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Brufen Retard

Last Updated on eMC 31-Aug-2016 View document  | Mylan Products Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Updated on 31-Aug-2016 and displayed until Current

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text
  • Company name change or merger

Date of revision of text on the SPC: 26-Aug-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



7.         Marketing Authorisation Holder

 

20 Station Close

Potters Bar

Herts

EN6 1TL

United Kingdom

BGP Products Limited

Abbott House

Vanwall Business Park

Vanwall Road

Maidenhead

Berkshire

SL6 4XE

 

8.         Marketing Authorisation Number

 

           

PL 46302/0010

PL 43900/0010

 

  

10.       Date of (Partial) Revision of the Text

 

Updated on 23-Jun-2016 and displayed until 31-Aug-2016

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 05-Jun-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



2.         Qualitative and Quantitative Composition

 

            Active Ingredient: Ibuprofen BP (800 mg)

 

For a full list of excipients see section 6.1.

 

 

4.2.      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:  Two tablets taken as a single daily dose, preferably in the early evening well before retiring to bed.  The tablets should be swallowed whole with plenty of fluid and not chewed, broken, crushed or sucked on to avoid oral discomfort and throat irritation.  In severe or acute conditions, total daily dosage may be increased to three tablets in two divided doses. 

 

            Children:  Not recommended for children under 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.

 

 

4.4.      Special Warnings and Precautions for Use

 

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below). 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).

 

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).

 

Paediatric population

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 4.8).

 

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.

 

CardiovascularCardiac, 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 Renal function should be monitored in these 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 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 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 effects

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.

 

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal 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 failureprecipitate overt renal decompensation. 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).

 

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Brufen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. 

 

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

 

Aseptic meningitis

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

 

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 be considered.

 

4.5.      Interactions with other Medicaments 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.

[..]

4.6.      Pregnancy and Lactation

 

            Pregnancy

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.

[..]


4.8.      Undesirable Effects

           

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 havehas been observed. Gastrointestinal perforation has been rarely reported with ibuprofen use. Pancreatitis has also been reported very rarely.

 

            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, more very rarely, erythema multiforme, exfoliative and bullous dermatoses (including Stevens- Johnson syndrome, and toxic epidermal necrolysis and erythema multiforme ).

 

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).

 

            Other adverse events reported less commonly and for which causality has not necessarily been established include:

 

            Blood and lymphatic system disorders: Leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

 

                        Psychiatric disorders: Insomnia, anxiety, depression, confusional state, hallucination

 

                        Nervous system disorders: Optic neuritis, headache, paraesthesia, dizziness, somnolence

 

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 without delay.

 

 

              Eye disorders: Visual impairment and toxic optic neuropathy

 

              Ear and labyrinth disorders: Hearing impaired, tinnitus and vertigo

 

            Hepatobiliary disorders: Abnormal liver function, hepatic failure, hepatitis and jaundice.

 

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")  Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reaction.

           

            Renal and urinary disorders: Impaired renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

 

            General disorders and administration site conditions: Malaise, fatigue

 

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 (³1/10), Common (³1/100 to <1/10), Uncommon (³1/1,000 to <1/100), Rare (³1/10,000 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

 

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

 

Uncommon

Paraesthesia, somnolence

 

Rare

Optic neuritis

 

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

 

Very rare

Pancreatitis

 

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

 

Rare

Oedema

 

Cardiac disorders

Very rare

Cardiac failure, myocardial infarction (also

see section 4.4)

Vascular disorders

Very rare

Hypertension

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: www.mhra.gov.uk/yellowcard

 

Updated on 04-Jan-2016 and displayed until 23-Jun-2016

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 14-Dec-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.3.      Contraindications

[..]

Brufen is contraindicated in patients with severe heart failure (NYHA Class IV), hepatic failure and renal failure (see section 4.4).

4.4       Special warnings and precautions for use

 

[..]

Epidemiological Clinical studies data suggest that use of ibuprofen, particularly at a high dose (2400 mg/ dailyday) and in long term treatment, 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 daily) is associated with an increased risk of arterial thrombotic events, particularly myocardial infarction.

 

            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. Similar Careful consideration should also be made exercised before initiating longer-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.

4.5       Interaction with other medicinal products and other forms of interaction

 

[..]

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.  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 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 No clinically relevant effect is considered to be likely for occasional use (see section 5.1).

 

4.8.      Undesirable Effects

[..]

Cardiac disorders and vascular disorders:  Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Epidemiological dataClinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg/day daily), and in long term treatment, may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4).

5.1       Pharmacodynamic properties

 

[..]

 

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 In one study, when a single doses of ibuprofen 400mg was 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.  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 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 No clinically relevant effect is considered to be likely for occasional ibuprofen use. (see section 4.5)

 

 

 

 

 

Updated on 04-Sep-2015 and displayed until 04-Jan-2016

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 27-Aug-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



5        PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

 

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 inhibit the effect of low dose aspirin on platelet aggregation when they are dosed 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 aspirin on the formation of thromboxane or platelet aggregation occurred.  However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Updated on 27-Apr-2015 and displayed until 04-Sep-2015

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text
  • Company name change or merger

Date of revision of text on the SPC: 16-Apr-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Due to Change of Ownership

  • In section 7 ( MA Holder ) has changed from  Abbott Laboratories Limited to BGP Products Ltd
  • In section 8 ( MA number ) has changed from PL00037/0338 to PL 43900/0010
  • In section 10 ( Date of revision of text) has been updated to 16/04/15

Updated on 04-Aug-2014 and displayed until 27-Apr-2015

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Jul-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.4.      Special Warnings and Precautions for Use

 

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below). 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).

 

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).

 

Paediatric population

                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 4.8).

 

Respiratory disorders

 Caution is required if Brufen is administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

 

Cardiovascular, renal and hepatic impairment

 The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these 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 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.

 

Epidemiological data suggest that use of ibuprofen, particularly at a high dose (2400 mg/ daily) and in long term treatment, 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 daily) is associated with an increased risk of arterial thrombotic events, particularly myocardial infarction.

 

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

 

Renal effects

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.

 

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal 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 precipitate overt renal decompensation. 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).

 

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Brufen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. 

 

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

 

Aseptic meningitis

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

  

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 be considered.

 

Updated on 30-May-2012 and displayed until 04-Aug-2014

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC: 08-Mar-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Addition of text to 4.2

The tablets should be swallowed whole with plenty of fluid and not chewed, broken, crushed or sucked on to avoid oral discomfort and throat irritation.

Updated on 24-Jan-2011 and displayed until 30-May-2012

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose

Date of revision of text on the SPC: 14-Jan-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.3 - revised to include additional wording contraindicating the use of Brufen in patients with an increased tendency for bleeding.

 

Section 4.4 – revision of the wording concerning the concomitant use of Brufen with other NSAIDs, specifying that there is an increased risk of ulceration and bleeding.

 

Section 4.5 – revised to include additional interactions between Brufen and cholestyramine, sulfonylureas and CYP2C9 inhibitors and to update the information concerning the interactions between Brufen and methotrexate, anti-hypertensives and mifepristone.

 

Section 4.6 – revision of the wording concerning pregnancy in accordance with the EMEA NSAID class labelling and new available data.

 

Section 4.8 – revised to add the adverse events of rhinitis, leukopaenia, insomnia, anxiety, toxic optic neuropathy and hearing impaired, in addition to including a further statement concerning gastrointestinal perforation.

 

Section 4.9 – revised to include an additional statement on toxicity in section 4.9 and to revise the wording surrounding the symptoms of overdose to reflect the most updated information found within the medical literature.

Updated on 08-Jan-2010 and displayed until 24-Jan-2011

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Date of revision of text on the SPC: 02-Jan-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 7 - Change of address of Marketing Authorisation Holder

Updated on 19-Mar-2009 and displayed until 08-Jan-2010

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 03-Mar-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to section 4.2 - dosage and administration
Text amended:

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. To be taken preferably with or after food.


Change to section 4.3 - contraindications
Text amended:

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 is contraindicated in patients with severe heart failure, hepatic failure and renal failure (see section 4.4).

 Brufen is contraindicated during the last trimester of pregnancy (see section 4.6).

Change to section 4.4 - warnings and precautions
Text amended:

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). 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 potential for additive effects (see section 4.5).

 

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).

 

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 4.8).

 

Respiratory disorders

            Caution is required if Brufen is administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

 

Cardiovascular, renal and hepatic impairment

           

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these 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 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.

 

Epidemiological data suggest that use of ibuprofen, particularly at a high dose (2400 mg/ daily) and in long term treatment, 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 daily) is associated with an increased risk of arterial thrombotic events, particularly myocardial infarction.

 

            Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

 

Renal effects

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.

 

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal 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 precipitate overt renal decompensation. 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).

 

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Brufen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. 

 

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

 

Aseptic meningitis

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systematic 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 be considered.

Change to section 4.5 - interactions
Text amended:

Methotrexate: Decreased elimination of methotrexate.

 

            Ciclosporin: Increased risk of nephrotoxicity.

 

            Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone        administration as NSAIDs can reduce the effects of mifepristone.

 

Other analgesics and cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4).

 

            Aspirin: 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).

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.

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 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.

Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

 
Change to section 4.6 - pregnancy and lactation
Text amended:

Pregnancy

            Congenital abnormalities have been reported in association with  NSAID 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 (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

 

            Lactation

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 breastfeeding.

 

See section 4.4 Special warnings and precautions for use, regarding female fertility.

Change to sectipn 4.7 - effects on ability to drive and use machines
Text amended:

 Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs.  If affected, patients should not drive or operate machinery.

Change to section 4.8 - undesirable effects
Text amended:

Gastrointestinal disorders: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease (see section 4.4) have been reported following ibuprofen administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

 

Immune system disorders: Hypersensitivity reactions have been reported following treatment withNSAIDs. 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, more rarely, exfoliative and bullous dermatoses (including Stevens- Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

 Cardiac disorders and vascular disorders:  Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. 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 such as myocardial infarction or stroke (see section 4.4).

 Other adverse events reported less commonly and for which causality has not necessarily been established include:

 Blood and lymphatic system disorders: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

  Psychiatric disorders: Depression, confusional state, hallucination

 Nervous system disorders: Optic neuritis, headache, paraesthesia, dizziness, somnolence

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).

 Eye disorders: Visual disturbance

Ear and labyrinth disorders: Tinnitus, vertigo

Hepatobiliary disorders: Abnormal liver function, hepatic failure, hepatitis and jaundice.

                Skin and subcutaneous tissue disorders: Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reaction.           

Renal and urinary disorders: Impaired renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

 General disorders and administration site conditions: Malaise, fatigue

Change to section 4.9 - overdose
Text amended:

Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, drowsiness, dizziness, tinnitus, fainting, depression of the CNS and respiratory system, coma, occasionally convulsions and rarely, loss of consciousness.   In cases of significant poisoning, acute renal failure and liver damage are possible.

           

            Therapeutic measures                      

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 toxic amounts.

 Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient’s clinical condition.

Change to section 10 - date of partial revision of text    
Text amended: 03 March 2009

Change to sction 5.1 
Text amended:

Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and antipyretic activity.  The drug's therapeutic effect 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 dosed 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 aspirin on the formation of thromboxane or platelet aggregation occurred.  However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Updated on 04-Mar-2009 and displayed until 19-Mar-2009

Reasons for adding or updating:

  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 25-Feb-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to section 9 and 10 renewal and revision date

Updated on 02-Mar-2007 and displayed until 04-Mar-2009

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Feb-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

4.2.      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).

 

4.3.      Contra-indications

 

Brufen is contraindicated in patients with severe heart failure.

 

4.4.      Special Warnings and Precautions for Use

 

            Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below). 

 

            Cardiovascular and cerebrovascular effects

 

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

 

Clinical trial data suggest that use of ibuprofen, particularly at a high dose (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. £ 1200mg daily) is associated with an increased risk of myocardial infarction.

 

            Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

 

           

4.8.      Undesirable Effects

 

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).

 

           

10.       Date of Revision of the Text

Updated on 24-Sep-2002 and displayed until 02-Mar-2007

Reasons for adding or updating:

  • New SPC for new product

Company contact details

Mylan Products Limited

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20 Station Close, Potters Bar, Hertfordshire, EN6 1TL, UK

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+44 (0)1707 853000

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Active ingredients

ibuprofen

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