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4.3 Contraindications
Brufen is contraindicated in patients with known hypersensitivity to the active substance or to any of the inactive ingredients.
Brufen is contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Brufen is contraindicated in patients with severe heart failure.
Brufen should not be used in patients with known hypersensitivity or with a history of bronchospasm, urticaria or rhinitis in response to Brufen, aspirin or other NSAIDs.
Brufen should not be used in patients with known hypersensitivity or who have experienced asthma, urticaria or allergic-type reactions after taking Brufen, aspirin or other NSAIDs. 4.5 Interactions with other Medicaments and other forms of Interaction It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision. Care should be taken in patients treated with any of the following drugs as interactions have been reported: Antihypertensives: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors.reduced antihypertensive effect. Diuretics: NSAIDs may reduce the reduced diuretic effect. Diuretics can also increase the risk of nephrotoxicity of NSAIDs. Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels. Lithium: NSAIDs may decreased elimination of lithium. Methotrexate: NSAIDs may decreased elimination of methotrexate. Cyclosporin: increased risk of nephrotoxicity with NSAIDs. Other NSAIDs: avoid concomitant use of two or more NSAIDs. 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). Corticosteroids: increased risk of gastrointestinal ulceration or bleeding with NSAIDs (See section 4.4) Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (See section 4.4). Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects. 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 use (see section 5.1). Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding with NSAIDs (See section 4.4). Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides. Quinolone antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have increased risk of developing convulsions. Probenacid: there have been no reports of interactions between probenacid and ibuprofen. However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites. Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia. Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone. 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. Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
4.5 Interactions with other Medicaments and other forms of Interaction
It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision.
Care should be taken in patients treated with any of the following drugs as interactions have been reported:
Antihypertensives: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors.reduced antihypertensive effect.
Diuretics: NSAIDs may reduce the reduced diuretic effect. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Lithium: NSAIDs may decreased elimination of lithium.
Methotrexate: NSAIDs may decreased elimination of methotrexate.
Cyclosporin: increased risk of nephrotoxicity with NSAIDs.
Other NSAIDs: avoid concomitant use of two or more NSAIDs.
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).
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding with NSAIDs (See section 4.4)
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (See section 4.4).
Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.
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 use (see section 5.1).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding with NSAIDs (See section 4.4). Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides. Quinolone antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have increased risk of developing convulsions. Probenacid: there have been no reports of interactions between probenacid and ibuprofen. However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites. Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia. Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone. 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. Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides. Quinolone antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have increased risk of developing convulsions. Probenacid: there have been no reports of interactions between probenacid and ibuprofen. However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites. Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia. Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone. 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. Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.
Quinolone antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have increased risk of developing convulsions.
Probenacid: there have been no reports of interactions between probenacid and ibuprofen. However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites.
Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
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.
Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
4.6 Pregnancy and Lactation
Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy should be avoided except under compelling circumstances. 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 ductus arteriosus), ibuprofen should not be used in the third trimester of pregnancy.
Labour and delivery: Administration of ibuprofen is not recommended during labour and delivery. The onset of labour may be delayed and the duration increased with a greater bleeding tendency in both mother and child.
In limited studies to date, ibuprofen appears in breast milk in very low concentrations. Brufen is not recommended for use in nursing mothers.
4.8 Undesirable Effects Immune system disorders: 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, very rarely less commonly, bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme). 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 - Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely. Other adverse event reports include: Cardiovascular: 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). Blood and lymphatic system disorders: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. Psychiatric disorders: depression, confusion, hallucinations Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness Eye disorders: disturbances of vision, optic neuritis Ear and labyrinth disorders: vertigo, tinnitus Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis, jaundice Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare). General disorders and administration site conditions: malaise, fatigue Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. 4.9 Overdose Symptoms include nausea, vomiting, dizziness, convulsion, and rarely, loss of consciousness and depression of the CNS and respiratory system. Large overdoses are generally well tolerated when no other drugs are involved.
Immune system disorders:
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, very rarely less commonly, bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme). 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 - Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely. Other adverse event reports include: Cardiovascular: 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). Blood and lymphatic system disorders: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. Psychiatric disorders: depression, confusion, hallucinations Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness Eye disorders: disturbances of vision, optic neuritis Ear and labyrinth disorders: vertigo, tinnitus Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis, jaundice Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare). General disorders and administration site conditions: malaise, fatigue Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. 4.9 Overdose Symptoms include nausea, vomiting, dizziness, convulsion, and rarely, loss of consciousness and depression of the CNS and respiratory system. Large overdoses are generally well tolerated when no other drugs are involved.
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 - Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely. Other adverse event reports include: Cardiovascular: 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). Blood and lymphatic system disorders: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. Psychiatric disorders: depression, confusion, hallucinations Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness Eye disorders: disturbances of vision, optic neuritis Ear and labyrinth disorders: vertigo, tinnitus Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis, jaundice Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare). General disorders and administration site conditions: malaise, fatigue Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. 4.9 Overdose Symptoms include nausea, vomiting, dizziness, convulsion, and rarely, loss of consciousness and depression of the CNS and respiratory system. Large overdoses are generally well tolerated when no other drugs are involved.
Other adverse event reports include:
Cardiovascular: 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).
Blood and lymphatic system disorders: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Psychiatric disorders: depression, confusion, hallucinations
Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness
Eye disorders: disturbances of vision, optic neuritis
Ear and labyrinth disorders: vertigo, tinnitus
Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis, jaundice
Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare).
General disorders and administration site conditions: malaise, fatigue
Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
4.9 Overdose
Symptoms include nausea, vomiting, dizziness, convulsion, and rarely, loss of consciousness and depression of the CNS and respiratory system. Large overdoses are generally well tolerated when no other drugs are involved.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 600 mg of Ibuprofen.
Also includes lactose monohydrate, 40mg per tablet.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablet (tablet)
A white, pillow-shaped, film-coated tablet with ‘Brufen 600’ printed in black on one face.
It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct supervision.
Antihypertensives: reduced antihypertensive effect.
Diuretics: reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Lithium: decreased elimination of lithium.
Methotrexate: decreased elimination of methotrexate.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (See section 4.4).
Aspirin: 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 use (see section 5.1).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (See section 4.4).
Aminoglycosides: Reduced in renal function in susceptible individuals, decreased elimination of aminoglycoside and increased plasma concentration.
5.1 Pharmacodynamic Properties
Ibuprofen is a phenylpropionic 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-oxygenase, which results in a marked reduction in prostaglandin synthesis.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dose 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 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 to be likely for occasional ibuprofen use.
Change to section 4.2 - Posology and Method of AdministrationChange to section 4.3 - Contra-indications
Change to section 4.4 - Special warnings and Precautions
Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction
Change to section 4.8 - Undesirable Effects
Change to section 4.3 - Contra-indications
Change to section 4.4 - Warnings or special precauitons for use
Change to section 4.5 - Drug interactions
Change to section 4.6 - Pregnancy or lactation
Change to section 4.8 - Side-effects