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BRUFEN TABLETS 600MG
Active substance(s): IBUPROFEN
NAME OF THE MEDICINAL PRODUCT
Brufen Tablets 600 mg
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Brufen Tablet contains 600 mg Ibuprofen.
Excipient with known effect: 40 mg Lactose monohydrate
For the full list of excipients, see section 6.1.
A white, pillow-shaped, film-coated tablet.
Brufen 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
In the treatment of non-articular rheumatic conditions, Brufen is indicated in
periarticular conditions such as frozen shoulder (capsulitis), bursitis,
tendonitis, tenosynovitis and low back pain; Brufen can also be used in softtissue injuries such as sprains and strains.
Brufen is also 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.
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 and children over 12 years of age: The recommended dosage of Brufen
is 1200-1800 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 dose does not exceed 2400 mg in divided doses.
In Juvenile Rheumatoid Arthritis, up to 40 mg/kg of body weight daily in
divided doses may be taken.
Tablets are not suitable for children under the age of 12 years.
Elderly: The elderly are at increased risk of 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 regularly for GI bleeding during NSAID therapy. If renal or
hepatic function is impaired, dosage should be assessed individually.
For oral administration. It is recommended that patients with sensitive
stomachs take Brufen with food. If taken shortly after eating, the onset of
action of Brufen may be delayed. To be taken preferably with or after food,
with plenty of fluid. Brufen tablets should be swallowed whole and not
chewed, broken, crushed or sucked on to avoid oral discomfort and throat
Brufen is contraindicated in patients with hypersensitivity to the active
substance or to any of the excipients.
Brufen should not be used in patients who have previously shown
hypersensitivity reactions (e.g. asthma, urticaria, angioedema or rhinitis) after
taking ibuprofen, aspirin or other NSAIDs.
Brufen is also contraindicated in patients with a history of gastrointestinal
bleeding or perforation, related to previous NSAID therapy. Brufen 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).
Brufen should not be given to patients with conditions involving an increased
tendency to bleeding.
Brufen is contraindicated in patients with severe heart failure (NYHA Class
IV), hepatic failure and renal failure (see section 4.4).
Brufen is contraindicated during the last trimester of pregnancy (see section
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
As with other NSAIDs, ibuprofen may mask the signs of infection.
The use of Brufen with concomitant NSAIDs, including cyclooxygenase-2
selective inhibitors, should be avoided due to the increased risk of ulceration
or bleeding (see section 4.5).
The elderly have an increased frequency of adverse reactions to NSAIDs,
especially gastrointestinal bleeding and perforation, which may be fatal (see
There is a risk of renal impairment in dehydrated children and adolescents.
Gastrointestinal bleeding, ulceration and perforation
GI bleeding, ulceration or perforation, which can be fatal, has been reported
with all NSAIDs at anytime 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 gastrointestinal disease, 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 ulceration or bleeding, such as oral
corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake
inhibitors or anti-platelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving Brufen, the
treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of ulcerative
colitis or Crohn’s disease as these conditions may be exacerbated (see section
Respiratory disorders and hypersensitivity reactions
Caution is required if Brufen is administered to patients suffering from, or
with a previous history of, bronchial asthma, chronic rhinitis or allergic
diseases since NSAIDs have been reported to precipitate bronchospasm,
urticaria or angioedema in such patients.
Cardiac, renal and hepatic impairment
The administration of an NSAID may cause a dose dependent reduction in
prostaglandin formation and precipitate renal failure. The habitual concomitant
intake of various similar painkillers further increases this risk. Patients at
greatest risk of this reaction are those with impaired renal function, cardiac
impairment, liver dysfunction, those taking diuretics and the elderly. For these
patients, use the lowest effective dose, for the shortest possible duration and
monitor renal function especially in long-term treated patients (see also section
Brufen should be given with care to patients with a history of heart failure or
hypertension since oedema has been reported in association with ibuprofen
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 (2400
mg/ day) may be associated with a small increased risk of arterial thrombotic
events such as 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 IIIII), established ischaemic heart disease, peripheral arterial disease, and/or
cerebrovascular disease should only be treated with ibuprofen after careful
consideration and high doses (2400mg/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, smoking), particularly if high doses of
ibuprofen (2400mg/day) are required.
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 perfusion. In these patients, administration of
an NSAID may cause a dose-dependant reduction in prostaglandin formation
and, secondarily, in renal blood flow, which may cause renal failure. Patients
at greatest risk of this reaction are those with 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 pre-treatment 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
below and section 4.8).
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. Brufen 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
prolong bleeding time in normal subjects.
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.
Impaired female fertility
The use of Brufen 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 Brufen should
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.
Antihypertensives, beta-blockers and diuretics: NSAIDs may reduce the effect
of anti-hypertensives, such as ACE inhibitors, angiotensin-II receptor
antagonists, beta-blockers and diuretics.
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.
Cholestyramine; The concomitant administration of ibuprofen and
cholestyramine may reduce the absorption of ibuprofen in the gastrointestinal
tract. However, the clinical significance is unknown.
Lithium: Decreased elimination of lithium.
Methotrexate: NSAIDs may inhibit the tubular secretion of methotrexate and
reduce clearance of methotrexate.
Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: A decrease in the efficacy of the medicinal product can
theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited
evidence suggests that coadministration of NSAIDs on the day of
prostaglandin administration does not adversely influence the effects of
mifepristone or the prostaglandin on cervical ripening or uterine contractility
and does not reduce the clinical efficacy of medicinal termination of
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 (Acetylsalicylic acid): 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 competitively inhibit the effect
of low dose aspirin on platelet aggregation when they are dosed
concomitantly. Although there are uncertainties regarding extrapolation of
these data to the clinical situation, the possibility that regular, long-term use of
ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic
acid cannot be excluded. No clinically relevant effect is considered to be
likely for occasional use (see section 5.1).
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).
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.
Sulfonylureas: NSAIDs may potentiate the effects of sulfonylurea
medications. There have been rare reports of hypoglycaemia in patients on
sulfonylurea medications receiving ibuprofen.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):
Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given
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.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.
Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with
CYP2C9 Inhibitors: Concomitant administration of ibuprofen with CYP2C9
inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a
study with voriconazole and fluconazole (CYP2C9 inhibitors), an increased
S(+)-ibuprofen exposure by approximately 80 to 100% has been shown.
Reduction of the ibuprofen dose should be considered when potent CYP2C9
inhibitors are administered concomitantly, particularly when high-dose
ibuprofen is administered with either voriconazole or fluconazole.
Fertility, pregnancy and lactation
Inhibition of prostaglandin synthesis may adversely affect the pregnancy
and/or embryo/foetal development. Data from epidemiological studies suggest
an increased risk of miscarriage and of cardiac malformation and gastroschisis
after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk
is believed to increase with dose and duration of therapy. In animals, the
administration of a prostaglandin synthesis inhibitor has been shown to result
in increased pre- and post-implantation losses and embryo/foetal lethality. In
addition, increased incidences of various malformations, including
cardiovascular, have been reported in animals given a prostaglandin synthesis
inhibitor during the organogenetic period.
During the first and second trimester of pregnancy, Brufen should not be given
unless clearly necessary. If Brufen is used by a woman attempting to conceive,
or during the first or second trimester of pregnancy, the dose should be kept as
low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors
may expose the foetus to the following:
• Cardiopulmonary toxicity (with premature closure of the ductus
arteriosus and pulmonary hypertension)
• Renal dysfunction, which may progress to renal failure with
At the end of pregnancy, prostaglandin synthesis inhibitors may expose the
mother and the neonate to the following:
• Possible prolongation of bleeding time
• Inhibition of uterine contractions, which may result in delayed or
Consequently, Brufen is contraindicated during the third trimester of
In the limited studies so far available, NSAIDs can appear in the breast milk in
very low concentrations. NSAIDs should, if possible, be avoided when
See section 4.4 Special warnings and precautions for use, regarding female
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.
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, gastrointestinal haemorrhage
and exacerbation of colitis and Crohn’s disease (see section 4.4) have been
reported following ibuprofen administration. Less frequently, gastritis,
duodenal ulcer, gastric ulcer and gastrointestinal perforation have been
Immune system disorders: 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, pruritus, urticaria, purpura,
angioedema and, very rarely, erythema multiforme, bullous dermatoses
(including Stevens- Johnson syndrome and toxic epidermal necrolysis).
Cardiac disorders and vascular disorders: Oedema, hypertension and cardiac
failure have been reported in association with NSAID treatment. Clinical
studies suggest that use of ibuprofen, particularly at high dose (2400 mg/day)
may be associated with a small increased risk of arterial thrombotic events
such as myocardial infarction or stroke (see section 4.4).
Infections and infestations: Rhinitis and 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 or disorientation (see section 4.4).
Exacerbation of infection-related inflammations coinciding with the use of
NSAIDs has been described. If signs of an infection occur or get worse during
use of Ibuprofen the patient is therefore recommended to go to a doctor
Skin and subcutaneous tissue disorders: In exceptional cases, severe skin
infections and soft-tissue complications may occur during a varicella infection
(see also "Infections and infestations")
The following adverse reactions possibly related to ibuprofen and displayed by
MedDRA frequency convention and system organ classification. Frequency
groupings are classified according to the subsequent conventions: very
common ( 1/10), Common ( 1/100 to <1/10), Uncommon ( 1/1,000 to
<1/100), Rare ( 1/10,000 to <1/1,000), Very rare (<1/10,000) and Not known
(cannot be estimated from the available data).
System organ class
Blood and lymphatic
Meningitis aseptic (see
anaemia , haemolytic
Immune system disorders
Ear and labyrinth
Respiratory, thoracic and
Skin and subcutaneous
Renal and urinary
General disorders and
Toxic optic neuropathy
Hearing impaired , tinnitus,
abdominal pain, flatulence,
Gastritis, duodenal ulcer,
gastric ulcer, mouth
Exacerbation of Colitis and
Hepatitis, jaundice, hepatic
Urticaria, pruritus, purpura,
Severe forms of skin
reactions ( e.g. Erythema
Nephrotoxity in various
syndrome and renal failure
Cardiac failure, myocardial
see section 4.4)
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:
Signs and symptoms of toxicity have generally not been observed at doses
below 100mg/kg in children or adults. However, supportive care may be
needed in some cases. Children have been observed to manifest signs and
symptoms of toxicity after ingestion of 400mg/kg or greater.
Most patients who have ingested significant amounts of ibuprofen will
manifest symptoms within 4 to 6 hours.
The most frequently reported symptoms of overdose include nausea, vomiting,
abdominal pain, lethargy and drowsiness. Central nervous system (CNS)
effects include headache, tinnitus, dizziness, convulsion, and loss of
consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects,
gastrointestinal bleeding, coma, apnoea, diarrhoea and depression of the CNS
and respiratory system have also been rarely reported. Disorientation,
excitation, fainting and cardiovascular toxicity, including hypotension,
bradycardia and tachycardia have been reported. In cases of significant
overdose, renal failure and liver damage are possible. Large overdoses are
generally well tolerated when no other drugs are being taken.
Patients should be treated symptomatically as required. Within one hour of
ingestion of a potentially toxic amount, activated charcoal should be
considered. Alternatively, in adults, gastric lavage should be considered within
one 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 four hours after ingestion of potentially
Frequent or prolonged convulsions should be treated with intravenous
diazepam. Other measures may be indicated by the patient’s clinical condition.
Pharmacotherapeutic classification: Anti-inflammatory and antirheumatic
products, nonsteroidal; propionic acid derivatives.
ATC code: M01AE01
Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and
anti-pyretic activity. The drug's therapeutic effects as an NSAID is 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 competitively inhibit the effect
of low dose aspirin on platelet aggregation when they are dosed
concomitantly. Some pharmacodynamic studies show that when single doses
of ibuprofen 400mg were 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. Although
there are uncertainties regarding extrapolation of these data to the clinical
situation, the possibility that regular, long-term use of ibuprofen may reduce
the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded.
No clinically relevant effect is considered to be likely for occasional ibuprofen
use. (see section 4.5)
Ibuprofen is rapidly absorbed from the gastrointestinal tract, peak serum
concentrations occurring 1-2 hours after administration. The elimination halflife is approximately 2 hours.
Ibuprofen is metabolised in the liver to two inactive metabolites and these,
together with unchanged ibuprofen, are excreted by the kidney either as such
or as conjugates. Excretion by the kidney is both rapid and complete.
Ibuprofen is extensively bound to plasma proteins.
Preclinical safety data
List of excipients
Colloidal anhydrous silica
Opaspray white M-1-7111B*
Dry colour dispersion, white 06A28611**
*Opaspray white M-1-7111B comprises industrial methylated spirit, purified
water, hypromellose 2910 and titanium dioxide
** or combination of Opaspray white M-1-7111B, hypromellose and talc
NB industrial methylated spirit and purified water are removed during the drying process
PVC or PVC/PVDC blister packs: 36 months
Special precautions for storage
PVC or PVC/PVDC blister packs: Do not store above 25°C, store in the
Nature and contents of container
Blister pack comprising of transparent polyvinyl chloride (PVC) with
aluminium foil backing – pack size 60 tablets or 100 tablets.
Blister pack comprising of transparent polyvinyl chloride (PVC) film coated
on one face with polyvinylidene chloride (PVDC) with aluminium foil backing
– pack size 60 or 100 tablets.
Not all pack sizes are marketed.
Special precautions for disposal
MARKETING AUTHORISATION HOLDER
BGP Products Ltd.
Vanwall Business Park
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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