BREXIDOL

Main information

  • Trade name:
  • BREXIDOL Tablets Effervescent 20mg Milligram
  • Dosage:
  • 20mg Milligram
  • Pharmaceutical form:
  • Tablets Effervescent
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BREXIDOL Tablets Effervescent 20mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0743/010/003
  • Authorization date:
  • 30-08-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0743/010/003

CaseNo:2028971

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

Trinity-ChiesiPharmaceuticals

CheadleRoyalBusinessPark,Highfield,SK83GY,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

BREXIDOL20mgEffervescentTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom19/10/2006until31/08/2007.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Brexidol20mgEffervescenttablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachEffervescenttabletcontains20mgpiroxicam(asbetadex).

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Effervescenttablet

Paleyellow,circulartabletwithaflattenedendsurfaceandamedianscorelineononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthesymptomatictreatmentofosteoarthritis.

Asananti-inflammatoryanalgesicinthetreatmentof:

arthritisandrelateddisorders(e.g.,rheumatoidarthritis,ankylosingspondylitis)

acutemusculoskeletaldisorders(e.g.,bursitis,tendinitis)

acutegout

primarydysmenorrhoea

post-operativepain

4.2Posologyandmethodofadministration

RouteofAdministration

Fororaluse

Alloweachtablettocompletelydissolveinaglassofwaterbeforedrinkingcontentsofglass.

Tohalveatablet,placeitonaflatsurfacewiththescorelinefacingupandcutalongthescorelineusingatableknife.

DosageRecommendations

Adults

Therecommendeddoseisoneeffervescenttablet(20mgpiroxicam),asonesingledailydose,preferablywithorafter

food.

Children

Theuseofpiroxicaminchildrenisnotrecommended.

TheElderly

Inelderlypatients,itmaybenecessarytoreducethedosage(halfaneffervescenttablet),andlimitthedurationof

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NSAIDsshouldbeusedwithparticularcautioninelderlypatientswhoaremorepronetoadverseevents.Thelowest

dosecompatiblewithadequate,safe,clinicalcontrolshouldbeemployedandthepatientshouldbemonitoredfor

gastrointestinalbleedingfor4weeksfollowinginitiationofNSAIDtherapy(seesection4.4).

Treatmentshouldbereviewedatregularintervalsanddiscontinuedifnobenefitisseenorintoleranceoccurs.

4.3Contraindications

Brexidol20mgEffervescentTabletsshouldnotbegiventopatientswith:

knownhypersensitivitytoanyoftheconstituentsorpiroxicam

ahistoryof,oractive,pepticulcerationorrecurrentpepticulceration

ahistoryofhypersensitivityreactions(eg.,bronchospasm,asthma,rhinitis,urticaria),inresponsetopiroxicam,

aspirin,ibuprofenorothernon-steroidalanti-inflammatorydrugs

porphyria

Brexidol20mgEffervescentTabletscontainaspartameasasweetener.Therefore,useiscontra-indicatedin

phenylketonuricpatients.

Brexidol20mgEffervescentTabletsarecontra-indicatedinchildren.

4.4Specialwarningsandprecautionsforuse

Undesirableeffectsmaybeminimisedbyusingtheminimumeffectivedosefortheshortestpossibleduration.Patients

onprolongedtherapywithNSAIDsshouldundergoregularmedicalsupervisiontomonitorforadverseevents.

Toavoidtheriskofincreasedsideeffects,piroxicamshouldnotbegivenwithothernon-steroidalanti-inflammatory

agents.

ElderlypatientsareatincreasedriskoftheseriousconsequencesofadverseeffectsofNSAIDs.Theytendtobe

susceptibletogastrointestinalbleedingandtheyarealsolikelytosufferfromimpairedhepatic,renalorcardiac

function.

Therefore,NSAIDsshouldonlybegivenafterotherformsoftreatmenthavebeencarefullyconsidered.Prolongeduse

ofNSAIDsintheelderlyisnotrecommended.Whereprolongedtherapyisrequired,patientsshouldbereviewed

regularly.

Piroxicamshouldbeusedwithcautioninpatientswithahistoryofgastrointestinaldiseaseorinflammatorybowel

diseaseandshouldbewithdrawnifpepticulcerationorgastrointestinalbleedingoccurs.

Inpatientswithrenal,cardiacorhepaticimpairment,cautionisrequiredsincetheuseofNSAIDsmayresultin

deteriorationofrenalfunction.Assessmentofrenalfunctioninsuchpatients,shouldoccurpriortotheinitiationof

therapyandregularlythereafter.NSAIDsshouldbegivenwithcaretopatientswithheartfailureorhypertensionsince

oedemahasbeenreportedinassociationwithNSAIDadministration.

Piroxicammaycauseadecreaseinplateletaggregationandprolongationofbleedingtime.Thiseffectshouldbekept

inmindwhenbleedingtimesaredetermined.

AsNSAIDscaninterferewithplateletfunction,theyshouldbeusedwithcautioninpatientswithintracranial

haemorrhageandbleedingdiathesis.

Cautionisrequiredifpiroxicamisadministeredtopatientssufferingfromorwithaprevioushistoryofbronchial

asthmasinceNSAIDshavebeenreportedtocausebronchospasminsuchpatients.

Therearereportsofreversibleelevationofbloodurea,nitrogenandcreatinine.

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inhibitsynthesisofrenalprostaglandinthatplaysasupportiveroleinmaintainingrenalperfusioninpatientswith

reducedbloodvolumeandrenalbloodflow.Insuchpatients,administrationofaNSAIDmayprecipitateovertrenal

decompensation,whichisfollowedbyrecoverytothepre-treatmentstateupondiscontinuationofNSAIDtherapy.

Patientsatgreatestriskofsuchareactionarethosewithcongestiveheartfailure,livercirrhosis,nephroticsyndromeor

overtrenaldisease.SuchpatientsshouldbemonitoredcarefullywhilstreceivingNSAIDtherapy.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Careshouldbetakeninpatientstreatedwithanyofthedrugsmentionedbelowbecause,aswithotherNSAIDs,

piroxicamhasthepotentialtoinducethefollowinginteractions.

Anti-hypertensives

Theremaybeareductionintheeffectofanti-hypertensives.

Diuretics

Piroxicammaycausesodium,potassiumandfluidretention,andmayinterferewiththenatriureticactionofdiuretic

drugscausingareductioninthediureticeffect.DiureticscanincreasetheriskofnephrotoxicityofNSAIDs.These

propertiesshouldbekeptinmindwhentreatingpatientswithcompromisedcardiacfunctionorhypertension,toavoida

possibleworseningoftheseconditions.

CardiacGlycosides

NSAIDsmayexacerbatecardiacfailure,reduceGFRandincreaseplasmacardiacglycosideslevels.

Concomitantadministrationofantacidshadnoeffectonpiroxicamplasmalevels,nordidconcurrenttherapyof

piroxicamwithdigoxinordigitoxinaffecttheplasmalevelsofeitherdrug.

Anticoagulants,SulphonamidesandHydantoins

Piroxicamishighlyproteinbound,andtherefore,itmightbeexpectedtodisplaceotherproteinbounddrugseg.,

anticoagulants,sulphonamidesandhydantoinssuchasphenytoin.Patientsmustbemonitoredcloselyforchangein

dosagerequirementswhengivingBrexidoltopatientsalreadyreceivingotherhighlyproteinbounddrugs.

ItisconsideredunsafetotakeNSAIDsincombinationwithwarfarinorheparinunlessunderdirectmedical

supervision.Bleedinghasbeenreportedrarelywhenpiroxicamhasbeenadministeredtopatientsbeingtreatedwith

coumarin-typeanticoagulantdrugs.SuchpatientsshouldbemonitoredcloselyifBrexidolandoralanticoagulantsare

administeredtogether.

OtherAnalgesics

Humanstudieshaveshownthatconcomitantadministrationofpiroxicamandaspirinreducedtheplasmalevelsof

piroxicamtoabout80%ofthenormalvalue.

TheuseofpiroxicamwithaspirinoritsconcurrentusewithotherNSAIDs,increasesthepotentialforadversereactions

andthereforeconcomitantuseoftwoormoreNSAIDsisnotrecommended.

Cimetidine

Thereissomeevidencethataslightbutsignificantincreaseinabsorptionofpiroxicammayoccurfollowing

administrationofcimetidine-withnosignificantchangesineliminationrateconstantsorhalf-life.Itisunlikelythat

thissmallincreaseinabsorptionisofclinicalsignificance.

Lithium

NSAIDs,includingpiroxicam,havebeenreportedtodecreasetheeliminationoflithium.Itisrecommendedthatthe

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QuinoloneAntibiotics

AnimaldataindicatethatNSAIDscanincreasetheriskofconvulsionsassociatedwithquinoloneantibiotics.Patients

takingNSAIDsandquinolonesmayhaveanincreasedriskofdevelopingconvulsions.

Mifepristone

IncommonwithotherNSAIDs,piroxicamshouldbeavoidedforatleast8to12daysfollowingmifepristone

administrationasNSAIDscanreducetheeffectofmifepristone.

Methotrexate

ThereisdecreasedeliminationofmethotrexatewithNSAIDs.

Ciclosporin

NSAIDsmayincreasecyclosporinnephrotoxicityasaresultoftheireffectonrenalprostaglandins.

Corticosteroids

Thereisincreasedriskofgastrointestinalbleedingwithcorticosteroids.

Aminoglycosides

Reductioninrenalfunctioninsusceptibleindividuals,decreasedeliminationofaminoglycosidesandincreasedplasma

concentrationshavebeenreported.

Probenecid

ReductioninmetabolismandeliminationofNSAIDandmetabolitesoccurswithprobenecid.

OralHypoglycaemicAgents

Inhibitionofmetabolismofsulphonylureadrugs,prolongedhalf-lifeandincreasedriskofhypoglycaemiaisknownto

occurwithoralhypoglycaemicagents.

4.6Pregnancyandlactation

Althoughnoteratogeniceffectshavebeendemonstratedinanimaltoxicologystudies,theuseofNSAIDsduring

pregnancyshould,ifpossible,beavoided.CongenitalabnormalitieshavebeenreportedinassociationwithNSAID

administrationinman.However,thesearelowinfrequencyanddonotappeartofollowanydiscerniblepattern.

Piroxicaminhibitsprostaglandinsynthesisandreleasethroughareversibleinhibitionofthecyclo-oxygenaseenzyme.

Thiseffect,aswithotherNSAID,isassociatedwithanincreasedincidenceofdystociaanddelayedparturitionin

pregnantanimalswhendrugadministrationwascontinuedintolatepregnancy.NSAIDsarealsoknowntoinduce

closureoftheductusarteriosusininfantsandtherefore,useinlatepregnancyshouldbeavoided.

Astudyindicatesthatpiroxicamisfoundinbreastmilkatabout1%to3%ofthematernalplasmaconcentrations.No

accumulationofpiroxicamoccurredinmilkrelativetothatinplasmaduringtreatmentforupto52days.Brexidolis

notrecommendedforuseinnursingmothersbecauseclinicalsafetyinneonateshasnotbeenestablished.

4.7Effectsonabilitytodriveandusemachines

Piroxicamcanalterthestateofalertnesstosuchanextentthatdrivingvehiclesorperformingactivitieswhichrequire

quickreflexes(suchasoperatingmachinery),maybeaffected.

Sinceswolleneyes,blurredvisionandeyeirritationhavebeenreportedinassociationwiththeuseofpiroxicam,and

dizziness,drowsinessorheadachesarepossiblesideeffectsassociatedwithtakingNSAIDs,patientsshouldbewarned

totakecarewhenundertakingsuchactivities.

Althoughroutineophthalmologyandslit-lampexaminationshavenotshownevidenceofocularchangessuch

examinationsshouldbeperformedifthesesymptomsdevelop.

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Gastrointestinal

Gastrointestinalsymptomsassociatedwithpiroxicamadministrationarethemostcommonsideeffects,butinmost

casesdonotinterferewithcontinuationoftherapy.Theseincludeulcerativestomatitis,anorexia,epigastricor

abdominaldiscomfortorpain,nausea,constipation,flatulence,diarrhoeaandindigestion,vomiting,dyspepsia,melaena

andhaematemesis.

Gastriculceration,duodenalulcerandgastrointestinalperforationandgastrointestinalbleeding,inrarecasesfatal,have

beenreportedwithpiroxicam.Long-termadministrationofpiroxicaminadoseof30mgperdayormorecarriesan

increasedriskofgastrointestinalsideeffects.

HypersensitivityReactions

Therearerarereportsofpiroxicamcausingcutaneoushypersensitivityreactionssuchasrashorpruritus,urticaria,

angioedema,onycholysisoralopecia.AswithotherNSAIDs,epidermalnecrolysis(Lyell'sdisease),Stevens-Johnson

syndromeorvesiculo-bullousreactionsmayoccurrarely.

Thesereactionsmayalsoconsistofrespiratorytractreactivitycomprisingofasthma,aggravatedasthma,bronchospasm

ordyspnoea.

Theremaybeothernon-specificallergicreactionsandanaphylaxis.

Otherhypersensitivityreactionssuchasvasculitisandserumsicknesshavebeenrarelyreported.

DermatologicalReaction

Photosensitivityreactionsoccurinfrequently.

Renal

Rarely,NSAIDsmaycauseinterstitialnephritis,glomerulo-nephritis,nephroticsyndromeandrenalfailure.

HaematologicalReactions

Decreasesinhaemoglobinandhaematocritintheabsenceofobviousgastrointestinalbleedinghaveoccurredand

anaemiahasbeenreported,ashavethrombocytopenia,non-thrombocytopenicpurpura(Henoch-Schoenlein),

leucopeniaandeosinophilia.Therearerarereportsofaplasticanaemia,haemolyticanaemiaandepistaxis.

Hepatic

Changesinvariousliverfunctionparametershavebeenseenwithpiroxicamand,aswithotherNSAIDs,somepatients

mayshowanincreaseinserumtransaminaseconcentrationduringpiroxicamtreatment;also,severehepaticreactions,

includingjaundiceandcasesoffatalhepatitishaveoccurred.

Eventhoughsucheventsarerare,whereabnormalliverfunctiontestspersistorworsenorclinicalsignsconsistentwith

liverdiseasedevelop,ortherearesystemicmanifestations(suchasarashoreosinophilia),treatmentshouldbe

discontinued.

Cardiovascular

AswithotherNSAIDs,oedema(mainlyoftheankle),hasbeenreportedinsomepatients;thepossibilityof

precipitatingcongestivecardiacfailureintheelderlyorthosewithcompromisedcardiacfunctionshouldbe

remembered.

Equally,elderly,frailordebilitatedpatientsrequirecarefulsupervisionbecausetheymaytoleratesideeffectslesswell;

theelderlyrequirecautionsincetheyaremorelikelytohaveimpairedrenal,hepaticorcardiacfunction.

NeurologicalandSpecialSenses

CNSeffectsincludingdizziness,headache,somnolence,insomnia,depression,nervousness,hallucinations,mood

alterations,dreamabnormalities,mentalconfusion,paraesthesias,vertigo,visualdisturbances,opticneuritis,tinnitus,

malaise,fatigueanddrowsinesshaveallbeenreported.

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positiveANAorhearingimpairmenthaveallbeenreported. Irish Medicines Board

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4.9Overdose

Symptoms

Themostlikelysymptomsofoverdoseareheadache,vomiting,drowsiness,dizzinessandfainting.

Management

IntheeventofanoverdosewithBrexidol,supportiveandsymptomaticmanagementisnecessaryandmayinclude

gastriclavageandtheuseoforalactivatedcharcoaltoreduceabsorptionofpiroxicam.Thecorrectionofsevere

electrolyteabnormalitiesmayneedtobeconsidered.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Brexidolisaninclusioncomplexofpiroxicamandbeta-cyclodextrin(piroxicambetadex).Itisanon-steroidalanti-

inflammatorydrug.

Thefasterdissolutioncharacteristicsofpiroxicambetadex(about100%in10minutes)withrespecttopiroxicam

alone,resultsinaquickerabsorptionoftheactiveingredientandpromotesamorerapidonsetofanalgesicaction(see

Pharmacokinetics).

5.2Pharmacokineticproperties

AsaNSAID,piroxicamiswellabsorbedafteroraladministrationandisextensivelymetabolisedbytheliverwith

eliminationoccurringviathekidneys.

Thedrughasaplasmahalf-lifeofabout50hourswiththemaintenanceofplasmalevelsforupto24hours.Steady

statelevelsarereachedin7to12daysandmaintainedwithlittlechangeforuptoayearoftreatment.

Theabsorptionofpiroxicamfrompiroxicambetadexismorerapidthanthatofpiroxicamalone,sothatthetimetaken

toreachthemaximumplasmaconcentration(T ),ismuchshorter;clinicallythisisreflectedbyamorerapidonsetof

acuteanalgesiaaftersingledoses.

Studiesonhealthyvolunteersdemonstratedthat,aftersingleoraladministrationatequivalentdoses(20mgas

piroxicam),piroxicamfrompiroxicambetadexwasabsorbedatleast2timesfasterthanitwasastheplaindrug.The

maximumplasmaconcentration(C )ofpiroxicamwasreachedwithin30to60minuteswithpiroxicambetadexand

washigherthanthatobtainedafter2hourswithplainpiroxicam.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicology,genotoxicologyandtoxicologyofreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumglycinecarbonate

Fumaricacid(E.297)

Aspartame(E.951)

Macrogol6000

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6.2Incompatibilities

Notapplicable.

6.3ShelfLife

24months.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

Theeffervescenttabletsareenclosedinstripscomposedof30µmaluminium/35gmpolyethylene.

Thestripsareboxedincardboardcartonscontaining10or20effervescenttabletsandauserleaflet.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TrinityChiesiPharmaceuticalsLtd

CheadleRoyalBusinessPark

Highfield

Cheadle

SK83GY

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA743/10/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:30 th

August2002

10DATEOFREVISIONOFTHETEXT

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