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Brufen 400 mg bruisgranulaat

RegistratienummerRVG 110571
ProcedurenummerSE/H/1184/001
Farmaceutische vormBruisgranulaat
ToedieningswegOraal gebruik
ATCM01AE01 - Ibuprofen
AfleverstatusUitsluitend recept
Registratiedatum20 december 2012
RegistratiehouderAbbott B.V.
Wegalaan 9
2132 JD HOOFDDORP
Werkzame stof(fen)IBUPROFEN
Hulpstof(fen)APPELZUUR, (DL)(+-)(E 296)
CARMELLOSE (E 466)
MALTODEXTRINE
NATRIUMCARBONAAT 0-WATER (E 500 (I))
NATRIUMLAURILSULFAAT (E 487)
NATRIUMWATERSTOFCARBONAAT (E 500 (II))
POVIDON K 30 (E 1201)
SACCHAROIDE NATRIUM 0-WATER (E 954)
SACCHAROSE
SINAASAPPELSMAAKSTOF
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SUMMARY OF PRODUCT CHARACTERISTICS 
 
 

NAME OF THE MEDICINAL PRODUCT 
 
Brufen 400 mg bruisgranulaat 
 
 

QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One sachet contains 400 mg ibuprofen. 
 
Excipients with known effect 
One sachet also contains 666.7 mg sucrose and 100 mg sodium. 
 
For a full list of excipients, see section 6.1. 
 
 

PHARMACEUTICAL FORM 
 
Effervescent granules. 
 
White granules, with orange flavour. 
 
 

CLINICAL PARTICULARS 
 
4.1 
Therapeutic indications 
 
Mild to moderate pain. 
 
Primary dysmenorrhoea. 
 
Fever. 
 
Rheumatic conditions such as arthritic diseases e.g. rheumatoid arthritis, degenerative arthritic 
conditions (e.g. osteoarthritis), non-articular rheumatic conditions, other muscular and joint 
disorders, and soft tissue injuries. 
  
 
4.2 
Posology and method of administration 
 
Posology 
 
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration 
necessary to control symptoms (see section 4.4). 
 
The ibuprofen dose depends on the patient’s age and body weight. The maximum single daily dose 
for adults should not exceed 800 mg of ibuprofen. 
 
Method of administration 
 
In order to achieve a faster onset of action, the dose may be taken on an empty stomach. 
 

 
 
 
The effervescent granules should be mixed with water to make an orange flavoured, fizzy drink. 
Empty the contents of the sachet into a glass of water, stir and drink immediately. A transient 
sensation of burning in the mouth or throat may occur with Brufen ; ensure that the granules are 
dissolved in plenty of water. 
 
Mild to moderate pain and fever 
Adults and adolescents older than 12 years (≥40 kg): 
400 mg given as a single dose or up to 3 times a day with an interval of 4 to 6 hours.  
The maximum daily dose should not exceed 1200 mg. 
 
Primary dysmenorrhoea 
Adults and adolescents over 12 years of age (≥40 kg): 
400 mg 1‑3 times a day, with an interval of 4‑6 hours, as needed. The maximum daily dose should 
not exceed 1200 mg. 
  
Rheumatic diseases 
Adults: 
The usual dose is 400 mg 3 times a day. Maintenance doses of 1200 mg daily may be effective in 
some patients. In acute and severe conditions the dose may be increased to a maximum of 2400 mg 
in divided doses. 
 
Adolescents over 12 years of age (≥40 kg) 
The recommended dose is 20 mg/kg to a maximum of 40 mg/kg body weight daily in 3 to 4 divided 
doses. The maximum daily dose should not exceed 2400 mg. 
 
Paediatric population 
Brufen is not suitable for use in children under 12 years. Other more appropriate Ibuprofen 
formulations are available for this population. 
  
Elderly 
NSAIDs should be used with particular caution in elderly patients who are more prone to adverse 
events (see section 4.4 and 4.8). If treatment is considered necessary, the lowest dose for the shortest 
duration necessary to control symptoms should be used. Treatment should be reviewed at regular 
intervals and discontinued if no benefit is seen or intolerance occurs. 
  
Impaired renal function 
In patients with mild or moderate reduction of renal function, the dose should be kept as low as 
possible for the shortest duration necessary to control symptoms and renal function monitored. (For 
patients with severe renal failure see section 4.3). 
 
Impaired liver function 
In patients with mild or moderate reduction of liver function, the dose should be kept as low as 
possible for the shortest duration necessary (For patients with severe liver failure see section 4.3). 
 
 
4.3 
Contraindications 
 
Brufen is contraindicated in patients with: 
- hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- previous hypersensitivity reactions (e.g. asthma, rhinitis, urticaria or angioedema) in response to   
  acetylsalicylic acid or other NSAIDs 
- 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) 
- severe hepatic or severe renal insufficiency 

 
 
 
- severe heart failure or coronary heart disease 
- last trimester of pregnancy (see section 4.6) 
- significant dehydration (caused by vomiting, diarrhoea or insufficient fluid intake) 
- cerebrovascular or other active bleeding 
- dishaematopoiesis of unknown origin 
- children younger than 12 years of age. 
 
 
4.4 
Special warnings and precautions for use 
 
The use of Brufen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, 
should be avoided. 
 
Asthmatic patients are to seek their doctor’s advice before using ibuprofen (see below). 
 
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 
treated with NSAIDs long term should undergo regular medical supervision to monitor for adverse 
events. 
 
Brufen should only be administered under strict consideration of the benefit-risk ratio in the 
following conditions: 
 

Systemic Lupus Erythematosus (SLE) or other autoimmune diseases. 

Congenital disturbance of porphyrin metabolism (e.g. acute intermittent porphyria) 

The first and second trimester of pregnancy 

Lactation 
 
Special care has to be taken in the following cases: 
 

Gastrointestinal diseases including chronic inflammatory intestinal disease (ulcerative 
 
colitis, Crohn’s disease) 

Cardiac insufficiency and hypertension 

Reduced renal function 

Hepatic dysfunction 

Disturbed haematopoiesis 

Blood coagulation defects 

Allergies, hay fever, chronic swelling of nasal mucosa, adenoids, chronic obstructive 
 
airway disease or bronchial asthma 

Immediately after major surgical interventions 
 
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 
acetylsalicylic acid, or other medicinal products 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 or 
heparin, selective serotonin-reuptake inhibitors or anti-platelet agents such as acetylsalicylic acid 
(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 gastrointestinal disease (ulcerative 
colitis, Crohn’s disease) as their condition may be exacerbated. (See section 4.8). 
 
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). 
 
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, hypertension and oedema have been 
reported in association with NSAID therapy. 
 
Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses 
(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). Overall, epidemiological studies do 
not suggest that low-dose ibuprofen (e.g. ≤ 1200 mg 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 and smoking). 
 
Skin reactions 
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 in the majority of cases within the first month 
of treatment.  Brufen must 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 tissues 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 Brufen in case of varicella. 
 
Renal effect 
Ibuprofen may cause the retention of sodium, potassium and fluid in patients who have not 
previously suffered from renal disorders because of its effect on renal perfusion. This may cause 
oedema or even lead to cardiac insufficiency or hypertension in predisposed patients. 
 
As with other NSAIDs, the prolonged administration of ibuprofen to animals has resulted in renal 
papillary necrosis and other pathological renal changes. In humans, there have been reports of acute 
interstitial nephritis with haematuria, proteinuria and occasionally nephrotic syndrome. Cases of 
renal toxicity have also been observed in patients in whom prostaglandins play a compensatory role 

 
 
 
in the maintenance of renal perfusion. In these patients, administration of NSAIDs 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 suffering this reaction are 
those with renal dysfunction, heart failure, hepatic dysfunction, those taking diuretics and ACE 
inhibitors and the elderly. Discontinuation of NSAID treatment is generally followed by recovery to 
the pre-treatment state. 
 
Other precautions 
Bronchospasm, urticaria or angioedema may be precipitated in patients suffering from or with a 
previous history of bronchial asthma, chronic rhinitis, sinusitis, nasal polyps, adenoids or allergic 
diseases. 
 
Ibuprofen may mask the signs or symptoms of an infection (fever, pain and swelling). 
 
Prolonged use of any type of painkiller for headaches can make them worse. If this situation is 
experienced or suspected, medical advice should be obtained and treatment should be discontinued. 
The diagnosis of medication overuse headache (MOH) should be suspected in patients who have 
frequent or daily headaches despite (or because of) the regular use of headache medications. 
 
In general terms, the habitual intake of painkillers particularly on combination of several pain-
relieving active substances, may lead to permanent renal damage with the risk of renal failure. This 
risk may be increased under physical strain associated with loss of salt and dehydration. Therefore it 
should be avoided. 
 
During treatment with ibuprofen, some cases with symptoms of aseptic meningitis, such as stiff 
neck, headache, nausea, vomiting, fever or disorientation have been observed in patients with 
existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue 
disease). 
 
Ibuprofen may temporarily inhibit platelet aggregation and prolong the bleeding time. Therefore, 
patients with coagulation defects or on anticoagulant therapy should be observed carefully. 
 
In case of long-term treatment with ibuprofen, a periodical monitoring of hepatic and renal function 
as well as the blood count is necessary, especially in high risk patients. 
 
Consumption of alcohol should be avoided since it may intensify side effects of NSAIDs, especially 
if affecting the gastrointestinal tract or the central nervous system. 
 
Patients on ibuprofen should report to their doctor signs or symptoms of gastro-intestinal ulceration 
or bleeding, blurred vision or other eye symptoms, skin rash, weight gain or oedema. 
 
There is some evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may 
cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of 
treatment (see section 4.6).  
 
 Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or 
sucrase-isomaltase insufficiency should not take this medicine. 
This medicinal product contains 100 mg sodium per dose. To be taken into consideration by patients 
on a controlled sodium diet. 
 
 
 
 
 

 
 
 
4.5 
Interactions with other medicinal products and other forms of interaction 
 
 
Concomitant use of 
Possible effects: 
ibuprofen with: 
Other NSAIDs including 
As a result of synergistic effects, the concurrent use of several 
cyclooxygenase-2 selective 
NSAIDs can increase the risk of gastrointestinal ulcers and 
inhibitors  
haemorrhage. Co-administration of ibuprofen with other NSAIDs 
should therefore be avoided (see section 4.4). 
Cardiac glycosides (Digoxin) 
NSAIDs may exacerbate cardiac failure, reduce GFR and increase 
plasma levels of cardiac glycosides. Monitoring of serum digoxin is 
recommended. 
Corticosteroids 
Increased risk of gastrointestinal ulceration or bleeding (see section 
4.4). 
Anticoagulants 
NSAIDs may enhance the effects of anticoagulants, such as warfarin 
or heparin (see section 4.4). In case of simultaneous treatment, 
monitoring of the coagulation state is recommended. 
Antiplatelet-Agents 
Increased risk of gastrointestinal bleeding (see section 4.4). 
(e.g. clopidogrel and 
ticlopidine):  
Acetylsalicylic acid  
Ibuprofen should be avoided in combination with acetylsalicylic 
acid unless low dose acetylsalicylic acid has been advised by a 
doctor, as this may increase the risk of adverse reactions. 
Experimental data suggest that ibuprofen may inhibit the effect of 
low dose acetylsalicylic acid 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) 
Selective serotonin-reuptake 
Increased risk of gastrointestinal bleeding (see section 4.4). 
inhibitors (SSRI) 
 
Lithium  
Co-administration of ibuprofen with lithium preparations can 
increase the serum level of these medicinal products. Checking the 
serum lithium level is necessary. 
 
Ticlopidin 
NSAIDs should not be combined with ticlopidine due to a risk of an 
additive effect in the inhibition of the platelet function. 
 
 
Potassium sparing diuretics 
concomitant use may cause hyperkaliaemia (check of serum 
potassium is recommended) 
Captopril  
Experimental studies indicate that ibuprofen counteracts the effect 
of captopril of increased sodium excretion.  
Antihypertensive drugs  
Diuretics and ACE-inhibitors can increase the nephrotoxicity of 
NSAIDs.  NSAIDs can reduce the effect of diuretics and 
(Diuretics, ACE inhibitors, 
antihypertensives, including ACE-inhibitors and beta-blockers. In 
angiotensin-II-antagonists) 
patients with reduced kidney function (e.g. dehydrated patients or 
elderly patients with reduced kidney function), the concomitant use 
of an ACE inhibitor and angiotension II antagonist with a 
cyclooxygenase-inhibiting medicinal product can lead to further 
impairment of kidney function and through to acute renal failure. 

 
 
 
This is usually reversible. Such combinations should therefore only 
be used with caution, especially in elderly patients. The patients 
have to be instructed to drink sufficient liquid and periodic 
monitoring of the kidney values should be considered for the time 
immediately after the start of the combination therapy. 
The concomitant administration of ibuprofen and potassium-sparing 
diuretics or ACE-inhibitors can result in hyperkalaemia. Careful 
monitoring of potassium levels is necessary. 
Methotrexate 
NSAID inhibits the tubular secretion of methotrexate and certain 
metabolic interactions can occur resulting in decreased clearance of 
methotrexate. The administration of ibuprofen within 24 hours 
before or after the administration of methotrexate can lead to an 
elevated concentration of methotrexate and an increase in its toxic 
effects. Therefore, concomitant use of NSAIDs and high doses of 
methotrexate should be avoided. Also, the potential risk of 
interactions in low dose treatment with methotrexate should be 
considered, especially in patients with impaired renal function.  In 
combined treatment, renal function should be monitored. 
Cyclosporin 
The risk of kidney damage by ciclosporine is increased by the 
concomitant administration of certain NSAIDs. This effect can not 
be ruled out for the combination of ciclosporine and ibuprofen, 
either.  
Tacrolimus 
Elevated risk of nephrotoxicity.  
Zidovudine 
There is evidence of an increased risk of haemarthrosis and 
haematoma in HIV positive haemophilia patients receiving 
concurrent treatment with zidovudine and ibuprofen. There may be 
an increased risk of haematotoxicity during concomitant use of 
zidovudine and NSAIDs. Blood counts 1-2 weeks after starting use 
together are recommended. 
Quinolone antibiotics 
Animal data indicate that NSAID’s can increase the risk of 
convulsions associated with quinolone antibiotics. Patients taking 
NSAID’s and quinolones may have an increased risk of developing 
convulsions. 
CYP2C9 inhibitors 
Concomitant administration of ibuprofen with CYP2C9 inhibitors 
may increase the exposure to ibuprofen (CYP2C9 substrate). In a 
(e.g. voriconazole or 
study with voriconazole and fluconazole (CYP2C9 inhibitors), an 
fluconazole) 
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. 
Oral antidiabetics 
NSAIDs can increase the hypoglycemic effect of sulphonylureas. In 
the case of simultaneous treatment, monitoring of blood glucose 
levels is recommended. 
Cholestyramine 
Concomitant treatment with cholestyramine and ibuprofen results in 
prolonged and reduced (25%) absorption of ibuprofen. The 
medicinal products should be administered with at least two hours 
interval. 
Aminoglycosides 
NSAIDs can slow down the elimination of aminoglycosides and 
increase their toxicity. 
Herbal extracts 
Ginkgo biloba may potentiate the risk of bleeding with NSAIDs. 
Alcohol 
The use of ibuprofen in individuals with chronic alcohol 
consumption (14-20 drinks/week or more) should be avoided due to 

 
 
 
increased risk of significant GI adverse effects, including bleeding. 
Mifepristone 
If NSAIDs are used within 8-12 days after mifepristone 
administration, they can reduce the effect of mifepristone. 
 
 
4.6 
Fertility, pregnancy and lactation 
 
Pregnancy 
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the 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 absolute risk for cardiovascular malformation was increased from less than 1% up to 
approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, 
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 trimesters of 
pregnancy, Brufen should not be given unless clearly necessary. If Brufen is used by a woman 
attempting to conceive or during the first and second trimester, the dose should be kept as low as 
possible and duration of treatment as short as possible. 
 
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose: 
  
The foetus to: 
  Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary 
hypertension), 
  Renal dysfunction, which may progress to renal failure with oligohydramnios.  
 
The mother and the neonate, at the end of pregnancy, to: 
  Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very 
low doses 
  Inhibition of uterine contractions, resulting in delayed or prolonged labour. 
 
Consequently, Brufen is contraindicated during the last trimester of pregnancy. 
 
Breastfeeding 
Ibuprofen is excreted in breast milk, but with therapeutic doses during short term treatment, the risk 
for influence on the infant seems unlikely. If, however, longer treatment is prescribed, early weaning 
should be considered. 
 
Fertility 
The use of ibuprofen may impair fertility and is not recommended in women attempting to conceive. 
In women who have difficulties conceiving or who are undergoing an investigation of infertility, 
withdrawal of ibuprofen should be considered. 
 
 
4.7 
Effects on the ability to drive and use machines 
 
Ibuprofen generally has no adverse effects on the ability to drive and use machinery. However since 
at high dosage side effects such as fatigue, somnolence, vertigo (reported as common) and visual 
disturbances (reported as uncommon) may be experienced, the ability to drive a car or operate 
machinery may be impaired in individual cases. This effect is potentiated by simultaneous 
consumption of alcohol. 
 

 
 
 
 
4.8 
Undesirable effects 
 
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, 
heamatemesis, ulcerative stomatits, exacerbation of colitis and Crohn’s disease (see section 4.4) 
have been reported following administration. Less frequently, gastritis has been observed. 
 
Undesirable effects are mostly dose-dependent. Especially the risk for the occurrence of 
gastrointestinal bleedings depends on the dosage range and duration of the treatment. Other known 
risk factors, see section 4.4. 
 
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).  
 
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID 
treatment. 
 
 
Adverse events at least possibly related to ibuprofen are displayed by MedDRA frequency 
convention and system organ class. The following frequency groupings are used: 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 
Frequency 
Adverse Reaction  
 
Blood and lymphatic 
Very rare 
haematopoietic disorders (anaemia, leucopoenia, 
system disorders 
thrombocytopenia, pancytopenia, agranulocytosis). The first 
symptoms or signs may include: fever, sore throat, surface 
mouth ulcers, flu-like symptoms, severe fatigue, nasal and skin 
bleeding 
Immune system  
Uncommon 
hypersensitivity reactions such as urticaria, pruritus, purpura 
disorders 
 
and exanthema as well as asthma attacks (sometimes with 
 
hypotension) 
 
 
Rare 
lupus erythematosus syndrome 
 
Very rare 
severe hypersensitivity reactions. The symptoms may include: 
facial oedema, swelling of the tongue, internal laryngeal 
swelling with constriction of the airways, dyspnoea, 
tachycardia, fall of blood pressure to the point of life-
threatening shock 
Psychiatric disorders  Rare 
depression, confusion, hallucinations 
Nervous system 
Common 
headache, somnolence, vertigo, fatigue, agitation, dizziness, 
disorders 
insomnia, irritability 
Very rare  
aseptic meningitis 
Eye disorders 
Uncommon 
visual disturbances 
Rare 
toxic amblyopia 
Ear and labyrinth 
Very rare 
tinnitus 
disorders 
Cardiac disorders 

Very rare 
palpitations, heart failure, myocardial infarction, acute 
pulmonary oedema, oedema 

 
 
 
Vascular disorders 
Very rare 
hypertension 
Respiratory, thoracic   Uncommon 
rhinitis, bronchospasm 
and mediastinal  
disorders
 
Gastrointestinal  
common 
gastrointestinal disorders, such as heartburn, dyspepsia, 
disorders 
abdominal pain and nausea, vomiting, flatulence, diarrhoea, 
constipation 
Uncommon  
gastrointestinal ulcers, sometimes with bleeding and 
perforation (see section 4.4), occult blood loss which may lead 
to anaemia, melaena, haematemesis, ulcerative stomatitis, 
colitis, exacerbation of inflammatory bowel disease, 
complications of colonic diverticula (perforation, fistula), 
gastritis 
 
 
Very rare 
oesophagitis, pancreatitis, intestinal strictures 
Hepatobiliary 
Rare  
Increase of blood urea nitrogen, serum transaminases and 
disorders 
alkaline phosphatase 
Very rare 
liver dysfunction, liver damage, especially in long-term use, 
liver failure, acute hepatitis, jaundice 
Skin and 
Uncommon 
photosensitivity 
subcutaneous tissue 
Very rare 
severe forms of skin reactions (erythema multiforme, 
disorders 
exfoliative dermatitis, bullous reactions including 
Stevens-Johnson syndrome and toxic epidermal necrolysis, 
alopecia, necrotising fascitis 
Renal and urinary  
Uncommon 
development of oedema especially in patients with arterial 
disorders 
hypertension or renal insufficiency, nephrotic syndrome, 
interstitial nephritis which can be associated with renal failure 
Very rare 
renal papillary necrosis in long-term use (see section 4.4) 
Investigations 
Rare 
decrease in haemoglobin and haematocrit values, inhibition of 
platelet aggregation, prolonged bleeding time, decrease of 
serum calcium, increase in serum uric acid 
 
 
 
4.9 
Overdose 
 
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, dizziness, 
vertigo and gastrointestinal bleeding may also occur. 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. Children may also develop myoclonic cramps. In 
serious poisoning metabolic acidosis may occur and the prothrombin time/INR may be prolonged, 
probably due to the actions of circulating clotting factors. Acute renal failure, liver damage, 
hypotension, respiratory depression and cyanosis may occur. Exacerbation of asthma is possible in 
asthmatics.  
 
Treatment 
Treatment should be symptomatic and supportive and include the maintenance of a clear airway and 
monitoring of cardiac and vital signs until stable. Gastric emptying or oral administration of 
activated charcoal is indicated if the patient presents within one hour of the ingestion of more than 
400 mg per kg of body weight. If the Brufen has already been absorbed, alkaline substances should 
be administered to promote the excretion of the acid ibuprofen in the urine. If frequent or prolonged, 
convulsions should be treated with intravenous diazepam or lorazepam. Other measures may be 

 
 
 
indicated by the patient's clinical condition. Bronchodilators should be given for asthma. No specific 
antidote is available. 
 
Renal and liver function should be closely monitored.  
Patients should be observed for at least four hours after ingestion of potentially toxic amounts.  
 
 

PHARMACOLOGICAL PROPERTIES 
 
5.1 
Pharmacodynamic properties 
 
Pharmacotherapeutic classification: Anti-inflammatory and antirheumatic products, non-steroids; 
propionic acid derivatives.   ATC code: M01AE01 
 
Mechanism of action 
 
Ibuprofen is a NSAID that possesses anti-inflammatory, analgesic and antipyretic activity. Animal 
models for pain and inflammation indicate that ibuprofen effectively inhibits the synthesis of 
prostaglandins. In humans, ibuprofen reduces pain possibly caused by inflammation or connected 
with it, swelling and fever. Ibuprofen exerts an inhibitory effect on prostaglandin synthesis by 
inhibiting the activity of cyclo-oxygenase.  In addition,ibuprofen has an inhibitory effect on ADP 
(adenosine diphosphate) or collagen-stimulated platelet aggregation. 
 
Pharmacodynamic effects 
 
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 hour before or within 30 min after immediate release acetylsalicylic acid 
dosing (81 mg), a decreased effect of acetylsalicylic acid 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. 
 
Ibuprofen inhibits prostaglandin synthesis in the uterus, thereby reducing intrauterine rest and active 
pressure, the periodic uterine contractions and the amount of prostaglandins released into the 
circulation. These changes are assumed to explain the alleviation of menstrual pain. Ibuprofen 
inhibits renal prostaglandin synthesis which can lead to renal insufficiency, fluid retention and heart 
failure in risk patients (see section 4.3). 
Prostaglandins are connected with ovulation and the use of medicinal products inhibiting 
prostaglandin synthesis may therefore affect the fertility of women (see section 4.4, 4.6 and 5.3). 
 
 
5.2 
Pharmacokinetic properties 
 
Absorption 
Ibuprofen is rapidly absorbed from the gastrointestinal tract with a bioavailability of 80-90%. Peak 
serum concentrations occurred 1.7 hours (median value) after administration of ibuprofen in the 
fasted state. If administered with food, peak serum concentrations were 34% lower and achieved 
approximately 2 hours later than when taken on an empty stomach. Food does not markedly affect 
total bioavailability. 
 
 
 

 
 
 
Distribution 
Ibuprofen is extensively bound to plasma proteins (99%). Ibuprofen has a small volume of 
distribution being about 0.12-0.2 L/kg in adults. 
 
Biotransformation 
Ibuprofen is rapidly metabolized in the liver through cytochrome P450, preferentially CYP2C9, to 
two primary inactive metabolites, 2-hydroxyibuprofen and 3-carboxyibuprofen. Following oral 
ingestion of the drug, slightly less than 90% of an oral dose of ibuprofen can be accounted for in the 
urine as oxidative metabolites and their glucuronic conjugates. Very little ibuprofen is excreted 
unchanged in the urine. 
 
Elimination 
Excretion by the kidney is both rapid and complete. The elimination half-life is approximately 2 
hours. The excretion of ibuprofen is virtually complete 24 hours after the last dose. 
 
Special populations 
 
Elderly 
Given that no renal impairment exists, there are only small, clinically insignificant differences in the 
pharmacokinetic profile and urinary excretion between young and elderly. 
 
Children 
The systemic exposure of ibuprofen following weight adjusted therapeutic dosage (5mg/kg to 10 
mg/kg bodyweight) in children aged 1 year or over, appears similar to that in adults. 
 
Children 3 months to 2.5 years appeared to have a higher volume of distribution (L/kg) and 
clearance (L/kg/h) of ibuprofen than did children >2.5 to 12 years of age. 
 
Renal impairment 
For patients with mild renal impairment increased unbound (S)-ibuprofen, higher AUC values for 
(S)-ibuprofen and increased enantiomeric AUC (S/R) ratios as compared with healthy controls have 
been reported. 
 
In end-stage renal disease patients receiving dialysis the mean free fraction of ibuprofen was about 
3% compared with about1% in healthy volunteers. Severe impairment of renal function may result 
in accumulation of ibuprofen metabolites. The significance of this effect is unknown. The 
metabolites can be removed by haemodialysis (see sections 4.2, 4.3 and 4.4). 
 
Hepatic impairment 
Alcoholic liver disease with mild to moderate hepatic impairment did not result in substantially 
altered pharmacokinetic parameters. 
In cirrhotic patients with moderate hepatic impairment (Child Pugh’s score 6-10) treated with 
racemic ibuprofen an average 2-fold prolongation of the half-life was observed and the enantiomeric 
AUC ratio (S/R) was significantly lower compared to healthy controls suggesting an impairment of 
metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer (see sections 4.2, 4.3 and 4.4). 
 
 
5.3 
Preclinical safety data 
 
As a well established and widely used product, the pre-clinical safety of ibuprofen is well 
documented. 
 
Ibuprofen's subchronic and chronic toxicity was mainly shown by animal tests as gastric tract 
damage and ulcers. 
 

 
 
 
The vitro and in vivo tests have not shown any clinically significant signs about ibuprofen's 
mutagenicity. Furthermore, no carcinogenic effects have been observed in mice and rats. 
Ibuprofen inhibits ovulation in rabbits and impairs implantation in various animal species (rabbit, 
rat, and mouse). In reproduction tests undertaken with rats and rabbits, ibuprofen passed across the 
placenta. When using doses toxic to the mother, malformations occur more frequently (i.e. 
ventricular septum defects). 
 
 

PHARMACEUTICAL PARTICULARS 
 
6.1 
List of excipients 
 
Anhydrous sodium carbonate 
Malic acid 
Sodium saccharin  
Sodium hydrogen carbonate 
Sucrose 
Povidone  
Orange flavour 
Sodium lauril sulfate 
 
 
6.2 
Incompatibilities 
 
Not applicable. 
 
 
6.3 
Shelf life 
 
2 years 
 
 
6.4 
Special precautions for storage 
 
Store below 25C.  Store in the original package in order to protect from light and moisture. 
 
 
6.5 
Nature and contents of container 
 
Sachet consisting of a paper/polyethylene/aluminium foil and polyethylene laminate. 
 
Pack sizes: 20, 30 or 40 sachets.  Not all pack sizes may be marketed 
 
 
6.6 
Special precautions for disposal <and other handling> 
 
No special requirements 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 

MARKETING AUTHORISATION HOLDER 
 
Abbott B.V. 

 
 
 
Wegalaan 9 
2132 JD Hoofddorp 
Nederland 
088 822 2688 
 
 
 

MARKETING AUTHORISATION NUMBER 
 
RVG 110571 
 
 

DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION 
 
20 december 2012 
 
10 
DATE OF REVISION OF THE TEXT 
 
 
 





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