite Laboratories

Huddersfield

HD7 5QH

United Kingdom

PL 00240/0132

13/03/2000 / 05/03/2009

11/03/2024