ARTISS POWDERS AND SOLVENT FOR SEALANT

Main information

  • Trade name:
  • ARTISS POWDERS AND SOLVENT FOR SEALANT
  • Pharmaceutical form:
  • Powder and Solvent for Sealant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ARTISS POWDERS AND SOLVENT FOR SEALANT
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/131/002
  • Authorization date:
  • 03-07-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0167/131/002

CaseNo:2039539

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

BaxterHealthcareLimited

CaxtonWay,Thetford,NorfolkIP243SE,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

ARTISSLYOPowdersandsolventsforsealant,lyophilized

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom03/07/2009until02/07/2014.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 07/07/2009 CRN 2039539 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ARTISSLYOPowdersandSolventsforSealant,lyophilized

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Component1:

SealerProteinSolution

(SealerProteinConcentrate-Lyophilized-reconstitutedwithAprotininSolution)

HumanFibrinogen(asclottableprotein) 91mg[ 1

]/ml

Aprotinin 3000KIU[ 2

]/ml

Component2:

ThrombinSolution

(Thrombin-Lyophilized-reconstitutedwithCalciumChlorideSolution)

HumanThrombin 4IU[ 3

]/ml

CalciumChloride 40µmol/ml

<1ml><2ml><5ml>SealerProteinSolutionand<1ml><2ml><5ml>ThrombinSolution,respectively,resultin

<2ml><4ml><10ml>finalproductreadyforuse.

1.Containedinatotalproteinconcentrationof96-125mg/ml

2.1EPU(EuropeanPharmacopoeiaUnit)correspondsto1800KIU(KallidinogenaseInactivatorUnit)

3.ThrombinactivityiscalculatedusingthecurrentWHOInternationalStandardforThrombin

ARTISSLYOcontainsHumanFactorXIIIco-purifiedwithHumanFibrinogeninarangeof0.6-5IU/ml.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

PowderandSolventforSealant

Freeze-driedconstituentsarehygroscopic,whiteorpaleyellowpowdersorfriablesolids;liquidconstituentsareclear,

Aftermixing 1ml 2ml 4ml 10ml

Component1:Sealerprotein

solution

HumanFibrinogen

(asclottableprotein)

Aprotinin 45.5mg

1,500KIU 91mg

3,000KIU 182mg

6,000KIU 455mg

15,000KIU

Component2:Thrombin

Solution

HumanThrombin

CalciumChloride 2IU

20µmol 4IU

40µmol 8IU

80µmol 20IU

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4CLINICALPARTICULARS

4.1TherapeuticIndications

ARTISSisindicatedasatissuegluetoadhere/sealsubcutaneoustissueinplastic,reconstructiveandburnsurgery,asa

replacementoranadjuncttosuturesorstaples(see5.1).Inaddition,ARTISSisindicatedasanadjuncttohemostasis

onsubcutaneoustissuesurfaces.

4.2Posologyandmethodofadministration

ARTISSLYOisintendedforHospitalUseOnlybysuitablyexperiencedphysiciansorsurgeons.

Posology:

TheamountofARTISSLYOtobeappliedandthefrequencyofapplicationshouldalwaysbeorientedtowardsthe

underlyingclinicalneedsofthepatient.

Thedosetobeappliedisgovernedbyvariablesincluding,butnotlimitedto,thetypeofsurgicalintervention,thesize

oftheareaandthemodeofintendedapplication,andthenumberofapplications.

Applicationoftheproductmustbeindividualizedbythetreatingphysician.Inclinicaltrials,theindividualdosages

havetypicallyrangedfrom0.2-12ml.Forsomeprocedures(e.g.thesealingoflargeburnedsurfaces),largervolumes

mayberequired.ARTISShasnotbeenadministeredto>65yearsoldinclinicaltrials.

Theinitialamountoftheproducttobeappliedatachosenanatomicsiteortargetsurfaceareashouldbesufficientto

entirelycovertheintendedapplicationarea.Theapplicationcanberepeated,ifnecessary.

Asaguidelineforthegluingofsurfaces,1packofARTISSLYO2ml(i.e.,1mlSealerProteinSolutionplus1ml

ThrombinSolution)willbesufficientforanareaofatleast10cm 2

Toavoidtheformationofexcessgranulationtissueandtoensuregradualabsorptionofthesolidifiedfibrinsealant,

onlyathinlayerofthemixedSealerProtein-ThrombinSolution,oroftheindividualcomponents,shouldbeapplied.

Methodandrouteofadministration

Forepilesionaluse.

Preparethesolutionasdescribedat6.6.

Beforeapplication,thesurfaceofthewoundshouldbeasdryaspossible.

See6.6formoredetailedinstructions.

4.3Contraindications

ARTISSLYOisnotindicatedtoreplaceskinsuturesintendedtoclosesurgicalwound.

ARTISSLYOaloneisnotindicatedforthetreatmentofmassiveandbriskarterialorvenousbleeding.

ARTISSLYOmustneverbeappliedintravascularly.Hypersensitivitytotheactivesubstancesortoanyofthe

excipients.

4.4Specialwarningsandprecautionsforuse

Forepilesionaluseonly.Donotapplyintravascularly.

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SofttissueinjectionofARTISSLYOcarriestheriskoflocaltissuedamage.

ARTISSLYOisnotindicatedforhemostasisandsealinginsituationswhereafastclottingofthesealantisrequired.

EspeciallyincardiovascularproceduresinwhichsealingofvascularanastomosesisintendedARTISSLYOshouldnot

beused.

ARTISSLYOisnotindicatedforuseinneurosurgeryandasasuturesupportforgastrointestinalanastomosesor

vascularanastomosesasnodataareavailabletosupporttheseindications.

ARTISSLYOshouldonlybeappliedasathinlayer.Excessiveclotthicknessmaynegativelyinterferewiththe

product’sefficacyandthewoundhealingprocess.

BeforeadministrationofARTISScareistobetakenthatpartsofthebodyoutsidethedesignatedapplicationareaare

sufficientlyprotected/coveredtopreventtissueadhesionatundesiredsites.

Aswithanyprotein-containingproduct,allergictypehypersensitivityreactionsarepossible.Signsofhypersensitivity

reactionsmayincludehives,generalizedurticaria,tightnessofthechest,wheezing,hypotension,andanaphylaxis.If

thesesymptomsoccur,theadministrationmustbediscontinuedimmediately.

ARTISSLYOcontainsbovineprotein(aprotinin).Evenincaseofstrictlocalapplication,thereisariskofanaphylactic

reactionlinkedtothepresenceofbovineaprotinin.Theriskseemstobehigherincaseswheretherewasprevious

exposure,evenifitwaswelltolerated.Thereforeanyuseofaprotininoraprotinincontainingproductsshouldbe

recordedinthepatients’records.

Intheeventofanaphylacticorseverehypersensitivityreactions,administrationistobediscontinuedandstate-of-the-

artemergencymeasuresaretobetaken.Incaseofshock,standardmedicaltreatmentforshockshouldbeimplemented.

Standardmeasurestopreventinfectionsresultingfromtheuseofmedicinalproductspreparedfromhumanbloodor

plasmaincludeselectionofdonors,screeningofindividualdonationsandplasmapoolsforspecificmarkersof

infectionandtheinclusionofeffectivemanufacturingstepsfortheinactivation/removalofviruses.Despitethis,when

medicinalproductspreparedfromhumanbloodorplasmaareadministered,thepossibilityoftransmittinginfective

agentscannotbetotallyexcluded.Thisalsoappliestounknownoremergingvirusesorotherpathogens.

ThemeasurestakenareconsideredeffectiveforenvelopedvirusessuchasHIV,HBV,andHCV,andforthenon-

envelopedvirusHAV.

Themeasurestakenmaybeoflimitedvalueagainstnon-envelopedvirusessuchasparvovirusB19.ParvovirusB19

infectionmaybeseriousforpregnantwomen(fetalinfection)andforindividualswithimmunodeficiencyorincreased

erythropoiesis(e.g.,hemolyticanemia).

ItisstronglyrecommendedthateverytimethatARTISSLYOisadministeredtothepatient,thenameandbatch

numberoftheproductarerecordedinordertomaintainalinkbetweenthepatientandthebatchoftheproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noformalinteractionstudieshavebeenperformed.Similartocomparableproductsorthrombinsolutions,theproduct

maybedenaturedafterexposuretosolutionscontainingalcohol,iodineorheavymetals(e.g.antisepticsolutions).

Suchsubstancesshouldberemovedtothegreatestpossibleextentbeforeapplyingtheproduct.

4.6Pregnancyandlactation

Thesafetyoffibrinsealants/haemostaticsforuseinhumanpregnancyorbreastfeedinghasnotbeenestablishedin

controlledclinicaltrials.Animalstudieshavealsonotbeenperformed.

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4.7Effectsonabilitytodriveandusemachines

Notrelevant.

4.8Undesirableeffects

InadvertentintravascularinjectioncouldleadtothromboemboliceventsandDICandthereisalsoariskof

anaphylacticreactions(see4.4).

Hypersensitivityorallergicreactions(whichmayincludeangioedema,burningandstingingattheapplicationsite,

bradycardia,bronchospasm,chills,dyspnoea,flushing,generalizedurticaria,headache,hives,hypotension,lethargy,

nausea,pruritus,restlessness,tachycardia,tightnessofthechest,tingling,vomiting,wheezing)mayoccurinrarecases

inpatientstreatedwithfibrinsealants/hemostatics.

Inisolatedcases,thesereactionshaveprogressedtosevereanaphylaxis.Suchreactionsmayespeciallybeseenifthe

preparationisappliedrepeatedly,oradministeredtopatientsknowntobehypersensitivetoaprotinin(seesection4.4)

oranyotherconstituentsoftheproduct.

EvenifafirsttreatmentwithARTISSwaswelltolerated,asubsequentadministrationofARTISSorsystemic

administrationofaprotininmayresultinsevereanaphylacticreactions.

Antibodiesagainstcomponentsoffibrinsealantmayrarelyoccur.

Forsafetywithrespecttotransmissibleagents,seesection4.4.

Adversereactionsreportedfromclinicalstudiesaswellasfrompostmarketingsurveillancearesummarizedinthe

following.Knownfrequenciesoftheseadversereactionsarebasedonacontrolledclinicalstudyin138patientswhere

skingraftswerefixedtoexcisedburnwoundsusingARTISS.Noneoftheeventswereclassifiedasserious.Unknown

frequenciesarebasedonspontaneousreportsfrompostmarketingsurveillanceofBaxter'sfibrinsealants.

TheADRsandtheirfrequenciesaresummarizedbelow:

Common(1/100to<1/10)

Uncommon(1/1000to<1/100)

Unknown(cannotbeestimatedfromtheavailabledata)

Immunesystemdisorders:

Frequencyunknown:anaphylacticresponses,hypersensitivity;

Cardiacdisorders:

Frequencyunknown:bradycardia,tachycardia;

Vasculardisorders:

Frequencyunknown:hypotension,haematoma;

Respiratory,thoracicandmediastinaldisorders:

Frequencyunknown:dyspnoea;

Gastrointestinaldisorders:

Frequencyunknown:nausea;

Skinandsubcutaneoustissuedisorders:

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Uncommon *

:dermalcyst;

Frequencyunknown:urticaria;

Generaldisordersandadministrationsiteconditions:

Frequencyunknown:flushing,impairedhealing,oedema,pyrexia;

Injury,poisoningandproceduralcomplication:

Common *

:skingraftfailure;

Frequencyunknown:seroma;

*InthecontrolledclinicalstudytheseadversereactionsalsooccuredatthecontrolsitewithoutARTISSapplication.

4.9Overdose

Nocaseofoverdosehasbeenreported.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:localhemostatics,ATCcode:B02BC;tissueadhesives,ATCcode:V03AK

ARTISScanreplacesuturesorstapleswhenusedforfixationofskingraftstoburnedorotherwiseinjuredwound

areas.ARTISScanbeusedasanadjuncttosuturesorstaplestoadhereandsealskinflapsincaseswhere

sutures/staplesareexpectedtoyieldunsatisfactoryresultswithrespecttopostoperativehematomaorseromaformation.

Thefibrinadhesionsysteminitiatesthelastphaseofphysiologicalbloodcoagulation.Conversionoffibrinogeninto

fibrinoccursbythesplittingoffibrinogenintofibrinmonomersandfibrinopeptides.Thefibrinmonomersaggregate

andformafibrinclot.FactorXIIIa,whichisactivatedfromfactorXIIIbythrombin,crosslinksfibrin.Calciumionsare

requiredfortheconversionoffibrinogenandthecrosslinkageoffibrin.

Aswoundhealingprogresses,increasedfibrinolyticactivityisinducedbyplasmin,anddecompositionoffibrinto

fibrindegradationproductsisinitiated.Proteolyticdegradationoffibrinisinhibitedbyanti-fibrinolytics.Aprotininis

presentinARTISSLYOasanantifibrinolytictopreventprematuredegradationoftheclot.

Forefficacy,invivostudiesinananimalmodelcloselyimitatingthesituationinpatientswereused.ARTISS(frozen

andlyophilizedpresentations)demonstratedefficacyregardingsealingautologoussplitskingraftsandmeshgrafts.

ARTISS(frozen)wasinvestigatedforfixationofsplitthicknesssheetskingraftsinburnpatientsinaprospective,

randomised,controlled,multicenterclinicalstudy.Ineachofthe138patients,twocomparabletestsiteswere

identified.InonetestsitetheskingraftwasfixedwithARTISS(frozen),intheothertestsitethegraftwasfixedwith

staples(control).ARTISS(frozen)provedtobenon-inferiortostapleswithrespecttotheprimaryefficacyendpoint,

completewoundclosureatDay28wasevaluatedbyablindedevaluatorpanelfromphotographs.Thiswasachievedin

55/127patients(43.3%)treatedwithARTISS(frozen)and47/127patients(37%)treatedwithstaples.

Withrespecttosecondaryendpoints,ARTISS(frozen)showedasignificantlylowerincidenceandsizeof

hematoma/seromaonDay1(p<0.0001forincidenceaswellassize).IncidenceandareaofengraftmentonDay5and

woundclosureonDay14,aswellasareaofwoundclosureonDay28werenotdifferent.ARTISS(frozen)wasalso

superiortostapleswithrespecttopatientsatisfaction(p<0.0001)andpatientsexperiencedsignificantlylessanxiety

aboutpainwithARTISS(frozen)thanwithstaples(p<0.0001).Moreover,ARTISS(frozen)wassignificantly

superiortostapleswithrespecttotheinvestigator'sassessmentofqualityofgraftadherence,preferenceoffixation

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5.2Pharmacokineticproperties

ARTISSLYOisintendedforepilesionaluseonly.Intravascularadministrationiscontraindicated.Asaconsequence,

intravascularpharmacokineticstudieswerenotperformedinman.

Pharmacokineticstudiesindifferentspeciesoflaboratoryanimalswerenotconducted.

Fibrinsealants/hemostaticsaremetabolizedinthesamewayasendogenousfibrinbyfibrinolysisandphagocytosis.

5.3Preclinicalsafetydata

NopreclinicalsafetydataareavailableforARTISS(thrombin4IU/ml).ToxicitystudiesweredonewithFibrin

Sealantscontainingthrombin500IU/ml,asrepresentativeforproductscontainingthrombin4IU/ml.Single-dose

toxicitystudiesinratsandrabbitsindicatednoacutetoxicityofFibrinSealantVHS/D(500IU/ml).FibrinSealantVH

S/D(500IU/ml)alsoprovedwelltoleratedinwoundhealingmodelsinratsandrabbits,andininvitrohuman

fibroblastcultures.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Component1:SealerProteinSolution

HumanAlbuminSolution

L-Histidine

Niacinamide

Polysorbate80(Tween80)

SodiumCitrateDihydrate

WaterforInjections

Component2:ThrombinSolution

HumanAlbuminSolution

SodiumChloride

WaterforInjections

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproductsother

thanappropriatesolventsmentionedin6.6.

6.3ShelfLife

2years

6.4Specialprecautionsforstorage

Keepoutofthereachandsightofchildren.

DonotstoreARTISSLYOabove25°C.Donotfreeze.

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Usethereconstitutedsterilesolutionswithin4hours.Keepthereconstitutedsterilesolutionsat37°Coratroom

temperaturewithoutstirringifnotusedimmediately.Reconstitutedsolutionsmustnotberefrigeratedorfrozen.

6.5Natureandcontentsofcontainer

AllcomponentsofARTISSLYOarefilledintoglasscontainers(SealerProteinConcentrate-Lyophilized,:typeI

glassandtypeIIglass,allothervials:typeIglass)conformingtoPh.Eur.requirements.ThevialcontainingSealer

ProteinConcentrate-Lyophilizedisequippedwithamagneticstirrer.

EachpackofARTISSLYOcontains:

1vialPowderforSealant-Component1(Lyophilized)containingHumanFibrinogen91mg/ml

1vialPowderforSealant-Component2(Lyophilized)containingThrombin4IU/ml

1vialSolventforComponent1(Solution)containingAprotinin3000KIU/ml

1vialSolventforComponent2(Solution)containingCalciumChloride40µmol/ml

1Kitforreconstitutionandapplication(DUPLOJECTSystem:4transferneedles,2blue-scaledsyringes,2

black-scaledsyringes,1Dupoljecttwo-syringeclip,2joiningpiecesand4applicationcanulas)

ARTISSLYOisavailableinthefollowingpacksizes:

ARTISSLYO2ml

(reconsitutedproductcontains:1mlofSealerProteinSolutionand1mlofThrombinSolution)

ARTISSLYO4ml

(reconsitutedproductcontains:2mlofSealerProteinSolutionand2mlofThrombinSolution)

ARTISSLYO10ml

(reconsitutedproductcontains:5mlofSealerProteinSolutionand5mlofThrombinSolution)

TheKitforReconstitutionandApplication(DUPLOJECTSystem)isforsingleuseonly.Donotre-sterilize!

Notallpacksizesmaybemarketed.

OtheraccessoriesforapplicationoftheproductcanbeobtainedfromBAXTER.

6.6Specialprecautionsfordisposalandotherhandling

General

TopreventARTISSLYOfromadheringtoglovesandinstruments,wetthesewithsodiumchloridesolutionbefore

contact.

Asaguidelineforthegluingofsurfaces,1packofARTISSLYO2ml(i.e.,1mlSealerProteinSolutionplus1ml

ThrombinSolution)willbesufficientforanareaofatleast10cm 2

TherequireddoseofARTISSLYOdependsonthesizeofthesurfacetobecovered.Preparationand

reconstitution

Priortoreconstitutionofthefibrinsealantcomponentstherubberstoppersofallvialsshouldbecleansed.

Directcontactbetweendisinfectantandproductmustbeavoided(seesection4.5).

PreparationofComponent1-SealerProteinSolution

TheSealerProteinConcentrate–LyophilizedisdissolvedwiththeAprotininSolutiontoformtheSealerProtein

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SealerProteinConcentrate–LyophilizedisreconstitutedusingtheFIBRINOTHERMwarmingandstirringdevice

(recommendedmethod).Alternatively,asterilewaterbathatatemperatureof33-37°Ccanbeused.

ReconstitutionusingtheFIBRINOTHERMdevice:

TheFIBRINOTHERMdevicemaintainsaconstanttemperatureof37°C.Italsoshortensthedissolutiontimeofthe

SealerProteinConcentrate–LyophilizedbyrotatingthemagneticstirrercontainedineachSealerProteinConcentrate

–Lyophilizedvial.

PlacethevialscontainingSealerProteinConcentrate-LyophilizedandAprotininSolutionintotheappropriate

openingsofthepre-heatedFIBRINOTHERMdeviceandheatthevialsforapproximately3minutes.

TransfertheAprotininSolutionintothevialcontainingtheSealerProteinConcentrate-Lyophilizedusingone

needleandtheblue-scaledsyringeprovidedinthesingle-sterilekitforreconstitution.PlacethesealerProtein

vialintothestirringwelloftheFIBRINOTHERMdevice(usetheadaptor,ifnecessary)andstiruntilcomplete

dissolution.Reconstitutioniscompleteassoonasnoparticlesarevisibleanymorewhenholdingthevialagainst

thelight.Ifparticlesarepresent,keeponstirringthesolutionat37°Cforafewmoreminutesuntilcomplete

dissolution.Turnoffthemagneticstirrerwhendissolutioniscomplete.

Note:Excessivestirringmightcompromiseproductquality!

KeeptheSealerProteinSolutionat37°Coratroomtemperaturewithoutstirringifitisnotusedimmediately.

Beforeusethesolutionmustbewarmedto37°C.Toensurehomogeneitystirorswirlbrieflybeforedrawingup

theSealerProteinSolutionintotheblue-scaledsyringeprovidedinthedouble-sterilekitforapplication.

WithdrawthereconstitutedSealerProteinSolutionfromthevialundersterileconditions.

ForfurtherinstructionspleaserefertotheinstructionsforuseoftheFIBRINOTHERMdevice.

Reconstitutionusingawaterbath:

PreheatthevialscontainingtheSealerProteinConcentrate-LyophilizedandtheAprotininSolutionfor

approximately3minutesinawaterbathatatemperatureof33-37°C.(Heatingbeyond37°Cmustbeavoided!)

TransfertheAprotininSolutionintothevialcontainingtheSealerProteinConcentrate-Lyophilizedusing

oneneedleandtheblue-scaledsyringeprovidedinthesingle-sterileKitforreconstitution.

ReturntheSealerProteinvialtothewaterbathat33°C-37°Cforoneminute.

Swirlbrieflybutavoidexcessivefrothing.Thenreturnthevialtothewaterbathandcheckperiodicallyfor

completedissolution.Reconstitutioniscompleteassoonasnoparticlesarevisiblewhenholdingthevialagainst

thelight.Ifparticlesarepresent,keepthevialat33°C-37°Cforafewmoreminutesandagitatethesolution

untilcompletedissolution.

KeeptheSealerProteinSolutionat33°C-37°Coratroomtemperatureifnotusedimmediately.Beforeusethe

solutionmustbewarmedto33°C-37°C.ToensurehomogeneityswirlbrieflybeforedrawinguptheSealer

ProteinSolutionintotheblue-scaledsyringeprovidedinthedouble-sterilekitforapplication.

WithdrawthereconstitutedSealerProteinSolutionfromthevialundersterileconditions.

Note:WhenusingawaterbathforreconstitutioninsteadoftheFIBRINOTHERMdevice,specialprecautions

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PreparationofComponent2-ThrombinSolution

TheThrombin–LyophilizedisdissolvedwiththeCalciumChlorideSolutiontoformtheThrombinSolution.Transfer

thecontentsoftheCalciumChlorideSolutionvialintotheThrombin–Lyophilizedvial.Usethesecondneedleandthe

black-scaledsyringeprovidedinthesingle-sterileKitforreconstitution.

Swirlbrieflytodissolvethelyophilizedmaterial.TowarmtheThrombinSolutioneithertheFIBRINOTHERMdevice

orawaterbathcanbeused.KeeptheThrombinSolutionat33-37°Coratroomtemperatureifnotusedimmediately.

Beforeuse,thesolutionmustbewarmedto33-37°C.Priortouse,drawuptheThrombinSolutionfromthevialusing

thesecondneedleandtheblack-scaledsyringeprovidedinthedouble-sterileKitforapplication.

Note:Syringesandneedlesusedforthereconstitutionofonecomponentmustnotbere-usedforthereconstitutionof

theothercomponent,asthiswouldleadtosolidificationofthatcomponentinthevialorsyringe.

III.UseofreconstitutedARTISSLYOComponents

Bothfibrinsealantcomponentsmustbeusedwithin4hoursafterreconstitution.Reconstitutedsolutionsmustnotbe

refrigeratedorfrozen.

TheSealerProteinandtheThrombinSolutionsshouldbeclearorslightlyopalescent.Donotusesolutionsthatare

cloudyorhavedeposits.Inspectreconstitutedproductsbyeyeforparticulatematteranddiscolorationpriorto

administration.

Administration

Forapplication,clipthetwosingle-usesyringeswiththereconstitutedSealerProteinSolutionandThrombinSolution

intotheDUPLOJECTTwo-SyringeClipandconnectthisassemblytoajoiningpieceandanapplicationcannula.The

double-sterileKitcontainsalldevicesnecessaryforapplication.

ThecommonplungeroftheDUPLOJECTTwo-SyringeClipensuresthatequalvolumesarefedthroughthejoining

piece,beforebeingmixedintheapplicationneedleandejected.

OperatingInstructions

PlacethetwosyringesfilledwithSealerProteinSolutionandwithThrombinSolutionintotheclip.Bothsyringes

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Connectthenozzlesofthetwosyringestothejoiningpieceensuringthattheyarefirmlyfixed.Securethejoiningpiece

byfasteningthetetherstraptotheDUPLOJECTTwo-SyringeClip.Shouldthepullstraptear,usethesparejoining

piece.Ifnoneisavailable,furtheruseisstillpossiblebuttightnessoftheconnectionneedstobeensuredtopreventany

riskofleaking.

Fitanapplicationcannulaontothejoiningpiece.

Donotexpeltheairremaininginsidethejoiningpieceorapplicationcannulauntilyoustartactualapplicationas

theapertureofthecannulamayclogotherwise.

ApplythemixedSealerProtein-ThrombinSolutionontotherecipientsurfaceorsurfacesofthepartstobe

sealed.

Ifapplicationofthefibrinsealantcomponentsisinterrupted,cloggingmayoccurinthecannula.Replacethe

applicationcannulawithanewoneonlyimmediatelybeforeapplicationisresumed.Iftheaperturesofthe

joiningpieceareclogged,usethesparejoiningpieceprovidedinthepackage.

ApplicationisalsopossiblewithotheraccessoriessuppliedbyBAXTERthatareparticularlysuitedfor,e.g.minimally

invasivesurgery,applicationtolargeordifficult-to-accessareas.Whenusingtheseapplicationdevices,strictlyfollow

theInstructionsforUseofthedevices.

Afterthetwocomponentshavebeenapplied,approximatethewoundareas.Fixorholdthegluedpartswithcontinuous

gentlepressureinthedesiredpositionforabout3–5minutestoensurethatthesettingfibrinsealantadheresfirmlyto

thesurroundingtissue.

Disposal

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

BaxterHealthcareLtd.

CaxtonWay

Thetford

NorfolkIP243SE

8MARKETINGAUTHORISATIONNUMBER

PA167/131/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3rdJuly2009.

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