Ibuprofen 400mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 400mg Tablets BP
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ibuprofen 400mg For excipients see 6.1
3 PHARMACEUTICAL FORM
Coated tablets.
Appearance:
Pink, circular, biconvex, sugar coated tablets. Embossed IBU 400 on one side and plain on the reverse
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 disease.
4.2 Posology and method of administration
For oral administration.
The tablets should be swallowed with a drink of water or milk and should be taken preferably with or after food.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Adults: 0.6-1.2g daily in 3 or 4 divided doses preferably after food, increased if necessary to a maximum of 2.4 g daily.
Children: 20mg per kg of bodyweight daily.
Children under 30 Kg: a maximum of 500 mg in 24 hours.
Elderly: The elderly are at an increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored for GI bleeding during NSAID therapy.
4.3 Contraindications
Hypersensitivity to ibuprofen or to any of the excipients.
This drug should not be given to patients with active, or history of re-current ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
NSAIDs are contra-indicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other NSAIDs.
Severe heart failure, hepatic failure and renal failure (see section 4.4).
During the last trimester of pregnancy (see section 4.6).
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).
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).
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).
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 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) especially 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 treament 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.
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).
Impaired female fertility:
The use of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty 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
Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients:
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 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 to be likely for occasional ibuprofen use (see section 5.1).
.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.
Corticosteroids: Increased risk of GI ulceration or bleeding (see section 4.4).
Anticoagulants: NSAIDs may enhance the effects of anticoagulants 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.
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.
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 discernable pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (closure of the ductus arteriosis), use in the 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 (sees ection 4.3). 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 limited studies so far available, NSAIDa can appear in breast milk in very low concentrations. 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 ibuprofen. If affected, patients should not drive or operate machinery.
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
> 1/1,000 to < 1/100
Uncommon:
> 1/10,000 to < 1/1,000
Rare:
Very rare: Not known:
> 1/10,000
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 antiinflammatory 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 advised to go to a doctor without delay. It should be investigated whether anti-infective/antibiotic therapy is required.
Gastrointestinal disorders: Not known: The most commonly observed adverse events 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, exacerbation of colitis and Crohn’s disease (see section 4.4) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
Immune system disorders: Not known: Hypersensitivity reactions have been reported following treatment with NSAIDs. 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, pruritis, urticaria, purpura, angiodema and, less commonly, bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Cardiovascular and cerebrovascular: Not known: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.
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).
Other adverse events reported less commonly include:
Renal and urinary disorders: Not known: Nephrotoxicity in various forms, including interstitial nephritis, nephritic syndrome and renal failure.
Hepatobiliary disorders: Not known: Abnormal liver function, hepatitis and jaundice.
Nervous system disorders: Not known: Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing autoimmune disorders such as SLE, 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.
Blood and lymphatic system disorders: Not known: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Skin and subcutaneous tissue disorders:
Dermatological: Very rare: 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 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, fainting, 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 maintainance of a clear airway and monitoring of cardiac and vital signs until stable. Within 1 hour of ingestion of a potentially toxic amount, consider oral administration of activated charcoal. Alternatively, in adults, gastric lavage should be considered within 1 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 4 hours after ingestion of potentially toxic amounts. If frequent or prolonged, convulsions should be treated with intravenous diazepam. Give bronchodilators for asthma. Other measures maybe indicated by the patient’s clinical condition.
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.
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 hours before or within 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of aspirin 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 to be like for occasional ibuprofen use.
5.2 Pharmacokinetic properties
Ibuprofen is rapidly absorbed following oral administration to man, and peak concentrations in plasma are observed after 1 to 2 hours. The half life in plasma is about 1 to 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 the 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.
Not available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate, maize starch, methylcellulose (M450), sodium starch glycollate, magnesium stearate, colloidal anhydrous silica.
Sugar Coated excipients: Polyvinylacetate phthalate, stearic acid, talc, calcium carbonate, acacia, titanium dioxide (E171), sucrose, sodium benzoate (E211), erythrosine aluminium lake (E127), yellow carnauba wax, white beeswax, shellac.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 25°C. Keep the container tightly closed. Store in the original container.
6.5 Nature and contents of container
Polypropylene tubes with low-density polyethylene caps. Pack sizes: 84, 100, 250 and 500 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Medley Pharma Limited Unit 2A,
Olympic Way Sefton Business Park Liverpool L30 1RD UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 43870/0022
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
08/06/2009
10 DATE OF REVISION OF THE TEXT
31/03/2015