BUPLEX RX

Main information

  • Trade name:
  • BUPLEX RX
  • Dosage:
  • 800 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BUPLEX RX
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1380/088/004
  • Authorization date:
  • 31-07-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BuplexRx800mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm -coatedtabletcontains800mgibuprofen.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film -coatedtablet.

White,oval,biconvexfilm -coatedtabletswithascoreononeface.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Rheumaticconditionssuchasarthriticdiseases(e.g.rheumatoidarthritisincludingjuvenilerheumatoidarthritis),

degenerativearthriticconditions(e.g.osteoarthritis),non-articularrheumaticconditions,othermuscularandjoint

disorders,andsofttissueinjuries.

4.2Posologyandmethodofadministration

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.4).

Theibuprofendosedependsonthepatient’sageandbodyweight.Themaximumsingledailydoseforadultsshould

notexceed800mgofibuprofen.

Thetabletshouldbeswallowedwithaglassofwaterduringorafterameal.

Rheumaticdiseases

Adults:

Theusualdoseis400 -600mg3timesaday.Maintenancedosesof600mg-1200mgdailymaybeeffectiveinsome

patients.Inacuteandsevereconditionsthedosemaybeincreasedtoamaximumof2400mgin3or4divideddoses.

Adolescentsover12yearsofage(>40kg):

Therecommendeddoseis20mg/kgtoamaximumof40mg/kgbodyweightdailyin3to4divideddoses.

Thereareotherdosageformswhichmaybemoresuitabletoattaintherequiredposologyinthisageandbodyweight

group.

Elderly

NSAIDsshouldbeusedwithparticularcautioninelderlypatientswhoaremorepronetoadverseeventsandareat

increasedriskofpotentiallyfatalgastrointestinalhaemorrhage,ulcerationorperforation(seesection4.4).Iftreatment

isconsiderednecessary,thelowestdosefortheshortestdurationnecessarytocontrolsymptomsshouldbeused.

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Impairedrenalfunction

Inpatientswithmildormoderatereductionofrenalfunction,thedoseshouldbekeptaslowaspossiblefortheshortest

durationnecessarytocontrolsymptomsandrenalfunctionmonitored.(Forpatientswithsevererenalfailureseesection

4.3).

Impairedliverfunction

Inpatientswithmildormoderatereductionofliverfunctionthedoseshouldbekeptaslowaspossiblefortheshortest

durationnecessarytocontrolsymptomsandrenalfunctionmonitored.(Forpatientswithsevereliverfailureseesection

4.3).

4.3Contraindications

BuplexRxiscontraindicatedinpatientswith:

hypersensitivitytotheactivesubstanceortoanyoftheexcipientsofBuplexRx

previoushypersensitivityreactions(e.g.asthma,rhinitis,urticariaorangioedema)inresponsetoacetylsalicylic

acidorotherNSAIDs

historyofgastrointestinalbleedingorperforation,relatedtopreviousNSAIDstherapy

active,orhistoryofrecurrentpepticulcer/haemorrhage(twoormoredistinctepisodesofprovenulcerationor

bleeding)

severehepaticorsevererenalinsufficiency

severeheartfailureorcoronaryheartdisease

lasttrimesterofpregnancy(seesection4.6)

significantdehydration(causedbyvomiting,diarrhoeaorinsufficientfluidintake)

cerebrovascularorotheractivebleeding

dishaematopoiesisofunknownorigin

childrenyoungerthan6yearsofage.

4.4Specialwarningsandprecautionsforuse

TheuseofBuplexRxwithconcomitantNSAIDsincludingcyclooxygenase -2selectiveinhibitorsshouldbeavoided.

Asthmaticpatientsaretoseektheirdoctor’sadvicebeforeusingibuprofen(seebelow).

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.2,andGIandcardiovascularrisksbelow).PatientstreatedwithNSAIDslongtermshould

undergoregularmedicalsupervisiontomonitorforadverseevents.

BuplexRxshouldonlybeadministeredunderstrictconsiderationofthebenefit-riskratiointhefollowingconditions:

SystemicLupusErythematosus(SLE)orotherautoimmunediseases.

Congenitaldisturbanceofporphyrinmetabolism(e.g.acuteintermittentporphyria)

Thefirstandsecondtrimesterofpregnancy

Lactation

Specialcarehastobetakeninthefollowingcases:

Gastrointestinaldiseasesincludingchronicinflammatoryintestinaldisease(ulcerativecolitis,Crohn'sdisease)

Cardiacinsufficiencyandhypertension

Reducedrenalfunction

Hepaticdysfunction

Disturbedhaematopoiesis

Bloodcoagulationdefects

Allergies,hayfever,chronicswellingofnasalmucosa,adenoids,chronicobstructiveairwaydiseaseorbronchial

asthma

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Gastrointestinalbleeding,ulcerationandperforation

GIbleeding,ulcerationorperforation,whichcanbefatal,hasbeenreportedwithallNSAIDsatanytimeduring

treatment,withorwithoutwarningsymptomsoraprevioushistoryofseriousGIevents.

TheriskofGIbleeding,ulcerationorperforationishigherwithincreasingNSAIDdoses,inpatientswithahistoryof

ulcer,particularlyifcomplicatedwithhaemorrhageorperforation(seesection4.3),andintheelderly.Thesepatients

shouldcommencetreatmentonthelowestdoseavailable.

Combinationtherapywithprotectiveagents(e.g.misoprostolorprotonpumpinhibitors)shouldbeconsideredforthese

patients,andalsoforpatientsrequiringconcomitantlow-doseacetylsalicylicacid,orothermedicinalproductslikelyto

increasegastrointestinalrisk.(Seebelowandsection4.5).

PatientswithahistoryofGItoxicity,particularlywhenelderly,shouldreportanyunusualabdominalsymptoms

(especiallyGIbleeding)particularlyintheinitialstagesoftreatment.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchasoralcorticosteroids,anticoagulantssuchaswarfarinorheparin,selectiveserotonin-reuptake

inhibitorsoranti-plateletagentssuchasacetylsalicylicacid(seesection4.5).

WhenGIbleedingorulcerationoccursinpatientsreceivingBuplexRx,thetreatmentshouldbewithdrawn.

NSAIDsshouldbegivenwithcaretopatientswithahistoryofgastrointestinaldisease(ulcerativecolitis,Crohn’s

disease)astheirconditionmaybeexacerbated.(Seesection4.8).

Elderly

TheelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDs,especiallygastrointestinalbleedingand

perforationwhichmaybefatal(seesection4.2).

Cardiovascularandcerebrovasculareffects

Appropriatemonitoringandadvicearerequiredforpatientswithahistoryofhypertensionand/ormildtomoderate

congestiveheartfailureasfluidretention,hypertensionandoedemahavebeenreportedinassociationwithNSAID

therapy.

Clinicaltrialandepidemiologicaldatasuggestthatuseofibuprofen,particularlyathighdoses(2400mgdaily)andin

long -termtreatment,maybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexample

myocardialinfarctionorstroke).Overall,epidemiologicalstudiesdonotsuggestthatlow-doseibuprofen(e.g.

1200mgdaily)isassociatedwithanincreasedriskofmyocardialinfarction.

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheralarterial

disease,and/orcerebrovasculardiseaseshouldonlybetreatedwithibuprofenaftercarefulconsideration.Similar

considerationshouldbemadebeforeinitiatinglonger-termtreatmentofpatientswithriskfactorsforcardiovascular

events(e.g.hypertension,hyperlipidaemia,diabetesmellitusandsmoking).

Skinreactions

Seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs(seesection4.8).Patients

appeartobeathighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthereactionoccurringinthe

majorityofcaseswithinthefirstmonthoftreatment.BuplexRxshouldbediscontinuedatthefirstappearanceofskin

rash,mucosallesions,oranyothersignofhypersensitivity.

Renaleffect

Ibuprofenmaycausetheretentionofsodium,potassiumandfluidinpatientswhohavenotpreviouslysufferedfrom

renaldisordersbecauseofitseffectonrenalperfusion.Thismaycauseoedemaorevenleadtocardiacinsufficiencyor

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AswithotherNSAIDs,theprolongedadministrationofibuprofentoanimalshasresultedinrenalpapillarynecrosis

andotherpathologicalrenalchanges.Inhumans,therehavebeenreportsofacuteinterstitialnephritiswithhaematuria,

proteinuriaandoccasionallynephroticsyndrome.Casesofrenaltoxicityhavealsobeenobservedinpatientsinwhom

prostaglandinsplayacompensatoryroleinthemaintenanceofrenalperfusion.Inthesepatients,administrationof

NSAIDsmaycauseadose-dependentreductioninprostaglandinformationand,secondarily,inrenalbloodflow,which

mayprecipitateovertrenaldecompensation.Patientsatgreatestriskofsufferingthisreactionarethosewithrenal

dysfunction,heartfailure,hepaticdysfunction,thosetakingdiureticsandACEinhibitorsandtheelderly.

DiscontinuationofNSAIDtreatmentisgenerallyfollowedbyrecoverytothepre-treatmentstate.

Otherprecautions

Bronchospasm,urticariaorangioedemamaybeprecipitatedinpatientssufferingfromorwithaprevioushistoryof

bronchialasthma,chronicrhinitis,sinusitis,nasalpolyps,adenoidsorallergicdiseases.

Ibuprofenmaymaskthesignsorsymptomsofaninfection(fever,painandswelling).

Duringthelong -term,high-doseuseofanalgesicsheadachesmayoccurwhichshouldnotbetreatedwithelevated

dosesofthemedicinalproduct.Ingeneralthehabitualintakeofanalgesics,particularlythecombinationuseof

differentanalgesicsubstances,maycausepermanentrenaldamageandariskofrenalfailure(analgesicsnephropathy).

Duringtreatmentwithibuprofen,somecaseswithsymptomsofasepticmeningitis,suchasstiffneck,headache,

nausea,vomiting,feverordisorientationhavebeenobservedinpatientswithexistingauto-immunedisorders(suchas

systemiclupuserythematosus,mixedconnectivetissuedisease).

Ibuprofenmaytemporarilyinhibitplateletaggregationandprolongthebleedingtime.Therefore,patientswith

coagulationdefectsoronanticoagulanttherapyshouldbeobservedcarefully.

Incaseoflong -termtreatmentwithibuprofenaperiodicalmonitoringofhepaticandrenalfunctionaswellasthe

bloodcountisnecessary,especiallyinhighriskpatients.

ConsumptionofalcoholshouldbeavoidedsinceitmayintensifysideeffectsofNSAIDs,especiallyifaffectingthe

gastrointestinaltractorthecentralnervoussystem.

Patientsonibuprofenshouldreporttotheirdoctorsignsorsymptomsofgastro-intestinalulcerationorbleeding,blurred

visionorothereyesymptoms,skinrash,weightgainoroedema.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Concomitantuseofibuprofenandthefollowingsubstancesshouldbeavoided:

Acetylsalicylicacid,lowdose:Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdose

acetylsalicylicacidonplateletaggregationwhentheyaredosedconcomitantly.However,thelimitationsofthesedata

andtheuncertaintiesregardingextrapolationofexvivodatatotheclinicalsituationimplythatnofirmconclusionscan

bemadeforregularibuprofenuse,andnoclinicallyrelevanteffectisconsideredtobelikelyforoccasionalibuprofen

use(seesection5.1)

OtherNSAIDs:Asaresultofsynergisticeffects,theconcurrentuseofseveralNSAIDscanincreasetheriskof

gastrointestinalulcersandhaemorrhage.Co -administrationofibuprofenwithotherNSAIDsshouldthereforebe

avoided(seesection4.4).

Anti-coagulants:NSAIDsmayenhancetheeffectsofanticoagulants,suchaswarfarinorheparin(seesection4.4).In

caseofsimultaneoustreatment,monitoringofthecoagulationstateisrecommended.

Ticlopidin:NSAIDsshouldnotbecombinedwithticlopidineduetoariskofanadditiveeffectintheinhibitionofthe

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Methotrexate:NSAIDinhibitsthetubularsecretionofmethotrexateandcertainmetabolicinteractionscanoccur

resultingindecreasedclearanceofmethotrexate.TheadministrationofBuplexRxwithin24hoursbeforeorafterthe

administrationofmethotrexatecanleadtoanelevatedconcentrationofmethotrexateandanincreaseinitstoxiceffects.

Therefore,concomitantuseofNSAIDsandhighdosesofmethotrexateshouldbeavoided.Also,thepotentialriskof

interactionsinlowdosetreatmentwithmethotrexateshouldbeconsidered,especiallyinpatientswithimpairedrenal

function.Incombinedtreatment,renalfunctionshouldbemonitored.

Ibuprofen(likeotherNSAIDs)shouldbetakenonlywithcautionincombinationwiththefollowingsubstaces:

Moclobemide:Enhancestheeffectofibuprofen.

Phenytoin,lithium:Co -administrationofBuplexRxwithphenytoinorlithiumpreparationscanincreasetheserum

levelofthesemedicinalproducts.Checkingtheserumlithiumlevelisnecessaryanditisrecommendedtocheckthe

serumphenytoinlevels.

Cardiacglycosides(e.gdigoxin):NSAIDsmayexacerbatecardiacfailure,reduceGFRandincreaseplasmalevelsof

cardiacglycosides.Monitoringofserumdigoxinisrecommended.

Diurectisandantihypertensives:DiureticsandACE-inhibitorscanincreasethenephrotoxicityofNSAIDs.NSAIDs

canreducetheeffectofdiureticsandantihypertensives,includingACE-inhibitorsandbeta-blockers.Inpatientswith

reducedkidneyfunction(e.g.dehydratedpatientsorelderlypatientswithreducedkidneyfunction),theconcomitant

useofanACEinhibitorandangiotensionIIantagonistwithacyclooxygenase-inhibitingmedicinalproductcanleadto

furtherimpairmentofkidneyfunctionandthroughtoacuterenalfailure.Thisisusuallyreversible.Suchcombination

shouldthereforeonlybeusedwithcaution,especiallyinelderlypatients.Thepatientshavetobeinstructedtodrink

sufficientliquidandperiodicmonitoringofthekidneyvaluesshouldbeconsideredforthetimeimmediatelyafterthe

startofthecombinationtherapy.

TheconcomitantadministrationofBuplexRxandpotassium -sparingdiureticsorACE-inhibitorscanresultin

hyperkalaemia.Carefulmonitoringofpotassiumlevelsisnecessary.

Captopril:Experimentalstudiesindicatethatibuprofencounteractstheeffectofcaptoprilofincreasedsodium

excretion.

Aminoglycosides:NSAIDscanslowdowntheeliminationofaminoglycosidesandincreasetheirtoxicity.

Selectiveserotoninreuptakeinhibitors(SSRIs):Increasedriskofgastrointestinalbleeding(seesection4.4).

Ciclosporine:Theriskofkidneydamagebyciclosporinisincreasedbytheconcomitantadministrationofcertain

NSAIDs.Thiseffectcannotberuledoutforthecombinationofciclosporineandibuprofen,either.

Cholestyramine:Concomitanttreatmentwithcholestyramineandibuprofenresultsinprolongedandreduced(25%)

absorptionofibuprofen.Themedicinalproductsshouldbeadministeredwithatleastonehourinterval.

Tacrolimus:Elevatedriskofnephrotoxicity.

Zidovudine:ThereisevidenceofanincreasedriskofhaemarthrosisandhaematomainHIVpositivehaemophilia

patientsreceivingconcurrenttreatmentwithzidovudineandibuprofen.Theremaybeanincreasedriskof

haematotoxicityduringconcomitantuseofzidovudineandNSAIDs.Bloodcounts1 -2weeksafterstartinguse

togetherarerecommended.

Ritonavir:MayincreasetheplasmaconcentrationsofNSAIDs.

Mifepristone:IfNSAIDsareusedwithin8 -12daysaftermifepristoneadministrationtheycanreducetheeffectof

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Probenecidorsulfinpyrazone:Maycauseadelayintheeliminationofibuprofen.Theuricosuricactionofthese

substancesisdecreased.

Quinoloneantibiotics:PatientstakingNSAIDsandquinolonesmayhaveanincreasedriskofdevelopingconvulsions.

Sulphonylureas:NSAIDscanincreasethehypoglycemiceffectofsulphonylureas.Inthecaseofsimultaneous

treatment,monitoringofbloodglucoselevelsisrecommended.

Corticosteroids:Increasedriskofgastrointestinalulcerationorbleeding(seesection4.4).

Anti-plateletaggregationagents(e.g.clopidogrelandticlopidine):Increasetheriskofgastrointestinalbleeding(see

section4.4).

Alcohol,bisphosphonatesandoxpentifylline(pentoxyflline):MaypotentiatetheGIside-effectsandtheriskofbleeding

andulceration.

Baclofen:Elevatedbaclofentoxicity.

4.6Fertility,pregnancyandlactation

Pregnancy

Inhibitionofprostaglandinsynthesismayadverselyaffectthepregnancyand/ortheembryo/foetaldevelopment.Data

fromepidemiologicalstudiessuggestanincreasedriskofmiscarriageandofcardiacmalformationandgastroschisis

afteruseofaprostaglandinsynthesisinhibitorinearlypregnancy.Theabsoluteriskforcardiovascularmalformation

wasincreasedfromlessthan1%,uptoapproximately1.5%.Theriskisbelievedtoincreasewithdoseanddurationof

therapy.Inanimals,administrationofaprostaglandinsynthesisinhibitorhasbeenshowntoresultinincreasedpre-and

post-implantationlossandembryo-foetallethality.Inaddition,increasedincidencesofvariousmalformations,

includingcardiovascular,havebeenreportedinanimalsgivenaprostaglandinsynthesisinhibitorduringthe

organogeneticperiod.Duringthefirstandsecondtrimesterofpregnancy,BuplexRxshouldnotbegivenunlessclearly

necessary.IfBuplexRxisusedbyawomanattemptingtoconceive,orduringthefirstandsecondtrimesterof

pregnancy,thedoseshouldbekeptaslowanddurationoftreatmentasshortaspossible.

Duringthethirdtrimesterofpregnancy,allprostaglandinsynthesisinhibitorsmayexposethefoetusto:

cardiopulmonarytoxicity(withprematureclosureoftheductusarteriosusandpulmonaryhypertension);

renaldysfunction,whichmayprogresstorenalfailurewitholigo-hydramniosis;

themotherandtheneonate,attheendofpregnancyto:

possibleprolongationofbleedingtime,ananti-aggregatingeffectwhichmayoccurevenatverylowdoses.

inhibitionofuterinecontractionsresultingindelayedorprolongedlabour.

ConsequentlyBuplexRxiscontraindicatedduringthelasttrimesterofpregnancy.

Lactation

Ibuprofenisexcretedinbreastmilk,butwiththerapeuticdosesduringshorttermtreatmenttheriskforinfluenceon

infantseemsunlikely.If,however,longertreatmentisprescribed,earlyweaningshouldbeconsidered.

Fertility

Theuseofibuprofenmayimpairfertilityandisnotrecommendedinwomenattemptingtoconceive.Inwomenwho

havedifficultiesconceivingorwhoareundergoinginvestigationofinfertility,withdrawalofibuprofenshouldbe

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4.7Effectsonabilitytodriveandusemachines

Ibuprofengenerallyhasnoadverseeffectsontheabilitytodriveandusemachinery.Howeversinceathighdosageside

effectssuchasfatigue,somnolence,vertigo(reportedascommon)andvisualdisturbances(reportedasuncommon)

maybeexperienced,theabilitytodriveacaroroperatemachinerymaybeimpairedinindividualcases.Thiseffectis

potentiatedbysimultaneousconsumptionofalcohol.

4.8Undesirableeffects

Themostcommonlyobservedadverseeventsaregastrointestinalinnature.Pepticulcers,perforationorGIbleeding,

sometimesfatal,particularlyintheelderly,mayoccur(seesection4.4).Nausea,vomiting,diarrhoea,flatulence,

constipation,dyspepsia,abdominalpain,melaena,heamatemesis,ulcerativestomatits,exacerbationofcolitisand

Crohn’sdisease(seesection4.4)havebeenreportedfollowingadministration.Lessfrequently,gastritishasbeen

observed.

Undesirableeffectsaremostlydose-dependent.Especiallytheriskfortheoccurrenceofgastrointestinalbleedings

dependsonthedosagerangeanddurationofthetreatment.Otherknownriskfactors,seesection4.4.

Clinicaltrialandepidemiologicaldatasuggestthatuseofibuprofen,particularlyathighdose(2400mgdaily)andin

longtermtreatmentmaybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexample

myocardialinfarctionorstroke)(seesection4.4).

Oedema,hypertension,andcardiacfailure,havebeenreportedinassociationwithNSAIDtreatment.

Theundesirableeffectsarelessfrequentwhenthemaximumdailydoseis1200mg.

Assessmentofadversereactionsisnormallybasedonthefollowingoccurrencefrequency:

Verycommon(1/10)

Common(1/100to<1/10)

Uncommon(1/1,000to<1/100)

Rare(1/10,000to<1/1,000)

Veryrare(<1/10,000),notknown(cannotbeestimatedfromtheavailabledata)

Investigations

Rare: increaseofbloodureanitrogen,serumtransaminasesandalkalinephosphatase,decreasein

haemoglobinandhaematocritvalues,inhibitionofplateletaggregation,prolongedbleedingtime,

decreaseofserumcalcium,increaseinserumuricacid

Cardiacdisorders

Veryrare: palpitations,heartfailure,myocardialinfarction,acutepulmonaryoedema,oedema,

Bloodandlymphaticsystemdisorders

Veryrare: haematopoieticdisorders(anaemia,leucopoenia,thrombocytopenia,pancytopenia,agranulocytosis).

Thefirstsymptomsorsignsmayinclude:fever,sorethroat,surfacemouthulcers,flu-likesymptoms,

severefatigue,nasalandskinbleeding

Nervoussystemdisorders

Common: headache,somnolence,vertigo,fatigue,agitation,dizziness,insomnia,irritability

Veryrare: asepticmeningitis

Eyedisorders

Uncommon: visualdisturbances

Rare: toxicamblyopia

Earandlabyrinthdisorders

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Respiratory,thoracicandmediastinaldisorders

Uncommon: rhinitis,bronchospasm

Gastrointestinaldisorders

Verycommon: gastrointestinaldisorders,suchasheartburn,dyspepsia,abdominalpainandnausea,vomiting,

flatulence,diarrhoea,constipation

Common: gastrointestinalulcers,sometimeswithbleedingandperforation(seesection4.4),occultbloodloss

whichmayleadtoanaemia,melaena,haematemesis,ulcerativestomatitis,colitis,exacerbationof

inflammatoryboweldisease,complicationsofcolonicdiverticula(perforation,fistula)

Uncommon: gastritis

Veryrare: oesophagitis,pancreatitis,intestinalstrictures

Renalandurinarydisorders

Uncommon: developmentofoedemaespeciallyinpatientswitharterialhypertensionorrenalinsufficiency,

nephroticsyndrome,interstitialnephritiswhichcanbeassociatedwithrenalfailure

Veryrare: renalpapillarynecrosisinlong -termuse(seesection4.4)

Skinandsubcutaneoustissuedisorders

Uncommon: photosensitivity

Veryrare: severeformsofskinreactions(erythemamultiforme,exfoliativedermatitis,bullousreactions

includingStevens -Johnsonsyndromeandtoxicepidermalnecrolysis,alopecia,necrotisingfascitis

Vasculardisorder

Veryrare: hypertension

Immunesystemdisorders

Uncommon: hypersensitivityreactionssuchasurticaria,pruritus,purpuraandexanthemaaswellasasthmaattacks

(sometimeswithhypotension)

Rare: lupuserythematosussyndrome

Veryrare: severehypersensitivityreactions.Thesymptomsmayinclude:facialoedema,swellingofthetongue,

internallaryngealswellingwithconstrictionoftheairways,dyspnoea,tachycardia,fallofblood

pressuretothepointoflife-threateningshock

Hepatobiliarydisorders

Veryrare: liverdysfunction,liverdamage,especiallyinlong -termuse,liverfailure,acutehepatitis,jaundice

Psychiatricdisorder

Rare: depression,confusion,hallucinations

4.9Overdose

Symptoms

MostpatientswhohaveingestedclinicallyimportantamountsofNSAIDswilldevelopnomorethannausea,vomiting,

epigastricpain,ormorerarely,diarrhoea.Tinnitus,headache,dizziness,vertigoandgastrointestinalbleedingmayalso

occur.Inmoreseriouspoisoning,toxicityisseeninthecentralnervoussystem,manifestingasdrowsiness,

occasionallyexcitationanddisorientationorcoma.Occasionallypatientsdevelopconvulsions.Childrenmayalso

developmyocloniccramps.Inseriouspoisoningmetabolicacidosismayoccurandtheprothrombintime/INRmaybe

prolonged,probablyduetotheactionsofcirculatingclottingfactors.Acuterenalfailure,liverdamage,hypotension,

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Treatment

Treatmentshouldbesymptomaticandsupportiveandincludethemaintenanceofaclearairwayandmonitoringof

cardiacandvitalsignsuntilstable.Gastricemptyingororaladministrationofactivatedcharcoalisindicatedifthe

patientpresentswithinonehourofingestionofmorethan400mgperkgofbodyweight.IfBuplexRxhasalready

beenabsorbed,alkalinesubstancesshouldbeadministeredtopromotetheexcretionoftheacidibuprofenintheurine.

Iffrequentorprolonged,convulsionsshouldbetreatedwithintravenousdiazepamorlorazepam.Bronchodilators

shouldbegivenforasthma.Nospecificantidoteisavailable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Anti-inflammatoryandantirheumaticproducts,non-steroids;propionicacidderivatives.

ATCcode:M01AE01

IbuprofenisaNSAIDthatpossessesanti-inflammatory,analgesicandantipyreticactivity.Animalmodelsforpainand

inflammationindicatethatibuprofeneffectivelyinhibitsthesynthesisofprostaglandins.Inhumans,ibuprofenreduces

painpossiblycausedbyinflammationorconnectedwithit,swellingandfever.Ibuprofenexertsaninhibitoryeffecton

prostaglandinsynthesisbyinhibitingtheactivityofcyclo-oxygenase.Inadditionibuprofenhasaninhibitoryeffecton

ADP(adenosinediphosphate)orcollagen-stimulatedplateletaggregation.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

aredosedconcomitantly.Inonestudy,whenasingledoseofibuprofen400mgwastakenwithin8hourbeforeor

within30minafterimmediatereleaseacetylsalicylicaciddosing(81mg),adecreasedeffectofASAontheformation

ofthromboxaneorplateletaggregationoccurred.However,thelimitationsofthesedataandtheuncertaintiesregarding

extrapolationofexvivodatatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofen

use,andnoclinicallyrelevanteffectisconsideredtobelikelyforoccasionalibuprofenuse.

Ibuprofeninhibitsprostaglandinsynthesisintheuterus,therebyreducingintrauterinerestandactivepressure,the

periodicuterinecontractionsandtheamountofprostaglandinsreleasedintothecirculation.Thesechangesareassumed

toexplainthealleviationofmenstrualpain.Ibuprofeninhibitsrenalprostaglandinsynthesiswhichcanleadtorenal

insufficiency,fluidretentionandheartfailureinriskpatients(seesection4.3).

Prostaglandinsareconnectedwithovulationandtheuseofmedicinalproductsinhibitingprostaglandinsynthesismay

thereforeaffectthefertilityofwomen(seesection4.4,4.6and5.3).

5.2Pharmacokineticproperties

Absorption

Ibuprofenisrapidlyabsorbedfromthegastrointestinaltract,peakserumconcentrationsoccurring1 -2hoursafter

administration.

Distribution

Ibuprofenisrapidlydistributedthroughoutthewholebody.Theplasmaproteinbindingisapproximately99%.

Metabolism

Ibuprofenismetabolisedintheliver(hydroxylation,carboxylation).

Elimination

Theeliminationhalf-lifeisapproximately2.5hoursinhealthyindividuals.Pharmacologicallyinactivemetabolitesare

mainlyexcreted(90%)bythekidneysbutalsoinbile.

5.3Preclinicalsafetydata

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Ibuprofen'ssubchronicandchronictoxicitywasmainlyshownbyanimaltestsasgastrictractdamageandulcers.

Thevitroandinvivotestshavenotshownanyclinicallysignificantsignsaboutibuprofen'smutagenicity.Furthermore

nocarcinogeniceffectshavebeenobservedinmiceandrats.

Ibuprofeninhibitsovulationinrabbitsandimpairsimplantationinvariousanimalspecies(rabbit,rat,andmouse).In

reproductiontestsundertakenwithratsandrabbits,ibuprofenpassedacrosstheplacenta.Whenusingdosestoxictothe

mother,malformationsoccurmorefrequently(i.e.ventricularseptumdefects).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore

Cellulose,microcrystalline

Silica,colloidalanhydrous

Hydroxypropylcellulose

Sodiumlaurylsulfate

Croscarmellosesodium

Talc

Filmcoating(Opadry(white)06B28499)

Hypromellose

Macrogol400

Titaniumdioxide(E171).

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

OpaquePVC/Aluminiumblisterpacks.

ClearPVC/Aluminiumblisterpacks.

Tabletcontainers(polyethylene)withpolypropylenecaps.

Packsizes:

Blisters:6,10,12,20,24,30,50,60,90,100and250film -coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

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7MARKETINGAUTHORISATIONHOLDER

ActavisGroupPTCehf

Reykjavikurvegi76-78

220Hafnarfjordur

Iceland

8MARKETINGAUTHORISATIONNUMBER

PA1380/088/004

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

July2009

10DATEOFREVISIONOFTHETEXT

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