DICLOFENAC SODIUM

Main information

  • Trade name:
  • DICLOFENAC SODIUM
  • Dosage:
  • 25 Milligram
  • Pharmaceutical form:
  • Tablets Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DICLOFENAC SODIUM
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1046/007/001
  • Authorization date:
  • 13-07-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA1046/007/001

CaseNo:2034402

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

WinthropPharmaceuticalsUKLimited

OneOnslowStreet,Guildford,Surrey,GU14YS,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DiclofenacSodium25MilligramTabletsGastro-Resistant

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom05/07/2007until12/07/2008.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiclofenacSodium25mgGastro-ResistantTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Diclofenacsodium25mg.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Gastro-resistanttablet.

Biconvex,mustardyellowcolouredgastro-resistantcoatedtabletswithS/26onesideandplainontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthesymptomaticmanagementofrheumatoidarthritisincludingjuvenilechronicarthritis,osteoarthrosis,ankylosing

spondylitis,psoriaticarthropathy,lowbackpain,andacutemusculoskeletaldisordersincludingperiarthritis,tendinitis,

tenosynovitis,bursitis,sprains,strains,dislocationsandinacutegout.

Inthemanagementofpostoperativepainandinflammationinorthopaedic,dentalandotherminorsurgery.

4.2Posologyandmethodofadministration

RouteofAdministration

Oral.

Adults

Theusualtotaldailydosageis75-150mgindivideddoses.

Elderly

Althoughthepharmacokineticsofdiclofenacsodiumarenotimpairedtoanyclinicallyrelevantextentinelderly

patients,non-steroidalanti-inflammatorydrugsshouldbeusedwithparticularcautioninsuchpatients,whoare

generallymorepronetoadversereactions.Inparticular,itisrecommendedthatthelowesteffectivedosebeusedin

frailelderlypatientsorthosewithalowbodyweight.(SeealsoPrecautions.)

Children

Theusualtotaldailydoseis1to3mg/kgindivideddoses.

Treatmentshouldbereviewedatregularintervalsanddiscontinuedifintoleranceoccursorifnobenefitisseen.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

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4.3Contraindications

Useinpatientshypersensitivetodiclofenacoranyoftheotherexcipients.

Useinpatientswithactiveorsuspectedpepticulcerationorpepticulcerdisease,orwithgastrointestinalbleeding.

Useinpatientsinwhomattacksofasthma,urticariaoracuterhinitisareprecipitatedbyaspirinorothernon-steroidal

anti-inflammatoryagents.

Historyofgastrointestinalbleedingorperforation,relatedtopreviousNSAIDstherapy.Active,orhistoryofrecurrent

pepticulcer/haemorrhage(twoormoredistinctepisodesorprovenulcerationorbleeding).

Severeheartfailure

4.4Specialwarningsandprecautionsforuse

TheuseofDiclofenacsodiumwithconcomitantNSAIDsincludingcyclooxygenase-2-selectiveinhibitorsshouldbe

avoided.

Undesirableeffectsmaybeminimisedbyusingtheminimumeffectivedoseortheshortestdurationnecessaryto

controlsymptoms.PatientstreatedwithNSAIDsforlongperiodsshouldundergoregularmedicalsupervisionto

monitorforadverseevents.

Renal:Patientswithrenal,cardiacorhepaticimpairmentandtheelderlyshouldbekeptundersurveillance,sincethe

useofNSAIDsmayresultindeteriorationofrenalfunction.Thelowesteffectivedoseshouldbeusedandrenal

functionmonitoredpriortotheinitiationoftreatmentandregularlythereafter.

Theimportanceofprostaglandinsinmaintainingrenalbloodflowshouldbetakenintoaccountinpatientswith

impairedcardiacorrenalfunction,thosebeingtreatedwithdiureticsorrecoveringfrommajorsurgery.Effectson

renalfunctionareusuallyreversibleonwithdrawalofDiclofenacSodium.

Hepatic:Ifabnormalliverfunctiontestspersistorworsen,clinicalsignsorsymptomsconsistentwithliverdisease

developorifothermanifestationsoccur(eosinophilia,rash)DiclofenacSodiumshouldbediscontinued.Hepatitismay

occurwithoutprodromalsymptoms.UseofDiclofenacSodiumwithhepaticporphyriamaytriggeranattack.

Haematological:DiclofenacSodiummayreversiblyinhibitaggregation(seeanticoagulantsinInteractions)andshould

beusedwithcautioninpatientswithintracranialhaemorrhage,bleedingdiathesisorhaematologicalabnormalities.

LongTermTreatment:Allpatientswhoarereceivingnon-steroidalanti-inflammatoryagentsshouldbemonitoredasa

precautionarymeasuree.g.renalfunction,hepaticfunction(elevationofliverenzymesmayoccur)andbloodcounts.

Thisisparticularlyimportantintheelderly.

Gastrointestinal:Closemedicalsurveillanceisimperativeinpatientswithsymptomsindicativeofgastrointestinal

disorders,withahistorysuggestiveofgastrointestinalulceration,withulcerativecolitisorwithCrohn’sdisease.

Gastrointestinalbleedingorulceration/perforation,haematemesisandmelaenahaveingeneralmoreserious

consequencesintheelderly.Theycanoccuratanytimeduringtreatmentwithorwithoutwarningsymptomsora

previoushistory.Intherareinstanceswheregastrointestinalbleedingorulcerationoccursinpatientsreceiving

DiclofenacSodiumthedrugshouldbewithdrawn.

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beenreportedwithallNSAIDsatanytimeduringtreatment,withorwithoutwarningsymptomsoraprevioushistoryof

GIevents.

TheriskofGIbleeding,ulcerationorperforationishigherwithincreasingNSAIDdoses,inpatientswithahistoryof

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

shouldcommencetreatmentonthelowestdoseavailable.Combinationtherapywithprotectiveagents(e.g.

misoprostolorprotonpumpinhibitors)shouldbeconsideredforthesepatients,andalsoforpatientsrequiring

concomitantlowdoseaspirin,orotherdrugslikelytoincreasegastrointestinalrisk(seebelowand4.5)

PatientswithahistoryofGItoxicity,particularlywhenelderly,shouldreportanyunusualabdominalsymptoms

(especiallyGIbleeding)particularlyintheinitialstagesoftreatment.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchasoralcorticosteroids,anticoagulantssuchaswarfarin,selectiveserotonin-reuptakeinhibitorsoranti-

plateletagentssuchasaspirin(seesection4.5)

WhenGIbleedingorulcerationoccursinpatientsreceivingDiclofenacsodium,thetreatmentshouldbewithdrawn.

NSAIDsshouldbegivenwithcaretopatientswithahistoryofgastrointestinaldisease(ulcerativecolitis,Crohn's

disease)astheirconditionmaybeexacerbated(seesection4.8-undesirableeffects).

Elderly:TheelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDsespeciallygastrointestinalbleeding

andperforationwhichmaybefatal(seesection4.2)

Hepatic:Closemedicalsurveillanceisalsoimperativeinpatientssufferingfromsevereimpairmentofhepatic

function.

HypersensitivityReactions:Aswithothernon-steroidalanti-inflammatorydrugs,allergicreactions,including

anaphylactic/anaphylactoidreactions,canalsooccurwithoutearlierexposuretothedrug.

Seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs(see4.8).Patientsappear

tobeatthehighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthereactionoccurringinthe

majorityofcaseswithinthefirstmonthoftreatment.Diclofenacsodiumshouldbediscontinuedatthefirstappearance

ofskinrash,mucosallesions,oranyothersignofhypersensitivity.

Cautionisrequiredinpatientswithahistoryofhypertensionand/orheartfailureasfluidretentionandoedemahave

beenreportedinassociationwithNSAIDtherapy.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.2,andGIcardiovascularrisksbelow)

Cardiovascularandcerebrovascular

Appropriatemonitoringandadvicearerequiredforpatientswithahistoryofhypertensionand/ormildtomoderate

congestiveheartfailureasfluidretentionandoedemahavebeenreportedinassociationwithNSAIDtherapy.

Clinicaltrialandepidemiologicaldatasuggestthatuseofdiclofenac,particularlyathighdose(150mgdaily)andin

longtermtreatmentmaybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexample

myocardialinfarctionorstroke).

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheral

arterialdisease,and/orcerebrovasculardiseaseshouldonlybetreatedwithdiclofenacaftercarefulconsideration.

Similarconsiderationshouldbemadebeforeinitiatinglonger-termtreatmentofpatientswithriskfactorsfor

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Theuseofdiclofenacsodiummayimpairfemalefertilityandisnotrecommendedinwomenattemptingtoconceive.

Inwomenwhohavedifficultiesconceivingorwhoareundergoinginvestigationofinfertility,withdrawalofdiclofenac

sodiumshouldbeconsidered.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

LithiumandDigoxin:DiclofenacSodiummayincreaseplasmaconcentrationsoflithiumanddigoxin.

Corticosteroids:increasedriskofgastrointestinalulcerationorbleeding(seesection4.4)

Anticoagulants:NSAIDsmayenhancetheeffectsofanticoagulants,suchaswarfarin(seesection4.4)Itisconsidered

unsafetotakeNSAIDsincombinationwithwarfarinorheparinunlessunderdirectmedicalsupervision.

AlthoughclinicalinvestigationsdonotappeartoindicatethatDiclofenacSodiumhasaninfluenceontheeffectsof

anticoagulants,thereareisolatedreportsofanincreasedriskofhaemorrhagewiththecombineduseofdiclofenacand

anticoagulanttherapy.Therefore,tobecertainthatnochangeinanticoagulantdosageisrequired,closemonitoringof

suchpatientsisrequired.Aswithothernon-steroidalanti-inflammatoryagents,diclofenacinhighdosecanreversibly

inhibitplateletaggregation.

Anti-plateletagentsandselectiveserotoninreuptakeinhibitors(SSRIs):increasedriskofgastrointestinalbleeding(see

section4.4)

AntidiabeticAgents:ClinicalstudieshaveshownthatDiclofenacSodiumcanbegiventogetherwithoralantidiabetic

agentswithoutinfluencingtheirclinicaleffect.Howevertherehavebeenisolatedreportsofhypoglycaemicand

hyperglycaemiceffectswhichhaverequiredadjustmenttothedosageofhypoglycaemicagents.

Ciclosporin:CasesofnephrotoxicityhavebeenreportedinpatientsreceivingconcomitantciclosporinandNSAIDs,

includingDiclofenacSodium.Thismightbemediatedthroughcombinedrenalantiprostaglandineffectsofboththe

NSAIDandciclosporin.

Methotrexate:CasesofserioustoxicityhavebeenreportedwhenmethotrexateandNSAIDsaregivenwithin24hours

ofeachother.Thisinteractionismediatedthroughaccumulationofmethotrexateresultingfromimpairmentofrenal

excretioninthepresenceoftheNSAID.

QuinoloneAntimicrobials:ConvulsionsmayoccurduetoaninteractionbetweenquinolonesandNSAIDs.Thismay

occurinpatientswithorwithoutaprevioushistoryofepilepsyorconvulsions.Therefore,cautionshouldbeexercised

whenconsideringtheuseofaquinoloneinpatientswhoarealreadyreceivinganNSAID.

OtherNSAIDsandSteroids:Co-administrationofDiclofenacSodiumwithothersystemicNSAIDsandsteroidsmay

increasethefrequencyofunwantedeffects.Concomitanttherapywithaspirinlowerstheplasmalevelsofeach,

althoughnoclinicalsignificanceisknown.

Diuretics:VariousNSAIDsareliabletoinhibittheactivityofdiuretics.Concomitanttreatmentwithpotassium-

sparingdiureticsmaybeassociatedwithincreasedserumpotassiumlevels,henceserumpotassiumshouldbe

monitored.

4.6Pregnancyandlactation

Diclofenacsodiumtabletsshouldnotbeprescribedduringpregnancy,unlesstherearecompellingreasonsfordoing

so.Thelowesteffectivedosageshouldbeused.Useofprostaglandinsynthetaseinhibitorsmayresultinpremature

closureoftheductusarteriosusifgiveninthelasttrimesterofpregnancy.

Followingoraldosesof150mgdaily,tracesofactivesubstanceshavebeendetectedinbreastmilk,butinquantitiesso

smallthatnoundesirableeffectsontheinfantaretobeexpected.

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PatientswhoexperiencedizzinessorotherCNSdisturbanceswhiletakingNSAIDsshouldrefrainfromdrivingor

operatingmachinery.

4.8Undesirableeffects

Ifserioussideeffectsoccur,DiclofenacSodium25mgTabletsshouldbewithdrawn.

Frequencyestimate:frequent:>10%,occasional:>1-10%,rare:>0.001-1%,isolatedcases:<0.001%.

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

Gastro-intestinaltract

Occasional:Epigastricpain,othergastro-intestinaldisorders(e.g.nausea,vomiting,diarrhoea,abdominalcramps,

dyspepsia,flatulence,anorexia).

Rare:Gastro-intestinalbleeding(haematemesis,melaena,bloodydiarrhoea),gastro-intestinalulcerswithorwithout

bleedingorperforation.

Isolatedcases:Aphthousstomatitis,glossitis,oesophageallesions,lowergutdisorders(e.g.non-specifichaemorrhagic

colitisandexacerbationsofulcerativecolitisorCrohn’sproctocolitis,colonicdamageandstrictureformation),

pancreatitis,constipation.

CentralNervousSystem:

Occasional:Headache,dizzinessorvertigo.

Rare:Drowsiness,tiredness.

Isolatedcases:Disturbancesofsensation,paraesthesia,memorydisturbance,disorientation,insomnia,irritability,

convulsions,depression,anxiety,nightmares,tremor,psychoticreactions,asepticmeningitis.

Specialsenses:

Isolatedcases:Disturbancesofvision(blurredvision,diplopia),impairedhearing,tinnitus,tastedisturbances.

Skin:

Occasional:Rashesorskineruptions.

Rare:Urticaria.

Isolatedcases:Bullouseruptions,eczema,erythemamultiforme,Stevens-Johnsonsyndrome,Lyell’ssyndrome,(acute

toxicepidermolysis),erythroderma(exfoliativedermatitis),lossofhair,photosensitivityreactions,purpuraincluding

allergicpurpura.

BullousreactionsincludingStevens-Johnsonsyndromeandtoxicepidermalnecrolysis(verrare).

Kidney:

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Isolatedcases:Acuterenalinsufficiency,urinaryabnormalities(e.g.haematuria,proteinuria),interstitialnephritis,

nephroticsyndrome,papillarynecrosis.

Liver:

Occasional:Elevationofserumaminotransferaseenzymes(ALT,AST).

Rare:Liverfunctiondisordersincludinghepatitis(inisolatedcasesfulminant)withorwithoutjaundice.

Blood:

Isolatedcases:Thrombocytopenia,leucopenia,agranulocytosis,haemolyticanaemia,aplasticanaemia.

Hypersensitivity:

Rare:Hypersensitivityreactions(e.g.bronchospasm,anaphylactic/anaphylactoidsystemicreactionsincluding

hypotension).

Isolatedcases:Vasculitis,pneumonitis.

Cardiovascularsystem:

Isolatedcases:Palpitations,chestpain,hypertension,congestiveheartfailure.

Oedema,hypertensionandcardiacfailurehavebeenreportedinassociationwithNSAIDtreatment.

Clinicaltrialandepidemiologicaldatasuggestthatuseofdiclofenac,particularlyhighdoses(150mgdaily)andinlong

termtreatmentmaybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexamplemyocardial

infarctionorstroke)(seesection4.4)

4.9Overdose

ThereisnospecificantidotetoDiclofenacSodiumTablets,andthetreatmentissymptomatic.Symptomatologyof

overdosewithDiclofenacSodiumTabletsisnotwelldefined;hypotension,convulsions,respiratorydepression,

gastrointestinal,renalandhepaticeffectsarepossible.

Immediatetreatmentconsistsofforcedemesisorgastriclavagetorecoverundigestedtablets,andtreatmentwith

activatedcharcoal.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:M01AB05,Anti-inflammatoryandantirheumaticproducts,non-steroids.

Diclofenacsodiumisanon-steroidalanti-inflammatoryagentandinhibitorofPGsynthetase.

5.2Pharmacokineticproperties

Thedrugiswellabsorbedwithpeakplasmalevelsachievedbetween1and4hours.Itisextensivelymetabolisedinthe

liverandexcretedthroughbileandurine.Thedrugisstronglyprotein-bound.Ithasahalflifeof1to2hours.

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Therearenopreclinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose(crystalline)

Maizestarch

PovidoneK25

Microcrystallinecellulose

Silicondioxide

Magnesiumstearate

CoatingConstituents

Hypromellose

Macrogol400

OpasprayM-1-8461[containstitaniumdioxide(E171),quinolineyellow,aluminiumlake(E104),ironoxideyellow

(E172),hypromellose,sunsetyellowaluminiumlake(E110)]

EudragitL30D[containspurifiedwater,methacrylicacidcopolymerTypeC,polysorbate80,sodiumlaurilsulfate]

Macrogol8000

Polysorbate80

Talc

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6.2Incompatibilities

Notapplicable.

6.3ShelfLife

4years

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

ThetabletsarecontainedinPVC/aluminiumfoilblistersandenclosedincardboardcartonsinpacksizes28,30,56,60,

84and100.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

WinthropPharmaceuticalsUKLimited

OneOnslowStreet

Guildford

SurreyGU14YS

UnitedKindom

Tradingas:

WinthropPharmaceuticalsUKLimited

POBox611

Guildford

SurreyGU14YS

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1046/7/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation: 13July1993

DateofLastRenewal: 13July2003

10DATEOFREVISIONOFTHETEXT

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