Ibuprofen Tablets 400mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets 400mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ibuprofen 400 mg.
3 PHARMACEUTICAL FORM
Film-coated tablet.
Appearance:
Rosy red, circular biconvex, film-coated coated tablets plain on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mild to moderate pain: Pain and mild inflammation in rheumatic disease (including Still’s disease) and other musculoskeletal disorders.
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).
Adults: 0.6 - 1.2 g daily in 3 to 4 divided doses preferably after food, increased if necessary to a maximum of 2.4 g daily.
Children: 20 mg per kg of bodyweight daily.
Children under 30 kg: A maximum of 500 mg in 24 hours.
Elderly: The elderly are at increased risk of the serious consequences of
adverse reactions. If an NSAID (non-steroidal anti-inflammatory drug) is considered necessary, the lowest dose should be used and the patient should be monitored for GI bleeding for 4 weeks following initiation of the NSAID therapy.
The tablets should be swallowed with a drink of water or milk, preferably with or after food.
4.3 Contraindications
This drug should not be given to patients with active peptic ulceration, a history of recurrent ulceration or chronic dyspepsia.
Ibuprofen is contra-indicated in patients with a history of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Ibuprofen is contra-indicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angiodema or urticaria) in response to ibuprofen, aspirin or other NSAIDs.
Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors is contra-indicated (see section 4.5 Interactions).
Ibuprofen should not be given to patients with severe hepatic , renal and cardiac failure (see section 4.4 - Special warnings and precautions for use).
Ibuprofen should not be administered during the last trimester of pregnancy (see section 4.6 - Pregnancy and lactation).
Severe Heart Failure.
4.4 Special warnings and precautions for use
In all patients:
Undesirable effect may be minimised by using the minimum effective dose for the shortest possible duration.
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 - Psology and administration).
Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since ibuprofen has been reported to cause bronchospasm in such patients.
Gastrointestinal bleeding, ulceration and perforation:
Gastrointestinal bleeding 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 gastrointestinal events.
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 gastrointoxicity or bleeding, such as corticosteroids, anticoagulants such as warfarin, or anit-platelet agents such as aspirin (see section 4.5 - Interactions).
When gastrointestinal bleeding occurs in patients receiving ibuprofen the treatment should be withdrawn.
Ibuprofen should only 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).
Cardiovascular, Renal and Hepatic impairment:
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formulation 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.
In patients with renal, cardiac or hepatic impairment caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored in these patients (see also section 4.3 - Contra-indications).
Ibuprofen should be given with care to patients with a history of heart failure or hypertension since fluid retention and oedema has been reported in association with ibuprofen administration.
SLE or 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).
Female fertility:
The use of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ibuprofen should be considered.
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).
Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice are-required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial data suggest that use of ibuprofen, particularly at a high dose (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 myocardial infarction.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients:
Anti-hypertensives: Reduced anti-hypertensive 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 glycoside levels.
Lithium: Decreased elimination of lithium.
Methotrexate: Decreased elimination of 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.
Other analgesics: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.3 -Contra-indications).
Corticosteroids: Increased risk of GI bleeding. (see section 4.4 - Special warnings and precautions for use).
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4 - Special warnings and precautions for use).
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.
Aminoglycosides: Increased renal toxicity has been reported in a few patients receiving concomitant ibuprofen and aminoglycoside therapy.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
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
Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy should if possible be avoided. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (closure of the ductus arteriosus), use in the last trimester of pregnancy is contra-indicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendancy in both mother and child (see section 4.3 - Contra-indications). 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 the limited studies so far available, ibuprofen appears in the breast milk in very low concentrations and is unlikely to adversely affect the breast-fed infant.
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (2400 mg daily), 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: The most commonly observed adverse events are gastrointestinal in nature. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis and gastrointestinal haemorrhage have been reported following administration. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed. Fatalities have occurred, particularly in the elderly. Epidemiological data indicate that of the most widely-used oral, non-aspirin NSAIDs, ibuprofen presents the lowest risk of upper gastrointestinal toxicity. Exacerbation of colitis and Crohn’s disease has been reported (see section 4.4 - Special warnings and precautions for use).
Hypersensitivity: 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) assorted skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema and less commonly, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Cardiovascular: Oedema has been reported in association with ibuprofen treatment.
Other adverse events reported less commonly for which causality has not necessarily been established include:
Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, papillary necrosis and renal failure.
Hepatic: Abnormal liver function, hepatitis and jaundice.
Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness. There have been reports of aseptic meningitis, especially in patients with existing auto-immune disorders such as systemic lupus erythematosus or mixed connective tissue disease. Symptoms of aseptic meningitis include stiff neck, headache, nausea, vomiting, fever or disorientation.
Haematological: Thrombocytopenia, neutropenia, agranulocytosis, anaemia, pancytopenia, aplastic anaemia and haemolytic anaemia
Dermatological: Photosensitivity.
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 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, a derivative of propionic acid, has useful anti-inflammatory, analgesic and antipyretic activity. Similar to other propionic acid derivatives such as naproxen and fenoprofen it can cause gastrointestinal erosions (gastric, duodenal and intestinal) in experimental animals. All produce gastrointestinal side effects in man but are usually less severe than with aspirin. The propionic acid derivatives are all effective inhibitors of the cyclo-oxygenase responsible for the biosynthesis of prostaglandins. All of these agents alter platelet function and prolong bleeding time.
5.2 Pharmacokinetic properties
Ibuprofen is rapidly absorbed following oral administration to man, and is rapidly distributed throughout the whole body.
Maximum peak concentrations in plasma are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak concentrations in plasma are observed after 1 to 2 hours. These times may vary with different dosage forms.
The half life in plasma is about 2 hours.
Ibuprofen is extensively (99 %) and firmly bound to plasma proteins, but the drug occupies only a fraction of the total drug-binding sites at usual concentrations. Ibuprofen passes slowly into the synovial spaces and may remain there in higher concentration as the concentrations in plasma decline. In experimental animals, ibuprofen and its metabolites pass easily across the placenta. The excretion of ibuprofen is rapid and complete. Greater than 90 % of an ingested dose is excreted in the urine as metabolites or their conjugates, and no ibuprofen per se is found in the urine. The major metabolites are a hydroxylated and a carboxylated compound.
In limited studies, ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
Not available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core Lactose Maize starch Methylcellulose (A4M) Sodium starch glycollate Magnesium stearate
Colloidal silicon dioxide (Aerosil 200)
Coating and printing ink Hydroxypropylmethylcellulose E15 Titanium dioxide (E171)
Talc
Propylene glycol Erythrosine Supra (colourant)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months
6.4 Special precautions for storage
No special requirements.
6.5 Nature and contents of container
PVC/Aluminium blister strips in cardboard cartons.
Pack sizes: 12, 24, 48, 84, 100, 250 and 500 tablets.
6.6 Special precautions for disposal
Not applicable.
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 20417/0049
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26/08/2011
10 DATE OF REVISION OF THE TEXT