Brufen Paediatric 100mg/5ml Oral Suspension

7. MARKETING AUTHORISATION HOLDER
Mylan IRE Healthcare Limited
Unit 35/36
Grange Parade
Baldoyle Industrial Estate
Dublin 13
BGP Products Ireland Limited
4051 Kingswood Drive
Citywest Business Campus
Dublin 24

10. DATE OF REVISION OF THE TEXT
February 2017June 2017

 Changes to SmPC affecting sections

4.2 Posology and Method of administration – to include age/weight  qualifiers and information related to use of product with renal and hepatic impairment

Section 4.4 Special warnings and precautions for use.

·         Warnings added with respect to use low dose especially in long term use.

·         Use may cause headaches do not take additional painkillers

·         Concomitant consumption of alcohol may increase adverse events (particularly those that are GI)

·         Addition of elderly when discussing risk of dehydrated patients

·         Warnings related to varicella have been added.

Section 4.7 Effects on ability to drive and use machines – advised risks enhanced if tablets and alcohol combined.

Section 4.8

Section 4.3 - (Contraindications) added "NYHA IV after sever heart failure
Section 4.4 - (Special Warnings and Precautions for Use) in section Cardiovascular and cerebrovascular effects warnings updated based on clinical studies and warning of use of high doses.
Section 4.5 - (Interaction with Other medicinal products and other forms of interaction - table amended possible effects concomitant use with Acetylsalicylic acid/aspirin.
Section 4.8 - (Undesirable effects) - warnings changed in section "Cardiac disorders and vascular disorders"
Section 5.1 - (Pharmacodynamic properties) information changed relating from data/studies related to use with acetylsalicylic acid and possible reduction of cardioprotective effect of low dose aspirin.

Section 4.2:
Updates to paragraph headers & addition of a paragraph relating to Method of Administration.

Section 4.3:
Update to the list of contraindications
Editorial changes

Section 4.4:
Editorial changes
Addition of excipient warning
Addition of respiratory disorder caution
 
Section 4.5:
Addition of new interaction table
 
Section 4.6:
Editorial changes

Section 4.8:
Addition of paragraphs relating to Infections and infestations and Skin and subcutaneous tissue disorder,  
Addition of a new MedDRA table
Addition of Adverse Event reporting details

Section 5.1:
Addition of pharmacotherapeutic classification
Editorial changes
Addition of paragraphs relating to Absorbtion, Distribution, Biotransformation, Elimination.
Addition of paragraphs relating to Special populations (Elderly, Paediatric population, Renal Impairment and Hepatic Impairment)

Section 5.3:
Editorial changes

Section 10:
Update to revision date

Section 7:
MA Holder changed from Abbott Laboratories Ireland Limited to BGP Products Ireland Limited

Section 8:
PA number changed from PA 38/80/06 to PA 2010/2/6

Section 4.4 - Special Warnings and Precautions for use:-
Addition of "There is a risk of renal impairment in dehydrated children and adolescents"

Significant change to safety sections of SPC

The following text was added to section 4.2:

A transient sensation of burning in the mouth or throat may occur with ibuprofen suspension; ensure the bottle is thoroughly shaken before use.

The following text was added to section 4.8:

A transient sensation of burning in the mouth or throat may occur with ibuprofen suspension.

Date of Revision amended to Dec 2012

In section 2. Qualitative and Quantitative Composition the following has been added:

 

Excipients: Each 5ml also contains: 

5mg methyl parahydroxybenzoate  (E218)

2.5mg propyl parahydroxybenzoate (E216)

500mg sorbitol solution non-crystallising (E420)         

3.3 g sucrose

0.5mg sunset yellow FC edicol (E110)

In section 4.4 Special Warnings and Precautions for Use the following has been added:

 

Brufen contains 3.3 g of sucrose per 5ml dose.  This should be taken into account in patients with diabetes mellitus. May be harmful to the teeth.

The excipients methyl parahydroxybenzoate  (E218), propylparahydroxybenzoate (E216) and  sunset yellow FC edicol (E110) may cause allergic reactions (possibly delayed).

In section 6.4 Special Precautions for Storage the information has been changed to:

No special storage conditions

In section 9. Date of Renewal of Authorisation has been updated to:

Date of last renewal of authorisation: 02 March 2011

In section 10. Date of (Partial) revision of the text has been updated to:

November 2011

In section 6.3, the statement "Once opened, the contents of the bottle should be used within 12 months" has been added

In section 6.5 (Nature  and contents of Container), details of the amber glass bottle and the statement "Not all pack sizes may be marketed has been removed. 

In relation to the description of the PET bottle, "thermoplastic screw cap fitted with low density polythene cone" has been removed and replaced with "aluminium cap fitted with a LDPE liner".

PLEASE INGNORE THE YELLOW BACKGROUND 


4.3       Contraindications

 

Brufen is contraindicated in patients with known hypersensitivity to the active substance or to any of the inactive ingredients.

 

Brufen is contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

 

Brufen is contraindicated in patients with severe heart failure.

 

Brufen should not be used in patients with known hypersensitivity or with a history of bronchospasm, urticaria or rhinitis in response to Brufen, aspirin or other NSAIDs.

 

Brufen should not be used in patients with known hypersensitivity or who have experienced asthma, urticaria or allergic-type reactions after taking Brufen, aspirin or other NSAIDs.

 

4.5       Interactions with other Medicaments and other forms of Interaction

 

It is considered unsafe to take NSAIDs in combination with warfarin or heparin unless under direct medical supervision.

 

Care should be taken in patients treated with any of the following drugs as interactions have been reported:

 

Antihypertensives: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors.reduced antihypertensive effect.

 

Diuretics: NSAIDs may reduce the reduced diuretic effect.  Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

 

Cardiac glycosides:  NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

 

Lithium: NSAIDs may decreased elimination of lithium.

 

Methotrexate: NSAIDs may decreased elimination of methotrexate.

 

Cyclosporin: increased risk of nephrotoxicity with NSAIDs.

 

Other NSAIDs:  avoid concomitant use of two or more NSAIDs.

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

 

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding with NSAIDs (See section 4.4)

 

Anticoagulants: NSAIDs may enhance the effects of  anticoagulants, such as warfarin (See section 4.4).

 

Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.

 

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly.  However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional use (see section 5.1).

 

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding with NSAIDs (See section 4.4).

 

Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

 

Quinolone antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics.  Patients taking NSAIDs and quinolones may have increased risk of developing convulsions.

 

Probenacid: there have been no reports of interactions between probenacid and ibuprofen.  However, probenacid produces a reduction in metabolism and elimination of some NSAIDs and metabolites.

 

Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.

 

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

 

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

 

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine.  There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

 

Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

4.6       Pregnancy and Lactation

 

Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy shouldbe avoided except under compelling circumstances.  Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern.  In view of the known effects of NSAIDs on the foetal cardiovascular system (closure of the ductus arteriosus), ibuprofen should not be used in the third trimester of pregnancy.

 

            Labour and delivery: Administration of ibuprofen is not recommended during labour and delivery.  The onset of labour may be delayed and the duration increased with a greater bleeding tendency in both mother and child.

 

In limited studies to date, ibuprofen appears in breast milk in very low concentrations. Brufen Paediatric Oral Suspension is not recommended for use in nursing mothers.

 

4.8       Undesirable Effects

 

Immune system disorders:

Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely less commonly, bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

 

Gastrointestinal disorders:

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

 

Other adverse events reported include:

 

Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (2400 mg/ daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

 

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

 

Psychiatric disorders: depression, confusion, hallucinations

 

Nervous system disorders: headaches, paraesthesia, dizziness, drowsiness

 

Eye disorders: disturbances of vision, optic neuritis

 

Ear and labyrinth disorders: vertigo, tinnitus

 

Hepatobiliary disorders:  abnormal liver function, hepatic failure, hepatitis, jaundice

 

Skin and subcutaneous tissue disorders: photosensitivity, bullous reactions including Steven's Johnson syndrome and toxic epidermal necrolysis (very rare).

 

General disorders and administration site conditions: malaise, fatigue. 

 

Renal and urinary disorders: impaired renal function, renal nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

 

 

 

 

 

4.9       Overdose

 

            Symptoms include nausea, vomiting, dizziness, convulsion, and rarely, loss of consciousness and depression of the CNS and respiratory system.  Large overdoses are generally well tolerated when no other drugs are involved.

 

Treatment consists of gastric lavage and, if necessary, correction of serum electrolytes and appropriate supportive measures.

 

There is no specific antidote to ibuprofen.

 

 

 

 

Change in date to reflect the renewal date

Change to section 4.2 - Posology and Method of Administration
Change to section 4.3 - Contra-indications

Change to section 4.4 - Special warnings and Precautions

Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction

Change to section 4.8 - Undesirable Effects 

 

Change to section 4.3 - Contra-indications

Change to section 4.4 - Warnings or special precautions for use

Change to section 4.5 - Drug interactions

Change to section 4.6 - Pregnancy or lactation

Change to section 4.8 - Side-effects