4.1. Therapeutic indications

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, earache, headache, minor aches and sprains

4.2. Posology and method of administration

The lowest effective dose for the shortest duration necessary to relieve symptoms (see section 4.4, Special warnings and precautions for use)

For short-term use only

The recommended daily dose of the product is 20-30 mg per kg of body weight. Doses should be given approximately every 6 to 8 hours, (or with a minimum of 4 hours between each dose if required). Do not take more than the recommended dose in 24 hours. The recommended dose should not be exceeded. Using the spoon or dosing syringe device provided this can be achieved as follows:

Infants 3 – 6 months weighing more than 5kg (body weight 5-7.6kg): One 2.5ml dose may be taken 3 times in 24 hours.

Infants 6 - 12 months (body weight 7.7-9kg): One 2.5ml dose may be taken 3 to 4 times in 24 hours.

Children 1 - 3 years (body weight 10-16kg): One 5ml dose may be taken 3 times in 24 hours.

Children 4 - 6 years (body weight 17-20kg): 7.5ml (5ml + 2.5ml) may be taken 3 times in 24 hours.

Children 7 - 9 years (body weight 21-30kg): Two 5ml doses may be taken 3 times in 24 hours.

Children 10 – 12 years (body weight 31-40kg): Three 5ml doses may be taken 3 times in 24 hours.

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

Do not use this product in children weighing less than 5 kg.

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

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

For children under 6 months medical advice should be sought after 24 hours use (3 doses) if the symptoms persist.

For post immunisation pyrexia: One 2.5ml dose followed by one further 2.5ml 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.

Method of administration

For oral administration.

For patients with sensitive stomachs the product can be taken with or after food.

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 (NYHA Class IV), renal failure or hepatic failure (see section 4.4, Special warnings and precautions for use).

Third trimester of pregnancy (See section 4.6, Fertility, 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).

Masking of symptoms of underlying infections

Ibuprofen 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 Boots Ibuprofen 3 Months Plus 100mg/5ml Oral Suspension Strawberry Flavour is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In nonhospital settings, the patient should consult a doctor if symptoms persist or worsen.

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 cyclo-oxygenase-2 selective inhibitors should be avoided (see section 4.5 Interaction with other medicinal products and other forms of interaction).

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 sections 4.3 Contraindications and 4.8 Undesirable effects).

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

The risk of renal impairment is increased in children, adolescents and elderly, particularly in volume depleted states (e.g. dehydration, which may be due to nausea and vomiting, hypotension, sepsis) and hypovolaemia related to other known effects (e.g. GI haemorrhage).

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 Contraindications and 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 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 be made 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 hypersensitivity 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 Undesirable effects).

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 Contraindications), 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 anti-platelet agents such as aspirin (see section 4.5 Interaction with other medicinal products and other forms of interaction).

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

Dermatological:

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 generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with the use of ibuprofen (see section 4.8 Undesirable effects). Patients appear to be at highest risk of these reactions early in the course of therapy: Most of these reactions occurred within the first month.

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

Exceptionally, varicella can be at the origin of serious cutaneous and soft tissue 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 (see section 4.8).

This product contains maltitol liquid (E965): patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicinal product contains 11 mg of sodium per 5 ml dosage, equivalent to 1.65% of the recommended maximum daily intake of sodium for a child. A maximum dosage of 15 ml would provide 33 mg of sodium and so this should be taken into consideration by children on a controlled sodium diet.

The label will state:

Read the enclosed leaflet before taking this product.

Do not give this product if your baby or child:

• Is under 3 months old or weighs less than 5 kg

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

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

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

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 pregnant

• You are trying to get pregnant

• You are breastfeeding

• Are elderly

• Are a smoker

Do not exceed the stated dose.

Keep out of the reach and sight of children.

For short term use.

For infants aged 3-6 months, if symptoms worsen or do not go away, talk to your doctor within 24 hours.

For a child of 6 months of age and over, if this medicinal product is required for more than 3 days or if symptoms worsen talk to your doctor.

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

Ibuprofen should be avoided in combination with:

Acetylsalicylic acid (aspirin): Unless low-dose aspirin (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.

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 Pharmacodynamic properties).

Other NSAIDs including cyclo-oxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (See section 4.4 Special warnings and precautions for use)

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. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking a coxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.

Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see Section 4.4 Special warnings and precautions for use).

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):

increased risk of gastrointestinal bleeding (see section 4.4 Special warnings and precautions for use).

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.

4.6. Fertility, pregnancy and lactation

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 malformation, 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):

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 (see section 4.3).

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.

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 list of adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200 mg ibuprofen per day), in short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.

Adverse events which have been associated with ibuprofen are given below, tabulated by system organ class and frequency. Frequencies are defined as:

very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness. The most commonly observed adverse events are gastrointestinal in nature.

System Organ Class

Frequency

Adverse Events

Blood and Lymphatic System Disorders

Very rare

Haematopoietic disorders, anaemia, leucopenia, thrombocytopenia, pancytopenia and agranulocytosis1

Immune System Disorders

Uncommon

Hypersensitivity with urticaria and pruritus2

Very rare

Severe hypersensitivity reactions, including facial, tongue and throat swelling, dyspnoea, tachycardia, and hypotension (anaphylaxis, angioedema or severe shock)2

Nervous System Disorders

Uncommon

Headache

Very rare

Aseptic meningitis3

Cardiac Disorders

Not known

Cardiac failure and oedema4

Kounis syndrome2

Vascular Disorders

Not known

Hypertension4

Respiratory, Thoracic And Mediastinal Disorders

Not known

Respiratory tract reactivity comprising asthma, bronchospasm or dyspnoea2

Gastrointestinal Disorders

Uncommon

Abdominal pain, nausea and dyspepsia5

Rare

Diarrhoea, flatulence, constipation and vomiting

Very rare

Peptic ulcer, gastrointestinal perforation or gastrointestinal haemorrhage, melaena, and haematemesis6. Mouth ulceration and gastritis. Exacerbation of colitis and Crohn's disease7

Hepatobiliary Disorders

Very rare

Liver disorder

Skin and Subcutaneous Tissue Disorders

Uncommon

Skin rash2

Very rare

Severe cutaneous adverse reactions (SCARs) (including Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) 2

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 oedema8

Not known

Renal tubular acidosis9.

Acute interstitial nephritis (AIN).

Investigations

Very rare

Haemoglobin decreased

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.

Metabolism and nutrition disorders

Not known

Decreased appetite

Hypokalaemia9

Description of Selected Adverse Reactions

1 First signs are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

2 Hypersensitivity reactions: These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity, including asthma, aggravated asthma, bronchospasm, and dyspnoea, or (c) various skin reactions, including pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens-Johnson Syndrome and erythema multiforme, or (d) kounis syndrome.

3 The pathogenic mechanism of drug-Induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with ibuprofen in patients with existing auto-immune disorders (such as systemic lupus erythematosus and mixed connective tissue disease).

4 Clinical trial and epidemiological data suggest that use of ibuprofen (particularly at high doses 2400 mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke), (see section 4.4).

5 The adverse events observed most often are gastrointestinal in nature.

6 Sometimes fatal.

7 See section 4.4.

8 Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

9 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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

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.