DOPACARD

Main information

  • Trade name:
  • DOPACARD Concentrate for Soln for Inf 10
  • Dosage:
  • 10
  • Pharmaceutical form:
  • Concentrate for Soln for Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOPACARD Concentrate for Soln for Inf 10
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1260/004/001
  • Authorization date:
  • 23-06-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1260/004/001

CaseNo:2071684

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

CephalonLimited

1AlbanyPlace,HydeWay,WelwynGardenCity,HertfordshireAL73BT,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Dopacard10mg/mlConcentrateforSolutionforInfusion

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom13/04/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dopacard10mg/mlConcentrateforSolutionforInfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each5mlampoulecontains50mgdopexaminehydrochloride(10mg/ml).

Forafulllistofexcipientsseesection6.1

3PHARMACEUTICALFORM

Concentrateforsolutionforinfusion.

Colourlessliquid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dopacardisindicatedforshorttermadministration(experienceinclinicalstudieshasincludedadministrationforupto

48h)topatientswhorequireperipheralvasodilator(afterloadreduction),renalvasodilatorandmildpositiveinotropic

therapyinthetreatmentofheartfailuresuchasmaybeassociatedwithexacerbationofchronicheartfailureorwith

cardiacsurgery.Dopexamineshouldonlybeusedinspecialistunitsinwhichadequatefacilitiesareavailablefor

patientsurveillanceandmonitoringofresponses.

4.2Posologyandmethodofadministration

Dosage

Thedosagerequiredisvariableandmustbedeterminedforeachpatientbydosetitration.Patientswhoareacutelyillwi

ahighsympatheticdrivemayrequireandtoleratelowerdosesthanthosewithseverechronicdisease.

Adultsandtheelderly:

Infusionshouldbeginatadoseof0.5microgram/kg/minandmaybeincreasedto1microgram/kg/minandthenin

increments(0.5-1microgram/kg/min)upto6micrograms/kg/minatnotlessthan15minuteintervalsaccordingtothe

patient’shaemodynamicandclinicalresponse.Smallerincrements(0.5microgram/kg/min)maybejustifiedincertain

patientsaccordingtohaemodynamicandclinicalresponse.

Children:

ThesafetyandefficacyofDopacardforuseinchildrenhavenotbeenestablished.

Administration:

Dopacardshouldbeonlyadministeredintravenouslybyinfusionthroughacannulaorcatheterinacentralorlarge

peripheralvein.

Contactwithmetalpartsininfusionapparatusshouldbeminimised.Adevicewhichprovidesaccuratecontrolofthe

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Centraladministration:

Dopacardcanbeadministeredviaacannulaorcathetersitedinacentralvein.Theconcentrationoftheinfusion

solutionforadministrationviathisroutemustnotexceed4mg/ml.

PeripheralAdministration:

Dopacardcanbeadministeredviaacannulainalargeperipheralvein.Theconcentrationoftheinfusionsolutionfor

administrationviathisroutemustnotexceed1mg/ml.Thrombophlebitishasoccasionallybeenreportedwith

peripheraladministrationusingconcentrationsofDopacardexceeding1mg/ml.

DuringtheadministrationofDopacard,aswithanyparenteralcatecholamine,therateofadministrationanddurationof

therapyshouldbeadjustedaccordingtothepatient’sresponseasdeterminedbyheartrateandrhythm(ECG),blood

pressure,urineflowand,ifpossible,measurementofcardiacoutput.

ItisrecommendedthattheinfusionofDopacardisreducedgraduallyratherthanwithdrawnabruptly.

Thedurationoftherapyisdependentuponthepatient’soverallresponsetotreatment.Extendedtherapybeyond48

hourshasnotbeenfullyevaluated.

SpecialinstructionsforthepreparationofDopacardInfusionSolutions:

Dopacardmustbedilutedbeforeuse.Forinstructionsondilutionoftheproductbeforeadministrationseesection6.6

4.3Contraindications

Knownsensitivitytodopexaminehydrochlorideorexcipients(disodiumedetate).

Useinpatientswhoarereceivingmonoamineoxidaseinhibitors(MAOIs)orhavereceivedsuchtreatmentwithinthe

past14days.

Phaeochromocytoma.

Thrombocytopenia.

Useinpatientswithleftventricularoutletobstructionsuchashypertrophicobstructivecardiomyopathyoraortic

stenosis.Insuchpatients,positiveinotropicactivitymayincreaseleftventricularoutflowobstructionandsudden

vasodilatationmaycausehypotension.

Useinpatientswithuncorrectedhypovolaemia.

4.4Specialwarningsandprecautionsforuse

CorrectionofhypovolaemiamustbeachievedbeforetheadministrationofDopacard.Hypovolaemiashouldalsobe

correctedduringtherapyasvasodilatationoccursduetotreatment.

CareshouldbeexercisedsoastorestrictthesodiumandfluidloadduringadministrationofDopacard.

Dopacardshouldnotbeadministeredtopatientswithseverehypotensionoramarkedlyreducedsystemicvascular

resistanceuntilspecificresuscitativemeasureshavebeentakentorestorebloodpressuretoaclinicallyacceptable

level.

Inpatientswithamarkedreductioninsystemicvascularresistance,Dopacardshouldnotbeusedasadirectsubstitute

forpressoragentsorotherinotropes.

Aswithothercatecholamines,Dopacardshouldbeadministeredwithcautiontopatientswithaclinicalhistoryof

ischaemicheartdiseaseespeciallyfollowingacutemyocardialinfarctionorrecentepisodesofanginapectorisasa

tachycardiamayincreasemyocardialoxygendemandandfurtherexacerbatemyocardialischaemia.

Ashasbeenobservedwithsomeotherb

-adrenergicagonists,asmallreversiblefallincirculatingplateletnumbershas

beenobservedinsomepatients.Noadverseeffectsattributabletoalterationsinplateletcounthavebeenseeninclinical

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CaremustbeexercisedwhenadministeringDopacardinthepresenceofhypokalaemiaorhyperglycaemia.Incommon

withotherb

-agonists,Dopacarddepressesplasmapotassiumandraisesplasmaglucose.Theseeffectsareminorand

reversible.Monitoringofpotassiumandglucoseisadvisableinpatientslikelytobeatriskfromsuchchanges,e.g.

diabetics,patientswithmyocardialinfarctionorpatientsbeingtreatedwithdiureticsorcardiacglycosides.

Benignarrhythmiassuchasventricularprematurebeatsand,morerarely,seriousarrhythmiashavebeenreportedin

somepatients.IfexcessivetachycardiaoccursduringDopacardadministration,thenareductionortemporary

discontinuationoftheinfusionshouldbeconsidered.

Aswithotherparenteralcatecholamines,therehavebeenoccasionalreportsofpartialtolerance,withsomeattenuation

ofthehaemodynamicresponsedevelopingduringlong-terminfusionsofDopacard.

TheriskofthrombophlebitsandlocalnecrosismaybeincreasediftheconcentrationofDopacardadministeredviaa

peripheralveinexceeds1mg/ml.Thrombophlebitsisrarewhentheconcentrationofdrugusedforperipheral

administrationislessthan1mg/ml.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

AsDopacardinhibitsUptake-1,itmaypotentiatetheeffectsofexogenouscatecholaminessuchasnoradrenaline.

CautionisrecommendedwhentheseagentsareadministeredconcomitantlywithDopacardorsoonafter

discontinuationofitsuse.

Inthecaseofdopamine,thereisnoevidenceofaninteraction,otherthanpossibleattenuationoftheindirect

sympathomimeticinotropiceffectsofhigherdosesofdopamineduetoUptake-1blockadebyDopacard.

Concomitantusewithb

-adrenergicantagonistsanddopaminereceptorantagonistsrequirescautionsinceattenuation

ofthepharmacologicaleffectsofDopacardmayoccur.

4.6Pregnancyandlactation

ThereisnoexperienceoftheuseofDopacardinpregnantorlactatingwomenandthereforeitssafetyinthesesituations

hasnotbeenestablished.Thereisinsufficientevidencefromanimalstudiestoindicateitisfreefromhazard.Dopacard

isnotthereforecurrentlyrecommendedforuseinpregnantorlactatingwomen.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

ThemostcommonundesirableeffectreportedwithDopacardadministrationistachycardia(11.8%instudiesofacute

exacerbationsofchronicheartfailure;19.4%instudiesofuseincardiacsurgery).Theincreasesinheartratearedose

relatedandinmostcasesnotclinicallysignificant.

Otherundesirableeffectsreportedinclinicaltrialsinbothacuteexacerbationsofchronicheartfailureandcardiac

surgeryatanincidenceof1%ormoreinclude:

Cardiovascular:Anumberoftachyarrhythmiassuchasprematureventricularcontractions(PVCs)andatrial

fibrillation;bradycardia,bothsinusandnodal;worseningheartfailureleadingtoasystoleandcardiacarrest;angina;

myocardialinfarction;cardiacenzymechangesandnon-specificECGchanges.Hypotensionandhypertensionhave

alsobeenreported,thelatterwithahigherincidenceinpatientsfollowingcardiacsurgery.

Non-cardiovascular:Nauseaandvomiting;tremor;headache;diaphoresisanddyspnoea.

Carefultitrationofthedosemayminimisetheincidenceofadverseevents.

Morerarelyanumberofseriousadverseeventshavebeenreportedinpatientsundergoingcardiacsurgery:renal

failure,acuterespiratorydistresssyndrome(ARDS),pulmonaryoedema,pulmonaryhypertension,bleedingand

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4.9Overdose

Thehalf-lifeofDopacardinbloodisshort(approximately6-7minutesinhealthyvolunteersandaround11minutesin

patientswithcardiacfailure).

Consequently,theeffectsofoverdosagearelikelytobeshort-livedprovidedthatadministrationisdiscontinued.

Effectsofoverdosagearelikelytoberelatedtothepharmacologicalactionsandincludetachycardia,tremulousness

andtremor,nauseaandvomiting,andanginalpain.Treatmentshouldbesupportiveanddirectedtothesesymptoms.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

TheprimaryactionsofDopacard(dopexaminehydrochloride)arethestimulationofadrenergicb

-receptorsand

peripheraldopaminereceptorsofDA

andDA

subtypes.Inaddition,Dopacardisaninhibitorofneuronalre-uptakeof

noradrenaline(Uptake-1).Thesepharmacologicalactionsresultinanincreaseincardiacoutputmediatedbyafterload

reduction(b

,DA

)andmildpositiveinotropism(b

,Uptake-1inhibition)togetherwithanincreaseinbloodflowto

vascularbeds(DA

)suchastherenalandmesentericbedsandalsoperipherally.Dopacardisnotana-adrenergic

agonistanddoesnotcausevasoconstrictionandisnotapressoragent.

ExperienceinclinicaltrialshasshownthatDopacardcanincreasecardiacoutputbyover100%withinthe

recommendeddoserangeandincreasesoftheorderof50%arefrequentlyachievedatdosesof1-2micrograms/kg/min

withoutaclinicallysignificanteffectonheartrate.

5.2Pharmacokineticproperties

Dopacardisreadilyeliminatedfrombloodwithahalf-lifeofapproximately6-7minutesinhealthyvolunteersand

around11minutesinpatientswithcardiacfailure.Subsequenteliminationofthemetabolitesisbyurinaryandbiliary

excretion.TheresponsetoDopacardisrapidinonsetandeffectssubsiderapidlyondiscontinuationoftheinfusion.

Increasesindosemaybemadeatintervalsofnotlessthan15minutes.

5.3Preclinicalsafetydata

TherearenoadditionalsafetydataofrelevancetotheprescriberwhichhavenotalreadybeenstatedintheSmPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Disodiumedetate

Hydrochloricacid

Waterforinjections

6.2Incompatibilities

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthosementionedinsection6.6

DopacardshouldnotbeaddedtoSodiumBicarbonateoranyotherstronglyalkalinesolution,asinactivationwill

occur.

Contactwithmetalparts,ininfusionapparatusforexample,shouldbeminimised.

6.3ShelfLife

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Chemicalandphysicalin-usestabilityofpreparedintravenoussolutionsin0.9%SodiumChlorideInjectionor5%

DextroseInjectionhasbeendemonstratedfor24hoursat25ºC.

Fromamicrobiologicalpointofview,theproductshouldbedilutedandusedimmediatelyafteropening.Ifnotused

immediately,in-usestoragetimesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynot

belongerthan24hoursat2to8 o

C,unlessdilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Storebelow25ºC.Keeptheampouleintheoutercartoninordertoprotectfromlightandmoisture.

Forstorageofsterileproductsthathavebeenopened,diluted,orreconstitutedseesection6.3.

6.5Natureandcontentsofcontainer

Boxof10clearTypeIglassampouleseachcontaining5mlof1%(w/v)solutionofdopexaminehydrochloride(50mg

perampoule).

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Dopacardshouldonlybedilutedwith0.9%SodiumChlorideInjection,5%DextroseInjection,Hartmann'sSolution

(CompoundSodiumLactateIntravenousInfusion)orDextrose4%/Saline0.18%Injection.

Theappropriatevolumeofdiluentsolutionshouldbeasepticallyextractedfromtheinfusionbag,orthemetering

chamberoftheadministrationset,beforeaddingthecontentsoftheDopacardampoule(s)toarriveatthefinal

concentration-seetablebelow.

Careshouldbeexercisedinheartfailuretorestrictthesodiumloadandvolumebeingadministered.

Dopacard,incommonwithothercatecholamines,mayturnslightlypinkinpreparedsolutions.Thereisnosignificant

lossofpotencyassociatedwiththischange.

7MARKETINGAUTHORISATIONHOLDER

CephalonLimited

1AlbanyPlace

HydeWay

WelwynGardenCity

Hertfordshire

AL73BT

Volumeofdiluent

solution(ml) Volumetobe

extracted(ml) No.of5ml

Dopacardampoules

tobeadded FinalConcentration

(µg/ml)

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8MARKETINGAUTHORISATIONNUMBER

PA1260/4/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12October1988

Dateoflastrenewal:14June2009

10DATEOFREVISIONOFTHETEXT

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