CHROMIUM [51CR] EDTA INJECTION ,CHROMIUM [51CR] ED

Main information

  • Trade name:
  • CHROMIUM [51CR] EDTA INJECTION ,CHROMIUM [51CR] ED
  • Dosage:
  • 3.7 MBq/ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CHROMIUM [51CR] EDTA INJECTION ,CHROMIUM [51CR] ED
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0240/020/001
  • Authorization date:
  • 05-02-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0240/020/001

CaseNo:2067523

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

GEHealthcareLimited

AmershamPlace,LittleChalfont,Buckinghamshire,HP79NA,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Chromium[51Cr]EDTAInjection,Chromium[51Cr]EDTA3.7MBq/mlSolutionforInjection

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom05/11/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Chromium[ 51

Cr]EDTAInjection

Chromium[ 51

Cr]EDTA3.7MBq/mlSolutionforInjection.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Chromium[ 51

Cr]EDTA 37MBq/vial

(3.7MBq/ml

attheactivityreferencedate

Theformulationcontains0.64mg/mlchromiumedetate.

Chromium-51hasaphysicalhalf-lifeofapproximately28daysanddecaysbygammaemisisionwithaprincipal

energyof0.32MeV.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Solutionforinjection.

Clear,colourlesssolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thismedicinalproductisfordiagnosticuseonly.

Chromium-51edetateisindicatedforthedeterminationofglomerularfiltrationrateintheassessmentofrenalfunction.

4.2Posologyandmethodofadministration

Thenormallyrecommendeddoseforadultsandtheelderlyis1.1-6.0MBqbyintravenousinjectionorcontinuous

infusion.Theactualactivityadministeredwilldependonthetechniqueusedtodeterminetherenalclearanceandon

thatusedforradioactivitydetection.Higheractivitiesuptoamaximumof11MBqmaybeappropriateforusein

conjunctionwithexternalcountingtechniques.

Theactivitytobeadministeredtochildrenmaybecalculatedapproximatelybycorrectingonaweight,bodysurface

areaoragebasistheactivitytoadults.Forchildrenunderaboutoneyearofage,thetargetorgansizeinrelationtothe

wholebodymustalsobetakenintoconsideration.Chromium( 51

Cr)EDTAcontainsbenzylalcohol.Itmustnotbe

giventoprematurebabiesorneonates.

Thefollowingmethodsofadministrationarerecommended:

Singleintravenousinjection

Becauseofthecomplexitiesoftheinfusiontechnique(seebelow)asingleinjectiontechniqueisnormallyused.This

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suchpatients,equilibrationoftheadministeredchromium-51edetatebetweentheplasmaandinterstitialfluidmaytake

upto12hours.

Thesingleinjectionplasmaclearanceiscalculatedfromtheinjectedamountofchromium-51edetateandthedecrease

ofactivityinplasmasamplesasafunctionoftime.Anumberofdifferentmethodsareavailableforanalysisofthe

plasmadisappearancecurve,oneofwhichispresentedbelow.

Asingleintravenousadministrationof3.7MBqofchromium-51edetateisgiven.Venoussamplesaretakenat

appropriateintervals(forexample,two,three,andfourhoursafteradministration)withanotherat24hoursifrenal

failureissuspected.Thevenoussamplesarespunandtheplasmaseparatedandcounted,togetherwithanaliquotofthe

givendose.Thenetplasmaactivitiesarethenexpressedintermsoffractionaldoseandplottedagainsttimeonalog-

linearplot.Aregressionlineisthenfittedtothedataandthelineextrapolatedbacktotheordinateaxis.Theturnover

ratekisdeterminedfromtheslopeoftheline.TheapparentdistributionvolumeofthetracerVisobtainedbydividing

thecountrateduetotheadministereddosebytheplasmaconcentrationgivenbytheinterceptontheordinateaxis.The

plasmaclearanceCisthengivenby:

C=kV

Inordertocorrelatethechromium-51edetatevalueswithstandardinulinclearancevalues,acorrectionfactormaybe

appliedtothefinalresultifthisisrequired.

Continuousintravenousinfusion

Aprimingadministrationof1.85MBqisgivenintravenouslyfollowedbytheinfusionofasolutioncontaining37

kBq/mlatarateof0.5ml/minute.Afterabout40minutes,theplasmaconcentrationbecomesconstant.Aurine

collectionlastingabout15minutesisthenstartedandavenoussampletakenatthemid-time.Thisprocessisrepeated

withrapidseparationandcountingoftheplasmaradioactivityuntilconstantplasmaactivityisobservedintwo

successivesamples.Thevaluesoftheurineandtheplasmaconcentrationsandtheurineflowarethensubstitutedinto

theequation

C= UV

(whereC=vol.ofplasmaclearedperunittime,U=urineconcentration,V=urinaryflow,P=plasmaconcentration)

togivetheclearance.Whentheurinaryflowislow,itmaybenecessarytocatheterisethebladderinordertoremove

thewholeoftheurinesampleforaparticulartimeperiod.

Alternativemethodsfordeterminingglomerularfiltrationrate(GFR)usingchromium-51edetatemaybeusedin

certaincentres.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Mustnotbegiventoprematurebabiesorneonates.

4.4Specialwarningsandprecautionsforuse

Thismedicinalproductcontainsbenzylalcohol.Benzylalcoholmaycausetoxicreactionsandanaphylactoidreactions

ininfantsandchildrenupto3yearsold.

Toreducetheradiationdosetothebladderandanaccumulationofradioactivityinit,thepatientshouldbeaskedto

drinkadditionalfluidsandtovoidthebladderasoftenaspossibleinthehoursfollowingadministration.

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Nointeractionstudieshavebeenperformed.

4.6Pregnancyandlactation

Nodataareavailableontheuseofthisproductinhumanpregnancy.Animalreproductionstudieshavenotbeen

performed.

Whenitisnecessarytoadministerradioactivemedicinalproductstowomenofchildbearingpotential,information

shouldalwaysbesoughtaboutpregnancy.Anywomanwhohasmissedaperiodshouldbeassumedtobepregnant

untilprovenotherwise.Whereuncertaintyexistsitisimportantthatradiationexposureshouldbetheminimum

consistentwithachievingthedesiredclinicalinformation.Alternativetechniqueswhichdonotinvolveionising

radiationshouldbeconsidered.

Radionuclideprocedurescarriedoutonpregnantwomenalsoinvolveradiationdosestothefoetus.Onlyimperative

investigationsshouldbecarriedoutduringpregnancy,whenthelikelybenefitexceedstheriskincurredbythemother

andthefoetus.

Avoidanceofpregnancyfollowingadministrationofchromium-51edetateisnotnecessaryforawomanofchild-

bearingpotentialbecauseofthelowabsorbedradiationdoseassociatedwithsuchanadministration.

Beforeadministeringaradioactivemedicinalproducttoamotherwhoisbreastfeeding,considerationshouldbegiven

astowhethertheinvestigationcouldbereasonablydelayeduntilthemotherhasceasedbreastfeedingandasto

whetherthemostappropriatechoiceofradiopharmaceuticalhasbeenmade,bearinginmindthesecretionofactivityin

breastmilk.Iftheadministrationofchromium-51edetateisconsiderednecessary,breastfeedingshouldbeinterrupted

for4hoursandtheexpressedfeedsdiscarded,afterwhichtimethelevelofactivityinthemilkwillnotresultina

radiationdosetothechildgreaterthan1mSv.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

4.8Undesirableeffects

Unwantedeffectshavebeenreportedinfrequentlyaftersingleorrepeatedintravenousadministrationsofchromium-51

edetatesuchthattheincidenceofindividualreactionscannotbequantified.Limiteddetailsareavailable,butmild

allergicphenomenahavebeendescribed.Thecausationoftheadverseeventsreportedtodatehasnotbeenfirmly

established.

Foreachpatient,exposuretoionisingradiationmustbejustifiableonthebasisoflikelybenefit.Theactivity

administeredmustbesuchthattheresultingradiationdoseisaslowasreasonablyachievablebearinginmindtheneed

toobtaintheintendeddiagnosticortherapeuticresult.

Exposuretoionisingradiationislinkedwithcancerinductionandapotentialfordevelopmentofhereditarydefects.

Fordiagnosticnuclearmedicineinvestigationsthecurrentevidencesuggeststhattheseadverseeffectswilloccurwith

lowfrequencybecauseofthelowradiationdosesincurred.

Formostdiagnosticinvestigationsusinganuclearmedicineproceduretheeffectivedoseislessthan20mSv.Higher

dosesmaybejustifiedinsomeclinicalcircumstances.

4.9Overdose

Intheeventofanaccidentaladministrationofanoverdoseofchromium-51edetate,theabsorbedradiationdosetothe

patientshouldbereducedbyincreasingtheeliminationoftheradionuclidefromthebody.Thismaybedonebymore

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:diagnosticradiopharmaceuticals,renalsystem,chromium( 51

Cr)edetate,ATCcode:

V09CXO4

Chromium-51edetateisachemicallystable,hydrophilicmetalchelate.Itismetabolicallyinert.Renalfunctionis

unaffectedevenbylargeamountsofchromiumedetate.Atthechemicalconcentrationsandactivitiesused,chromium-

51edetatedoesnotappeartoexertanypharmacodynamiceffects.

5.2Pharmacokineticproperties

Followingintravenousadministration,thechromium-51edetatecomplexisexcretedalmostexclusivelybythekidneys

viatheglomerularmembrane(lessthan1%faecalexcretionin24hoursreportedforananuricpatient).Lessthan0.5%

plasmaproteinbindingoccurs.Inpatientswithnormalornear-normalglomerularfiltrationratetherecoveryof

unchangedchelateintheurineduringthefirst24hoursafteradministrationiscloseto100%oftheinjectedactivity,

cumulativefaecalclearanceaccountingforlessthan0.1%.Thereisnosignificanttubularsecretionorre-absorptionof

chromium-51edetate.However,asmallamountoftubularre-absorption,somewholebodyretentionorcomplex

dissociationhaveeachbeenpostulatedtoexplaintheknownbutsmallunderestimationofinulinclearanceby

chromium-51edetate.

Afterintravenousadministration,thechromium-51edetateequilibrateswithintheintra-andextravascularspaces,a

processtakingbetween30and90minutes.Beyondthisperiodaconstantpercentageofthechromium-51edetate

presentintheextracellularfluidisexcretedbythekidneysperunittime.Totalbodyretentionisdescribedbyadouble

exponentialfunction.

Themeanvalueoftheglomerularfiltrationrateinthenormaladultisapproximately130ml/mininmenand120

ml/mininwomen(normalisedforbodysurfaceareaof1.73m 2

5.3Preclinicalsafetydata

Ithasbeenreportedthatnotoxiceffectswerenotedindogsfollowingintravenousinfusionforaperiodof36hoursof

1.5gchromiumedetate/kg.

Intravenousadministrationofaformulationofchromium-51edetatetoratsandmicehasindicatedthattheaverage

lethaldoseismorethan1000timesthemaximumrecommendeddosetohumans.Repeatdosestudieswiththesame

formulationrevealednodetrimentalclinicalorhistologicaleffectswhentheequivalentofmorethan50timesthe

maximumrecommendedhumandosewasadministeredtoratsanddogsoveratwoweekperiod.Chromium-51edetate

isnotintendedforregularorcontinuousadministration.

Mutagenicitystudiesandlong-termcarcinogenicitystudieshavenotbeencarriedout.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

DisodiumEDTA

Benzylalcohol

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6.2Incompatibilities

Noneknown

6.3ShelfLife

Theshelf-lifeoftheproductisnotmorethan90daysafterthedateofrelease.

Thereferencedateoftheproductis60daysbeforeexpiry.

6.4Specialprecautionsforstorage

Theproductshouldbestoredbelow25 o

C.Donotfreeze.

Storageproceduresshouldbeinaccordancewithnationalregulationsforradioactivesubstances.

6.5Natureandcontentsofcontainer

Theproductissuppliedina10mlTypeIPh.Eur.,clear,colourless,borosilicateglassvialsealedwithaPTFEfaced

rubberclosureandoversealedwithanaluminiumoversealwithanaperture.Eachvialispackedwithinaradiation

shieldingcontainerofleadmetal.

Packsizes: 37MBq

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Theadministrationofradiopharmaceuticalscreatesrisksforotherpersonsfromexternalradiationoncontamination

fromspillsofurine,vomiting,etc.Radiationprotectionprecautionsinaccordancewithnationalregulationsmust

thereforebetaken.Storageproceduresandthedisposalofwasteshouldbeinaccordancewithnationalguidelines.

7MARKETINGAUTHORISATIONHOLDER

GEHealthcareLimited

AmershamPlace

LittleChalfont

Buckinghamshire

HP79NA

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0240/020/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:05February1999

Dateoflastrenewal:05February2009

10DATEOFREVISIONOFTHETEXT

November2009

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Dataonabsorbeddosefollowingadministrationofchromium[ 51

Cr]edetatearetakenfromICRP53,International

CommissiononRadiologicalProtection,RadiationDosetoPatientsfromRadiopharmaceuticals,PergamonPress,

1988.

Thedatapresentedaboveassumeabodyretentionhalf-timeof100minutesandarenaltransittimeof5minutes.Data

arealsopresentedforabnormalrenalfunctioninwhichtheretentionhalf-timeis1000minutesandtherenaltransit

Organ Absorbeddose

perunitactivityadministered(mGy/MBq)

Adult 15year 10year 5year 1year

Adrenals

Bladderwall

Bonesurfaces

Breast

GI-tract

Stomachwall

Smallintest

ULIwall

8.1E-04

2.3E-02

7.0E-04

5.6E-04

7.3E.04

1.1E-03

1.0E-03

9.1E-04

3.2E-02

8.2E-04

5.6E-04

8.4E-04

1.4E-03

1.2E-03

1.4E-03

4.6E-02

1.2E-03

8.3E-04

1.3E-03

2.1E-03

1.9E-03

2.2E-03

7.0E-02

1.9E-03

1.3E-03

2.1E-03

3.3E-03

3.0E-03

4.0E-03

1.3E-01

3.5E-03

2.6E-03

3.6E-03

5.8E-03

5.1E-03

7.6E-03

Kidneys

Liver

Lungs

Ovaries

Pancreas 1.8E-03

6.8E-04

5.7E-04

1.6E-03

7.8E-04 2.2E-03

8.3E-04

7.2E-04

2.0E-03

9.4E-04 3.2E-03

1.3E-03

1.1E-03

3.0E-03

1.5E-03 4.6E-03

2.1E-03

1.7E-03

4.5E-03

2.3E-03 8.1E-03

3.8E-03

3.2E-03

7.6E-03

4.1E-03

Redmarrow

Spleen

Testes

Thyroid

Uterus 8.7E-04

7.2E-04

1.2E-03

5.3E-04

2.8E-03 1.0E-03

8.6E-04

1.6E-03

7.3E-04

3.4E-03 1.5E-03

1.3E-03

2.8E-03

1.2E-03

5.3E-03 2.1E-03

2.0E-03

4.2E-03

1.9E-03

7.9E-03 3.5E-03

3.8E-03

7.8E-03

3.5E-03

1.3E-02

Othertissue 8.0E-04 9.5E-04 1.5E-03 2.2E-03 4.1E-03

Effective

doseequivalent

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Abnormalrenalfunction

Forthisproduct,theeffectivedoseequivalenttoa70kgadultresultingfromanadministeredactivityof1.1to6MBqis

typically0.0025to0.014mSvinthecaseofnormalkidneyfunctionandis0.0057to0.031mSvunderconditionsof

abnormalrenalfunction.

12INSTRUCTIONSFORPREPARATIONOFRADIOPHARMACEUTICALS

Theymaybereceived,usedandadministeredonlybyauthorisedpersonsindesignatedclinicalsettings.Theirreceipt,

storage,use,transferanddisposalaresubjecttotheregulationsand/orappropriatelicencesofthelocalcompetent

officialorganisations(seesection6.6).

Theadministrationofradiopharmaceuticalscreatesrisksforotherpersonsfromexternalradiationorcontamination

fromspillsofurine,vomiting,etc.Radiationprotectionprecautionsinaccordancewithnationalregulationsmust

Organ Absorbeddoseperunitactivityadministered

(mGy/MBq)

Adult 15year 10year 5year 1year

Adrenals

Bladderwall

Bonesurfaces

Breast

GI-tract

Stomachwall

Smallintest

ULIwall

4.5E-03

2.1E-02

3.6E-03

3.2E-03

4.1E-03

4.5E-03

4.3E-03

5.0E-03

2.9E-02

4.2E-03

3.2E-03

4.7E-03

5.5E-03

5.2E-03

7.7E-03

4.2E-02

6.4E-03

4.8E-03

7.2E-03

8.4E-03

7.7E-03

1.2E-02

6.4E-02

9.8E-03

7.6E-03

1.1E-02

1.3E-02

1.2E-02

2.1E-02

1.2E-01

1.8E-02

1.4E-02

1.9E-02

2.3E-02

2.1E-02

2.3E-02

Kidneys

Liver

Lungs

Ovaries

Pancreas 8.3E-03

3.8E-03

3.3E-03

4.6E-03

4.3E-03 1.0E-02

4.6E-03

4.2E-03

6.0E-03

5.2E-03 1.4E-02

7.2E-03

6.3E-03

9.1E-03

8.1E-03 2.1E-02

1.1E-02

9.7E-03

1.4E-02

1.2E-02 3.6E-02

2.0E-02

1.8E-02

2.5E-02

2.2E-02

Redmarrow

Spleen

Testes

Thyroid

Uterus 4.0E-03

4.0E-03

3.7E-03

3.1E-03

5.8E-03 4.8E-03

4.8E-03

4.6E-03

4.3E-03

7.1E-03 7.1E-03

7.3E-03

7.2E-03

6.8E-03

1.1E-02 1.0E-02

1.1E-02

1.1E-02

1.1E-02

1.7E-02 1.8E-02

2.0E-02

2.1E-02

2.0E-02

2.9E-02

Othertissue 3.4E-03 4.1E-03 6.3E-03 9.9E-03 1.8E-02

Effective

doseequivalent

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