- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
ElderlyThe elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2).
Paediatric populationThere is a risk of renal impairment in dehydrated children and adolescents.
Gastrointestinal bleeding, ulceration and perforationGI 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 4.8).
Respiratory disorders and hypersensitivity reactionsCaution 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 4.3). 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 administration.
Cardiovascular and cerebrovascular effectsAppropriate 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 II-III), 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.
Renal effectsCaution 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 diseaseIn 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).
Dermatological effectsSerious 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.
Haematological effectsIbuprofen, like other NSAIDs, can interfere with platelet aggregationand prolong bleeding time in normal subjects.
Aseptic meningitisAseptic 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 fertilityThe 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 be considered.
PregnancyInhibition 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 oligohydramnios.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 prolonged labour.Consequently, Brufen is contraindicated during the third trimester of pregnancy.
LactationIn the limited studies so far available, NSAIDs can appear in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.See section 4.4 Special warnings and precautions for use, regarding female fertility.
|System organ class||Frequency||Adverse reaction|
|Infections and infestations||Uncommon||Rhinitis|
|Rare||Meningitis aseptic (see section 4.4)|
|Blood and lymphatic system disorders||Rare||Leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia , haemolytic anaemia|
|Immune system disorders||Rare||Anaphylactic reaction|
|Psychiatric disorders||Uncommon||Insomnia, anxiety|
|Rare||Depression, confusional state|
|Nervous system disorders||Common||Headache, dizziness|
|Eye disorders||Uncommon||Visual impairment|
|Rare||Toxic optic neuropathy|
|Ear and labyrinth disorders||Uncommon||Hearing impaired , tinnitus, vertigo|
|Respiratory, thoracic and mediastinal disorders||Uncommon||Asthma, bronchospasm, dyspnoea|
|Gastrointestinal disorders||Common||Dyspepsia, diarrhoea, nausea, vomiting, abdominal pain, flatulence, constipation, melaena, haematemesis, gastrointestinal haemorrhage|
|Uncommon||Gastritis, duodenal ulcer, gastric ulcer, mouth ulceration, gastrointestinal perforation|
|Not known||Exacerbation of Colitis and Crohn´s disease|
|Hepatobiliary disorders||Uncommon||Hepatitis, jaundice, hepatic function abnormal|
|Very Rare||Hepatic failure|
|Skin and subcutaneous tissue disorders||Common||Rash|
|Uncommon||Urticaria, pruritus, purpura, angioedema, photosensitivity reaction|
|Very rare||Severe forms of skin reactions ( e.g. Erythema multiforme, bullous reactions, including Stevens-Johnson syndrome,and toxic epidermal necrolysis)|
|Renal and urinary disorders||Uncommon||Nephrotoxity in various forms e.g.Tubulointerstitial nephritis, nephrotic syndrome and renal failure|
|General disorders and administration site conditions||Common||Fatigue|
|Cardiac disorders||Very rare||Cardiac failure, myocardial infarction (also see section 4.4)|
|Vascular disorders||Very rare||Hypertension|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
ToxicitySigns and symptoms of toxicity have generally not been observed at doses below 100 mg/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 400 mg/kg or greater.
SymptomsMost 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.
Therapeutic measuresPatients 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 toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.
Extragranular excipients: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 talcNB industrial methylated spirit and purified water are removed during the drying process
Mylan Products Limited
20 Station Close, Potters Bar, Hertfordshire, EN6 1TL, UK
+44 (0)1707 853000
+44 (0)1707 853 000