AMERSCAN MEDRONATE II AGENT 6.25 MILLIGRAMS KIT FO

Main information

  • Trade name:
  • AMERSCAN MEDRONATE II AGENT 6.25 MILLIGRAMS KIT FO
  • Dosage:
  • 6.25 Milligram
  • Pharmaceutical form:
  • Pdr for Soln for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMERSCAN MEDRONATE II AGENT 6.25 MILLIGRAMS KIT FO
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0240/022/001
  • Authorization date:
  • 05-02-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AmerscanMedronateIIAgent6.25milligramskitforradiopharmaceuticalpreparation

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Methylenediphosphonicacid6.25milligrams/vial(asthesodiumsalt),equivalentto5.0mgmedronicacid/vial.

AmerscanMedronateIIAgentisreconstitutedwithSodiumPertechnetate( 99m

Tc)Injection(notincludedinthiskit)to

prepareTechnetium( 99m

Tc)MedronateInjection.

Technetium-99mdisintegrateswiththeemissionofgammaradiationwithanenergyof140keVandahalflifeof6

hourstotechnetium-99whichcanberegardedasquasistable.

Theproductbeforereconstitutioncontains:

Sodium:1.60mg/vial.Thisneedstobetakenintoconsiderationforpatientsonacontrolledsodiumdiet.

Sodiump-aminobenzoate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Kitforradiopharmaceuticalpreparation

Whitetooff-whitepowderysolid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thismedicinalproductisfordiagnosticuseonly.

AfterreconstitutionwithSodiumPertechnetate( 99m

Tc)Injectiontheagentmaybeusedforbonescintigraphy,whereit

delineatesareasofalteredosteogenesis.

4.2Posologyandmethodofadministration

Theaverageactivityadministeredbyasingleintravenousinjectionis500MBq(300-700MBq). Otheractivitiesmaybe

justifiable.

Imagesobtainedshortlyafterinjection(e.g.intheso-called"3-phasebonescan"procedure)willonlypartlyreflectmetabolic

boneactivity.Latephasestaticscintigraphyshouldbeperformednotearlierthan2hoursafterinjection.

Thepatientshouldvoidbeforescanning.

Thedosetobeadministeredtoachildshouldbeafractionoftheadultdosecalculatedfromthebodyweightaccordingtothe

followingtable.

Table: DosecalculationforuseofTechnetium( 99m

Tc)MedronateInjectioninChildren

3kg=0.10

4kg=0.14 22kg=0.50

24kg=0.53 42kg=0.78

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(PaediatricTaskGroup,EuropeanAssociationofNuclearMedicines)

Inveryyoungchildren(upto1year)aminimumdoseof40MBqisnecessaryinordertoobtainimagesofsufficientquality.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Thepossibilityofhypersensivityincludingseriousanaphylactic/anaphylactoidreactionsshouldalwaysbeconsidered.Advance

lifesupportfacilitiesshouldbereadilyavailable.

Thisproductcontainssodiump-aminobenzoate.Thismayincreasetheriskofjaundiceinnewbornbabies.

Ininfantsandchildrenparticularattentionshouldbepaidtotherelativelyhigherradiationexposureoftheepiphysesingrowing

bone.

Appropriateprecautionsshouldbetakenconcerningtheactivity,whichiseliminatedbythepatients,toavoidanycontamination.

Toreducetheradiationexposuretothebladderwall,sufficienthydrationofthepatientandfrequentvoidingisrecommended.

Toavoidaccumulationoftracerinthemusculatureitisadvisedthatstrenuousexercisebediscouragedimmediatelyafterinjection

untilsatisfactoryboneimaginghasbeeneffected.

Inadvertentoraccidentalsubcutaneousadministrationoftechnetium-99mmedronateshouldbeavoidedasperivascular

inflammationhasbeendescribedfortechnetium-99mdiphosphonates.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Potentialinteractionshavebeendescribed.Anincreasedextraosseousaccumulationoftheradiotracerisreportedforiron

containingcompounds,acuteadministrationofdiphosphonate,severalcytostaticandimmunosuppressivedrugs,aluminium-

containingantacids,X-raycontrastmedia,antibiotics,anti-inflammatorysubstances,injectionsofcalciumgluconate,heparin,

calciumand-aminocaproicacid.

4.6Fertility,pregnancyandlactation

Whenitisnecessarytoadministerradioactivemedicinalproductstowomenofchildbearingpotential,information

shouldalwaysbesoughtaboutpregnancy.Anywomanwhohasmissedaperiodshouldbeassumedtobepregnant

untilprovenotherwise.Whereuncertaintyexistsitisimportantthatradiationexposureshouldbetheminimum

consistentwithachievingthedesiredclinicalinformation.Alternativetechniqueswhichdonotinvolveionising

radiationshouldbeconsidered.

Radionuclideprocedurescarriedoutonpregnantwomenalsoinvolveradiationdosestothefoetus.

Onlyimperativeinvestigationsshouldbecarriedoutduringpregnancy,whenthelikelybenefitexceedstheriskincurredbythe

motherandthefoetus.

Administrationof700MBqtechnetium-99mmedronatetoapatientwithnormalboneuptakeresultsinanabsorbeddosetothe

uterusof4.27mGy.Thedosedecreasesto2.03mGyinpatientswithhighboneuptakeand/orseverelyimpairedkidneyfunction.

6kg=0.19

8kg=0.23

10kg=0.27

12kg=0.32

14kg=0.36

16kg=0.40

18kg=0.44

20kg=0.46 26kg=0.56

28kg=0.58

30kg=0.62

32kg=0.65

34kg=0.68

36kg=0.71

38kg=0.73

40kg=0.76 46kg=0.82

48kg=0.85

50kg=0.88

52-54kg=0.90

56-58kg=0.92

60-62kg=0.96

64-66kg=0.98

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Beforeadministeringaradioactivemedicinalproducttoamotherwhoisbreastfeeding,considerationshouldbegivenasto

whethertheinvestigationcouldbereasonablydelayeduntilthemotherhasceasedbreastfeedingandastowhetherthemost

appropriatechoiceofradiopharmaceuticalhasbeenmade,

bearinginmindthesecretionofactivityinbreastmilk.Iftheadministrationisconsiderednecessary,onebreast-feedshouldbe

bankedpriortoinjectionandthesubsequentonediscardedafterinjection.Breastfeedingcanberestarted4hourspostinjection.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

4.8Undesirableeffects

Occasionally(approximately0.5outof100,000investigations),hypersensitivityreactions,includingveryrarelife

threateninganaphylaxis,mayoccurfollowingintravenousadministrationoftechnetium-99mmedronate.Casesof

localrashorgeneralizedrashwithitchinganddermalirritationhavebeenreported;onsetofthereactioniscommonly

severalhourspost-injectionanditmaylastupto48hours.Treatmentwithanon-sedativehistamineH

antagonistis

helpful.

Otherreactionsreportedincludeafallinbloodpressureandhypotensivesymptoms,nausea,vomiting,cutaneous

vasodilation,headache,malaise,oedemaintheextremitiesandarthralgia.

Foreachpatient,exposuretoionisingradiationmustbejustifiableonthebasisoflikelybenefit.Theactivity

administeredmustbesuchthattheresultingradiationdoseisaslowasreasonablyachievablebearinginmindtheneed

toobtaintheintendeddiagnosticresult.

Exposuretoionisingradiationislinkedwithcancerinductionandapotentialfordevelopmentofhereditarydefects.

Fordiagnosticnuclearmedicineinvestigationsthecurrentevidencesuggeststhattheseadverseeffectswilloccurwith

lowfrequencybecauseofthelowradiationdosesincurred.

Formostdiagnosticinvestigationsusinganuclearmedicineproceduretheeffectivedoseislessthan20mSv.Higher

dosesmaybejustifiedinsomeclinicalcircumstances.

4.9Overdose

Intheeventoftheadministrationofaradiationoverdosewithtechnetium-99mmedronate,theabsorbeddosetothe

patientshouldbereducedwherepossiblebyincreasingtheeliminationoftheradionuclidefromthebodybyforced

diuresisandbladdervoiding.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:diagnosticradiopharmaceuticals,technetium( 99m

Tc)compounds,technetium( 99m

medronicacid,ATCcode:V09BA02

Atthechemicalconcentrationsofradiopharmaceuticalandexcipientsusedfordiagnosticprocedurestechnetium-99m

medronatedoesnotappeartoexertanypharmacodynamiceffect.

5.2Pharmacokineticproperties

Inthefirst3minutesafterinjectionoftechnetium-99mmedronatethereissofttissueuptakeandrenalaccumulation.

Withincreasingclearancefromthesecompartments,progressiveaccumulationintheskeletalsystemisseeninitiallyin

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mediumphase(t½=27min.)and3:slowphase(t½=144min.). Therapidphaserepresentsthetransferofthe

radioactivesubstancefromthecirculationintotheextravascularsystem,themediumphaseinvolvingskeletaluptake.

Theslowphaseisprobablyassociatedwiththereleaseofthetechnetium-99mmedronatecomplexfromaprotein

boundcomplex.About50%ofthedoseinjectedaccumulatesintheskeleton.Maximumboneaccumulationisreached

1hourafterinjectionandremainspracticallyconstantupto72hours.Thecirculatingunboundcomplexiseliminated

viathekidneys.

Thepeakofactivitythroughthekidneysisreachedafterapproximately20minutes.Within1hour,withnormalrenal

function,around32%ofthetotalquantityofunboundcomplexhasundergoneglomerularfiltration,within2hours

47.5%andwithin6hours60%.Thequantityofphosphonate,withintherecommendeddoserange,hasnoeffecton

renalexcretion.Thequantityeliminatedviatheintestinesisinsignificant.

Thelevelofaccumulationintheskeletalsystemdependsonthecirculationandtheextentofregenerationofbasicbone

material.Wholebodyretentionsof31.6±5%arereportedinhealthyindividuals,38.2±7%inthosewithextensive

metastases,49±11%inprimaryhyperparathyroidismand45%inosteoporosis.

5.3Preclinicalsafetydata

Thisagentisnotintendedforregularorcontinuousadministration. Mutagenicitystudiesandlong-term

carcinogenicitystudieshavenotbeencarriedout.Repeateddosetoxicitystudiesinratswith50-100timesthehuman

dosedoesnotcausemacroscopicormicroscopicalterations.Repeatedadministrationofveryhighdosesof

diphosphonatescancausemineralizationdisorders.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Stannousfluoride

Sodiump-aminobenzoate

6.2Incompatibilities

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthosementionedinsection12.

6.3ShelfLife

78weeksfromthedayofmanufacture.

Thereconstitutedproductshouldbestoredbelow25 o

C.Donotfreeze.Thereconstitutedproductshouldbeinjectedwithin8

hoursofreconstitution.

6.4Specialprecautionsforstorage

Storebelow25 o

Storageshouldbeinaccordancewithnationalregulationsforradioactivematerial.

6.5Natureandcontentsofcontainer

10mltypeIPh.Eur.,clear,colourless,borosilicateglassvialsealedwithachlorobutylrubberclosureandoversealed

withanaluminiumoversealwithablueflipoffcap.

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6.6Specialprecautionsfordisposalandotherhandling

Normalsafetyprecautionsforhandlingradioactivematerialsshouldbeobserved.Afteruse,allmaterialsassociated

withthepreparationandadministrationofradiopharmaceuticals,includinganyunusedproductanditscontainer,

shouldbedecontaminatedortreatedasradioactivewasteanddisposedofinaccordancewiththeconditionsspecified

bythelocalcompetentauthority.Contaminatedmaterialmustbedisposedofasradioactivewasteviaanauthorised

route.

7MARKETINGAUTHORISATIONHOLDER

GEHealthcareLimited,

AmershamPlace,

LittleChalfont,

Buckinghamshire

HP79NA

UnitedKingdom.

8MARKETINGAUTHORISATIONNUMBER

PA240/22/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:5 th

February1999

Dateoflastrenewal:5 th

February2009

10DATEOFREVISIONOFTHETEXT

July2010

11DOSIMETRY

ThetablebelowshowsthedosimetryascalculatedaccordingtothePublication80oftheICRP(International

CommissiononRadiologicalProtection,RadiationDosetoPatientsfromRadiopharmaceuticals,PergamonPress

1998.

Radiationexposure(normalboneuptake)asabsorbeddose/injectedactivity(mGy/MBq).

Organ Absorbeddoseperunitactivity

administered(mGy/MBq)

Adult 15years 10years 5years 1year

Adrenals 2.1E-03 2.7E-03 3.9E-03 5.8E-03 1.1E-02

Bladder 4.8E-02 6.0E-02 8.8E-02 7.3E-02 1.3E-01

Bonesurfaces 6.3E-02 8.2E-02 1.3E-01 2.2E-01 5.3E-01

Brain 1.7E-03 2.1E-03 2.8E-03 4.3E-03 6.1E-03

Breast 7.1E-04 8.9E-04 1.4E-03 2.2E-03 4.2E-03

Gallbladder 1.4E-03 1.9E-03 3.5E-03 4.2E-03 6.7E-03

GI-tract

Stomach 1.2E-03 1.5E-03 2.5E-03 3.5E-03 6.6E-03

2.3E-03 2.9E-03 4.4E-03 5.3E-03 9.5E-03

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ThetablebelowshowsthedosimetryascalculatedaccordingtothePublication53oftheICRP(International

CommissiononRadiologicalProtection,RadiationDosetoPatientsfromRadiopharmaceuticals,PergamonPress1987.

Radiationexposure(highboneupdateand/orseverelyimpairedkidneyfunction)asabsorbeddose/injectedactivity

(ULI 1.9E-03 2.4E-03 3.9E-03 5.1E-03 8.9E-03)_

(LLI 3.8E-03 4.7E-03 7.2E-03 7.5E-03 1.3E-02)

Heart 1.2E-03 1.6E-03 2.3E-03 3.4E-03 6.0E-03

Kidneys 7.3E-03 8.8E-03 1.2E-02 1.8E-02 3.2E-02

Liver 1.2E-03 1.6E-03 2.5E-03 3.6E-03 6.6E-03

Lungs 1.3E-03 1.6E-03 2.4E-03 3.6E-03 6.8E-03

Muscles 1.9E-03 2.3E-03 3.4E-03 4.4E-03 7.9E-03

Oesophagus 1.0E-03 1.3E-03 1.9E-03 3.0E-03 5.3E-03

Ovaries 3.6E-03 4.6E-03 6.6E-03 7.0E-03 1.2E-02

Pancreas 1.6E-03 2.0E-03 3.1E-03 4.5E-03 8.2E-03

Redmarrow 9.2E-03 1.0E-02 1.7E-02 3.3E-02 6.7E-02

Skin 1.0E-03 1.3E-03 2.0E-03 2.9E-03 5.5E-03

Spleen 1.4E-03 1.8E-03 2.8E-03 4.5E-03 7.9E-03

Testes 2.4E-03 3.3E-03 5.5E-03 5.8E-03 1.1E-02

Thymus 1.0E-03 1.3E-03 1.9E-03 3.0E-03 5.3E-03

Thyroid 1.3E-03 1.6E-03 2.3E-03 3.5E-03 5.6E-03

Uterus 6.3E-03 7.6E-03 1.2E-02 1.1E-02 1.8E-02

Remaining

organs 1.9E-03 2.3E-03 3.4E-03 4.5E-03 7.9E-02

Effectivedose

(mSv/MBq) 5.7E-03 7.0E-03 1.1E-02 1.4E-02 2.7E-02

Organ Absorbed dose per unit activity administered

(mGy/MBq)

Adult 15year 10year 5year 1year

Adrenals

Bladderwall

Bonesurfaces

Breast

GI-tract

Stomachwall

Smallintestine

Upperlargeintestine

Lowerlargeintestine

Kidneys

Liver

Lungs

Ovaries

Pancreas

RedMarrow

3.5E-03

2.5E-03

1.2E-01

2.1E-03

2.6E-03

3.1E-03

2.9E-03

3.4E-03

3.0E-03

2.7E-03

3.0E-03

2.9E-03

3.2E-03

1.8E-02

5.0E-03

3.5E-03

1.6E-01

2.1E-03

3.2E-03

3.8E-03

3.6E-03

4.2E-03

3.7E-03

3.3E-03

3.7E-03

4.1E-03

4.0E-03

2.3E-02

7.2E-03

5.4E-03

2.6E-01

3.2E-03

5.1E-03

5.7E-03

5.3E-03

6.5E-03

5.6E-03

4.9E-03

5.3E-03

5.9E-03

5.9E-03

3.7E-03

1.1E-02

7.4E-03

4.3E-01

5.1E-03

7.3E-03

8.5E-03

8.6E-03

9.6E-03

8.7E-03

7.5E-03

8.1E-03

8.9E-03

8.9E-03

7.2E-02

2.1E-02

1.5E-02

1.0E+00

9.6E-03

1.4E-02

1.6E-02

1.5E-02

1.8E-02

1.6E-02

1.4E-02

1.5E-02

1.6E-02

1.6E-02

1.4E-01

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Forthisproducttheeffectivedoseresultingfromanadministeredactivityof700MBqistypically4.0mSv(per70kg

individual),(ICRP80,1998).

Foranadministeredactivityof700MBqthetypicalradiationdosetothetargetorgan(bone)is44.1mGyandthetypical

radiationdosetothecriticalorgan(bladderwall)is35mGy.

Incasesofhighboneuptakeand/orseverelyimpairedkidneyfunction,theeffectivedoseequivalentresultingfroman

administeredactivityof700MBqoftechnetium-99mmedronateis5.7mSv.Thetypicalradiationdosetothetarget

organis84mGyandthetypicalradiationdosetothecriticalorgan(redmarrow)is12.6mGy.

12INSTRUCTIONSFORPREPARATIONOFRADIOPHARMACEUTICALS

Thisradiopharmaceuticalmaybereceived,usedandadministeredonlybyauthorizedpersonsinhospitals.Itsreceipt,

storage,use,transferanddisposalaresubjecttotheregulationsandtheappropriatelicensesofthelocalcompetent

officialorganizations(seesection6.6).

Theadministrationofradiopharmaceuticalscreatesrisksforotherpersonsfromexternalradiationorcontamination

fromspillsofurine,vomiting,etc.Radiationprotectionprecautionsinaccordancewithnationalregulationsmust

thereforebetaken.

Normalsafetyprecautionsforthehandlingofradioactivematerialsshouldbeobservedinadditiontotheuseofaseptic

techniquetomaintainsterilityofthevialcontents.

Methodofpreparationofthefinaldosageformforinjection

Useaseptictechniquethroughout.

Placeoneofthevialsinasuitableshieldingcontainerandswabtherubberclosurewiththesanitizingswab

supplied.

Usinga10mlsyringe,injectasuitablequantity(seenotes1and2)oftheeluatefromatechnetium-99msterile

generatorintotheshieldedvial.Beforeremovingthesyringefromthevial,withdrawanequivalentvolumeof

gasfromthespaceabovethesolutiontonormalisethepressureinthevial.

Shaketheshieldedvialfor10secondstoensurecompletedissolutionofthepowder.

Assaythetotalactivity,completethelabelprovidedandattachtovial.

Notes:

Upto18.5GBqtechnetium-99mmaybeaddedtothevial.

Reconstitutewith2-8ml.Theeluatemay,ifnecessary,bedilutedto2-8mlusingsalineforinjection.

Imagesfromboneagentsbasedonsodiummedronateimproveifthepreparedinjectionisstoredatroom

temperatureforashorttimefollowingreconstitution.Itisthereforerecommendedthat15minutesormore

shouldnormallyelapsebeforeinjection.

Theuseofatechnetium-99mpertechnetatesolutioncomplyingwiththespecificationsprescribedbytheUSPand

BP/Ph.EuronSodiumPertechnetate( 99m

Tc)Injectionwillyieldapreparationofanappropriatequality.

Radiochemicalpuritymeasurement

Acombinationoftwochromatographicsystemsisnecessaryforthedeterminationoftheradiochemicalpurityofthe

Testes

Thyroid

Uterus

Othertissue 2.3E-03

2.4E-03

2.9E-03

3.0E-03 2.7E-03

3.7E-03

3.7E-03

3.6E-03 3.9E-03

5.4E-03

5.4E-03

5.3E-03 6.0E-03

8.3E-03

8.2E-03

8.1E-03 1.1E-02

1.4E-02

1.5E-02

1.5E-02

Effectivedoseequivalent

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Testsamplesareappliedbyneedleapproximately2.5cmfromthebottomoftwoGelmanITLC/SGstrips(2.5cmx20

cm).Thestripsarethenimmediatelyplacedinpreparedascendingchromatographydevelopmenttanks,one

containingbutan-2-oneandtheother1.0Msodiumacetate(1cmdepthfreshsolvent).Aftera15cmelutionthestrips

areremoved,solventfrontsmarked,thestripsdriedandthedistributionofactivitydeterminedusingsuitable

equipment.

Interpretationofchromatograms

System1(ITLC:butan-2-onemethylethylketone)

Technetium-99mmedronatecomplexandcolloidaltechnetiumremainattheorigin.

PertechnetatemigratesatRf0.8-1.0.

System2(ITLC:1.0Msodiumacetate)

Colloidaltechnetiumremainsattheorigin.Technetium-99mmedronatecomplexandpertechnetatemigrateatRf0.8-

1.0.

Thepercentageofradioactivitycorrespondingtopertechnetateionisobtainedfromsystem1.

Thisshouldbenotgreaterthan2.0%.

Thesumofthepercentagesofimpuritiesobtainedfromsystems1(pertechnetate)andsystem2(Hydrolysed

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