DRAXMIBI

Main information

  • Trade name:
  • DRAXMIBI Kit for radiopharmaceutical preparation 1 Milligram
  • Dosage:
  • 1 Milligram
  • Pharmaceutical form:
  • Kit for radiopharmaceutical preparation
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DRAXMIBI Kit for radiopharmaceutical preparation 1 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1419/001/001
  • Authorization date:
  • 10-07-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DRAXMIBI1mgkitforradiopharmaceuticalpreparation

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1vialcontains:

Activesubstance

Tetrakis(2-methoxyisobutylisonitrile)copper(I)Tetrafluoroborate1mg

Excipients:

Thismedicinalproductcontains0.61mgofSodiumpervial.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Kitforradiopharmaceuticalpreparation.

Lyophilized,whitepowder.

Tobereconstitutedwithsodiumpertechnetate( 99m

Tc)solutionforinjection(notincludedinthiskit).

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thismedicinalproductisfordiagnosticuseonly.

Afterreconstitutionwithsodiumtechnetiumpertechnetate( 99m

Tc)solutionforinjection,thesolutionoftechnetium

Tc)sestamibiobtainedisindicatedfor:

Myocardialperfusionscintigraphy

Detectionandlocalizationofcoronaryarterydiseaseandmyocardialinfarction.

Assessmentofglobalventricularfunction

First-passtechniquefordeterminationofejectionfractionand/orECG-triggered,gatedSPECTforevaluationofleft

ventricularejectionfraction,volumesandregionalwallmotion.

Scinti-mammographyforthedetectionofsuspectedbreastcancer

Detectionofsuspectedbreastcancerwhenmammographyisequivocal,inadequateorindeterminate

Localisationofhyperfunctioningparathyroidtissueinpatientswithrecurrentorpersistenthyperparathyroidism,and

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4.2Posologyandmethodofadministration

Forintravenoususe.

Thesuggestedactivityrangeforintravenousadministrationtoapatientofaverageweight(70kg)is:

Diagnosisofreducedcoronaryperfusionandmyocardialinfarction:

400-900MBq

Assessmentofglobalventricularfunction:

600-800MBqinjectedasabolus.

Fordiagnosisofischaemicheartdiseasetwoinjections(stressandrest)arerequiredinordertodifferentiatetransiently

frompersistentlyreducedmyocardialuptake.Therecommendedactivityrangefordiagnosisofischemicheartdisease

accordingtotheEuropeanproceduralguidelineis

-Two-dayprotocol:600–900MBq/study

-One-dayprotocol:400–500MBqforthefirstinjection,threetimesmoreforthesecondinjection.

Notmorethanatotalof2000MBqshouldbeadministeredforaone-dayprotocoland1800MBqforatwo-day-

protocolbythesetwoinjectionswhichshouldbedoneatleasttwohoursapartbutmaybeperformedineitherorder.

Afterthestressinjection,exerciseshouldbeencouragedforanadditionaloneminute(ifpossible).

Ineachcountrynuclearmedicinephysiciansshouldrespectthediagnosticreferencelevels(DRLs)andtheruleslaid

downbythelocallegislation.TheinjectionofactivitiesgreaterthanlocalDRLsshouldbejustified.

Fordiagnosisofmyocardialinfarctiononeinjectionatrestmaybesufficient.

Forbreastimaging: 740-925MBqinjectedasabolusinthearmoppositetothelesion.

Forparathyroidimaging: 185-740MBqinjectedasabolus.

(Theactivityusedshouldineverycasebeaslowasreasonablypractical).

Safetyandefficacyinchildrenbelowtheageof18yearshavenotbeenestablished.Whereappropriateandpractical,

aninvestigationthatdoesnotinvolveradiationshouldbeemployed.

Theuseinchildrenandadolescentshastobeconsideredcarefully,baseduponclinicalneedsandassessingthe

risk/benefitratiointhispatientgroup.Theactivitiestobeadministeredforchildrenshouldbemodifiedaccordingto

therecommendationsofthePaediatricTaskGroupoftheEANM(1990).Thisactivitycanbedeterminedfromthe

recommendedactivityforadultsonthebasisofbodymass,usingthefollowingmultiplyingcoefficient:

CardiacImaging

Ifpossible,patientsshouldfastforatleastfourhourspriortothestudy.Itisrecommendedthatpatientseatalight

fattymealordrinkaglassortwoofmilkaftereachinjection,priortoimaging.Thiswillpromoterapidhepatobiliary

clearanceoftechnetium( 99m

3kg=0.10 22kg=0.50 42kg=0.78

4kg=0.14 24kg=0.53 44kg=0.80

6kg=0.19 26kg=0.56 46kg=0.82

8kg=0.23 28kg=0.58 48kg=0.85

10kg=0.27 30kg=0.60 50kg=0.88

12kg=0.32 32kg=0.62 52-54kg=0.90

14kg=0.36 34kg=0.64 56-58kg=0.92

16kg=0.40 36kg=0.66 60-62kg=0.96

18kg=0.44 38kg=0.68 64-66kg=0.98

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Imagingshouldbeginapproximatelyafter60minafterinjectiontoallowforhapatobiliaryclearance.Longerdelaycan

berequiredforrestingimagesandforstresswithvasodilatatorsalonebecauseoftheriskofhighersubdiaphragmatic

Tcactivity.Thereisnoevidenceforsignificantchangesinmyocardialtracerconcentrationorredistribution,

thereforeimagingforupto6hourspostinjectionispossible.Testsmaybedoneinaonedayortwodaysprotocol.

Tomographicimaging(SPECT)withorwithoutECGgatingshouldbeperformedaccordingtocurrentinternational

guidelines.

Breastimagingisoptimallyinitiated5to10minutespostinjectionwiththepatientinthepronepositionwithbreast

freelypendant.A10minutelateralimageofthebreastsuspectedofcontainingcancershouldbeobtainedwiththe

camerafaceasclosetothebreastaspractical.

Thepatientshouldthenberepositionedsothatthecontralateralbreastispendantandalateralimageofitshouldbe

obtained.Ananteriorsupineimagemaythenbeobtainedwiththepatient’sarmsbehindherhead.

Parathyroidimagingdependsonwhethersubtractiontechniqueorwash-outtechniqueisused.Forthesubtraction

techniqueeither 123

Tcor 201

TIcanbeusedandshouldbeperformedaccordingtoliterature,guidelineand

recommendedactivites:

Ifdoublephasewash-outtechniqueisused,370to740MBqoftechnetium( 99m

Tc)sestamibiareinjectedandthefirst

neckandthoraximageobtained10minuteslater.Afterawash-outperiodof1to2hours,neckandthoraximagingis

againperformed.BetweenthetwoimagesSPECTorSPECT/CTcanbeperformed.

Incaseofkidneyfailure,exposuretoionisingradiationcanbeincreased.Thismustbetakenintoaccountwhen

calculatingtheactivitytobeadministered.

Ingeneral,activityselectionforpatientswithadecreasedhepaticfunctionshouldbecautious,usuallystartingatthe

lowendofthedosingrange.

Fortheinstructionforpreparationandcontroloftheradiochemicalpurityoftheradiopharmaceutical,seesection12.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Pregnancy,seesection4.6.

Contentsofthevialareintendedonlyforuseinthepreparationoftechnetium( 99m

Tc)sestamibiandarenottobe

administereddirectlytothepatientwithoutfirstundergoingthepreparativeprocedure.

Newborns,infants,childrenandadolescents,seesection4.2.

Inmyocardialscintigraphyinvestigationsunderstressconditions,thegeneralcontraindicationsandprecautions

associatedwiththeinductionofergometricorpharmacologicalstressshouldbeconsidered.

Becauseofpotentialtissuedamageextravasalinjectionofthisradioactiveproducthastobestrictlyavoided.

Inpatientswithreducedhepatobiliaryfunction,averycarefulconsiderationisrequiredsinceanincreasedradiation

exposureispossibleinthesepatients.

Breastlesionslessthan1cmindiametermaynotallbedetectedwithscintimammographyasthesensitivityof

technetium( 99m

Tc)sestamibiforthedetectionoftheselesionsis52%relativetohistologicaldiagnosis.Anegative

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Properhydrationandfrequenturinationarenecessarytoreducebladderirradiation.

Radiopharmaceuticalagentsshouldbeusedonlybyqualifiedpersonnelwiththeappropriategovernmentauthorisation

foruseandmanipulationofradionuclides.Theirreceipt,storage,use,transferanddisposalaresubjecttothe

regulationsand/orappropriatelicencesofthelocalcompetentofficialorganisation.

Foreachpatient,exposuretoionisingradiationmustbejustifiedonthebasisoflikelybenefit.

Theactivityadministeredmustbesuchthattheresultingradiationdoseisaslowasreasonablyachievablebearingin

mindtheneedtoobtaintheintendeddiagnosticortherapeuticresult.

Radiopharmaceuticalsshouldbepreparedbytheuserinamannerwhichsatisfiesbothradiationsafetyand

pharmaceuticalqualityrequirements.Appropriateasepticprecautionsshouldbetaken,complyingwiththe

requirementsofGoodManufacturingPracticeforpharmaceuticals.

Thismedicinalproductcontainslessthan1mmolSodium(23mg)perdose,i.e.essentially‘Sodium-free’.

Ifhypersensitivityreactionsoccur,theadministrationofthemedicinalproductmustbediscontinuedimmediatelyand

intravenoustreatmentinitiated,ifnecessary.Toenableimmediateactioninemergencies,thenecessarymedicinal

productsandequipmentsuchasendotrachealtubeandventilatormustbeimmediatelyavailable.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nodruginteractionshavebeendescribedtodate.Medicinalproductswhichaffectmyocardialfunctionand/orblood

flowmaycausefalsenegativeresultsinthediagnosisofcoronaryarterialdisease.Forthisreason,concomitant

medicationshouldbetakenintoconsiderationwheninterpretingtheresultsofthescintigraphicexamination.

4.6Fertility,pregnancyandlactation

Womenofchildbearingpotential

Whenitisnecessarytoinjectradiopharmaceuticalstowomenofchildbearingpotential,informationshouldalwaysbe

soughtaboutpregnancy.Anywomanwhohasmissedaperiodshouldbeassumedtobepregnantuntilproven

otherwise.Whereuncertaintyexistsitisimportantthatradiationexposureshouldbetheminimumconsistentwith

achievingthedesiredclinicalinformation.Alternativetechniques,whichdonotinvolveionisingradiation,shouldbe

considered.

Pregnancy

Radionuclideprocedurescarriedoutonpregnantwomenalsoinvolveradiationtothefoetus.Onlyimperative

investigationsshouldthereforebecarriedoutduringpregnancy,whenthelikelybenefitfarexceedstheriskincurredby

themotherandfoetus.

Lactation

Beforeadministeringaradiopharmaceuticalstoamotherwhoisbreastfeedingconsiderationshouldbegivenasto

whethertheinvestigationcouldbereasonablydelayeduntilafterthemotherhasceasedbreastfeedingandasto

whetherthemostappropriatechoiceofradiopharmaceuticalshasbeenmade,bearinginmindthesecretionofactivity

inbreastmilk.

Iftheadministrationisconsiderednecessary,breastfeedingshouldbeinterruptedfor24hoursandtheexpressedfeeds

discarded.Closecontactwithinfantshouldberestrictedduringthisperiod.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

Thefollowingtablepresentshowthefrequenciesarereflectedinthissection:

Immunesystemdisorders:

Rare:Severehypersensitivityreactionssuchasdyspnoea,hypotension,bradycardia,astheniaandvomiting(usually

withintwohoursofadministrationofDRAXMIBI),angioedema.

Nervoussystemdisorders:

Uncommon:Headache

Rare:Seizures(shortlyafteradministrationofDRAXMIBI),syncope.

Cardiacdisorders:

Uncommon:Chestpain/anginapectoris,abnormalECG.

Rare:Arrhytmia.

Gastrointestinaldisorders:

Uncommon:Nausea

Rare:Abdominalpain.

Skinandsubcutaneoustissuedisorders:

Rare:Allergicskinandmucosareactionswithexanthema(pruritus,urticaria,oedema),vasodilatation,localreactionsat

theinjectionsite,hypoaesthesiaandparaesthesia,flushing.

Veryrare:Otherhypersensitivityreactionshavebeendescribedinpredisposedpatients.

Ifhypersensitivityreactionsoccur,theadministrationofthemedicinalproductmustbediscontinuedimmediatelyand,

ifnecessary,intravenoustreatmentinitiated.Respectivemedicinalproductsandequipment(e.g.endotrachealtubeand

ventilator)havetobereadilyavailable.

Generaldisordersandadministrationsiteconditions:

Common:Immediatelyafterinjection,ametallicorbittertaste,partlyincombinationwithdrymouthandanalteration

inthesenseofsmellmaybeobserved.

Rare:Fever,fatigue,dizziness,transientarthritic-likepain.

Otherdisorders:

Exposuretoionisingradiationislinkedwithcancerinductionandapotentialfordevelopmentofhereditarydefects.As

mostdiagnosticnuclearmedicinalproductinvestigationsaredonewithlowradiationdosesoflessthan20mSvthese

adverseeventsareexpectedtooccurwithalowprobability.Theeffectivedosecalculatedwithanaverageamountof

activityof2000MBq(500MBqatrestand1500MBqatstress)fora1-day-protocolis16.4mSv(4.5mSvatrestand

11.9mSvatstress).Theeffectivedoseis8.32mSvwhenthemaximalrecommendedactivityof925MBqis

administered.

4.9Overdose

Intheeventofadministrationofaradiationoverdosewithtechnetium( 99m

Tc)sestamibitheabsorbeddosetothe

patientshouldbereducedwherepossiblebyincreasingtheeliminationoftheradionuclidefromthebodybyfrequent

Verycommon( ≥1/10)

Common( ≥1/100to<1/10)

Uncommon( ≥1/1,000to<1/100)

Rare( ≥1/10,000to<1/1,000)

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Technetium( 99m

Tc)compounds

ATCcode:V09GA01

Pharmacodynamiceffectsarenotexpectedafteradministrationoftechnetium( 99m

Tc)sestamibi.

AfterreconstitutionwithSodiumPertechnetate( 99m

Tc)Injection,thefollowingcomplexforms(technetium( 99m

sestamibi):

Tc-(MIBI)

Where:MIBI=2-methoxyisobutylisonitrile

Technetium( 99m

Tc)sestamibi,whenadministratedinusualdosesandbytheusualway,hasnopharmacodynamic

effectsdetectableclinically.

5.2Pharmacokineticproperties

Technetium( 99m

Tc)sestamibiisacationiccomplexwhichaccumulatesintheviablemyocardialtissueproportionalto

theregionalcoronarybloodflow.

Technetium( 99m

Tc)sestamibifromthebloodisrapidlydistributedintothetissue:5minutesafterinjectiononlyabout

8%oftheinjecteddoseisstillincirculation.

Thetissueuptakeoftechnetium( 99m

Tc)sestamibidependsprimarilyonthevascularisationwhichisgenerally

increasedintumourtissue.Duetoitslipophilicityanditspositivecharge,thetechnetium( 99m

Tc)sestamibicomplex

crossesthecellmembraneandconcentratesinthemostnegativelychargedcompartmentofthecell,themitochondria.

Cardiacindication

Technetium( 99m

Tc)sestamibibindstothemitochondrialmembraneandanintactmitochondrialmembranepotentialis

importantforintracellularbinding.

Theuptakeoftechnetium( 99m

Tc)Sestamibiinthemyocardiumisproportionaltobloodflowinthephysiologicflow

range.Therateofpassiveuptakeisdeterminedbythemembranepermeabilityofthedrugandthesurfaceareaofthe

vascularbedstowhichitisexposed.Sincetheradiotracerentersthecellviadiffusion,itwillunderestimatebloodflow

athighflowrates(>2.0ml/g/min).

Whencoronaryflowvariedfrom0.52to3.19ml/g/min,myocardialextractionfortechnetium( 99m

Tc)sestamibi

averaged0.38+/-0.09.Technetium( 99m

Tc)sestamibifromthebloodisrapidlydistributedintothetissue.Five

minutesafterinjectiononlyabout8percentoftheinjecteddoseisstillincirculation.

Technetium( 99m

Tc)sestamibiundergoesminimalredistributionovertime.Thismayimpactonlesiondetectionasthe

differentialwashoutbetweenthenormalandischemicmyocardiummayresultinareductionindefectsizeorseverity

withtime.

Mastologyindication

Thecellularconcentrationoftechnetium( 99m

Tc)sestamibiwasdemonstratedtobeincreasedinmammarytumour

tissueprobablybecauseofthehighcontentofmitochondriaintumourcellsandthehighmembranepotentialoftumour

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Severalinvitrostudiesdemonstratedthattechnetium( 99m

Tc)sestamibiisasubstrateofPglycoprotein.Adirect

correlationbetweentheP-glycoproteinexpressionandtheeliminationoftechnetium( 99m

Tc)sestamibifromtumours

hasbeenestablished.Thecellularover-expressionofP-glycoproteincouldresultinfalsenegativeimagesoftumours,

especiallyoftumourslargerthan1cm.

Parathyroidindication

Inadenomaoftheparathyroidglandsbloodflowandthenumberofmitochondriaareincreased.Thisfactmayexplain

theelevateduptakeandtrappingoftechnetium( 99m

Tc)sestamibiinparathyroidadenoma.Localizationoftechnetium

Tc)sestamibiappearstobedependentonbloodflowtothetissue,theconcentrationoftechnetium( 99m

sestamibipresentedtothetissue,andthesizeoftheparathyroidadenoma.

Myocardialuptakewhichiscoronaryflowdependentis1.5%oftheinjecteddoseatstressand1.2%oftheinjected

doseatrest.

AnimalexperimentshaveshownthatuptakeisnotdependentonthefunctionalcapabilityoftheSodium-potassium

pump.Irreversiblydamagedcellshoweverdonottakeuptechnetium( 99m

Tc)sestamibi.Themyocardialextraction

levelisreducedbyhypoxia.

Theclearanceofthemyocardialfractionisminimalandtheredistributionisinsignificantduringatleast4hoursafter

aninducedischemiainthedog.Technetium( 99m

Tc)sestamibiisrapidlydistributedfromthebloodintothetissue:5

minutesafterinjectiononlyabout8%oftheinjecteddoseisstillincirculation.

Howeversomeexperimentalandclinicalstudiesindicatedaredistributioninseverelyischaemicareas.Apotential

influenceonthediagnosticqualityofthetesthasnotbeenestablished.

Elimination

Themajormetabolicpathwayforclearanceoftechnetium( 99m

Tc)sestamibiisthehepatobiliarysystem.Activityfrom

thegallbladderappearsintheintestinewithinonehourofinjection.About27%oftheinjecteddoseisclearedthrough

renaleliminationafter24hoursandapproximately33%oftheinjecteddoseisclearedthroughthefaecesin48hours.

Half-Life

ThebiologicalmyocardialT½isapproximately7hoursatrestandstress.TheeffectiveT½(whichincludesbiological

andphysicalhalf-lives)isapproximately3hours.

5.3Preclinicalsafetydata

Inacuteintravenoustoxicitystudiesinmice,ratsanddogs,thelowestdoseoftechnetium( 99m

Tc)sestamibithat

resultedinanydeathswas7mg/kg(expressedasCu(MIBI)

content)infemalerats.Thiscorrespondsto500

timesthemaximalhumandose(MHD)of0.014mg/kgforadults(70kg).Neitherratsnordogsexhibitedtreatment

relatedeffectsattechnetium( 99m

Tc)sestamibidosesof0.42mg/kg(30timesMHD)and0.07mg/kg(5timesMHD)

respectivelyfor28days.Atrepeateddoseadministration,thefirsttoxicitysymptomsappearedduringthe

administrationof150timesthedailydoseduring28days.

Studiesonreproductivetoxicityhavenotbeenconducted.

Cu(MIBI)

showednogenotoxicactivityintheAmes,CHO/HPRTandsisterchromatidexchangetests.At

cytoxicconcentrations,anincreaseinchromosomeaberrationwasobservedintheinvitrohumanlymphocyteassay.

Nogenotoxicactivitywasobservedintheinvivomousemicronucleustestat9mg/kg.

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

SodiumCitrateDihydrate

L-CysteineHydrochlorideMonohydrate

Mannitol

StannousChlorideDihydrate

HydrochloricAcid(forpH-adjustment)

SodiumHydroxide(forpH-adjustment)

6.2Incompatibilities

Thetechnetiumlabellingreactionsinvolveddependonmaintainingthestannouslevelinthereducedstate.Hence,

SodiumPertechnetate( 99m

Tc)Injectioncontainingoxidantsshouldnotbeemployed.

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthosementionedinsection12.

6.3Shelflife

Beforereconstitution:12months.

Afterreconstitution:10hours.Donotstoreabove25°C.Donotrefrigerateorfreeze.

6.4Specialprecautionsforstorage

Storeintheoriginalpackageinordertoprotectfromlight.

Unlabelledproduct:Donotstoreabove25 °

C.Donotrefrigerateorfreeze.

Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

Storageshouldbeinaccordancewithnationalregulationsforradioactivematerial.

6.5Natureandcontentsofcontainer

10mlglassvials,typeIborosilicateglasssealedwithabutylrubberstopper.Packsizes:2,5and10vialsinacarton.

Notallpacksizemaybemarketed.

Thisproductisinmulti-dosevials.

6.6Specialprecautionsfordisposal

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

DRAXIMAGE(UK)Limited

5OldBailey

Floor

LondonEC4M7BA

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10thJuly2009

10DATEOFREVISIONOFTHETEXT

11DOSIMETRY

Technetium( 99m

Tc)isproducedbymeansofa( 99

Tc)generatoranddecayswiththeemissionofgamma

radiationwithmeanenergyof140keVandhalf-lifeof6.02hourstotechnetium( 99m

Tc)which,inviewofitslong

half-lifeof2.13x10 5

yearscanberegardedasquasistable.

ThedatalistedbelowarefromICRP80andarecalculatedaccordingtothefollowingassumptions:Afterintravenous

injectionthesubstanceisrapidlyclearedfromthebloodandaccumulatesmainlyinmusculartissues(includingheart),

liver,kidneys,andasmalleramountinsalivaryglandsandthyroid.Whenthesubstanceisinjectedinconjunctionwith

astresstest,thereisaconsiderableincreaseoftheuptakeinorgansandtissues.Thesubstanceisexcretedbytheliver

andkidneysintheproportions75%and25%,respectively.

Organ Doseabsorbedperactivityadministered[mGy/MBq]

(restingtest)

Adults 15-year-olds 10-year-olds 5-year-olds 1-year-olds

Adrenalglands

Bladderwalls

Bonesurface

Brain

Breasts

Gallbladder

Alimentarytract:

Stomach

Smallintestine

Colon

Heart

Kidneys

Liver

Lungs

Muscles

Oesophagus

Ovaries

Pancreas

Bonemarrow

Salivaryglands

Skin

Spleen

Testicles

Thymus

Thyroid

Uterus

Otherorgans

Effectivedose

0.0075

0.011

0.0082

0.0052

0.0038

0.039

0.0065

0.015

0.024

0.027

0.019

0.0063

0.036

0.011

0.0046

0.0029

0.0041

0.0091

0.0077

0.0055

0.014

0.0031

0.0065

0.0038

0.0041

0.0053

0.0078

0.0031

0.009

0.014

0.010

0.0071

0.0053

0.045

0.0090

0.018

0.031

0.035

0.025

0.0082

0.043

0.014

0.0064

0.0037

0.0057

0.012

0.010

0.0071

0.017

0.0041

0.0086

0.0050

0.0057

0.0079

0.010

0.0039

0.015

0.019

0.016

0.011

0.0071

0.058

0.015

0.029

0.050

0.057

0.041

0.012

0.059

0.021

0.0097

0.0054

0.0086

0.018

0.016

0.011

0.022

0.0064

0.014

0.0075

0.0086

0.012

0.015

0.0060

0.022

0.023

0.021

0.016

0.011

0.10

0.021

0.045

0.079

0.089

0.065

0.018

0.085

0.030

0.014

0.0076

0.013

0.025

0.024

0.030

0.015

0.0098

0.020

0.011

0.013

0.024

0.022

0.0088

0.038

0.041

0.038

0.027

0.020

0.32

0.035

0.080

0.015

0.17

0.12

0.030

0.015

0.052

0.025

0.014

0.023

0.045

0.039

0.044

0.026

0.019

0.034

0.021

0.023

0.045

0.038

0.016

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Theeffectivedoseperunitofadministeredactivityhasbeencalculatedaccordingtoavoidingfrequencyof3.5hours

inadults.

Myocardialperfusionscintigraphy

Theeffectivedosecalculatedwithanaverageamountofactivityof1800MBq(900MBqatstressand900MBqat

rest)fora2-day-protocolis15.2mSv.

Theeffectivedosecalculatedwithanaverageamountofactivityof2000MBq(500MBqatrestand1500MBqat

stress)fora1-day-protocolis16.4mSv.

Evaluationofventricularfunction

Afterinjectionof800MBq,theeffectivedoseis7.2mSvatrest.Afterinjectionof800MBq,theeffectivedoseis6.3

mSvatstress.

Scinti-mammography

Afterinjectionof925MBq,theeffectivedoseis8.32mSv.

Parathyroidimagingofhyperfunctioningtissue

Organ Doseabsorbedperactivityadministered[mGy/MBq]

(exercisetest)

Adults 15-year-olds 10-year-olds 5-year-olds 1-year-olds

Adrenalglands

Bladderwalls

Bonesurface

Brain

Breasts

Gallbladder

Alimentarytract:

Stomach

Smallintestine

Colon

Heart

Kidneys

Liver

Lungs

Muscles

Oesophagus

Ovaries

Pancreas

Bonemarrow

Salivaryglands

Skin

Spleen

Testicles

Thymus

Thyroid

Uterus

Otherorgans

Effectivedose

0.0066

0.0098

0.0078

0.0044

0.0034

0.033

0.0059

0.012

0.019

0.022

0.016

0.0072

0.026

0.0092

0.0044

0.0032

0.0040

0.0081

0.0069

0.0050

0.0092

0.0029

0.0058

0.0037

0.0040

0.0044

0.0072

0.0033

0.0087

0.013

0.0097

0.0060

0.0047

0.038

0.0081

0.015

0.025

0.028

0.021

0.0094

0.032

0.012

0.0060

0.0041

0.0055

0.011

0.0091

0.0064

0.011

0.0037

0.0076

0.0048

0.0055

0.0064

0.0093

0.0043

0.013

0.017

0.014

0.0093

0.0062

0.049

0.013

0.024

0.041

0.046

0.034

0.010

0.044

0.018

0.0087

0.0060

0.0080

0.015

0.014

0.0095

0.0015

0.0058

0.012

0.0071

0.0080

0.0099

0.014

0.0064

0.019

0.021

0.020

0.014

0.0097

0.086

0.019

0.037

0.064

0.072

0.053

0.021

0.063

0.025

0.013

0.0090

0.012

0.023

0.021

0.013

0.0020

0.0090

0.017

0.011

0.012

0.019

0.020

0.0098

0.033

0.038

0.036

0.023

0.018

0.26

0.032

0.066

0.12

0.13

0.099

0.035

0.11

0.044

0.023

0.017

0.023

0.040

0.035

0.023

0.0029

0.017

0.030

0.020

0.023

0.035

0.035

0.018

Irish Medicines Board

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Date Printed 19/08/2011 CRN 2094519 page number: 10

12INSTRUCTIONSFORPREPARATIONOFRADIOPHARMACEUTICALS

Thecontentsofthekitbeforepreparationarenotradioactive.However,afterSodiumPertechnetate( 99m

Tc)Injection

isadded,adequateshieldingofthefinalpreparationmustbemaintained.

Theadministrationofradiopharmaceuticalscreatesrisksforotherpersonsfromexternalradiationorcontamination

fromspillofurine,vomitingetc.Radiationprotectionprecautionsinaccordancewithnationalregulationsmust

thereforebetaken.

Aswithanypharmaceuticalproduct,ifatanytimeinthepreparationofthisproducttheintegrityofthisvialis

compromiseditshouldnotbeused.

Themedicinalproductshouldnotcomeintocontactwithair.

ThelabellingofthekitshouldbemadeaccordingtoeithermethodAormethodB.

InstructionsforPreparationoftechnetium( 99m

Tc)sestamibi

A.Boilingprocedure:

Preparationoftechnetium( 99m

Tc)sestamibifromDRAXMIBIistobedoneaccordingtothefollowingaseptic

procedure:

Waterproofglovesshouldbewornduringthepreparationprocedure.RemovetheplasticdiscfromtheDRAXMIBI

vialandswabthetopofthevialclosurewithalcoholtodisinfectthesurface.

Placethevialinasuitableradiationshieldappropriatelylabelledwithdate,timeofpreparation,volumeand

activity.

Withasterileshieldedsyringe,asepticallyobtainadditive-free,sterile,non-pyrogenicsodiumpertechnetate

Tc)solution(max.11.1GBq)inapproximately1to3ml.Notlessthan3mlsodiumpertechnetate( 99m

solutionwillbeuseforthemaximumactivityof11.1GBq.

Asepticallyaddthesodiumpertechnetate( 99m

Tc)solutiontothevialintheleadshield.Withoutwithdrawingthe

needle,removeanequalvolumeofheadspacetomaintainatmosphericpressurewithinthevial.

Shakevigorously,about5to10quickupward-downwardmotions.

Removethevialfromtheleadshieldandplaceuprightinanappropriatelyshieldedandcontainedboilingwater

bath,suchthatthevialissuspendedabovethebottomofthebath,andboilfor10minutes.Thebathmustbe

shielded.Timingforthe10minutescommencesassoonasthewaterbeginstoboilagain.

Note:Thevialmustremainuprightduringtheboilingstep.Useawaterbathwherethestopperwillbeabovethelevel

ofthewater.

Removetheshieldedvialfromthewaterbathandallowcoolingforfifteenminutes.

Inspectvisuallyfortheabsenceofparticulatematteranddiscolorationpriortoadministration.

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10RadiochemicalpurityshouldbecheckedpriortopatientadministrationaccordingtotheRadio-TLCMethodas

detailedbelow.

Note:thepotentialforcrackingandsignificantcontaminationexistswhenevervialscontainingradioactivematerialare

heated.

B. ThermalCyclerprocedure:

Preparationoftechnetium( 99m

Tc)sestamibifromDRAXMIBIistobedoneaccordingtothefollowingaseptic

procedure:

Waterproofglovesshouldbewornduringthepreparationprocedure.Removetheplasticdiscfromthe

DRAXMIBIvialandswabthetopofthevialclosurewithalcoholtodisinfectthesurface.

Placethevialinasuitableradiationshieldappropriatelylabelledwithdate,timeofpreparation,volumeand

activity.

Withasterileshieldedsyringe,asepticallyobtainadditive-free,sterile,non-pyrogenicsodiumpertechnetate

Tc)solution(max.11.1GBq)inapproximately1to3ml.Notlessthan3mlsodiumpertechnetate( 99m

solutionwillbeuseforthemaximumactivityof11.1GBq.

Asepticallyaddthesodiumpertechnetate( 99m

Tc)solutiontothevialintheleadshield.Withoutwithdrawingthe

needle,removeanequalvolumeofheadspacetomaintainatmosphericpressurewithinthevial.

Shakevigorously,about5to10quickupward-downwardmotions.

Placetheshieldinthesampleblock.Whileslightlypressingdownwards,givetheshieldaquarterturntomake

certainthereisafirmfitbetweentheshieldandthesampleblock.

Presstheproceedbuttontoinitiatetheprogram(thethermalcyclerautomaticallyheats&coolsthevialand

contents).PleaseseetheRecon-o-statInstructionManualforfurtherdetails.

Inspectvisuallyfortheabsenceofparticulatematteranddiscolorationpriortoadministration.

Asepticallywithdrawmaterialusingasterileshieldedsyringe.Usewithinten(10)hoursofpreparation.

10RadiochemicalpurityshouldbecheckedpriortopatientadministrationaccordingtotheRadio-TLCMethodas

detailedbelow.

Radio-TLCMethodfortheQuantificationoftechnetium( 99m

Tc)sestamibi

1.Materials

1.1Baker-Flex-AluminiumOxideplate,#1B-F,pre-cutto2.5cmx7.5cm.

1.2Ethanol,>95%.

1.3Capintec,orequivalentinstrumentformeasuringradioactivityinthe0.74–11.12GBqrange.

1.41mlsyringewitha22-26gaugeneedle.

1.5Smalldevelopingtankwithcover,(100mlbeakercoveredwithParafilm ®

issufficient).

Irish Medicines Board

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Date Printed 19/08/2011 CRN 2094519 page number: 12

Pourenoughethanolintothedevelopingtank(beaker)tohaveadepthof3-4mmofsolvent.Coverthetank

(beaker)withParafilm ®

andallowittoequilibrateforapproximately10minutes.

Apply1dropofethanol,usinga1mlsyringewitha22-26gaugeneedleontotheAluminiumOxideTLCplate,

1.5cmfromthebottom.Donotallowthespottodry.

Apply1dropofthekitsolutionontopoftheethanolspot.Drythespot.Donotheat!

Developtheplateadistanceof5.0cmfromthespot.

Cutthestrip2.5cm(onethird)fromthebottomofthestrip,andmeasureeachpieceinyourdosecalibrator.

Calculatethe%radiochemicalpurityas:

%( 99m

Tc)sestamibi=(Activitytopportion)/(Activitybothpieces)x100.

%( 99m

Tc)sestamibishouldbe ≥94%;otherwisethepreparationshouldbediscarded.

Note:Donotusematerialiftheradiochemicalpurityislessthan94%.

Afterreconstitutionthecontainerandanyunusedcontentsshouldbedisposedofinaccordancewithlocalrequirements

Irish Medicines Board

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Date Printed 19/08/2011 CRN 2094519 page number: 13