DOBUTREX

Main information

  • Trade name:
  • DOBUTREX Concentrate for Soln for Inf 12.5 Mg/Ml
  • Dosage:
  • 12.5 Mg/Ml
  • Pharmaceutical form:
  • Concentrate for Soln for Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOBUTREX Concentrate for Soln for Inf 12.5 Mg/Ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1226/003/001
  • Authorization date:
  • 02-12-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dobutrex250mg/20ml,concentrateforsolutionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

DobutamineHydrochlorideequivalenttoDobutamine250mg/20ml(12.5mg/ml).

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Concentrateforsolutionforinfusion

Aclear,colourlesstofaintstraw-colouredsolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Actions:Theprimaryactionofdobutamineistoaugmentcardiaccontractilitybystimulatingthebeta-1receptorsof

theheart.Itisadirect-actingagent.

Indications:Dobutrexisindicatedforadultswhorequireinotropicsupportinthetreatmentofcardiacfailure

associatedwithmyocardialinfarction,openheartsurgeryorcardiomyopathies.Dobutrexisalsoindicatedforadults

withcardiogenicorsepticshockwhoarenotseverelyhypotensive.Dobutrexcanincreaseormaintaincardiacoutput

duringpositiveendexpiratorypressure(PEEP)ventilation.

4.2Posologyandmethodofadministration

Forintravenousadministrationonly.

Dobutrexshouldonlybeusedinspecialistunitsinwhichadequatefacilitiesareavailableforpatientsurveillanceand

themonitoringofresponses.

DobutrexSolutionmustbefurtherdilutedtoatleast50mlpriortoadministrationinani.v.containerwithoneofthe

intravenoussolutionslistedbelow:

SodiumChlorideIntravenousInfusionBP

5%DextroseIntravenousInfusionBP

5%Dextrose+0.9%SodiumChlorideIntravenousInfusionBP

5%Dextrose+0.45%SodiumChlorideIntravenousInfusionBP

SodiumLactateIntravenousInfusionBP

Ifdilutingto250mlor500ml,dilutionwillgiveaconcentrationforadministrationasfollows:

250mlcontains1,000micrograms/mlofdobutamine

500mlcontains500micrograms/mlofdobutamine

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Administration:Duetoitsshorthalf-life,Dobutrexmustbeadministeredasacontinuousintravenousinfusion.After

dilution,Dobutrexshouldbeadministeredintravenouslythroughanintravenousneedleorcatheter.Ani.v.drip

chamberorothersuitablemeteringdeviceisessentialforcontrollingtherateofflowindropsperminute.

Recommendeddosageforadultsandtheelderly:Dosageisinverselydependentupontheextentofhealthy

myocardium.Mostpatientswillrespondsatisfactorilytodosesrangingfrom2.5to10micrograms/kg/minute.

Occasionallyadoseaslowas0.5micrograms/kg/minutewillelicitaresponse.Rarely,adoseashighas40

micrograms/kg/minuteisrequired.

Therateofadministrationandthedurationoftherapyshouldbeadjustedaccordingtothepatient'sresponseas

determinedbyheartrate,bloodpressure,urineflow,and,ifpossible,measurementofcardiacoutput.

RatherthanabruptlydiscontinuingtherapywithDobutrex,itisoftenadvisabletodecreasethedosagegradually.

Side-effects,whicharedose-related,areinfrequentwhenDobutrexisadministeredatratesbelow10

micrograms/kg/minute.Ratesashighas40micrograms/kg/minutehavebeenusedoccasionallywithoutsignificant

adverseeffects.

Thefinalvolumeadministeredshouldbedeterminedbythefluidrequirementsofthepatient.Concentrationsashighas

5,000micrograms/mlhavebeenusedinpatientsonarestrictedfluidintake.

Highconcentrationsofdobutamineshouldonlybegivenwithaninfusionpump,toensureaccuratedosage.

Paediatricuse:Thesafetyandefficacyofdobutamineforuseinchildrenhavenotbeenestablished.

4.3Contraindications

Previoushypersensitivitytodobutamine.Hypovolaemia(seeSection4.4).

4.4Specialwarningsandprecautionsforuse

Iftachycardiaoranundueincreaseinsystolicbloodpressureoccursorifanarrhythmiaisprecipitated,thedoseof

dobutamineshouldbereducedorthedrugshouldbediscontinuedtemporarily.

Dobutaminemayprecipitateorexacerbateventricularectopicactivity;rarelyhasitcausedventriculartachycardiaor

fibrillation.Becausedobutaminefacilitatesatrioventricularconduction,patientswithatrialflutterorfibrillationmay

developrapidventricularresponses.

Extremecautionshouldbeexercisedwhendobutamineisusedinpatientswithacutemyocardialinfarctionbecauseany

significantincreaseinheartrateorexcessiveincreasesinarterialpressurethatoccurmayintensifyischaemiaandcause

anginalpainandSTsegmentelevation.Extremecautionshouldalsobeexercisedinpatientswithatrialfibrillationor

idiopathichypertrophicsubaorticstenosis.

Inotropicagents,includingdobutamine,donotimprovehaemodynamicsinmostpatientswithmechanicalobstruction

thathinderseitherventricularfillingoroutflow,orboth.Inotropicresponsemaybeinadequateinpatientswith

markedlyreducedventricularcompliance.Suchconditionsarepresentincardiactamponade,valvularaorticstenosis,

andidiopathichypertrophicsubaorticstenosis.

Duringtheadministrationofdobutamine,aswithanyparenteralcatecholamine,heartrateandrhythm,arterialblood

pressure,andinfusionrateshouldbemonitoredclosely.Wheninitiatingtherapy,electrocardiographicmonitoringis

advisableuntilastableresponseisachieved.Thedevelopmentofincreaseinheartrateorbloodpressure,or

arrhythmiasmayrequirethetemporaryreductionordiscontinuationofdosage.

Precipitousdecreasesinbloodpressure(hypotension)haveoccasionallybeendescribedinassociationwithdobutamine

therapy.Decreasingthedoseordiscontinuingtheinfusiontypicallyresultsinrapidreturnofbloodpressureto

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Dobutamineshouldbeusedwithcautioninthepresenceofseverehypotensioncomplicatingcardiogenicshock(mean

arterialpressurelessthan70mmHg).

Hypovolaemiashouldbecorrectedwhennecessarywithwholebloodorplasmabeforedobutamineisadministered.

Ifarterialbloodpressureremainslowordecreasesprogressivelyduringadministrationofdobutaminedespiteadequate

ventricularfillingpressureandcardiacoutput,considerationmaybegiventotheconcomitantuseofaperipheral

vasoconstrictoragent,suchasdopamineornoradrenaline.

Dobutrexcontainssodiummetabisulphite.Sulphitesmaycauseallergic-typereaction,includinganaphylactic

symptomsandlife–threateningorlesssevereasthmaticepisodesincertainsusceptiblepeople.Sulphitesensitivityis

seenmorefrequentlyinasthmaticthannon–asthmaticpeople.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Thepotencyofdobutaminemaybedecreasedifthepatientisgivenbeta-adrenergicreceptorantagonists.Insucha

case,theunopposedalpha-agonisteffectsofdobutaminemaybecomeapparent,includingperipheralvasoconstriction

andhypertension.Conversely,alpha-adrenergicblockademaymakethebeta-1andbeta-2effectsapparent,resultingin

tachycardiaandvasodilatation.

4.6Pregnancyandlactation

Reproductionstudiesperformedinratsandrabbitshaverevealednoevidenceofharmtothefoetusorteratogenic

effectsduetodobutamine.Animalstudiestoevaluateeffectsonfertilityhavenotbeenperformed.Asthereareno

adequateandwell-controlledstudiesinpregnantwomenandasanimalreproductionstudiesarenotalwayspredictive

ofhumanresponse,dobutamineshouldnotbeusedduringpregnancyunlessthepotentialbenefitsoutweighthe

potentialriskstothefoetus.

Itisnotknownwhetherthisdrugisexcretedinhumanmilk,socautionshouldbeexercised.Ifamotherrequires

dobutaminetreatment,breastfeedingshouldbediscontinuedforthedurationoftreatment.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

Forcardiovasculareffects,see‘Section4.4’.

Reactionsatsiteofintravenousinfusion:Phlebitishasoccasionallybeenreported.Localinflammatorychangeshave

beendescribedfollowinginadvertentinfiltration.Isolatedcasesofcutaneousnecrosishavebeenreported.

Thefollowingside-effectshavebeenreportedrarely:nausea,headache,anginalpain,non-specificchestpain,

palpitations,shortnessofbreath,andreactionssuggestiveofhypersensitivity,includingrash,fever,eosinophiliaand

bronchospasm.Isolatedcasesofthrombocytopeniahavebeenreported.

Aswithothercatecholamines,decreasesinserumpotassiumconcentrationshaveoccurred,rarelytohypokalaemic

values.Considerationshouldbegiventomonitoringserumpotassium.

Long-termsafety:Infusionsforupto72hourshaverevealednoadverseeffectsotherthanthoseseenwithshorter

infusions.Thereisevidencethatpartialtolerancedevelopswithcontinuousinfusionsofdobutaminefor72hoursor

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4.9Overdose

Overdosesofdobutaminehavebeenreportedrarely.Thesymptomsoftoxicitymayincludeanorexia,nausea,vomiting,

tremor,anxiety,palpitations,headache,shortnessofbreathandanginalandnon-specificchestpain.Thepositive

inotropicandchronotropiceffectsofdobutaminemaycausehypertension,tachyarrhythmias,myocardialischaemiaand

ventricularfibrillation.Hypotensionmayresultfromvasodilatation.

Thedurationofactionofdobutaminehydrochlorideisgenerallyshort(half-life,approximately2minutes).

Temporarilydiscontinuedobutamineuntilthepatient'sconditionstabilises.Thepatientshouldbemonitoredandany

appropriateresuscitativemeasuresinitiatedpromptly.

Forceddiuresis,peritonealdialysis,haemodialysis,orcharcoalhaemoperfusionhavenotbeenestablishedasbeneficial.

Iftheproductisingested,unpredictableabsorptionmayoccurfromthemouthandgastro-intestinaltract.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Theprimaryactionofdobutamineistoaugmentcardiaccontractilitybystimulatingthebeta-1receptorsoftheheart.It

isadirect-actingagent.

5.2Pharmacokineticproperties

TheonsetactionofDobutrexiswithinonetotwominutes;theprincipalroutesofmetabolismaremethylationofthe

catecholandconjugation.Inhumanurinethemajorexcretionproductsaretheconjugatesofdobutamineand3-0-

methyldobutamine.The3-0-methylderivativeofdobutamineisinactive.

5.3Preclinicalsafetydata

Therearenopre-clinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSummaryofProductCharacteristics.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiummetabisulphite

Waterforinjections

Hydrochloricacid

Sodiumhydroxide

6.2Incompatibilities

Becauseofpotentialphysicalincompatibilities,itisrecommendedthatDobutrexnotbemixedwithotherdrugsinthe

samesolution.

DonotaddDobutrexto5%SodiumBicarbonateIntravenousInfusionBPortoanyotherstronglyalkalinesolutions.

Dobutaminehydrochlorideshouldnotbeusedinconjunctionwithotheragentsordiluentscontainingbothsodium

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6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

DonotstoreundilutedvialsofDobutrexSolutionabove25°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2

to8°Cunlessdilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.5Natureandcontentsofcontainer

AType1Ph.Eur.clearglassvialwithrubberstopperandaluminiumseal.

Packs:singledose,20mlvial.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Seesection4.2and6.2.

SolutionscontainingDobutrexmayturnpink;thecolourmayintensifywithtime.Thiscolourchangeisduetoslight

oxidationofthedrug,butthereisnosignificantlossofpotencyduringtherecommendedstorageperiods.

7MARKETINGAUTHORISATIONHOLDER

FlynnPharmaLimited

AltonHouse

4HerbertStreet

Dublin2

RepublicofIreland

8MARKETINGAUTHORISATIONNUMBER

PA1226/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14December1977

Dateoflastrenewal:14December2002

10DATEOFREVISIONOFTHETEXT

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