Actilyse Cathflo

Main information

  • Trade name:
  • Actilyse Cathflo 2 mg Powder for injection
  • Dosage:
  • 2 mg
  • Pharmaceutical form:
  • Powder for injection
  • Units in package:
  • Combination pack, powder + diluent, 1 dose unit
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Boehringer Ingelheim Pharma GmbH & Co KG

Documents

Localization

  • Available in:
  • Actilyse Cathflo 2 mg Powder for injection
    New Zealand
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • ACTILYSE CATHFLO is indicated for thrombolytic treatment of occluded central venous access devices including those used for haemodialysis. The 2 mg strength of alteplase (ACTILYSE CATHFLO) is the only recommended presentation for use in this indication.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 13161
  • Authorization date:
  • 21-05-2007
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

NewZealandDatasheet

NameofMedicine

ACTILYSE ®

CATHFLO ®

Alteplase(recombinanthumantissue-typeplasminogenactivator:rt-PA)

Presentation

ACTILYSE2mg: clearglassinjectionvialcontaining2mgalteplaseasasterilewhitetooff-

whiteand 2.2mlampoule ofwaterforinjection.

Uses

Actions

ACTILYSECATHFLOisatissueplasminogenactivatorproducedbyrecombinantDNA

technology.Itisapurifiedfibrinolyticglycoproteinof527aminoacids,synthesisedusingthe

complementaryDNA(cDNA)fornaturalhumantissue-typeplasminogenactivator.The

manufacturingprocessinvolvesthesecretionoftheserineproteaset-PAintotheculturemedium

byanestablishedmammaliancelllineintowhichthecDNAfortissueplasminogenactivatorhas

beengeneticallyinserted.

ACTILYSECATHFLOisintendedforintra-catheterinstillationintodysfunctionalcentralvenous

accessdevices,includingthoseusedforhaemodialysis,afterreconstitutionwithsterileWaterfor

Injections.

ACTILYSECATHFLOisa serineprotease whichhasthepropertyoffibrin-enhanced conversion of

plasminogentoplasmin.ACTILYSECATHFLOproducesminimalconversionofplasminogenin

theabsenceoffibrin;andwhenintroducedintothesystemiccirculation,ACTILYSECATHFLO

bindstofibrininathrombusandconvertstheentrappedplasminogentoplasmin.Thisinitiates

localfibrinolysiswith minimalsystemic effects.

InstillationofACTILYSECATHFLOatadoseof2mgintotheoccludedcatheterallowsfibrinolysis

tooccurlocallywithinthecatheterandatthecathetertipwithoutcausingpharmacodynamic

effectsinthecirculation.

ACTILYSECATHFLOdiffersfromotherplasminogenactivatorsinthatitisfibrin-dependent.

RelativelyselectivefibrinolysiswithACTILYSECATHFLO,i.e.localisedactivationofthefibrinolytic

system,ispossibleduetoseveralfactorssuchasthehighaffinityoftissueplasminogenactivator

forfibrin,thefibrin-dependentactivationoftissueplasminogenactivator,andthecoprecipitationof

plasminogenwithinthefibrinclot.Asaresult,ACTILYSECATHFLOproducesclotdissolutionin

vivowith minimalsystemiceffects.

Pharmacokinetics

ACTILYSECATHFLOisclearedrapidlyfromthecirculatingbloodandmetabolisedmainlybythe

liver(plasmaclearance550-680mL/min.).Therelevantplasmahalf-lifeT1/2alphais4-5

minutes.Thismeansthatafter20minuteslessthan10%oftheinitialvalueispresentinthe

plasma.Fortheresidualamountremaininginadeepcompartment,abeta-half-lifeofabout40

minuteswas measured.

WhenACTILYSECATHFLOisadministeredforrestorationofdysfunctionalcentralvenousaccess

devicesaccordingtotheinstructionscirculatingplasmalevelsofalteplasearenotexpectedto

reachpharmacologicconcentrations.Ifa2mgdoseofalteplasewasadministeredbybolus

injectiondirectlyintothesystemiccirculation(ratherthaninstilledintothecatheter),the

concentrationofcirculatingalteplasewouldbeexpectedtoreturntoundetectablelimitswithin30-

60minutes.

Indications

ACTILYSECATHFLOisindicatedforthrombolytictreatmentofoccludedcentralvenousaccess

devicesincludingthoseusedforhaemodialysis.The2mgstrengthofalteplase(ACTILYSE

CATHFLO)istheonlyrecommendedpresentationforuseinthisindication.

DosageandAdministration

Forthethrombolytictreatmentofoccludedcentralvenousaccessdevicesincludingthoseusedfor

haemodialysis,adoseofupto2mgalteplaseadministereduptotwotimesforanyoneocclusion,

canbeusedtorestorefunctionofports,singleandmultiplelumencathetersincludingthoseused

forhaemodialysis,whichbecamedysfunctionaldue tothromboticocclusion.

Inpatientswithabodyweightof30kgormore,atotaldoseof2 mgin2mlshouldbeinstilledinto

thedysfunctionalcentralvenousaccessdevice.

Inpatientswithabodyweightbelow30kg,thevolumeofreconstitutedsolutiontobeinstilledinto

thedysfunctionalcentralvenousaccessdevicesshouldcorrespondto110%oftheinternallumen

volumeofthedevice.The totaldoseshould notexceed 2mg.

Ifcentralvenousaccessdevicefunctionisnotrestoredat120minutesafterthefirstdose,a

seconddoseofequalamountmaybeinstilled.

Thereisnoefficacyorsafetyinformationondosinginexcessof2mgperdoseforthisindication.

Studies have notbeenperformedwith administrationoftotaldosesgreaterthan 4mg (two x2 mg

doses).

Reconstitution

Do notuse vialifvacuumisnotpresent.

ACTILYSECATHFLOshouldbereconstitutedtoafinalconcentrationof1mgalteplasepermlby

asepticallyaddingtheappropriatevolumeofsterileWaterforInjectionsintotheACTILYSE

CATHFLOdrypowdervial.

ForACTILYSECATHFLO:

ReconstitutetheACTILYSECATHFLO2mginjectionvialwith2.2mlsterileWaterforInjections

in theaccompanyingampoule.

Reconstitutioncanbecarriedoutusingalargeboreneedle(e.g.18gauge),directingthestream

ofsterileWaterforInjectionsintothelyophilisedcake.Slightfoaminguponreconstitutionisnot

unusual;standingundisturbedforseveralminutesisusuallysufficienttoallowdissipationofany

largebubbles.Excessiveorvigorousshakingshould beavoided.

ItisimportantthatACTILYSECATHFLObereconstitutedonlywithsterileWaterforInjections

withoutpreservatives.Do notuse bacteriostaticWaterforInjections.

Thereconstitutedlyophilisedpreparationresultsinacolourlesstopaleyellowtransparentsolution

containingACTILYSECATHFLO1mgpermlatapHof7.3.Theosmolalityofthissolutionis

approximately215 mOsm/kg.

ACTILYSECATHFLOshouldnotbemixedwithotherdrugs,neitherinthesameinjectionvialnor

within thecatheterlumen.Before dilution oradministration,thereconstituted preparationshould be

visuallyinspectedforparticulatematteranddiscolourationpriortoadministrationwhenever

solution and containerpermit.

Dilution

Thereconstitutedsolution(1mgalteplaseperml)maybedilutedfurther,immediatelybefore

administration,withsterilephysiologicalsalinesolution(0.9%SodiumChlorideforInjection)upto

aminimalconcentrationof0.2mgalteplaseperml.Furtherdilutionofthereconstitutedsolution

withsterilephysiologicalsalinesolution(0.9%SodiumChlorideforInjection)belowaminimal

concentrationof0.2mgalteplasepermlisnotrecommendedsincetheoccurrenceofturbidityof

thereconstitutedsolutioncannotbeexcluded.

AdilutionofthereconstitutedsolutionwithsterileWaterforInjections,carbohydrateinfusion

solutions(e.g.glucose)orpreservativecontainingsolutionsisnotrecommendedduetoincreasing

formation ofturbidityofthereconstitutedsolution.

Excessiveagitationduringdilutionshouldbeavoided;mixingshouldbeaccomplishedwithgentle

swirlingand/orslowinversion.

NoothermedicationshouldbeaddedtoACTILYSECATHFLOsolution.BecauseACTILYSE

CATHFLOcontainsnopreservatives,itshould bereconstitutedimmediatelybefore use.

Instructions forAdministration

1.ReconstitutethecontentoftheACTILYSECATHFLO2mginjectionvialtothefinal

concentrationof1mgalteplaseperml.Forcatheterswithalumenvolumegreaterthan2

ml,ACTILYSECATHFLOcanbefurtherdilutedwithsterilephysiologicalsalinesolution

(0.9%SodiumChlorideforInjection)tothedesiredvolume(seeReconstitutionand

Dilution).

2.InstiltheappropriatedoseofACTILYSECATHFLOintothedysfunctionalcentralvenous

accessdevice.

3.After30minutesofdwelltime,assesscatheterfunctionbyattemptingtoaspirateblood.If

thecatheterisfunctional,goto Step6.Ifthecatheterisnotfunctional,goto Step4.

4.After120minutesofdwelltime,assesscatheterfunctionbyattemptingtoaspirateblood

andcathetercontents.Ifthecatheterisfunctional,gotoStep6.Ifthecatheterisnot

functional,goto Step5.

5.Ifcatheterfunctionisnotrestoredat120 minutesofdwelltime afterthefirstdose,asecond

doseofequalamountmaybeinstilled.RepeattheprocedurebeginningwithStep1.Ifafter

aseconddoseofACTILYSECATHFLOthedeviceremainsdysfunctional,considerthe

needfordevice replacement.

6.Ifcatheterfunctionhasbeenrestored,aspirate4-5mlofbloodinpatientswithabody

weightof10kgormore,or3mlinpatientwithabodyweightoflessthan10kg,toremove

ACTILYSECATHFLOandresidualclot,andgentlyirrigatethecatheterwithsterile

physiologicalsalinesolution (0.9%SodiumChlorideforInjection).

Contraindications

ACTILYSECATHFLOshouldnotbeadministeredtopatientswithknownhypersensitivitytothe

activesubstancealteplase,gentamicin(atraceresiduefromthemanufacturingprocess)ortoany

oftheexcipients

WarningsandPrecautions

Theappropriatepacksize ofalteplaseshouldbechosencarefullyand inaccordancewith the

intended use.The2mgdoseofalteplase(ACTILYSECATHFLO)isnotsuitableforusein the

indications acutemyocardialinfarction,acute pulmonaryembolismoracute ischaemicstroke.

Forthetreatmentofoccludedcentralvenousaccessdevicesincludingthoseusedfor

haemodialysis:

General

ThecoadministationofheparinwithACTILYSECATHFLOhasnotbeenshowntoimprovethe

ratesofcatheterfunctionrestorationandisnotrecommended.Ifheparinisconsiderednecessary

topreventreocclusionthisshouldbeadministeredseparatelyaftercatheterfunctionhasbeen

restored.

Catheterdysfunctionmaybecausedbyavarietyofconditionsotherthanthrombusformation,

suchascathetermalposition,mechanicalfailure,constrictionbyasuture,andlipiddepositsor

drugprecipitateswithinthecatheterlumen.Becauseoftheriskofdamagetothevascularwallor

collapseofsoft-walledcatheters,vigoroussuctionshouldnotbeappliedduringattemptsto

determinecatheterocclusion.ExcessivepressureshouldbeavoidedwhenACTILYSECATHFLO

isinstilledintothecatheter.Suchforcecouldcauseruptureofthecatheterorexpulsionoftheclot

intothecirculation.

Bleeding

Themostfrequentadversereactionassociatedwithallthrombolyticsinallapprovedindicationsis

bleeding.ACTILYSECATHFLOhasnotbeenstudiedinpatientswithoccludedcathetersknownto

beatriskforbleedingeventsthatmaybeassociatedwith theuseofthrombolytics.

Cautionshould beexercised with patients:

whohave active internalbleeding;

whohavehadanyofthefollowingwithin48hours:surgery,obstetricaldelivery,

percutaneousbiopsyofvisceraordeeptissues,orpunctureofnon-compressible vessels;

whohavethrombocytopeniaotherhaemostaticdefects(includingthosesecondaryto

severehepaticorrenaldisease);

whohaveanyconditionforwhichbleedingconstitutesasignificanthazardorwouldbe

particularlydifficulttomanagebecauseofitslocation;or

whoareathighriskofemboliccomplications(e.g.venousthrombosisintheregionofthe

catheter).

Deathandpermanentdisabilityhavebeenreportedinpatientswhohaveexperiencedstrokeand

otherseriousbleedingepisodeswhenreceivingpharmacologicdosesofathrombolytic.Should

seriousbleedinginacriticallocation(e.g.,intracranial,gastrointestinal,retroperitoneal,pericardial)

occur,treatmentwithACTILYSECATHFLOshouldbestoppedandthedrugshouldbewithdrawn

fromthecatheter.

Infection

ACTILYSECATHFLOshould beused with caution inthepresenceofknown orsuspectedinfection

inthecatheter.UsingACTILYSECATHFLOinpatientswhosecathetersareoccludedbyinfected

thrombimayreleasemicro-organismsintothesystemiccirculationleadingtosepsis.Aswithall

catheterisationprocedures,careshouldbetakentomaintainaseptictechniqueandappropriate

antibiotic treatmentusedas necessary.

Re-administration

Patientsmayreceive upto 2mg ofACTILYSECATHFLOadministeredup to two timesforanyone

occlusion.Intheeventofcontinuingcatheterdysfunctionothercausesfordysfunctionshouldbe

sought.Subsequentocclusionsmaybetreatedsimilarlyalthoughitshouldbenotedthatfrequent

re-occlusionsmayindicatetheneedforcatheterreplacement.

Hypersensitivity

Antibodyformationinpatientsreceivingoneormoredosesofalteplaseforrestorationof

dysfunctionalcentralvenousaccessdeviceshasnotbeenstudied.Althoughphysiologically

relevantplasmaconcentrationsarenotreached,hypersensitivitymightoccur.Anaphylactoid

reactionsassociatedwiththeadministrationofACTILYSECATHFLOcanbecausedby

hypersensitivitytotheactivesubstancealteplase,gentamicin(atraceresiduefromthe

manufacturingprocess)ortoanyoftheexcipients.ThestopperoftheglassvialwithACTILYSE

CATHFLOpowdercontainsnaturalrubber(aderivativeoflatex)whichmaycauseallergic

reactions.Ifananaphylactoidreactionoccurs,theinstillationshouldbediscontinuedand

appropriatetreatmentshould beinitiated.

Effectson Fertility

StudieswithACTILYSECATHFLOhavenotbeenperformedtodetermineeffectonfertilityor

reproduction.

Use inPregnancy

CategoryB1

Studies have shown thatACTILYSECATHFLOisnotteratogenicintheratand rabbitanddoes not

crosstheplacentalbarrierinthepregnantrat.Intherabbit,however,adose-relatedincreasein

abortionsandresorptionratewasseeninthedoserange3-10mg/kg/day.ACTILYSECATHFLO

should begivento pregnantwomenonlyiftheneedclearlyoutweighs thepotentialrisk.

Use in Lactation

ItisnotknownwhetherACTILYSECATHFLOisexcretedinhumanmilk.Becausemanydrugsare

excretedbythisroute,cautionshouldbeexercisedwhenACTILYSECATHFLOisadministeredto

breastfeedingnursingwomen.

Use in Children

ThereisinsufficientdatatoestablishthesafetyandefficacyofACTILYSECATHFLOinpreterm

neonates.Theuse ofACTILYSECATHFLOinpretermneonatesisnotrecommended.

Use in the Elderly

In312patientsenrolledintheclinicaltrialswhowereage65yearsandover,noincidentsof

intracranialhaemorrhage,embolicevents,ormajorbleedingeventswereobserved.103ofthese

patientswereage 75yearsand over,and 12wereage 85yearsand over.TheeffectofACTILYSE

CATHFLOoncommonage-relatedco-morbiditieshasnotbeenstudied.Ingeneral,cautionshould

beusedinelderlypatientswithconditionsknowntoincreasetheriskofbleeding(seeWarnings

and Precautions –Bleeding).

Carcinogenicity

Studies with ACTILYSECATHFLOhave notbeen performedto determine carcinogenicity.

Genotoxicity

Studies with ACTILYSECATHFLOhave notbeen performedto determine mutagenesis.

AdverseEffects

Inprinciple,allsideeffectsasfoundforthesystemicapplication ofalteplasemayalsooccurduring

treatmentofoccludedcathetersincaseswhereACTILYSECATHFLOreachesthesystemic

circulation(e.g.hypersensitivity,anaphylactoidreaction),howeverpharmacokineticdataindicate

thatphysiologicallyrelevantplasmaconcentrationsarenotreachedusingthisdosage.Inclinical

trialsinvestigatingtreatmentofoccludedcatheterswithACTILYSECATHFLOthefollowingside

effectswereobserved.

Infectionsandinfestations:

sepsis

Generaldisordersand administrationsiteconditions:

catheterrelatedcomplication

pyrexia

Undersystemicapplicationofalteplase(i.e.highdoseinthrombo-embolicindications),the

followingsideeffectshave beenreported:

Immunesystemdisorders:

anaphylactoidreactions,whichareusuallymild,butcanbelifethreateninginisolated

cases.

Theymayappearas

rash

urticaria

bronchospasm

angioedema

hypotension

shockoranyothersymptomassociatedwith hypersensitivity.

Immunesystemdisorderscanberegardeddose-independentandhavethereforebeencopied

fromthesystemicapplication;theyhavehowevernotbeenobservedinclinicaltrialswith

ACTILYSECATHFLO.

Interactions

Theriskofhaemorrhagemaybeincreasedwiththeuseofcoumarinderivatives,antiplatelet

aggregationagents,heparinoranyotheragentwhichinfluenceshaemostasis(before,duringor

withinthefirst24hoursaftertreatmentwithACTILYSECATHFLO).TheconcomitantuseofGP

IIb/IIIaantagonistsincreasestheriskofbleeding.

TheinteractionofACTILYSECATHFLOwithotherdrugshasnotbeenstudied.Dataonadjunctive

pharmacotherapyduringthrombolysiswithACTILYSECATHFLO(e.g.calciumchannelblockers,

betaadrenergicblockersetc)areinadequatetoexcludeanypossibledruginteractions.

ConcomitanttreatmentwithAngiotensinConvertingEnzymes(ACE)inhibitorsmayenhancethe

riskofsufferingananaphylactoidreaction(seeAdverseEffects).Monitoringisrecommended

particularlyforpatientsreceivingconcomitantACEinhibitors.

Overdosage

Shouldseriousbleedingoccurinacriticallocation(e.g.intracranial,gastrointestinal,

retroperitoneal,pericardial),treatmentwithACTILYSECATHFLOshouldbestoppedandthedrug

shouldbewithdrawnfromthecatheter.Mostpatientscanbemanagedbyinterruptionof

thrombolytictherapy,volumereplacementandmanualpressureappliedtothebleedingvesselif

accessible.Ifnecessary,bloodlossandreversalofthebleedingtendencycanbemanagedwith

freshwholebloodorpackedredbloodcells.Intheeventofclinicallysignificantfibrinogen

depletion,freshfrozenplasmaorcryoprecipitatecanbeinfusedwithclinicalandlaboratory

reassessmentaftereachadministration.Atargetfibrinogenlevelof1g/Lisdesirablewith

cryoprecipitateinfusion.Antifibrinolyticagentsmaybeused asa lastoption.

PharmaceuticalPrecautions

ACTILYSECATHFLOmustbestoredat2-8ºCina refrigerator.Donotfreeze.

Chemicalandphysicalin-usestabilityofthereconstitutedsolutionhasbeendemonstratedforup

to 24hoursat2-8ºC.Froma microbiologicalpointofview,theproductshould beusedimmediately

afterreconstitution.Ifnotusedimmediately,thereconstitutedsolutionshouldbestoredat2-8ºC

fornotmorethan 24hours.

Forsingle usein onlyone patient.Discard anyunused solution.

Protectthelyophilisedmaterialduringstoragefromlight.Duringtheperiodofreconstitutionand

instillation,protectionfromlightisnotnecessary.

MedicineClassification

PrescriptionMedicine

PackageQuantities

ACTILYSECATHFLOisavailable inboxes containingeither:

1 vialofACTILYSECATHFLO2mg inupto93.3mg drypowderand 1ampoule of2.2ml

sterileWaterforInjectionsforreconstitution;or

5vialsofACTILYSECATHFLO2mginupto93.3mgdrypowderand5ampoulesof2.2

mlsterileWaterforInjectionsforreconstitution.

FurtherInformation

ACTILYSE ®

andCATHFLO ®

areregisteredtrademarks.

Excipients

L-arginine,phosphoric acid,polysorbate 80.ACTILYSECATHFLOmaycontain traceresiduesof

gentamicinfromthemanufacturingprocess

ClinicalTrials

Occludedcentralvenous accessdevicesincludingthose usedforhaemodialysis

Threeclinicalstudies wereperformedin patientswith improperlyfunctioningcentralvenousaccess

devices.

Aplacebo-controlled,double-blind,randomisedtrial(StudyA2055g)andalargeropen-labeltrial

(StudyA2065g)investigatedtheuseofalteplaseinpredominatelyadultpatientswhohadan

indwellingcentralvenousaccessdevicesforadministrationofchemotherapy,totalparenteral

nutrition,orlong-termadministrationofantibioticsorothermedications.

StudyA2055ginvestigatedtheefficacyofalteplaseinrestoringfunctiontooccludedcentral

venousaccessdevices in150 patientswith catheterocclusionsupto 24hoursin duration.Patients

wererandomisedtoreceiveeitheralteplase2mg(orlessforchildrenwhoweighedbelow30kg,

seeDosageandAdministration)orplaceboinstilledintothelumenofthecatheter.Catheter

functionwasassessedat120minutesafterinstillation.Allpatientswhosecatheterfunctionwas

notrestoredafter120minutesoftheinitialdosewerethenadministereduptotwodosesof

alteplase.Intention-to-treatanalysisshowsthatrestorationofcatheterfunctionwasachievedafter

administrationofthefirstbolusin74%(51/69)ofpatientsrandomisedtoalteplaseand17%

(12/70)ofpatientsrandomisedtoplacebo.Thetreatmentdifferencewasstatisticallysignificant

(p<0.0001).Intotal,90%(124/138)ofallpatientsachievedrestorationofcatheterfunctionafter

administrationofuptotwo doses ofalteplase.

StudyA2065gwasanopen-label,singlearmtrialin995patientswithcatheterdysfunctionand

includedpatientswithcatheterocclusionspresentforanyduration.Patientsweretreatedwithup

totwodosesalteplase2mg(orlessforchildrenwhoweighedbelow30kg,seeDosageand

Administration)instilledintothelumenofthecatheter.Assessmentforrestorationoffunctionwas

madeat30minutesaftereachinstillation.Iffunctionwasnotrestored,catheterfunctionwasre-

assessedat120minutes.Intotal,restorationofcatheterfunctionwasachievedin87%(844/968)

patientsfollowingadministrationofuptotwodosesofalteplaseafteradwelltimeof120minutes.

Successfulrestorationofcatheterfunctionwasachievedin52%(516/991)ofpatientsand77%

(747/976)ofpatientsfollowinginstillationofthefirstdoseofalteplaseafteradwelltimeof30

minutesand120minutes,respectively.Ofthe209patientswhoreceivedaseconddoseof

alteplase,restorationofcatheterfunctionwasachievedin33%(70/209)ofpatientsafteradwell

time of30minutesand 46%(97/209)ofpatientsafteradwelltime of120minutes.

AcrossStudiesA2505gandA2065g,68%(796/1043)ofpatientswithcatheterocclusionspresent

forlessthan14dayshadrestoredfunctionafteronedose,and88%hadfunctionrestoredafterup

totwodosesofalteplase.Ofthe53patientswithcatheterocclusionspresentforlongerthan14

days,57%ofpatientshadfunctionrestoredafterasingledose,and72%ofpatientshadrestored

functionafteruptotwo doses ofalteplase.

Thethirdpivotalstudy(StudyA2404g)wasanopen-label,single-armtrialin310childrenand

adolescentsbetween theages of2 weeksand 17yearswhohad catheterocclusionspresentedfor

anyduration.Patientsweretreatedwithuptotwodosesofalteplase2mginstilledintothe

catheterlumen(orlessforchildrenwhoweighedbelow30kg,seeDosageandAdministration).

Restorationoffunctionwasassessedat30and120minutes(ifrequired)afteradministrationof

eachdose.TheoverallrateofcatheterfunctionwassimilartothatobservedinStudyA2065g.In

total,restoration ofcatheterfunctionwas achieved in75%(233/310)ofpatientsfollowingone dose

ofalteplaseand83%(257/310)ofpatientsfollowingtwodosesofalteplase,afteradwelltimeof

120minutesrespectively.Restoredcatheterfunctionwasachievedin80%(44/55)ofpatients<2

yearsofageand83.5%(213/255)patientsin those aged ≥2 years.

Thethreetrialshadsimilarratesofcatheterfunctionrestorationamongthecathetertypesstudied

(single-,double-,andtriple-lumen,andimplantedports).Nogenderdifferenceswereobservedin

therateofcatheterfunctionrestoration.Resultsweresimilaracrossallagesubgroups.

Theuseofalteplasefortherestorationofpatencyofhaemodialysiscatheterswerereportedinthe

literature.Datafromwell-controlledclinicalstudiesarelimited.Asystematicreviewofthrombolysis

fortherestorationofhaemodialysiscatheters(includingfourliteraturestudiesontheuseof

alteplaseinatotalof154occludedcatheters)showedthattheoverallrestorationratesofcatheter

functionsrangedfrom88%to98%followingtreatmentswith alteplase.Haemodialysispatientswith

end-stagerenaldiseasehavealsobeenstudiedinavarietyoftrialsfollowingthesystematic

reviewofthrombolysisfortherestorationofhaemodialysiscatheters.

Source Document:AustralianPI29.4.08v01andCCDS0274-0112.11.09.

NameandAddress

BoehringerIngelheim(N.Z.)Limited

POBox76-216

ManukauCity

Auckland

NEWZEALAND

Telephone: (09)2748664

Facsimile: (09)271 0629

DateofPreparation

20November2009

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Ampicillin and Sulbactam for Injection USP, 3 g Single-Dose Vials by AuroMedics Pharma: Recall - Presence of Red Particulate Matter

Ampicillin and Sulbactam for Injection USP, 3 g/Single-Dose Vials by AuroMedics Pharma: Recall - Exposure to particulate may result in local site reaction, thromboembolic events and systemic immune response.

FDA - U.S. Food and Drug Administration

8-5-2018

Piperacillin and Tazobactam for Injection, USP 3.375 g Vials by AuroMedics Pharma: Recall - Vials Contain Particulate Matter

Piperacillin and Tazobactam for Injection, USP 3.375 g Vials by AuroMedics Pharma: Recall - Vials Contain Particulate Matter

Piperacillin and Tazobactam for Injection, USP 3.375 g by AuroMedics Pharma: Recall: Exposure to particulate matter may result in local irritation/swelling or more serious outcomes.

FDA - U.S. Food and Drug Administration

3-5-2018

May 3, 2018: Indictment: Kansas EMT Stole Morphine from Vials

May 3, 2018: Indictment: Kansas EMT Stole Morphine from Vials

May 3, 2018: Indictment: Kansas EMT Stole Morphine from Vials

FDA - U.S. Food and Drug Administration

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