Ibuprofen Tablets 400mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets 400mg
2. Qualitative and Quantitative Composition
Ibuprofen BP 400mg
3. Pharmaceutical Form
Tablet
4. Clinical Particulars
4.1 Therapeutic Indications
Ibuprofen is indicated for its anti-inflammatory effects in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still’s disease), ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.
In the treatment of non-articular rheumatic conditions, Ibuprofen is indicated in periarticular conditions such as frozen shoulder (capsulitis), fibrositis, lumbago, bursitis, tendinitis, tenosynovitis and low back pain. Ibuprofen can also be used in soft tissue injuries such as sprains and strains.
Ibuprofen is 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.
4.2 Posology and method of administration
Oral administration Adults
The recommended dosage for Ibuprofen is 1200 - 1800mg daily in 3- 4 divided doses preferably with or after food. Some patients can be maintained on 600 - 1200mg daily. The total daily dosage must not exceed 2400mg in divided doses.
Children
For children over the age of 12 years the daily dosage is 20mg per kg of body weight in divided doses preferably with or after food. In juvenile rheumatoid arthritis up to 40mg per kg of body weight daily in divided doses may be taken. The total daily dose given in 24 hours for children weighing less than 30kg should not exceed 500mg.
If in children aged from 12 years and in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Elderly
The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
As with other non-steroidal anti-inflammatory drugs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal or hepatic function.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
4.3 Contraindications
Ibuprofen should not be given to patients with severe heart failure, hepatic failure and renal failure (see section 4.4).
Ibuprofen in contraindicated where an active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Ibuprofen is also contraindicated for patients with a history of gastrointestinal bleeding or perforation, related to previous NSAID therapy.
Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma.
Ibuprofen should not be given to patients with hypersensitivity to Ibuprofen or to any of the excipients. NSAIDs are 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 antiinflammatory drugs.
Ibuprofen should not be administered during the last trimester of pregnancy (see section 4.6).
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).
The use of Ibuprofen 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 NSAID 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).
There is a risk of renal impairment in dehydrated children and adolescents. 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 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 (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 or smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
Gastrointestinal bleeding, ulceration and perforation:
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. 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 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 antiplatelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving Ibuprofen, the treatment should be withdrawn.
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).
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).
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 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.
Impaired 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.
4.5 Interaction with other medicinal products and other forms of interaction
Anti-coagulants: As with other non-steroidal anti-inflammatory agents, caution should be exercised in patients receiving anticoagulants as NSAIDs may enhance the anticoagulant effect such as warfarin (see section 4.4).
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: There is possible antagonism of hypotensive effect of anti-hypertensives. NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside.
Methotrexate: May also delay the excretion of methotrexate.
Lithium: Lithium excretion is also reduced by NSAIDs.
Cyclosporin: There is an increased risk of nephrotoxicity when cyclosporin is used in conjunction with NSAIDs.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as they can reduce the effect of mifepristone.
Other analgesics 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).
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitation of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered likely for occasional ibuprofen use (see section 5.1).
Corticosteroids: The use of corticosteroids with NSAIDs can increase the risk of gastrointestinal bleeding (see section 4.4).
Concomitant ingestion of excess alcohol may lead to spontaneous bleeding.
Quinolone antibiotics: Animal data indicates 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).
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 Pregnancy and lactation
Pregnancy:
Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Ibuprofen during pregnancy should, if possible, be avoided.
Congenital abnormalities have been reported in association with the administration of Ibuprofen in man; however, these are low in frequency and do not appear to follow any discernible pattern. Onset of labour may be delayed and duration of labour may be increased with an increased bleeding tendency in both mother and child (see section 4.3).
Regular use of prostaglandin synthetase inhibitors during pregnancy may result in closure of foetal ductus arteriosus and possibly pulmonary hypertension of the newborn. In view of this, use in the third trimester of pregnancy is contraindicated.
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.
Lactation:
In the limited studies so far available, Ibuprofen can appear in the breast milk in very low concentration. NSAIDs should, if possible be avoided when breastfeeding.
See section 4.4 Special warnings and precautions for use, 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
Gastrointestinal. The most common undesirable effects observed are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis and Crohn’s disease (see section 4.4) have been reported following administration of Ibuprofen. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
Hypersensitivity. Following treatment with Ibuprofen, hypersensitivity reactions have been reported. These consist of (a) non specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea or (c) assorted skin disorders including rashes of various types, pruritis, urticaria, purpura, angiodema and, more rarely exfoliative and, bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Cardiovascular and cerebrovascular: 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), 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).
Other less commonly reported undesirable effects include.
Renal. Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
Hepatic. Abnormal liver function, hepatitis and jaundice.
Haematological. Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Neurological and special senses. Visual disturbances, headaches, optic neuritis, paraesthesia, aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.
Dermatological. Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues 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.
Overdose
4.9
In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is les 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 phenyl propionic acid derivative. It has analgesic antiinflammatory and antipyretic properties; it is an inhibitor of prostaglandin synthetase.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 h before or within 30 min after immediate release aspirin dosing (81mg), a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered likely for occasional ibuprofen use.
5.2 Pharmacokinetic Properties
Ibuprofen is absorbed from the gastro-intestinal tract and peak plasma concentrations occur about 1 to 2 hours after ingestion. Ibuprofen is extensively bound to plasma proteins and has a half life of about 2 hours. It is rapidly excreted in the urine mainly as metabolites and their conjugates. About 1% is excreted in urine as unchanged Ibuprofen and about 14% as conjugated Ibuprofen.
5.3 Preclinical Safety Data
There are no preclinical safety data of relevance to the prescriber, which are additional to those already included in other sections of the SPC.
6. Pharmaceutical Particulars
6.1 List of Excipients
The tablet contains Lactose BP, Microcrystalline Cellulose BP, Povidone K26-32 BP, Dried Maize Starch BP, Purified Talc BP, Colloidal Silicon Dioxide USNF, Sodium Starch Glycollate BP and Magnesium Stearate BP.
The tablet is film coated. The film coating contains Hydroxypropylmethyl Cellulose (HPMC) BP, Diethyl Phthalate BP/USNF, HPMC 2910 5cp USP/EP, HPMC 2910 15cp USP/EP, Titanium Dioxide USP, Erythrosine Aluminium Lake, Hydoxypropyl Cellulose USNF and Carnauba Wax BP.
6.2 Incompatibilities
None known
6.3 Shelf Life
36 months
6.4 Special Precautions for Storage
Protect from light, store in a cool dry place.
6.5
Nature and Contents of Container
Polypropylene pots with polyethylene caps and polyethylene ullage filler in pack sizes of 100, 250 and 500.
6.6 Instructions for Use/Handling
None known
7. Marketing Authorisation Holder
Generics [UK] Limited T/A Mylan Station Close Potters Bar Hertfordshire EN6 1TL
8. Marketing Authorisation Number
PL 04569/0106
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/03/2009
10 DATE OF REVISION OF THE TEXT
16/09/2015