This information is intended for use by health professionals

1. Name of the medicinal product

Boots Ibuprofen 3 Months Plus 100mg/5ml Oral Suspension Strawberry Flavour

2. Qualitative and quantitative composition

Active Ingredient

Ibuprofen

Excipients:

Maltitol liquid (E965)

Sodium content

Per 5ml

100 mg

2.1 g

11 mg

See section 4.4 for further information.

For a full list of excipients, see Section 6.1

3. Pharmaceutical form

Oral suspension.

An off-white, strawberry-flavoured, syrupy suspension.

4. Clinical particulars
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

For oral administration.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4, Special warnings and precautions for use)

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.

For pain, fever and symptoms of cold and influenza: For children weighing 5kg or more: 20mg/kg bodyweight daily in divided doses.

Using the spoon or dosing syringe device provided this can be achieved as follows:

Infants 3 – 6 months weighing more than 5kg: One 2.5ml dose may be taken 3 times in 24 hours.

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

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

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

Children 7 - 9 years: Two 5ml doses may be taken 3 times in 24 hours.

Children 10 – 12 years: Three 5ml doses may be taken 3 times in 24 hours.

Doses should be given approximately every 6 to 8 hours, (or with a minimum of 4 hours between each dose if required).

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

For short term use only.

For infants aged 3-5 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.

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).

Last trimester of pregnancy (See section 4.6, 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).

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.

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.

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:

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 Undesirable effects). 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.

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.

Each 5 ml of this product contains 11 mg sodium (a maximum daily dose of 30 ml will provide 66 mg of sodium). This should be taken into consideration by patients 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

• 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

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

• 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 3-5 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. 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. 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. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose

the foetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension):

- renal dysfunction, 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.

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 Special warnings and precautions for use, 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

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

Not known:

cannot be estimated from the available data

Infections and infestations:

Very rare: Exacerbation of infection-related inflammations (e.g. development of necrotising fasciitis) coinciding with the use of non-steroidal anti-inflammatory drugs has been described. This is possibly associated with the mechanism of action of the non-steroidal anti-inflammatory drugs. If signs of an infection occur or get worse during use of Ibuprofen the patient is therefore recommended to go to a doctor without delay. It is to be investigated whether there is an indication for anti-infective/antibiotic therapy.

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.

Immune System:

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 Special warnings and precautions for use).

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).

Not known: Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, dyspnoea. Exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Nervous System:

Uncommon: Headache.

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

Cardiovascular and Cerebrovascular:

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

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), (see section 4.4 Special warnings and precautions for use).

Gastrointestinal:

The most commonly-observed adverse events are gastrointestinal in nature. 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 ulcerative colitis and Crohn's disease (See section 4.4 Special warnings and precautions for use).

Hepatic:

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: In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also "Infections and infestations"). Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Renal:

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

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.

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.

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

ATC Code, M01A E01

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 hours before or within 30 minutes 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. 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.

5.3 Preclinical safety data

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

6. Pharmaceutical particulars
6.1 List of excipients

Citric acid

Sodium citrate

Sodium chloride

Sodium saccharin

Domiphen bromide

Purified water

Polysorbate 80

Maltitol liquid

Xanthan gum

Strawberry flavour

Glycerol.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

100 ml, 150ml, 200ml - 3 years.

30 ml, 50 ml – 2 years.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Amber-coloured polyethylene terephthalate (PET) bottle with a child-resistant closure fitted with a low density polyethylene liner. The bottle contains 50 ml, 100 ml, 150 ml or 200ml of product. A double-ended spoon with measures of 2.5 ml and 5 ml will be provided.

OR

Amber-coloured polyethylene terephthalate (PET) bottle with a child-resistant closure fitted with a low density polyethylene liner or polyethylene plug. The bottle contains 50 ml, 100 ml, 150 ml or 200ml of product. Syringe composed of a natural polypropylene barrel and a polyethylene pigmented white plunger.

OR

A 30ml amber glass bottle fitted with a polypropylene child resistant closure and tamper evident band. A double-ended spoon with measures of 2.5 ml and 5 ml will be provided.

Not all pack sizes will be marketed.

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

The Boots Company PLC

1 Thane Road West

Nottingham NG2 3AA

Trading as: BCM

8. Marketing authorisation number(s)

PL 00014/0859

9. Date of first authorisation/renewal of the authorisation

17 July 2013

10. Date of revision of the text

8 February 2018