Ibuprofen Tablets Bp 400mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets B.P. 400 mg Lidifen Tablets B.P. 400 mg Kenfen Tablets B.P. 400 mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ibuprofen B.P. 400 mg For a full list of excipients see section 6.1.
3 PHARMACEUTICAL FORM
Ibuprofen Tablets 400 mg are pink, film coated oval tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ibuprofen 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 non-rheumatoid (seronegative) arthropathies.
In the treatment of non-articular rheumatic conditions, Ibuprofen is indicated in periarticular conditions such as frozen shoulder (capsulitis), 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 the symptomatic relief of headache including migraine headache.
4.2 Posology and method of administration
For oral administration.
To be taken preferably with or after food.
Adults and children over 12 years
The recommended dosage of Ibuprofen is 1200 to 1800 mg daily in 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 dosage does not exceed 2400 mg in divided doses.
Elderly
The elderly are at increased risk of the serious consequences of adverse reactions. If Ibuprofen is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding following initiation of Ibuprofen therapy. If renal or hepatic function is impaired, dosage should be assessed individually.
Children under 12 years
The daily dosage of Ibuprofen is 20 mg/kg of body weight in divided doses.
In juvenile Rheumatoid Arthritis up to 40 mg/kg of body weight daily in divided doses may be taken. In children weighing less than 30 kg the total dose given in 24 hours should not exceed 500mg.
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 is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Ibuprofen 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).
Ibuprofen is contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAID therapy. Ibuprofen should not be used in patients with active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Ibuprofen is contraindicated in patients with severe heart failure, hepatic failure and renal failure (see section 4.4).
Ibuprofen is contraindicated 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).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
As with other NSAIDs, ibuprofen may mask the signs of infection.
The use of Ibuprofen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the potential for additive effects (see section 4.5).
Elderly:
The elderly have an increased frequency of adverse reactions, and are at an increased risk of the serious consequences of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2).
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 gastro-intestinal disease, 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 corticosteroids, or 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 chronic inflammatory intestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated (see section 4.8).
Respiratory disorders:
Caution is required if Ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma since Ibuprofen has been reported to cause bronchospasms 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, hepatic dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3)
Caution in patients with a history of hypertension and/or cardiac impairment or failure, as renal function may deteriorate and/or fluid retention occur.
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).
Renal effects:
Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.
As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal profusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
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 effects:
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 of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.
Aseptic meningitis:
Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.
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, which is reversible upon withdrawal of treatment. Therefore 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
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 Ibuprofen.
Cardiac glycosides: Ibuprofen may exacerbate cardiac failure, reduce GFR and increase plasma glycosides levels.
Lithium: potential increases in plasma levels of lithium.
Anti-depressant drugs: Increased risk of bleeding with SSRIs and Venlafaxine Tacrolimus: Possible increased risk of nephrotoxicity Methotrexate: potential for an increase in plasma methotrexate.
Ciclosporins: Increased risk of nephrotoxicity
Mifepristone: Ibuprofen should not be used for 8 - 12 days after mifepristone administration as Ibuprofen can reduce the effect of mifepristone.
Other analgesics and cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4)
Aspirin: Avoid concomitant use of ibuprofen and aspirin, unless low dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (see section 4.3).
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).
Corticosteroids: may increase the risk of adverse reaction in the gastrointestinal tract, including increased risk of GI ulceration or bleeding (see section 4.4).
Anticoagulants: Anticoagulant effect of acenocoumarol, warfarin (and possibly phenindione) possibly enhanced by Ibuprofen (see section 4.4)
Quinolone Antibiotics: Animal data indicate that Ibuprofen can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding if administered with NSAIDs.
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.
Aminogylcosides: NSAIDs may decrease the excretion of aminoglycosides.
Herbal extracts: Ginko biloba may potentiate the risk of bleeding with NSAIDs.
4.6 Pregnancy and lactation
Pregnancy
The use of Ibuprofen should be avoided during the first 6 months of pregnancy, unless the potential benefit to the patient outweighs the potential risk to the foetus. 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. During the third trimester ibuprofen is contraindicated, as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension.
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).
Lactation
In the limited studies so far available, Ibuprofen appears in the breast milk in very low concentrations. Ibuprofen should, if possible, be avoided when breast-feeding. 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 disturbance are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
Gastrointestinal disorders: 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.
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 asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiooedema and, less commonly, bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Cardiac disorders and vascular disorders: Oedema, hypertension and cardiac failure have been reported in association with Ibuprofen treatment. Epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg/daily), and in long term treatment, may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4).
Other adverse events reported less commonly include:
Psychiatric disorders: Depression, confused state, hallucination
Renal and urinary disorders: Impaired renal function and nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis and jaundice.
Nervous system disorders: Visual disturbances, including reversible amblyopia, optic neuritis, headaches, paraesthesia, dizziness, malaise, fatigue and drowsiness.
Aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever and disorientation (see section 4.4).
Ear and labyrinth disorders: tinnitus, vertigo
Haematological and lymphatic system disorders: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Dermatological: Bullous reactions, including Stevens Johnson syndrome, toxic epidermal necrolysis (very rare) and photosensitivity reactions
General disorders and administration site conditions: malaise, fatigue
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
Pharmacotherapeutic group: Propionic acid deriviative ATC Code: M01AE
Ibuprofen is a propionic acid derivative non-Steroidal Anti - inflammatory drug (NSAID) that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swelling and fever. The drugs therapeutic effects as an NSAID are thought to result from its inhibitory effect on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis.
Ibuprofen like Aspirin and other NSAIDs can inhibit platelet function and prolong bleeding time, but the effects are reversible and not as long lasting as those of Aspirin.
Nevertheless, Ibuprofen should be administered with caution to patients on Anticoagulants.
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 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81 mg), 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 likely for occasional ibuprofen use.
5.2 Pharmacokinetic properties
Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. With single doses up to 800 mg linear relationship exists between amount of drug administered and the integrated area under the serum drug concentration V’s Time Curve. Above 800 mg however the area under the curve increases less than proportional to increases in dose, there is no evidence of drug accumulation or enzyme induction. The administration of Ibuprofen Tablets under fasting conditions or immediately before meals yields quite similar serum Ibuprofen concentration time profiles. When it is administered immediately after a meal, there is a reduction in the rate of absorption but no appreciable decrease in the extent of absorption. The bioavailability of Ibuprofen is altered by the presence of food. 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. Ibuprofen is rapidly metabolised and excretion is rapid; it is virtually completed 24 hours after the last dose. In limited studies, ibuprofen appears in the breast milk in very low concentrations. The serum half life of ibuprofen is 1.8 to 2.0 hours.
5.3 Preclinical safety data
Ibuprofen is a medicine that has been in use for many years and has an established profile. Reproductive studies have been carried out in animals and human beings, a dose of 8 mg/kg in women produced menstrual cycle changes. Oral toxicity in rats has been observed at doses of 840 mg/kg causing feotoxicity and pre-implantation mortality. Research in man has shown the oral dose of 120 mg/kg produces nephrotoxicity including heamaturia.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Magnesium Stearate (HSE).
Talc (BP).
Stearic Acid (USP).
Aerosil (Collodial Anhydrous Silica) (BP) Kollidon CL (Crosdovidone) (USP)
Starch 1500 (BP)
Povidone 25 (BP)
Opalux AS- 1320 (HSE)
Titanium Dioxide (BP)
Sucrose (BP) Shellac (BP)
6.2 Incompatibilities
None.
6.3 Shelf life
Unopened container: 3 years Blister pack: 3 years
6.4 Special precautions for storage
Store below 25°C in a dry place. Protect from light.
6.5 Nature and contents of container
Securitainers or opaque plastic containers with screw caps in quantities of 84, 250 and 500.
Or
White blister packs of 12, 24, 48, 84, 96, 100.
6.6 Special precautions for disposal
No Special Instructions.
7 MARKETING AUTHORISATION HOLDER
Athlone Laboratories Limited
Ballymurray
Co. Roscommon
Ireland
MARKETING AUTHORISATION NUMBER(S)
8
PL 06453/0036
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/03/2009
10 DATE OF REVISION OF THE TEXT
09/09/2009