GENOXEN

Main information

  • Trade name:
  • GENOXEN Tablets 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • GENOXEN Tablets 500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0073/090/002
  • Authorization date:
  • 04-07-1986
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0073/090/002

CaseNo:2049103

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

AntigenPharmaceuticalsLtd

ChandlerHouse,CastleStreet,Roscrea,CoTipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Genoxen500mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom28/01/2009until03/07/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Genoxen500mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains500mgofNaproxen.

Excipient:Eachtabletcontains62mglactosemonohydrate.

Forafulllistofexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet.

Yellow,capletshapeduncoatedtabletembossedwith'N500'ononesideandbisectinglineontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Asananti-inflammatoryanalgesicinthemanagementofosteoarthritis,rheumatoidarthritis(includingjuvenile

rheumatoidarthritisorStill'sdisease),ankylosingspondylitisandacutegout.Alsointenosynovitis,fibrositis,sprains

andvarioussofttissueinjuries.

4.2Posologyandmethodofadministration

Genoxentabletsarefororaladministrationonly.

Adults:

Forrheumatoidarthritis,osteoarthritisandankylosingspondylitis,theusualdoseis500mgto1gdailytakenintwo

dosesat12-hourintervalsorasasingleadministrationoftwotablets,morningorevening.Thedoseof1gperday

shouldnotbegivenformorethansixmonths.

Inthefollowingcases,aloadingdoseof750mgor1gperdayfortheacutephaseisrecommended:

Inpatientsreportingseverenight-timepainand/ormorningstiffness.

InpatientsbeingswitchedtoGenoxenfromahighdoseofanotheranti-rheumaticcompound.

Inosteoarthritiswherepainisthepredominantsymptom.

Forthepatientwhorequires750mgperday,thesizeofthemorningandeveningdosescanbeadjustedonthebasisof

thepredominantsymptoms,i.e.night-timepainormorningstiffness.

Inacutegout,therecommendeddosageis750mgatonce,then250mgeveryeighthoursuntiltheattackhaspassed.

Forthetreatmentofacutemusculoskeletaldisorders,therecommendeddoseis500mginitiallyfollowedby250mgat

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Useintheelderly:

Studiesindicatethatalthoughtotalplasmaconcentrationofnaproxenisunchanged,theunboundplasmafractionof

naproxenisincreasedintheelderly.TheimplicationofthisfindingforGenoxendosingisunknown.Aswithother

drugsusedintheelderly,itisprudenttousethelowesteffectivedose.Fortheeffectofreducedeliminationinthe

elderly,refertothesection'Useinpatientswithimpairedrenalfunction'.

Children:

Naproxeniseffectiveinthetreatmentofjuvenilerheumatoidarthritisinchildrenover5yearsofageatadoseof

10mg/kg/daytakenintwodosesat12-hourintervals.Naproxenisnotrecommendedforuseinanyotherindicationin

childrenunder16yearsofage.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.4)

4.3Contraindications

Useinactivepepticulcerationorgastro-intestinalinflammation.Historyofgastrointestinalbleedingorperforation,

relatedtopreviousNSAIDstherapy.Active,orhistoryofrecurrentpepticulcer/haemorrhage(twoormoredistinct

episodesofprovenulcerationorbleeding).Severeheartfailure.Hypersensitivitytonaproxenandnaproxensodium

formulations.Sincethepotentialexistsforcross-sensitivityreactions,Genoxenshouldnotbegiventopatientsin

whomaspirinorothernon-steroidalanti-inflammatory/analgesicdrugsinduceasthma,rhinitisorurticaria.

4.4Specialwarningsandprecautionsforuse

TheuseofGenoxenwithconcomitantNSAIDsincludingcyclooxygenase-2selectiveinhibitorsshouldbeavoided.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms.(seesection4.2,andGIandcardiovascularrisksbelow)

Elderly:TheelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDsespeciallygastrointestinalbleeding

andperforationwhichmaybefatal(Seesection4.2)

GastrointestinalBleeding,ulcerationandperforation:GIbleeding,ulcerationorperforation,whichcanbefatal,has

beenreportedwithallNSAIDsatanytimeduringtreatment,withorwithoutwarningsymptomsoraprevioushistoryof

seriousGIevents.

TheriskofGIbleeding,ulcerationorperforationishigherwithincreasingNSAIDdoses,inpatientswithahistoryof

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

shouldcommencetreatmentonthelowestdoseavailable.Combinationtherapywithprotectiveagents(e.gmisoprostol

orprotonpumpinhibitors)shouldbeconsideredforthesepatients,andalsoforpatientsrequiringconcomitantlowdose

aspirin,orotherdrugslikelytoincreasegastrointestinalrisk(seebelowand4.5)

PatientswithahistoryofGItoxicity,particularlywhenelderly,shouldreportanyunusualabdominalsymptoms

(especiallyGIbleeding)particularlyintheinitialstagesoftreatment.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchasoralcorticosteroids,anticoagulantssuchaswarfarin,selectiveserotonin-reuptakeinhibitorsoranti-

plateletagentssuchasaspirin(Seesection4.5).

WhenGIbleedingorulcerationoccursinpatientsreceivingGenoxen,thetreatmentshouldbewithdrawn.

NSAIDsshouldbegivenwithcaretopatientswithahistoryofgastrointestinaldisease(ulcerativecolitis,Crohn’s

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Episodesofgastro-intestinalbleedinghavebeenreportedinpatientswithnaproxentherapy.Naproxenshouldbegiven

underclosesupervisiontopatientswithahistoryofgastrointestinaldisease.

Bronchospasmmaybeprecipitatedinpatientssufferingfrom,orwithahistoryof,bronchialasthmaorallergicdisease.

Sporadicabnormalitiesinlaboratorytests(e.g.liverfunctiontests)haveoccurredinpatientsonnaproxentherapybut

nodefinitetrendwasseeninanytestindicatingtoxicity.

Naproxendecreasesplateletaggregationandprolongsbleedingtime.Thiseffectshouldbekeptinmindwhenbleeding

timesaredetermined.

Cautionisrequiredinpatientswithahistoryofhypertensionand/orheartfailureasfluidretentionandoedemahave

beenreportedinassociationwithNSAIDtherapy.

Useinpatientswithimpairedrenalfunction:

Asnaproxeniseliminatedtoalargeextent(95%)byurinaryexcretionviaglomerularfiltration,itshouldbeusedwith

greatcautioninpatientswithimpairedrenalfunctionandthemonitoringofserumcreatinineand/orcreatinine

clearanceisadvisedinthesepatients.Naproxenisnotrecommendedinpatientshavingbaselinecreatinineclearance

lessthan20ml/minute.

Certainpatients,specificallythosewhoserenalbloodflowiscompromised,suchasinextracellularvolumedepletion,

cirrhosisoftheliver,sodiumrestriction,congestiveheartfailure,andpre-existingrenaldisease,shouldhaverenal

functionassessedbeforeandduringnaproxentherapy.Someelderlypatientsinwhomimpairedrenalfunctionmaybe

expectedcouldalsofallwithinthiscategory.Areductionindailydosageshouldbeconsideredtoavoidthepossibility

ofexcessiveaccumulationofnaproxenmetabolitesinthesepatients.

Useinpatientswithimpairedliverfunction:

Chronicalcoholicliverdiseaseandprobablyalsootherformsofcirrhosisreducethetotalplasmaconcentrationof

naproxen,buttheplasmaconcentrationofunboundnaproxenisincreased.Theimplicationofthisfindingfornaproxen

dosingisunknownbutitisprudenttousethelowesteffectivedose.

Seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs(see4.8).Patientsappearto

beathighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthereactionoccurringinthemajorityof

caseswithinthefirstmonthoftreatment.Genoxenshouldbediscontinuedatthefirstappearanceofskinrash,mucosal

lesions,oranyothersignofhypersensitivity.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose–galactosemalabsorptionshouldnottakethismedication.

Cardiovascularandcerebrovasculareffects:

Appropriatemonitoringandadvicearerequiredforpatientswithahistoryofhypertensionand/ormildtomoderate

congestiveheartfailureasfluidretentionandoedemahavebeenreportedinassociationwithNSAIDtherapy.

ClinicaltrialandepidemiologicaldatasuggestthatuseofcoxibsandsomeNSAIDs(particularlyathighdosesandin

longtermtreatment)maybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexample

myocardialinfarctionorstroke).AlthoughdatasuggestthattheuseofNaproxen(1000mgdaily)maybeassociated

withalowerrisk,someriskcannotbeexcluded.

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheral

arterialdisease,and/orcerebrovasculardiseaseshouldonlybetreatedwithnaproxenaftercarefulconsideration.

Similarconsiderationshouldbemadebeforeinitiatinglonger-termtreatmentofpatientswithriskfactorsfor

cardiovascularevents(e.g.hypertension,hyperlipidaemia,diabetesmellitus,smoking).TheuseofNaproxenmay

impairfemalefertilityandisnotrecommendedinwomenattemptingtoconceive.Inwomenwhohavedifficulties

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Duetothehighplasmaproteinbindingofnaproxenpatientssimultaneouslyreceivinghydantoins,anti-coagulantsora

highlyprotein-boundsulphonamideshouldbeobservedforsignsofoverdosageofthesedrugs.Nointeractionshave

beenobservedinclinicalstudieswithnaproxenandanti-coagulantsorsulphonylureas,butcautionisnevertheless

advisedsinceinteractionhasbeenseenwithothernon-steroidalagentsofthisclass.

Thenatriureticeffectoffrusemidehasbeenreportedtobeinhibitedbysomedrugsofthisclass.

Inhibitionofrenallithiumclearanceleadingtoincreasesinplasmalithiumconcentrationshasalsobeenreported.

Naproxenandothernon-steroidalanti-inflammatorydrugscanreducetheanti-hypertensiveeffectofpropranololand

otherbeta-blockers.

Probenecidgivenconcurrentlyincreasenaproxenplasmalevelsandextendsitshalf-lifeconsiderably.

Cautionisadvisedwheremethotrexateisadministeredconcurrentlybecauseofpossibleenhancementofitstoxicity

sincenaproxen,amongothernon-steroidalanti-inflammatorydrugs,hasbeenreportedtoreducethetubularsecretion

ofmethotrexateinananimalmodel.

Itissuggestedthatnaproxentherapybetemporarilydiscontinued48hoursbeforeadrenalfunctiontestsareperformed

becausenaproxenmayartifactuallyinterferewithsometestsfor17-ketogenicsteroids.Similarly,naproxenmay

interferewithsomeassaysofurinary5-hydroxyindoleaceticacid.

Corticosteroids:increasedriskofgastrointestinalulcerationorbleeding(Seesection4.4)

Anti-plateletagentsandselectiveserotoninreuptakeinhibitors(SSRIs):increasedriskofgastrointestinalbleeding(See

section4.4).

Anti-coagulants:NSAIDsmayenhancetheeffectsofanti-coagulants,suchaswarfarin(seesection4.4)

4.6Pregnancyandlactation

Teratologystudiesinratsandrabbitsatdoselevelsequivalentonahumanmultiplebasistothosewhichhaveproduced

foetalabnormalitywithcertainothernon-steroidalanti-inflammatoryagents,e.g.aspirin,havenotproducedevidence

offoetaldamagewithnaproxen.Aswithotherdrugsofthistype,naproxendelaysparturitioninanimals(therelevance

ofthisfindingtohumanpatientsisunknown)andalsoaffectsthehumanfoetalcardiovascularsystem(closureofthe

ductusarteriosus).Goodmedicalpracticeindicatesminimaldrugusageinpregnancy,thususeofthisclassof

therapeuticagentrequirescautiousbalancingofpossiblebenefitagainstpotentialrisktothemotherandfoetus,

especiallyinthefirstandthirdtrimesters.Theuseofnaproxenshouldbeavoidedinpatientswhoarebreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Nil.

4.8Undesirableeffects

Cardiovascularsafety:Oedema,hypertensionandcardiacfailure,havebeenreportedinassociationwithNSAID

treatment.

Disordersofblood&theLymphaticsystemdisorder:Clinicaltrialandepidemiologicaldatasuggestthatuseofsome

NSAIDs(particularlyathighdosesandinlongtermtreatment)maybeassociatedwithasmallincreasedriskofarterial

thromboticevents(forexamplemyocardialinfarctionorstroke)(seesection4.4).

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Haematological:Thrombocytopenia,granulocytopenia,aplasticanaemiaandhaemolyticanaemiamayoccurrarely.

Gastrointestinal:Themostcommonlyobservedadverseeventsaregastrointestinalinnature.Pepticulcers,perforation

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

flatulence,constipation,dyspepsia,abdominalpain,melaena,haematemesis,ulcerativestomatitis,exacerbationof

colitisandCrohn’sdisease(seesection4.4–Specialwarningsandprecautionsforuse)havebeenreportedfollowing

administration.Lessfrequently,gastritishasbeenobserved.

Dermatological/hypersensitivity:skinrashes,urticaria,angio-oedema.Anaphylacticreactionstonaproxenand

naproxensodiumformulations,eosinophilicpneumonitis,alopecia,erythemamultiforme,Bullousreactionsincluding

StevensJohnsonsyndromeandtoxicepidermalnecrolysis(veryrare),andphotosensitivityreactionsincluding

photosensitivedermatitisandrarecasesinwhichskinresemblesporphyriacutaneatarda(pseudoporphyria)or

epidermolysisbullosamayoccurrarely.

Other:Tinnitus,hearingimpairment,vertigo,mildperipheraloedema.Jaundice,fatalhepatitis,nephropathy,

haematuria,visualdisturbances,vasculitis,asepticmeningitisandulcerativestomatitishavebeenreportedrarely.

4.9Overdose

Significantoverdosageofthedrugmaybecharacterisedbydrowsiness,heartburn,indigestion,nauseaorvomiting.A

fewpatientshaveexperiencedseizures,butitisnotclearwhetherthesewerenaproxen-relatedornot.Itisnotknown

whatdoseofthedrugwouldbelife-threatening.

Shouldapatientingestalargeamountofnaproxenaccidentallyorpurposefully,thestomachmaybeemptiedandusual

supportivemeasuresemployed.Animalstudiesindicatethatthepromptadministrationofactivatedcharcoalin

adequateamountswouldtendtoreducemarkedlytheabsorptionofthedrug.Haemodialysisdoesnotdecreasethe

plasmaconcentrationofnaproxenbecauseofthehighdegreeofproteinbinding.However,haemodialysismaystillbe

appropriateinapatientwithrenalfailurewhohastakennaproxen.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Naproxenisanon-steroidalanti-inflammatoryagentwithanalgesicandantipyreticproperties.

5.2Pharmacokineticproperties

Itisreadilyabsorbedfromthegastro-intestinaltract,metabolisedintheliverandexcretedmainlyintheurine,witha

halflifeof12-15hours.

5.3Preclinicalsafetydata

NofurtherrelevantinformationotherthanthatwhichisincludedinothersectionsoftheSummaryofProduct

Characteristics.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

LactoseMonohydrate

Maizestarch

Sodiumstarchglycollate

Povidone

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QuinolineyellowE104

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

ForSecuritainer-Donotstoreabove25 °

ForBlisterpack-Donotstoreabove30 °

Storeinoriginalcontainer/packageinordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Polypropylenesecuritainerswithtamperevidentpolypropylenecaps.

Packsize:100’s.

Blisterpacksof250micronclearPVC/PVDClaminatednontoxicfilmwith90gsmPVDCcoatingand0.02mmthick

hardtemperedAluminiumfoilwithmattfinish.

Packsize:28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AntigenPharmaceuticalsLimited

ChandlerHouse

CastleStreet

Roscrea

CoTipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA73/90/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:4 th

July1986

Dateoflastrenewal:4 th

July2006

10DATEOFREVISIONOFTHETEXT

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