DOBUTAMINE PFIZER

Main information

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

Documents

Localization

  • Available in:
  • DOBUTAMINE PFIZER
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/046/001
  • Authorization date:
  • 19-08-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DobutaminePfizer12.5mg/mlConcentrateforsolutionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each1mlcontains12.5mgofdobutamine(as14.01mgdobutaminehydrochloride).

Each20mlampoulecontains250mgofdobutamine(as280.2mgdobutaminehydrochloride).

Each1mlcontains0.15mgofSodiummetabisulphite.

Each20mlcontains3.0mgofSodiummetabisulphite.

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Concentrateforsolutionforinfusion

Clear,colourlessorslightlyyellowsolution

pHbetween2.50and4.00

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dobutamineisindicatedforadultswhorequirepositiveinotropicsupportinthetreatmentoflowoutputcardiacfailure

normallyassociatedwithmyocardialinfarction,open-heartsurgery,cardiomyopathies,septicshockandcardiogenic

shock.

Dobutaminecanalsobeusedforcardiacstresstesting,incaseswhenexercisestresstestingisnotfeasible.

4.2Posologyandmethodofadministration

Methodofadministration

DobutamineConcentrateshouldbedilutedbeforeuseandadministeredbyIVinfusiononly.

Theconcentrationofthedobutamineadministereddependsuponthedosageandfluidrequirementsoftheindividual

patient.Thefinalconcentrationsgenerallyusedforperfusionare250micrograms/ml,500micrograms/mlor1000

micrograms/ml.Forspecialprecautionsforstorageoftheprepareddilutedinfusionseesection6.4.Highconcentrations

ofdobutamineshouldonlybegivenwithaninfusionpumporothersuitableapparatustoensureaccuratedosage.Due

toitsshorthalf-lifedobutamineshouldbeadministeredasacontinuousintravenousinfusion.

Dobutamineshouldbeadministeredintravenouslythroughanintravenousneedleorcatheter.Thefollowingsterile

solutionsforIVinfusionmaybeusedforthedilutionofdobutaminebeforeuse:sodiumchloridesolution0.9%(9

mg/ml),glucosesolution5%(50mg/ml),dextrosesolution5%(50mg/ml),orRingerlactatesolution.

Forinstructionsondilutionofthemedicinalproductbeforeadministration,seesection6.6.

DosageforInfusiondeliverysystems:

OneampouleDobutamine12.5mg/ml(250mg/20ml)dilutedtoasolutionvolumeof500ml(finalconcentration0.5

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*Fordoubleconcentration,i.e.500mgDobutamineaddedto500ml,or250mgaddedto250mlsolution,infusion

ratesmustbehalved.

Thedosetobeadministeredcanbecalculatedtakingintoaccountthetablebelow.Infusionratesinmillilitres/mincan

beobtainedbymultiplyinginfusionratesforeachconcentration(ml/kg/min)bypatient’sweight(kg).

Dosageforsyringepumps:

OneampouleDobutamine12.5mg/ml(250mg/20ml)dilutedtoasolutionvolumeof50ml(finalconcentration5

Dosagerange Specificationsinml/h*

(drops/min)

Patient’sweight

50kg 70kg 90kg

2.5µg/kg/min ml/h

(drops/min) 15

Medium

5µg/kg/min ml/h

(drops/min) 30

(10) 42

(14) 54

(18)

High

10µg/kg/min ml/h

(drops/min) 60

(20) 84

(28) 108

(36)

One(1)ampoule Two(2)

ampoules Four(4)

ampoules

250mg

dobutaminein

1000mlof

solutionfor

infusion 500mg

dobutaminein

1000mlof

solutionfor

infusion 1000mg

dobutaminein

1000mlof

solutionfor

infusion

micrograms/ml 500

micrograms/ml 1000

micrograms/ml

Dose

micrograms/kg/min Infusionrate

ml/kg/min Infusionrate

ml/kg/min Infusionrate

ml/kg/min

0.01 0.005 0.0025

0.02 0.01 0.005

0.03 0.015 0.0075

0.04 0.02 0.01

12.5 0.05 0.025 0.0125

0.06 0.03 0.015

Dosagerange Specificationsinml/h

(ml/min)

Patient’sweight

50kg 70kg 90kg

2.5µg/kg/min ml/h

(ml/min) 1.5

(0.025) 2.1

(0.035) 2.7

(0.045)

Medium

5µg/kg/min ml/h

(ml/min) 3.0

(0.05) 4.2

(0.07) 5.4

(0.09)

High

10µg/kg/min ml/h

(ml/min) 6.0

(0.10) 8.4

(0.14) 10.8

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Posology

Adults:

Inotropicsupportofthemyocardium:

Theusualdoseis2.5to10micrograms/kg/min,whichshouldbeadjustedaccordingtothepatient'sheartrate,blood

pressure,cardiacoutputandurineoutput.Theinfusionmustbestartedatarateof2.5micrograms/kg/minandthedose

maybeincreasedinintervalsof10-30minutesuntildesiredhemodynamicresponseisachievedoruntilsideeffects,

suchasexcessivetachycardia,arrhythmia,headacheortremorlimitafurtherincreaseindosage.Thedoseshouldbe

adjustedindividuallyaccordingtoheartrateandrhythm,bloodpressureandurinaryflow.Occasionally,adoseaslow

as0.5micrograms/kg/minwillelicitaresponse.Upto40micrograms/kg/minmayoccasionallyberequired,butthisis

rare.

Duringprolongedcontinuousinfusion(48-72hours),adecreaseinhaemodynamicresponsemayoccur,whichmakes

anincreaseindosenecessary.

Dosageforcardiacstresstesting:

Theuseofdobutamineincardiacstresstestingshouldonlybeundertakeninunitswhichalreadyperformexercise

stresstestingandallnormalcareandprecautionsrequiredforsuchtestingarealsorequiredwhenusingdobutaminefor

thispurposeincludingtheavailabilityofadefibrillatorandpersonnelspeciallytrainedinresuscitationarepresent.

Therecommendeddosageisanincrementalincreaseininfusionratesfrom5micrograms/kg/minuteto10,20,30anda

maximumof40micrograms/kg/minute,eachdosebeinginfusedfor3minutes.Inadditionatropinecanbeadded

duringfurtherinfusionofthepeakdose.Continuouselectrocardiogram(ECG)monitoringisrequiredandtheinfusion

maybeterminatedintheeventofST-segmentdepressionof>0.2mV(2mm)measured80msaftertheJpoint,aST-

segmentelevateof>0.1mV(1mm)inpatientswithouthistoryofmyocardialinfarction,oranysignificantcardiac

arrhythmias.

Theinfusionofdobutamineshouldbeterminatediftheheartratereaches85%oftheage-predictedmaximum,systolic

bloodpressurerisesabove220mmHgorasymptomaticdecreaseinsystolicbloodpressure>40mmHgfrombaseline,

newcardiacwallmotionabnormalities,severechestpainoranynon-tolerableadverseeffectoccurs.

Elderly:

Novariationindosageissuggested.Closemonitoringisrequiredforbloodpressure,urineflowandperipheraltissue

perfusion.

Cardiacstresstesting:Whenusedasanalternativetoexerciseforcardiacstresstestingtherecommendeddoseshould

startat5micrograms/kg/minute,andthedoseshouldbeincreasedincrementallyby5micrograms/kg/minuteevery8

minutes,toamaximumrateof20micrograms/kg/minute.ContinuousECGmonitoringisessentialandtheinfusion

terminatedintheeventof>3mmSTsegmentdepressionoranyventriculararrhythmia.Theinfusionshouldalsobe

terminatedifheartratereachestheage/sexmaximum,systolicbloodpressurerisesabove220mmHgoranyside

effectsoccur

PaediatricPatients

Dosesof1to15µgdobutamine/kg/minhavebeenadministered.Thereisreasontobelievethattheminimumeffective

dosageforchildrenishigherthanforadults.Cautionshouldbetakeninapplyinghighdoses,becausethereisalso

reasontobelievethatthemaximumtolerateddosageforchildrenislowerthantheoneforadults.Mostadverse

reactions(tachycardiainparticular)areobservedwhendosagewashigherthan/equalto7.5µgdobutamine/kg/min.

Therequireddoseforchildrenshouldbetitratedinordertoallowforthesupposedlysmaller“therapeuticwidth”in

children.Aninitialdoseof0.5micrograms/kg/minisrecommended,whichisincreasedevery10-30minutesuntil

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4.3Contraindications

Patientswithknownorsuspectedhypersensitivitytodobutamine,sodiummetabisulphiteorothersulphatesorto

anyoftheotherexcipients.

Patientswithmarkedmechanicalobstructionaffectingventricularfillingoroutflow,orboth,suchascardiac

tamponade,severevalvularaorticstenosis,constrictivepericarditis,hypertrophicobstructivecardiomyopathiaor

idiopathichypertrophicsubaorticstenosis.

Patientswithhypovolaemiaunlessithasbeencorrectedbyvolumereplacement.

Uncontrolledseriousventriculararrhythmias.

Inaddition,forcardiacstresstest:Recentmyocardialinfarction(within30days),aorticdissection,aortic

aneurysm,unstableangina,uncontrolledhypertension,uncontrolledarrhythmias(includinguncontrolledatrial

fibrillation),knownsevereventriculararrhythmias,electrolyteimbalanceandsevereanaemia.

Phaeochromocytoma

4.4Specialwarningsandprecautionsforuse

Ifanundueincreaseinheartrateorsystolicbloodpressureoccursorifanarrhythmiaisprecipitatedthedoseof

dobutamineshouldbereducedorthedrugshouldbediscontinuedtemporarily.

Dobutaminemayprecipitateorexacerbateventricularectopicactivity,rarelyhasitcausedventriculartachycardiaor

fibrillation.Dobutamineincreasesatroventricularconduction,patientswithatrialflutterorfibrillationmaydevelop

rapidventricularresponses.

Thereisapossibilitythatdobutaminecancauseasignificantincreaseinheartrateorexcessiveincreaseinarterial

pressurewhichmayintensifyorextendmyocardialischaemia,causeanginalpainandSTsegmentelevation,therefore

careshouldbeexercisedfollowingmyocardialinfarction(seesection4.3).

Dobutaminewillnotimprovehaemodynamicsinmostpatientswithmechanicalobstructionaffectingventricularfilling

oroutflow,orboth(seesection4.3).

Inotropicresponsemaybeinadequateinpatientswithmarkedlyreducedventricularcompliance,e.g.withcardiac

tamponade,valvularaorticstenosis,andidiopathichypertrophicsubaorticstenosis(seesection4.3).

Viacompetitivereceptorinhibition,thecatecholaminergiceffectofdobutaminecanbereducedwithsimultaneous

administrationofabetareceptorblocker.Inaddition,thealphaeffectspredominantatthattimemaycauseaperipheral

vasoconstrictionwithaconsequentincreaseofbloodpressure.

Administration

Beforeadministrationofdobutamine,hypovolaemiashouldbecorrectedwithanappropriateplasmavolumeexpander

(seesection4.3).Likeotherdrugswithbeta-2-agonistactivity,dobutaminemayproduceslightreductionsinserum

potassiumconcentrationsandhypokalaemiamayoccuroccasionally.Considerationshouldbegiventomonitoring

serumpotassiumduringdobutaminetherapy.

Duringadministrationofdobutamine,heartrateandrhythm,arterialbloodpressure,andinfusionrateshouldbe

monitoredclosely.Whenstartingtherapy,electrocardiographicmonitoringisrecommendeduntilastableresponseis

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Caution

Dobutamineshouldbeusedwithcautioninseverehypotensioncomplicatingcardiogenicshock(meanarterialpressure

lessthan70mmHg).Ifthebloodpressuredropsquickly,decreasingthedoseorstoppingtheinfusiontypicallyresults

inareturntobase-linebloodpressurevalues.

Occasionallyinterventionmayberequiredandreversibilitymaynotbeimmediate.

Ifarterialbloodpressureremainslowordecreasesprogressivelyduringadministrationofdobutaminedespiteadequate

ventricularfillingpressureandcardiacoutput,considerationmaybegiventotheuseofaperipheralvasoconstrictor

agente.g.noradrenalineordopamine.

DobutamineConcentrateforsolutionforinfusioncontainssodiummetabisulphiteintheformulation.Thismay

causeallergictypereactionsincludinganaphylaxisandlife-threateningorlesssevereasthmaticepisodes,incertain

susceptibleindividuals.Theoverallprevalenceofsulphitesensitivityinthegeneralpopulationisunknownbutis

probablylow;suchsensitivityseemstooccurmorefrequentlyinasthmaticpatients(seesection4.3).

Dobutamineshouldonlybeusedunderthedirectsupervisionofphysicianstowhomfacilitiesforregular,intensive

monitoringofcardiovascularandrenalparameters,inparticular,bloodvolume,myocardialcontractility,

electrocardiography,urineflowrate,andbloodandpulsepressureand,ifpossible,cardiacoutputandpulmonary

wedgepressure(PWP)areavailable.

Aftercessationofalongtermtherapy(morethan7days)withdobutamineadecreaseincardiacoutputandanincrease

inPWPwasobserved.

Inpatientswithpre-existinghypertoniaanincreaseinbloodpressurecouldoccur.

Sincetheeffectofdobutamineonimpairedrenalandhepaticfunctionisnotknown,closemonitoringisadvisable.

Intravenouscontinuousdobutamineisoflimitedbenefitandmayinfactbeharmfultopatientswithadvancedheart

failure,withrespecttoqualityoflifeandsurvivalrates.

Dobutaminemayalterinsulinandglucoseplasmalevels.Consequently,indiabeticpatients,theglucoseconcentration

shouldbecontrolledandtheinsulindoseadjustedifnecessary.

Theuseofdobutamineasanalternativetoexerciseforcardiacstresstestingisnotrecommendedforpatientswith

unstableangina,bundlebranchblockoranycardiacconditionthatcouldmakethemunsuitableforexercisestress

testing.

Aswithothercatecholamines,dobutaminemaytriggeranonsetofanginainpatientswithischaemicheartdiseaseand

consequentlyparticularcareshouldbeexercisedwhendobutamineisadministeredtopatientswithischaemicheart

disease.

Particularcautionhastobeexercisedwhenusingdobutamineinpatientstreatedwithmonoamineoxidaseinhibitors

(MAOs)andinpatientswithpheochromocytomaorwithhyperthyroidismduetotheincreasedcatecholaminelevelsor

sensitivity,whichcouldresultinmarkedincreasesinbloodpressure,heartrateandhigherincidenceofarrhythmias

Cardiacruptureisapotentialcomplicationofmyocardialinfarction.Theriskofcardiacrupture(septalandfreewall)

maybeinfluencedbyavarietyoffactorsincludingsiteof,andtimesince,infarct.Therehavebeenveryrare,fatal

reportsofacutecardiacruptureduringdobutaminestresstesting.Theseeventshaveoccurredduringpre-discharge

examinationinpatientshospitalisedwithrecent(within4-12days)myocardialinfarction.Inthereportedcasesoffree

wallrupture,restingechocardiogramshowedadyskineticandthinnedinferiorwall.Patientsconsideredatriskof

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Dobutaminestressechocardiography

Becauseofpossiblelife-threateningcomplicationstheusewithinthescopeofischemiaandvitallydiagnosticsisonly

allowedbyaphysicianwithsufficientpersonalexperienceinstressechocardiography.

Dobutaminestressechocardiographywithinthescopeofischemiaandvitalitydiagnosticsmustbediscontinuedifone

ofthefollowingdiagnosticendpointsoccurs:

Reachingtheage-predictedmaximalheartrate[(220-ageinyears)x0.85],

systolicbloodpressuredecrease>20mmHg,

bloodpressureincreaseto>220/120mmHg,

progressivesymptoms(anginapectoris,dyspnoea,dizziness,ataxia),

progressivearrhythmia(e.g.coupling,ventricularsalvos),

progressiveconductiondisturbances,

recentlydevelopedwallmotilitydisordersin>1wallsegment

(16-segmentmodel),

increaseofendsystolicvolume,

developmentofrepolarisationabnormality(duetoischemiahorizontalordownslopingSTsegmentdepression

>0.2mVatanintervalof80(60)msaftertheJpointcomparedtobaseline,progressiveormonophasicST

segmentelevation>0.1mVinpatientswithoutapreviousmyocardialinfarction,

reachingpeakdose.

Alsoincaseofseriouscomplications(seesection4.8)aDobutaminestressechocardiographyhastobeimmediately

disrupted.

Afterterminationofinfusion,patientsmustbemonitoreduntilstabilised.

Thismedicinalproductcontains0.0504mmol(1.160mg)sodiumperdose.Tobetakenintoconsiderationbypatients

onacontrolledsodiumdiet.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Beta-adrenergicblockingagents

Inanimalsthecardiaceffectsofdobutamineareantagonisedbybeta-adrenergicblockingagentssuchaspropranolol

andmetoprolol,resultinginpredominanceofalpha-adrenergicblockingagentsandincreasedperipheralresistance.

Conversely,alpha-adrenergicblockademaymakethebeta1andbeta2effectsapparent,resultingintachycardiaand

vasodilatation.

Theadditionofdipyridamoletodobutamineforechocardiographycancausepotentiallyhazardoushypotension.The

combinationshouldnotbeusedinpatientssuspectedofcoronaryheartdisease.

Dobutaminestressechocardiography

Inthecaseofanti-anginaltherapy,inparticularheartrateloweringagentslikebeta-blockers,theischemicreactionto

stressislesspronouncedormaybenonexistentaltogether.

Thereforeantianginaltherapymayneedtobewithheldfor12hourspriortotheDobutaminestressechocadiography.

WhenaddingatropineatthehighesttitrationlevelofDobutamine,thefollowingcanbeobserved:

Duetotheprolongeddurationofthestressechocardiographyprotocol,thehighertotaldoseofDobutamineandthe

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Generalanaesthetics

Ventriculararrhythmiashavebeenreportedinanimalsreceivingusualdosesofdobutamineduringhalothaneor

cyclopropaneanaesthesia;therefore,cautionshouldbeexercisedwhenadministeringdobutaminetopatientsreceiving

theseanaesthetics.

ConcomitantuseofdobutamineandMAOIsmayresultinmarkedincreasesinbloodpressureandheartrateandin

increasedincidenceofarrhythmias.

Evenlife-threateningeventssuchashypertensivecrisis,cardiovascularcollapse,intracranialhaemorrhageand

arrythmiasmayresult.

Pre-treatmentorconcomitantadministrationofß-receptorblockingdrugsmayresultindecreaseininotropicand

chronotropiceffectsduetocompetitivebindingtotheß-receptorandinpredominanceofthealpha1-mediatedeffects

resultinginperipheralvasodilatation.

Peripheralvasodilators(e.g.nitrates,sodiumnitroprusside)incombinationwithdobutaminemayincreasecardiac

outputanddecreasesystemicperipheralresistanceandventricularfillingpressuremorethaneitherdrugalone.

Concomitantusetheophyllinewithdobutamineresultedinanincreaseintheheartrate,inoneclinicalstudy.

Concurrentuseofdobutamineanddopamineincreasessystemicarterialpressuremarkedlyandpreventstheincreasein

ventricularfillingpressureseenwithdopaminealone.

Concomitantuseofdobutamineandperipheralvasoconstrictoragentssuchasnoradrenalineincreasessystemicarterial

bloodpressuremoremarkedly,thaneitherdrugalone.

ConcomitantadministrationofdobutamineandACE-inhibitors(e.g.captopril)mayresultinanincreaseincardiac

outputaccompaniedbyincreasedmyocardialoxygenconsumption.Theoccurrenceofchestpainandarrhythmiashas

beenreportedwiththiscombination.

Theeffectsofdobutaminemaybeenhancedbytheconcomitantusewithentacapone.Thehypertensiveeffectsof

dobutaminemaybeantagonisedbyantipsychotics.

Thereisanincreasedriskofhypertensionwhendobutamineisgivenwithdoxapram.

Thereisanincreasedriskofergotismwhendobutamineisgivenwithergotamineandmethysergide.

Concomitantuseofdobutamineandoxytocinmaycausehypertension(duetotheenhancedvasopressoreffects).

Additionofatropinesulphateenhancestheincreasesinheartrateinducedbydobutamineandmaycounteractthe

decelerationinheartrateoccasionallyobservedindobutaminecardiacstresstesting.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenoadequatedataonthesafetyofdobutamineinhumanpregnancy.Animalstudiesdonotindicatedirector

indirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,parturitionandpost-natal

development,butitisnotknownwhetherdobutaminecrossestheplacenta(seesection5.3).Thepotentialriskfor

humansisunknown.Dobutamineshouldnotbeusedduringpregnancyunlessthepotentialbenefitstothewoman

outweighthepotentialriskstothefetus.

Lactation

Itisnotknownwhetherdobutamineisexcretedinanimalorhumanbreastmilk.Adecisiononwhetherto

continue/discontinuebreast-feedingortocontinue/discontinuetherapywithdobutamineshouldbemadetakinginto

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4.7Effectsonabilitytodriveandusemachines

Notrelevantinviewoftheindicationsforuseandtheshorthalf-lifeofdobutamine.

4.8Undesirableeffects

Infusionsforupto72hourshaverevealednoadverseeffectsotherthanthoseseenwithshorterinfusions.

ThereisevidencethatpartialtolerancedevelopswithcontinuousinfusionsofDobutamineConcentratefor72hoursor

more;therefore,higherdosesmayberequiredtomaintainthesameeffects.

Thefollowingterminologieshavebeenusedinordertoclassifytheoccurrenceofundesirableeffects:

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.

Immunesystemdisorders:

Common: Hypersensitivityreactionsincludingrash,fever,eosinophiliaandbronchospasmhavebeen

reported.

Rare: Sodiummetabisulphitemaycauseallergictypereactionsincludinganaphylaxisandlife-threatening

orlesssevereasthmaticepisodes(seesection4.4).

Metabolismandnutritiondisorders:

Veryrare: Aswithothercatecholamines,decreasesinserumpotassiumconcentrationshaveoccurred.

Considerationshouldbegiventomonitoringserumpotassium.

Nervoussystemdisorders:

Common: Headache

Veryrare: Myoclonushasbeenreportedinpatientswithsevererenalfailurereceivingdobutamine.

Cardiacdisorders:

Verycommon: Increasedheartrate,palpitations,severechestpain,irregularheartbeats,arrhythmia,ventricular

tachycardia,coronaryarteryspasm,electrocardiogramSTsegmentelevation.

Uncommon: Atrialfibrillation,ventricularfibrillation,leftventricularoutflowtractobstruction.

Veryrare: myocardialischaemia,myocardialinfarction,eosinophilicmyocarditis,fatalcardiacruptureduring

dobutaminestresstesting(seesection4.4).

Vasculardisorders:

Common: Hypertension.Markedincreaseinsystolicbloodpressureindicatesoverdose(seealsosection4.5).

Uncommon: Hypotension(seesections4.4&4.5).Slightvasoconstriction,especiallyinpatientswithpre-

treatedwithß-blockers.

Respiratory,thoracicandmediastinaldisorders:

Verycommon (1/10)

Common (1/100to<1/10)

Uncommon (1/1000to<1/100)

Rare (1/10000to<1/1000)

Veryrare (<1/10000)

Notknown (cannotbeestimatedfromtheavailable

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Gastrointestinaldisorders:

Common: Nausea.

Renalandurinarydisorder:

Notknown: urinaryurgency

Generaldisordersandadministrationsiteconditions:

Common: Non-specificchestpain.

Rare: Phlebitishasoccasionallybeenreportedandlocalinflammatorychangeshavebeendescribed

followinginadvertentinfiltration.

Veryrare: Cutaneousnecrosis

4.9Overdose

Overdosehasbeenrarelyreported.

Symptoms

Thesymptomsoftoxicitymayincludeanorexia,nausea,vomiting,tremor,anxiety,palpitations,headache,shortnessof

breath,fatigueandanginalandnon-specificchestpain.Thepositiveinotropicandchronotropiceffectsofdobutamine

maycausehypertension,tachyarrhythmias,myocardialischaemiaandventricularfibrillation.Hypotensionmayresult

fromvasodilation.Thedurationofactionofdobutamineisgenerallyshort(half-life,approximately2minutes).

Treatment

Duetotheshortdurationofactionofdobutamine,usuallyonlyareductionininfusionrateoratransientcessationof

infusionisnecessaryuntilstabilisationofthepatient.

Temporarilydiscontinuedobutamineuntilthepatient'sconditionstabilises.Thepatientshouldbemonitoredandany

appropriateresuscitativemeasuresstartedimmediately.

Forceddiuresis,peritonealdialyses,haemodialysisorcharcoalhaemoperfusionhavenotbeenestablishedasbeneficial.

Iftheproductisingested,unpredictableabsorptionmayoccurfromthemouthandgastrointestinaltract.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:cardiacstimulantsexcludingcardiacglycosides,adrenergicanddopaminergicagents

ATCcode:C01CA07

Dobutamineisaselectivebeta-adrenergicagonistwhosemechanismofactioniscomplex.

Itisbelievedthatthebeta-adrenergiceffectsresultfromstimulationofadenylcyclaseactivity.Intherapeuticdoses,

dobutaminealsohasmildbeta-2andalpha-1adrenergicreceptoragonisteffects,whicharerelativelybalancedand

resultinminimalnetdirecteffectonsystemicvasculature.Dobutaminedoesnotcausereleaseofendogenous

norepinephrine.Themaineffectoftherapeuticdosesofdobutamineiscardiacstimulation.

Whilethepositiveinotropiceffectofthedrugonthemyocardiumappearstobemediatedprincipallyviabeta-1-

adrenergicstimulation,experimentalevidencesuggeststhatalpha-1-adrenergicstimulationmayalsobeinvolvedand

thatthealpha-1-adrenergicactivityresultsmainlyfromthe(-)-stereoisomerofthedrug.

Thebeta-1-adrenergiceffectsofdobutamineexertapositiveinotropiceffectonthemyocardiumandresultinan

increaseincardiacoutputduetoincreasedmyocardialcontractilityandstrokevolume.Increasedleftventricularfilling

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Intherapeuticdoses,dobutaminecausesadecreaseinperipheralresistance;however,systolicbloodpressureandpulse

pressuremayremainunchangedorbeincreasedbecauseofaugmentedcardiacoutput.Withusualdoses,heartrateis

usuallynotsubstantiallychanged.Coronarybloodflowandmyocardialoxygenconsumptionareusuallyincreased

becauseofincreasedmyocardialcontractility.

Dobutaminefacilitatesatrioventricularconductionandshortensorcausesnoimportantchangeinintraventricular

conduction.Thetendencyofdobutaminetoinducecardiacarrhythmiasmaybeslightlylessthanthatofdopamineand

isconsiderablylessthanthatofisoproterenolorothercatecholamines.Pulmonaryvascularresistancemaydecreaseifit

iselevatedinitiallyandmeanpulmonaryarterypressuremaydecreaseorremainunchanged.Dobutaminedoesnot

seemtoaffectdopaminergicreceptorsandcausesnorenalormesentericvasodilation;however,urineflowmay

increasebecauseofincreasedcardiacoutput.

5.2Pharmacokineticproperties

Absorption:OrallyadministereddobutamineisrapidlymetabolisedintheGItract.FollowingIVadministration,the

onsetofactionofdobutamineoccurswithin2minutes.Peakplasmaconcentrationsofthedrugandpeakeffectsoccur

within10minutesafterinitiationofanIVinfusion.Theeffectsofthedrugceaseshortlyafterdiscontinuingan

infusion.

Distribution:Itisnotknownifdobutaminecrossestheplacentaorisdistributedintomilk.

Elimination:Theplasmahalf-lifeofdobutamineisabout2minutes.Dobutamineismetabolisedintheliverandother

tissuesbyCatechol-O-methyltransferasetoaninactivecompound,3-O-methyldobutamine,andbyconjugationwith

glucuronicacid.Conjugatesofdobutamineand3-O-methyldobutamineareexcretedmainlyinurineandtoaminor

extentinfaeces.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofrepeateddosetoxicity.Studieson

themutagenicorcarcinogenicpotentialofdobutaminehavenotbeenconducted.Studiesinratsandrabbitsrevealedno

evidenceoffetalharmorteratogeniceffect.Noinfluenceonfertilitywasseeninrats.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiummetabisulphite(E223)

Hydrochloricacid(forpHadjustment)

Sodiumhydroxide(forpHadjustment)

WaterforInjections

6.2Incompatibilities

DobutamineConcentratehasbeenreportedtobeincompatiblewithalkalinesolutionsandshouldnotbemixedwith

sodiumbicarbonate5%,orotherstrongalkalinesolutionsi.e.aminophylline,furosemide.Precipitationhasoccurred

withbumetanide,calciumgluconate,insulin,diazepamandphenytoin.Becauseofthepotentialphysical

incompatibilities,DobutamineConcentrateshouldnotbemixedwithotherdrugsinthesamesolution.

Dobutamineshouldnotbeusedwithdrugsordiluentscontainingbisulphitesorethanol.

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptforthosementionedinsection6.6.

6.3Shelflife

Irish Medicines Board

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Afterdilution

Chemicalandphysicalin-usestabilityhasbeendemonstratedfor24hoursat2-8°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2

to8 °

C,unlessreconstitution/dilution(etc)hastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Priortofirstuse,donotstoreabove25°C.

Infusionsmustbeasepticallyprepared.

Forstorageconditionsofthedilutedmedicinalproduct,seesection6.3.

Discardanyunusedproduct.

6.5Natureandcontentsofcontainer

20mlclearglassampoule(typeI)withapacksizeof5and1ampoules.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

DobutamineConcentrateshouldbedilutedbeforeuseandadministeredbyIVinfusiononly.

Thefinalconcentrationsgenerallyusedforperfusionare250micrograms/ml,500micrograms/mlor1000

micrograms/ml.Seesection4.2formethodanddurationofadministration.

ThefollowingsterilesolutionsforIVinfusionmaybeusedforthedilutionofdobutaminebeforeuse:sodiumchloride

solution0.9%(9mg/ml),glucosesolution5%(50mg/ml),dextrosesolution5%(50mg/ml),orRingerlactatesolution.

Solutionsofdobutaminehydrochloridemayhaveapinkdiscolouration.Thisdiscolouration,whichwillincreasewith

time,resultsfromaslightoxidationofthedrug.However,thereisnosignificantlossofdrugpotencywithinthe

recommendedmaximumin-usestoragetimeof24hoursat2°C-8°C.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk,NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/46/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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10DATEOFREVISIONOFTHETEXT Irish Medicines Board

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Date Printed 22/08/2011 CRN 2078199 page number: 12