Ibuprofen 100mg/5ml Oral Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 100 mg/5ml Oral Suspension.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen 100 mg/5 ml (equivalent to 2.0% w/v)
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Oral suspension.
White-coloured, orange-flavoured oral suspension.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ibuprofen Oral Suspension is indicated for its analgesic and anti-inflammatory effects in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis and other nonrheumatoid (seronegative) arthropathies.
In the treatment of non-articular rheumatic conditions, Ibuprofen Oral Suspension is indicated in periarticular conditions such as frozen shoulder (capsulitis), bursitis, tendinitis, tenosynovitis and low back pain; Ibuprofen Oral Suspension can also be used in soft tissue injuries such as sprains and strains.
Ibuprofen Oral Suspension is also indicated for its analgesic effect in the relief of mild to moderate pain such as dysmenorrhoea, dental and post-operative pain and for symptomatic relief of headache; including migraine headache.
Ibuprofen Oral Suspension is indicated in short-term use for the treatment of pyrexia in children over one year of age.
4.2 Posology and method of administration
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
For oral administration, preferably with or after food.
Adults: the recommended dosage of Ibuprofen Oral Suspension is 1200-1800 mg daily in three to four divided doses. Some patients can be maintained on 600-1200 mg daily. In severe or acute conditions, it can be advantageous to increase the dosage until the acute phase is brought under control, provided that the total daily dose does not exceed 2400 mg in divided doses.
Children: Not recommended for children weighing less than 7 kg.
For fever and pain the daily dosage of Ibuprofen Oral Suspension is 20-30mg/kg of bodyweight in divided doses. This can be achieved as follows:
Children 1-2 years: One 2.5 ml spoonful (50 mg) to be taken three to four times in 24 hours.
Children 3- 7 years: One 5 ml spoonful (100 mg) to be taken three to four times in 24 hours.
Children 8-12 years: Two 5 ml spoonfuls (200 mg) three to four 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).
For Juvenile Rheumatoid Arthritis: The usual daily dosage is 30-40 mg/kg/day in three to four divided doses.
Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If Ibuprofen Oral Suspension is considered necessary, the lowest effective dose should be used anxd for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy. If renal or hepatic function is impaired the dosage should be assessed individually.
4.3 Contraindications
Hypersensitivity to ibuprofen or to any of the excipients in the product.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) or chronic dyspepsia.
Ibuprofen Oral Suspension is contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
Severe heart failure (NYHA Class IV), Severe renal failure, and hepatic failure (see section 4.4).
During the last trimester of pregnancy (see section 4.6 Pregnancy and lactation).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
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 section 4.2, and GI and cardiovascular risks below).
Other NSAIDs:
The use of Ibuprofen Oral Suspension with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).
Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Cardiovascular, Renal and Hepatic Impairment:
The administration of an NS AID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3 and 4.8).
Renal:
Renal impairment as renal function may further deteriorate (see section 4.3 contraindications and Section 4.8 Undesirable effects)
There is a risk of renal impairment in dehydrated children.
Hepatic:
Hepatic dysfunction (see sections 4.3 contraindications and 4.8 Undesirable effects) 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).
Gastrointestinal 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 gastrointestinal 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. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal 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).
Where gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.
The elderly are at increased risk of the serious consequences of adverse reactions. Cardiovascular and cerebrovascular effects
Caution, appropriate monitoring and advice are-required prior to starting treatment for patients with a history of hypertension and/or mild to moderate congestive 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 (2400mg/day) 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/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 (2400mg/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 (2400mg/day) are required.
SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8 Undesirable effects).
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 higher 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.
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. In women attempting to conceive or who are undergoing investigation of infertility, withdrawal of Ibuprofen should be considered.
4.5 Interaction with other medicinal products and other forms of interaction
Other NSAIDs including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).
Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, it should be avoided as it may increase the risk of adverse reactions (see section 4.4).
Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.
Antihypertensives: reduced antihypertensive effect.
Diuretics: reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Lithium: Decreased elimination of lithium leading to increased plasma levels of lithium.
Methotrexate: Decreased elimination of methotrexate leading to increased plasma levels of methotrexate.
Ciclosporin: Increased risk of nephrotoxicity with NSAIDs.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).
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.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4).
Acetylsalicylic acid
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).
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.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. Whilst no teratogenic effects have been demonstrated in animals experiements,he use of Ibuprofen Oral Suspension should, if possible, be avoided during the first 6 months of pregnancy.
NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.
In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of foetal ductus arteriosus with possible persistent pulmonary hypertension), use in last trimester of pregnancy is contraindicated.
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).
Lactation:
In the limited studies so far available, NSAIDs can appear in the breast milk in very low concentrations, and should, if possible, be avoided when breast-feeding..
See section 4.4 Special warnings and precautions for use, regarding female fertility.
4.7 Effects on ability to drive and use machines
Dizziness, drowsiness, visual disturbances, fatigue or headaches are possible undesirable effects after taking NSAIDs. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of:
(a) Non-specific allergic reaction and anaphylaxis
(b) Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or
(c) Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Frequency of undesirable effects is classified as:
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)
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.
Blood and lymphatic system disorders:
Very rare: Haematopoietic disorders (thrombocytopenia, neutropenia, leucopenia, pancytopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
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.
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)
Psychiatric disorders:
Not known: depression, confusion, hallucinations
Nervous system disorders:
Uncommon: headache
Very rare: aseptic meningitis (See Immune system disorders and section 4.4)
Not known: optic neuritis, paraesthesia, tinnitus, vertigo, dizziness, and drowsiness.
Eye disorders:
Not known: visual disturbances
Cardiac disorders:
Not known: Cardiac failure
Clinical studies data 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).
Vascular disorders:
Not known: hypertension
Gastrointestinal disorders:
The most commonly observed adverse events are gastrointestinal in nature. Uncommon: Abdominal pain, nausea, dyspepsia Rare: Vomiting, diarrhoea, flatulence, constipation
Very rare: Peptic ulcer, perforation or gastrointestinal haemorrhage, sometimes fatal particularly in the elderly, may occur (see section 4.4), melaena, haematemesis, sometimes fatal particularly in the elderly, pancreatitis. Ulcerative stomatitis, gastritis. Exacerbation of colitis and Crohn’s disease (see section4.4) has been reported following ibuprofen administration.
Not known: duodenal ulcer
Epidemiological data indicate that of the seven most widely-used oral, non-aspirin NSAIDs, ibuprofen presents the lowest risk of upper gastrointestinal toxicity.
Hepatobiliary disorders:
Very rare: liver disorders
Not known: abnormal liver function, hepatitis and jaundice
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: Photosensitivity (see 'hypersensitivity' for other skin 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: nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome
General disorders and administration site conditions:
Not known: oedema, malaise, fatigue
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, dizziness, excitation and disorientation, fainting 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.
Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.
Good urine output should be ensured.
Renal and liver function should be closely monitored.
Patients should be observed for at least four hours after ingestion of potentially toxic amounts.
Frequent or prolonged convulsions should be treated with intravenous diazepam.
Other measures may be indicated by the patient’s clinical condition.
5.1 Pharmacodynamic properties
ATC code: MO1A EO1.
Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic product, nonsteroid, propionic derivative.
Mechanism of action:
Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and antipyretic activity. The drug's therapeutic effects as an NSAID are thought to result from its inhibitory effect on the enzyme cyclo-oxygense, which results in a marked reduction in prostaglandin synthesis.
Pharmacodynamic effects:
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 h before or within 30 min 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 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
Absorption:
Ibuprofen is rapidly absorbed from the gastrointestinal tract.
Distribution:
Peak serum concentrations occur 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed 1-2 hours after administration. These times may vary with different dosage forms.
Biotransformation:
Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney either as such or as conjugates. Ibuprofen is extensively bound to plasma proteins.
Elimination:
The elimination half-life is approximately 2 hours. Excretion by the kidney is both rapid and complete.
In limited studies, ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
6.1 List of excipients
Sodium methyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, xanthan gum, carboxymethylcellulose sodium, microcrystalline cellulose, liquid maltitol, citric acid monohydrate, sodium citrate, sodium benzoate, saccharin sodium, Polysorbate 80, Natural Orange Flavour, Orange Sweet No 1 Flavour (which contains propylene glycol), purified water.
6.2 Incompatibilities
Not to be mixed with other medicinal products.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Do not store above 25°C.
Keep container in the outer carton to protect from light.
6.5 Nature and contents of container
An amber-coloured polyethylene terephthalate (PET) bottle containing 500 ml Ibuprofen Oral Suspension sealed with a polypropylene, pilfer-proof child resistant cap fitted with a low density polyethylene liner.
6.6 Special precautions for disposal
Shake well before use.
7 MARKETING AUTHORISATION HOLDER
Fannin (UK) Limited 42-46 Booth Drive Park Farm South
Wellingborough
Northamptonshire
NN8 6GT UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20417/0105
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
05/02/2004
10 DATE OF REVISION OF THE TEXT
05/04/2016