BRUFEN RETARD

Main information

  • Trade name:
  • BRUFEN RETARD
  • Dosage:
  • 800 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BRUFEN RETARD
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0038/080/007
  • Authorization date:
  • 19-10-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BrufenRetard800mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains800mgofIbuprofen.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolongedreleasetablet.

Awhite,pillow-shaped,film-coatedtablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

BrufenRetardisindicatedforitsanalgesicandanti-inflammatoryeffectinthetreatmentofrheumatoidarthritis,

(includingjuvenilerheumatoidarthritisorStills'disease)ankylosingspondylitis,osteoarthritisandothernon

rheumatoid(seronegative)arthropathies.

Inthetreatmentofnonarticularrheumaticconditions,BrufenRetardisindicatedintheperiarticularconditionssuchas

frozenshoulder(capsulitis),bursitis,tendinitis,tenosynovitisandlowbackpain;BrufenRetardcanalsobeusedin

soft-tissueinjuriessuchassprainsandstrains.

BrufenRetardisalsoindicatedforitsanalgesiceffectinthereliefofmildtomoderatepainsuchas

dysmenorrhoea,dentalandpost-operativepainandforsymptomaticreliefofheadache,includingmigraine

headache.

BrufenRetardisnotsuitableforuseinchildren.

4.2Posologyandmethodofadministration

Fororaladministration.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.4,Specialwarningsandprecautionsforuse).

Adults:Twotabletstakenasasingledose,preferablyintheearlyeveningwellbeforeretiringtobed.Thetablets

shouldbeswallowedwholewithplentyoffluid.Insevereoracuteconditions,totaldailydosagemaybeincreasedto

threetabletsintwodivideddoses.

Children:Notrecommendedforuseinchildrenunder12years.

Elderly:Nospecialdosagemodificationsarerequired,unlessrenalorhepaticfunctionisimpaired,inwhichcase

dosageshouldbeassessedindividually.

NSAIDsshouldbeusedwithparticularcautioninelderlypatientswhoaremorepronetoadverseevents.Thelowest

dosecompatiblewithadequatesafeclinicalcontrolshouldbeemployed(seesection4.4,Specialwarningsand

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Treatmentshouldbereviewedatregularintervalsanddiscontinuedifnobenefitisseenorintoleranceoccurs.

4.3Contraindications

Brufeniscontraindicatedinpatientswithknownhypersensitivitytotheactivesubstanceortoanyoftheinactive

ingredients.

BrufenRetardiscontraindicatedinpatientswithahistoryofgastrointestinalbleedingorperforation,relatedto

previousNSAIDstherapy.Active,orhistoryofrecurrentpepticulcer/haemorrhage(twoormoredistinctepisodesof

provenulcerationorbleeding).

BrufenRetardiscontraindicatedinpatientswithsevereheartfailure.

Brufenshouldnotbeusedinpatientswithknownhypersensitivityorwhohaveexperiencedasthma,urticariaor

allergic-typereactionsaftertakingBrufen,aspirinorotherNSAIDs.

4.4Specialwarningsandprecautionsforuse

GeneralPrecautions

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.2,PosologyandmethodofadministrationandGIandcardiovascularrisksbelow).Patients

treatedwithNSAIDslongtermshouldundergoregularmedicalsupervisiontomonitorforadverseevents.

CautionisrequiredifBrufenRetardisadministeredtopatientssufferingfrom,orwithaprevioushistoryof,bronchial

asthmasinceibuprofenhasbeenreportedtocausebronchospasminsuchpatients.

Cautionisrequiredinpatientswithrenal,hepaticorcardiacimpairmentsincetheuseofNSAIDsmayresultin

deteriorationofrenalfunction.Thedoseshouldbekeptaslowaspossibleandassessmentofrenalfunctionshouldbe

monitoredpriortotheinitiationoftherapyandregularlythereafter.

Cautionisrequiredinpatientswithahistoryofheartfailureand/orhypertensionasfluidretentionandoedemahas

beenreportedinassociationwithNSAIDtherapy.

Theuseofibuprofenmayimpairfertilityandisnotrecommendedinwomenattemptingtoconceive.Inwomenwho

havedifficultiesconceivingorwhoareundergoinginvestigationofinfertility,withdrawalofibuprofenshouldbe

considered.

Elderly:theelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDsespeciallygastrointestinalbleeding

andperforationwhichmaybefatal(seesection4.2,Posologyandmethodofadministration).

AswithotherNSAIDs,ibuprofenmaymaskthesignsofinfection.

TheuseofBrufenwithconcomitantNSAIDsincludingcyclooxygenase-2selectiveinhibitorsshouldbeavoideddueto

thepotentialforadditiveeffects.

Gastrointestinalbleeding,ulcerationandperforation:

GIbleeding,ulcerationorperforation,whichcanbefatal,hasbeenreportedwithall

NSAIDsatanytimeduringtreatment,withorwithoutwarningsymptomsoraprevioushistoryofseriousGIevents.

TheriskofGIbleeding,ulcerationorperforationishigherwithincreasingNSAIDdoses,inpatientswithahistoryof

ulcer,particularlyifcomplicatedwithhaemorrhageorperforation(Seesection4.3,Contraindications),andinthe

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agents(e.g.misoprostolorprotonpumpinhibitors)shouldbeconsideredforthesepatients,andalsoforpatients

requiringconcomitantlowdoseaspirin,orotherdrugslikelytoincreasegastrointestinalrisk(Seebelowand4.5,

Interactionwithothermedicinalproductsandotherformsofinteractions).

PatientswithahistoryofGIdisease,particularlywhenelderly,shouldreportanyunusualabdominalsymptoms

(especiallyGIbleeding)particularlyintheinitialstagesoftreatment.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchasoralcorticosteroids,anticoagulantssuchaswarfarin,selectiveserotonin-reuptakeinhibitorsoranti-

plateletagentssuchasaspirin(Seebelowand4.5,Interactionwithothermedicinalproductsandotherformsof

interactions).

WhenGIbleedingofulcerationoccursinpatientsreceivingBrufen,thetreatmentshouldbewithdrawn.

NSAIDsshouldbegivenwithcaretopatientswithahistoryofgastrointestinaldisease(ulcerativecolitis,Crohn’s

disease)astheirconditionmaybeexacerbated(Seesection4.8,Undesirableeffects).

Cardiovascularandcerebrovasculareffects

Appropriatemonitoringandadvicearerequiredforpatientswithahistoryofhypertensionand/ormildtomoderate

congestiveheartfailureasfluidretentionandoedemahavebeenreportedinassociationwithNSAIDtherapy.

Clinicaltrialdatasuggeststhatuseofibuprofen,particularlyatahighdose(2400mg/daily)andinlongtermtreatment

maybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexamplemyocardialinfarctionor

stroke).Overall,epidemiologicalstudiesdonotsuggestthatlowdoseibuprofen(e.g. 1200mgdaily)isassociated

withanincreasedriskofmyocardialinfarction.

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheralarterial

disease,and/orcerebrovasculardiseaseshouldonlybetreatedwithibuprofenaftercarefulconsideration.Similar

considerationshouldbemadebeforeinitiatinglonger-termtreatmentofpatient’swithriskfactorsforcardiovascular

events(e.g.hypertension,hyperlipidaemia,diabetesmellitus,andsmoking).

RenalEffects

CautionshouldbeusedwheninitiatingtreatmentwithBrufenRetardinpatientswithconsiderabledehydration.

AswithotherNSAIDs,long-termadministrationofBrufenRetardhasresultedinrenalpapillarynecrosisandother

renalpathologicalchanges.Renaltoxicityhasalsobeenseeninpatientsinwhomrenalprostaglandinshavea

compensatoryroleinthemaintenanceofrenal

perfusion.Inthesepatients,administrationofanNSAIDmaycauseadose-dependantreductioninprostaglandins

formationand,secondarily,inrenalbloodflow,whichmayprecipitateovertrenaldecompensation.Patientsatgreatest

riskofthisreactionarethosewithimpairedrenalfunction,heartfailure,liverdysfunction,thosewhoaretaking

diureticsandACEinhibitorsandtheelderly.DiscontinuationofNSAIDtherapyisusuallyfollowedbyrecoverytothe

pre-treatmentstate.

HaematologicalEffects

AsNSAIDscaninterferewithplateletfunctionandmayprolongbleedingtime,Brufenshouldbeusedwithcautionin

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DermatologicalEffects

Seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs(Seesection4.8,

Undesirableeffects).Patientsappeartobeatthehighestriskofthesereactionsearlyinthecourseoftherapy,theonset

ofthereactionoccurringinthemajorityofcaseswithinthefirstmonthoftreatment.Brufenshouldbediscontinuedat

thefirstappearanceofskinrash,mucosallesions,oranyothersignofhypersensitivity.

AsepticMeningitis

AsepticmeningitishasbeenobservedonrareoccasionsinpatientswithBrufentherapy.

Althoughitisprobablymorelikelytooccurinpatientswithsystematiclupuserythematosusandrelatedconnective

tissuediseases,ithasbeenreportedinpatientswhodonothaveanunderlyingchronicdisease.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ItisconsideredunsafetotakeNSAIDsincombinationwithwarfarinorheparinunlessunderdirectmedical

supervson.

Careshouldbetakeninpatientstreatedwithanyofthefollowingdrugsasinteractionshavebeenreported:

Antihypertensives:NSAIDsmayreducetheeffectofanti-hypertensives,suchasACEinhibitors.

Diuretics:NSAIDsmayreducethediureticeffect.DiureticscanalsoincreasetheriskofnephrotoxicityofNSAIDs.

Cardiacglycosides:NSAIDsmayexacerbatecardiacfailure,reduceGFRandincreaseplasmacardiacglycosidelevels.

Lithium:NSAIDsmaydecreaseeliminationoflithium.

Methotrexate:NSAIDsmaydecreaseeliminationofmethotrexate.

Cyclosporin:increasedriskofnephrotoxicitywithNSAIDs.

Otheranalgesicsincludingcyclooxygenase-2selectiveinhibitors:avoidconcomitantuseoftwoormoreNSAIDs,

(includingaspirin)asthismayincreasetheriskofadverseeffects(seesection4.4,Specialwarningsandprecautions

foruse).

Corticosteroids:increasedriskofgastrointestinalulcerationorbleedingwithNSAIDS(Seesection4.4,Special

warningsandprecautionsforuse).

Anticoagulants:NSAIDsmayenhancetheeffectsofanticoagulants,suchaswarfarin(Seesection4.4,Special

warningsandprecautionsforuse).

Aspirin:AswithotherproductscontainingNSAIDs,concomitantadministrationofibuprofenandaspirinisnot

generallyrecommendedbecauseofthepotentialofincreasedadverseeffects.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

aredosedconcomitantly.However,thelimitationsofthesedataandtheuncertaintiesregardingextrapolationofex

vivodatatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofenuse,andno

clinicallyrelevanteffectisconsideredtobelikelyforoccasionaluse(seesection5.1).

Anti-plateletagentsandselectiveserotoninreuptakeinhibitors(SSRIs):increasedriskofgastrointestinalbleedingwith

NSAIDs(Seesection4.4,Specialwarningsandprecautionsforuse).

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Quinoloneantibiotics:animaldataindicatethatNSAIDscanincreasetheriskofconvulsionsassociatedwithquinolone

antibiotics.PatientstakingNSAIDsandquinolonesmayhaveincreasedriskofdevelopingconvulsions.

Probenacid:therehavebeennoreportsofinteractionsbetweenprobenacidandibuprofen.However,probenacid

producesareductioninmetabolismandeliminationofsomeNSAIDsandmetabolites.

Oralhypoglycaemicagents:inhibitionofmetabolismofsulfonylureadrugs,prolongedhalf-lifeandincreasedriskof

hypoglycaemia.

Mifepristone:NSAIDsshouldnotbeusedfor8-12daysaftermifepristoneadministrationasNSAIDscanreducethe

effectofmifepristone.

Tacrolimus:PossibleincreasedriskofnephrotoxicitywhenNSAIDsaregivenwithtacrolimus.

Zidovudine:IncreasedriskofhaematologicaltoxicitywhenNSAIDsaregivenwithzidovudine.Thereisevidenceof

anincreasedriskofhaemarthrosesandhaematomainHIV(+)haemophiliacsreceivingconcurrenttreatmentwith

zidovudineandibuprofen.

GinkgobilobamaypotentiatetheriskofbleedingwithNSAIDs.

4.6Fertility,pregnancyandlactation

Whilstnoteratogeniceffectshavebeendemonstratedinanimaltoxicologystudies,theuseofibuprofenduring

pregnancyshouldbeavoidedexceptundercompellingcircumstances.Congenitalabnormalitieshavebeenreportedin

associationwithibuprofenadministrationinman;however,thesearelowinfrequencyanddonotappeartofollowany

discerniblepattern.InviewoftheknowneffectsofNSAIDsonthefoetalcardiovascularsystem(closureofductus

arteriosus),ibuprofenshouldnotbeusedinthethirdtrimesterofpregnancy.

Labouranddelivery:Administrationofibuprofenisnotrecommendedduringlabouranddelivery.Theonsetoflabour

maybedelayedandthedurationincreasedwithagreaterbleedingtendencyinbothmotherandchild.

Inlimitedstudiestodate,ibuprofenappearsinbreastmilkinverylowconcentrations.Brufenisnotrecommendedfor

useinnursingmothers.

4.7Effectsonabilitytodriveandusemachines

None.

4.8Undesirableeffects

Immunesystemdisorders:

Hypersensitivityreactionshavebeenreportedfollowingtreatmentwithibuprofen.Thesemayconsistof(a)non-

specificallergicreactionandanaphylaxis,(b)respiratorytractreactivitycomprisingasthma,aggravatedasthma,

bronchospasmordyspnoea,or(c)assortedskindisorders,includingrashesofvarioustypes,pruritus,urticaria,purpura,

angioedemaand,veryrarely,bullousdermatoses(includingStevens-Johnsonsyndrome,toxicepidermalnecrolysisand

erythemamultiforme).

Gastrointestinaldisorders:

Themostcommonlyobservedadverseeventsaregastrointestinalinnature.Pepticulcers,perforationorGIbleeding,

sometimesfatal,particularlyintheelderly,mayoccur(seesection4.4,Specialwarningsandprecautionsforuse).

Nausea,vomiting,diarrhoea,flatulence,constipation,dyspepsia,abdominalpain,melaena,haematemesis,ulcerative

stomatitis,exacerbationofcolitisandCrohn’sdisease(seesection4.4-Specialwarningsandprecautionsforuse)have

beenreportedfollowingadministration.Lessfrequently,gastritishasbeenobserved.Pancreatitishasbeenreported

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Otheradverseeventsreportedinclude:

Cardiovascular:

Oedema,hypertensionandcardiacfailurehavebeenreportedinassociationwithNSAIDtreatment.Clinicaltrialand

epidemiologicaldatasuggestthatuseofibuprofen,particularlyathighdose(2400mg/daily),andinlongterm

treatmentmaybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexamplemyocardial

infarctionorstroke)(seesection4.4).

Bloodandlymphaticsystemdisorders:thrombocytopenia,neutropenia,agranulocytosis,aplasticanaemiaand

haemolyticanaemia.

Psychiatricdisorders:depression,confusion,hallucinations

Nervoussystemdisorders:headaches,paraesthesia,dizziness,drowsiness

Eyedisorders:disturbancesofvision,opticneuritis

Earandlabyrinthdisorders:vertigo,tinnitus

Hepatobiliarydisorders:abnormalliverfunction,hepaticfailure,hepatitis,jaundice

Skinandsubcutaneoustissuedisorders:photosensitivity,bullousreactionsincludingSteven'sJohnsonsyndromeand

toxicepidermalnecrolysis(veryrare).

Generaldisordersandadministrationsiteconditions:malaise,fatigue.

Renalandurinarydisorders:impairedrenalfunction,renalnephrotoxicityinvariousforms,includinginterstitial

nephritis,nephroticsyndromeandrenalfailure.

4.9Overdose

Symptomsincludenausea,vomiting,dizziness,convulsion,lossofconsciousnessanddepressionoftheCNSand

respiratorysystem.Largeoverdosesaregenerallywelltoleratedwhennootherdrugsareinvolved.

Gastriclavagemaybeofvalueforaconsiderabletimeafteringestion.Thetabletsmaynotbetotallyretrieved.If

necessary,correctserumelectrolytesandimplementappropriatesupportivemeasures.

Thereisnospecificantidotetoibuprofen.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Ibuprofenisaphenylpropionicacidderivativewithanalgesic,anti-inflammatoryandantipyreticactivity.Thedrug's

therapeuticeffectsasaNSAIDarethoughttoresultfromitsinhibitoryeffectontheenzymecyclo-oxygenase,which

resultsinamarkedreductioninprostaglandinsynthesis.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

aredosedconcomitantly.Inonestudy,whenasingledoseofibuprofen400mgwastakenwithin8hoursbeforeor

within30minutesafterimmediatereleaseaspirindosing(81mg),adecreasedeffectofASAontheformationof

thromboxaneorplateletaggregationoccurred.However,thelimitationsofthesedataandtheuncertaintiesregarding

extrapolationofexvivodatatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofen

use,andnoclinicallyrelevanteffectisconsideredtobelikelyforoccasionalibuprofenuse.

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ThepharmacokineticprofileofBrufenRetardcomparedwiththatofconventional-release400mgtabletsshowedthat

thesustained-releaseformulationreducedpeaksandtroughscharacteristicoftheconventional-releasetabletsandgave

higherlevelsat5,10,and15and24hours.Comparedwiththeconventional-releasetablets,theareaundertheplasma

concentrationtimecurveforsustained-releasetabletswasalmostidentical.

Bothmeanplasmaprofilesandthepre-doseplasmalevelsshowednomajordifferencesbetweentheyoungandelderly

agegroups.Inseveralstudies,BrufenRetardproducedadoublepeakplasmaprofilewhentakenunderfasting

conditions.Theeliminationhalf-lifeofibuprofenisapproximatelytwohours.Ibuprofenismetabolisedintheliverto

twoinactivemetabolitesandthesetogetherwiththeunchangedibuprofen,areexcretedbythekidneyeitherassuchor

asconjugates.Excretionbythekidneyisbothrapidandcomplete.Ibuprofenisextensivelyboundtoplasmaproteins.

5.3Preclinicalsafetydata

Notapplicable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Colloidalanhydroussilica

Povidone

StearicAcid

XanthanGum

Talc

Hypromellose

Coating

OpasprayWhiteM–17111Bcontaining:

TitaniumDioxide(E171)

Hypromellose

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

C.Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Blisterpackcomprisingofopaquepolyvinylchloride(PVC)filmcoatedononefacewithpolyvinylidene(PVDC)with

aluminiumfoilbacking.

Packsize60tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

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Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratoriesIrelandLimited,

4051KingswoodDrive,

CitywestBusinessCampus,

Dublin24.

8MARKETINGAUTHORISATIONNUMBER

PA38/80/7

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:03January1990

Dateoflastrenewal:03January2010

10DATEOFREVISIONOFTHETEXT

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