GAMMAGARD S/D

Main information

  • Trade name:
  • GAMMAGARD S/D
  • Dosage:
  • 100 Millilitre
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • GAMMAGARD S/D
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/079/004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

GammagardS/D.

Humannormalimmunoglobulinforintravenousadministration.

Powderandsolventforsolutionforinfusion.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

ActiveIngredient

HumanNormalImmunoglobulinG(IgG)

QuantitativeComposition

HumanNormalImmunoglobulinforIntravenousAdministration,GammagardS/D,maybereconstitutedwithsolvent

[WaterforInjections]toa5%(50mg/ml)solutionora10%(100mg/ml)solutionofproteinofwhichatleast90%is

gammaglobulin.

Containslessthan3 µ g/mlofIgAfora5%solution.

Forafulllistofexcipientsseesection6.1.

IgGSubclasses

DistributionofIgGsubclasses:

≥56.9%

≥16.0%

≥3.3%

≥0.3%

3PHARMACEUTICALFORM

Powderandsolventforsolutionforinfusion.

p.H.ofreconstitutedproductis6.4–7.2.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Replacementtherapy:

Primaryimmunodeficiencysyndromes(PID):

Congenitalagammaglobulinaemiaandhypogammaglobulinaemia

Commonvariableimmunodeficiencies.

Severecombinedimmunodeficiencies.

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Myelomaorchroniclymphocyticleukaemiawithseveresecondaryhypogammaglobulinaemiaandrecurrentinfections

ChildrenwithcongenitalAIDSandrecurrentinfections.

Immunomodulatoryeffect

Idiopathicthrombocytopenicpurpura(ITP)inadultsorchildrenathighriskofbleedingorpriortosurgerytocorrect

theplateletcount.

Allogeneicbonemarrowtransplantation.

Kawasakisyndrome.

Guillain-Barredisease.

4.2Posologyandmethodofadministration

Posology

Thedoseanddosageregimenisdependentontheindication.

Ingeneral,itisrecommendedthatpatientsbeginningtherapywithGGSDorswitchingfromoneIVIGbrandtoanother

bestartedatthelowerratesandthenadvancedtothemaximalrateiftheyhavetoleratedseveralinfusionsat

intermediateratesofinfusion.Pleasealsosee4.4

ItisrecommendedthatantecubitalveinsbeusedforGGSD10%solutions,ifpossible.Thismayreducethelikelihood

ofthepatientexperiencingdiscomfortattheinfusionsite.

Inreplacementtherapythedosagemayneedtobeindividualisedforeachpatientdependentonthepharmacokinetic

andclinicalresponse.Thefollowingdosageregimensaregivenasaguideline.

ReplacementTherapyinPrimaryImmunodeficiencies:

ThedosageregimenshouldachieveatroughleveloflgG(measuredbeforethenextinfusion)ofatleast4-6g/L.Three

tosixmonthsarerequiredaftertheinitiationoftherapyforequilibrationtooccur.Therecommendedstartingdoseis

0.4-0.8g/kgdependingonthecircumstances(e.g.activeinfection)followedby0.2g/kgeverythreeweeks.

Thedoserequiredtoachieveatroughlevelof6g/Lisoftheorderof0.2-0.8g/kg/month.Thedosageintervalwhen

steadystatehasbeenreachedvariesfrom2-4weekly.

Troughlevelsshouldbemeasuredinordertoadjustthedoseanddosageinterval.

Replacementtherapyinmyelomaorchroniclymphocyticleukaemiawithseveresecondary

hypogammaglobulinemiaandrecurrentinfections;replacementtherapyinchildrenwithAIDSandrecurrent

infections.

Therecommendeddoseis0.2-0.4g/kgeverythreetofourweeks.

Idiopathicthrombocytopenicpurpura(ITP)

Forthetreatmentofanacuteepisode,0.8-1g/kgondayone,repeatedondaythreeifnecessary,or0.4g/kgdailyfor

twotofivedays.Thetreatmentcanberepeatedifrelapseoccurs.

Kawasakidisease

1.6-2.0g/kgshouldbeadministeredindivideddosesovertwotofivedaysor2g/kgasasingledose.Patientsshould

receiveconcomitanttreatmentwithacetylsalicylicacid.

AllogeneicBoneMarrowTransplantation:

Humannormalimmunoglobulintreatmentcanbeusedaspartoftheconditioningregimenandafterthetransplant.For

thetreatmentofinfectionsandprophylaxisofgraftversushostdisease,dosageisindividuallytailored.Thestarting

doseisnormally0.5g/kg/week,startingsevendaysbeforetransplantationandforupto3monthsaftertransplantation.

Incaseofpersistentlackofantibodyproduction,dosageof0.5g/kg/monthisrecommendeduntilantibodylevelreturns

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Guillain-Barrésyndrome

0.4g/kg/dayfor5consecutivedays.Experienceinchildrenislimited.

MethodofAdministration

HumanNormalImmunoglobulinforIntravenousAdministration,GammagardS/D,5%(50mg/mL),shouldbeinfused

intravenouslyataninitialrateof0.5mL/kg/hr.Ifwelltolerated,theratemaybegraduallyincreasedtoamaximumrate

of8mL/kg/hrfortheremainderoftheinfusion.PatientswhotolerateGammagardS/D5%solutionscanbeinfused

withthe10%solutiontoamaximumrateof8mL/kg/hr.

4.3Contraindications

Hypersensitivitytoanyofthecomponents.

Hypersensitivitytohomologousimmunoglobulins,especiallyinveryrarecasesofIgAdeficiencywhenthepatienthas

antibodiesagainstIgA.HoweverGammagardS/DcontainsonlytraceamountsofIgA(notmorethan3µg/ml).

4.4Specialwarningsandprecautionsforuse

HumanNormalImmunoglobulinforIntravenousAdministration,GammagardS/Dshouldonlybeadministered

intravenously.

GammagardS/Disreconstitutedtoprovideaproteinsolutionof5gor10gper100mLofdiluent.Thisfluidvolume

willresultinbloodvolumeexpansionwiththeextentdependentonthedoseadministered.Whenadministeredinhigh

doseoverarelativelyshortperiodoftime,signsandsymptomatologyoffluidoverloadmayresult,especiallyin

susceptiblepatientssuchassmallchildrenorelderlyindividuals.

Certainsevereadversedrugreactionsmayberelatedtotherateofinfusion.Therecommendedinfusionrategiven

under“4.2Methodofadministration”mustbecloselyfollowed.Patientsmustbecloselymonitoredandcarefully

observedforanysymptomsthroughouttheinfusionperiod.

PatientsnaivetoIgGusuallyexperiencehigherfrequencyofminoreventsthanthosewellmaintainedonregular

therapyandmustbecloselymonitoredforthefirsthourafterthefirstinfusion.Forallotherinfusionspatientsshould

beobservedforatleast20minutesafteradministration.

Certainadversereactionsmayoccurmorefrequently

-incaseofhighrateofinfusion

-inpatientswithhypo-oragammaglobulinemiawithorwithoutIgAdeficiency

-inpatientswhoreceivehumannormalimmunoglobulinforthefirsttime,orinrarecases,whentherehasbeenalong

intervalsincethepreviousinfusion.

Incaseofadversereactionseithertherateofadministrationmustbereducedortheinfusionstoppeduntilsymptoms

disappear.

Ifseverityofreactionspersistsafterdiscontinuationoftheinfusion,appropriatetreatmentisrecommended.

Truehypersensitivityreactionsarerare.TheycanoccurintheveryseldomcasesofIgAdeficiencywithanti-IgA

antibodies.Rarely,humannormalimmunoglobulincaninduceafallinbloodpressurewithanaphylacticreaction,even

inpatientswhohadtoleratedprevioustreatmentwithhumannormalimmunoglobulin.

PatientswithantibodiestoIgAorwithIgAdeficienciesthatareacomponentofanunderlyingprimary

immunodeficiencydiseaseforwhichIVIGtherapyisindicatedmaybeatincreasedriskofanaphylacticreaction.

AnaphylaxishasbeenreportedwiththeuseofGAMMAGARDS/DeventhoughitcontainslowlevelsofIgA.(see

section4.8)

GAMMAGARDS/DisnotindicatedinpatientswithselectiveIgAdeficiencywheretheIgAdeficiencyistheonly

abnormalityofconcern.ThesepatientsshouldbetreatedonlyiftheirIgAdeficiencyisassociatedwithanimmune

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Patientswhohavehadaseverehypersensitivityreactionshouldonlyreceiveintravenousimmuneglobulinwithutmost

cautionandinasettingwheresupportivecareisavailablefortreatinglife-threateningreactions.

Incaseofshock,treatmentshouldfollowtheguidelinesforshocktherapy.

Potentialcomplicationscanoftenbeavoidedbyensuring:

-thatpatientsarenotsensitivetohumannormalimmunoglobulinbyinitiallyinjectingtheproductslowly-specify

productspecificrate0.5to1mL/kg/min;

-thatpatientsarecarefullymonitoredforanysymptomsthroughouttheinfusionperiod.Inparticular,patientsnaïveto

humannormalimmunoglobulin,patientsswitchedfromanalternativeIVIgproductorwhentherehasbeenalong

intervalsincethepreviousinfusion,shouldbemonitoredduringthefirstinfusionandforthefirsthourafterthefirst

infusion,inordertodetectpotentialadversesigns.Allotherpatientsshouldbeobservedforatleast20

minutesafteradministration;

-thattheglucosecontent(max.contentof0.4g/gofIgG)istakenintoaccountincaseoflatentdiabetes(where

transientglycosuriacouldappear),diabetes,orinpatientsonalowsugardiet.

Overdosageispossibleinoverweightandelderlysubjectsandinthosewhohaveimpairedrenalfunction(including

diabeticsatriskforrenalfailure).Inpatientswithsignsofcerebralorcardiacischemia,theincreaseinviscosity

causedbyanimmunoglobulininfusionmaybeariskinthesepatientsgroups,5-6%solutionsshouldbeusedandno

morethan0.4g/kginfuseddaily.Creatininelevelsshouldbemeasuredfor3daysafterIVIgInfusion.

Anasepticmeningitissyndrome(AMS)hasbeenreportedtooccurinfrequentlyinassociationwithimmunoglobulin

treatment.DiscontinuationofimmunoglobulintreatmenthasresultedinremissionofAMSwithinseveraldayswithout

sequelae.Thesyndromeusuallybeginswithinseveralhourstotwodaysfollowingimmunoglobulintreatment.Itis

characterizedbysymptomsandsignsincludingsevereheadache,nuchalrigidity,drowsiness,fever,photophobia,

painfuleyemovements,andnauseaandvomiting.

Cerebrospinalfluid(CSF)studiesarefrequentlypositivewithpleocytosisuptoseveralthousandcellspercubicmm,

predominantlyfromthegranulocyticseries,andelevatedproteinlevelsuptoseveralhundredmg/dL.Patients

exhibitingsuchsymptomsandsignsshouldreceiveathoroughneurologicalexamination,includingCSFstudies,torule

outothercausesofmeningitis.AMSmayoccurmorefrequentlyinassociationwithhighdose(2g/kg)

immunoglobulintreatment.

ThereisclinicalevidenceofanassociationbetweenIVIgadministrationandthromboemboliceventssuchas

myocardialinfarction,stroke,pulmonaryembolismanddeepveinthromboseswhichisassumedtoberelatedtoa

relativeincreaseinbloodviscositythroughthehighinfluxofimmunoglobulininat-riskpatients.

CautionshouldbeexercisedinprescribingandinfusingIVIginobesepatientsandinpatientswithpre-existingrisk

factorsforthromboticevents(suchasadvancedage,hypertension,diabetesmellitusandahistoryofvasculardiseaseor

thromboticepisodes,patientswithacquiredorinheritedthrombophilicdisorders,patientswithprolongedperiodsof

immobilization,severelyhypovolemicpatients,patientswithdiseaseswhichincreasebloodviscosity).

CasesofacuterenalfailurehavebeenreportedinpatientsreceivingIVIgtherapy.Inmostcases,riskfactorshavebeen

identified,suchaspre-existingrenalinsufficiency,diabetesmellitus,hypovolemia,overweight,concomitant

nephrotoxicmedicinalproductsorageover65.

Incasesofrenalimpairment,IVIgdiscontinuationshouldbeconsidered.Whilethesereportsofrenaldysfunctionand

acuterenalfailurehavebeenassociatedwiththeuseofmanyofthelicencedIVIgproducts,thosecontainingsucroseas

astabilizeraccountedforadisproportionateshareofthetotalnumber.

Inpatientsatrisk,theuseofIVIgproductsthatdonotcontainsucrosemaybeconsidered.GammagardS/Ddoesnot

containsucrose.

Therehavebeenreportsofnoncardiogenicpulmonaryedema(TransfusionRelatedAcuteLungInjury,TRALI)in

patientsadministeredIVIG.

Inpatientsatriskforacuterenalfailureorthromboembolicadversereactions,IVIgproductsshouldbeadministeredat

theminimumrateofinfusionanddosepracticable.

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medicinalproductspreparedfromhumanbloodorplasmaincludeselectionofdonors,screeningofindividual

donationsandplasmapoolsforspecificmarkersofinfectionandtheinclusionofeffectivemanufacturingstepsforthe

inactivation/removalofviruses.Despitethis,whenmedicinalproductspreparedfromhumanbloodorplasmaare

administered,thepossibilityoftransmittinginfectiveagentscannotbetotallyexcluded.Thisalsoappliestounknown

oremergingvirusesandotherpathogens,suchastheCreutzfeldt-Jacobdisease(CJD)agent.

ThemeasurestakenareconsideredeffectiveforenvelopedvirusessuchasHIV,HBVandHCV,andforthenon-

envelopedvirusesHAVandparvovirusB19.

ThereisreassuringclinicalexperienceregardingthelackofhepatitisAorparvovirusB19transmissionwith

immunoglobulinsanditisalsoassumedthattheantibodycontentmakesanimportantcontributiontotheviralsafety.

ItisstronglyrecommendedthateverytimethatGammagardS/Disadministeredtoapatient,thenameandbatch

numberoftheproductarerecordedinordertomaintainalinkbetweenthepatientandthebatchoftheproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

LiveAttenuatedVaccines

Immunoglobulinadministrationmayimpairtheefficacyofliveattenuatedvirusvaccinessuchasmeasles,rubella,

mumps,varicellaandyellowfeverforaperiodofatleast6weeksandupto3monthsfollowingtheinfusion.

Afteradministrationofthisproduct,anintervalof3monthsshouldelapsebeforevaccinationwithliveattenuatedvirus

vaccines.Inthecaseofmeasles,thisimpairmentmaypersistforupto1year.Therefore,patientsreceivingmeasles

vaccineshouldhavetheirantibodystatuschecked.

InterferencewithSerologicalTesting

Afterinjectionofimmunoglobulinthetransitoryriseofthevariouspassivelytransferredantibodiesinthepatients

bloodmayresultinmisleadingpositiveresultsinserologicaltesting.

-HumanNormalImmunoglobulinforIntravenousAdministration,GammagardS/Dispreparedfromplasmafrom

manydifferentdonors,eachwithvaryingtitresoflgGantibodiesdirectedatabroadspectrumofantigens.These

includeredbloodcellantigensofwhichtheRhantigenDisperhapsthemostimportant.

-Passivetransmissionofantibodiestoerythrocyteantigens,e.g.A,B,D,mayinterferewithsomeserologicaltestsfor

redcellallo-antibodies(e.g.Coombstest),reticulocytecountandhaptoglobin.Thisismorelikelytooccurwhenlarge

doses,inrelationshiptoplasmavolume,areadministered.Theconsequencesofthisreactionhavenotbeenreportedto

beassociatedwithadversereactions,haemolysis,oranaemia,althoughamildlyshortenedredcellsurvival,dueto

prematuresplenicsequestration,ispossible.

4.6Fertility,pregnancyandlactation

Thesafetyofthismedicinalproductforuseinhumanpregnancyhasnotbeenestablishedincontrolledclinicaltrials

andthereforeshouldonlybegivenwithcautiontopregnantwomenandbreast-feedingmothers.Clinicalexperience

withimmunoglobulinssuggeststhatnoharmfuleffectsonthecourseofpregnancy,oronthefoetusandtheneonateare

tobeexpected.

Immunoglobulinsareexcretedintothemilkandmaycontributetothetransferofprotectiveantibodiestotheneonate.

4.7Effectsonabilitytodriveandusemachines

Thereisnoevidenceofimmunoglobulinimpairingtheabilitytodriveorusemachinery.

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Withhumannormalimmunoglobulinsforintravenousadministration,adversereactionssuchaschills,headache,fever,

vomiting,allergicreactions,nausea,arthralgia,lowbloodpressureandmoderatebackpainmayoccuroccasionally.

Rarelyhumannormalimmunoglobulinsmaycauseafallinbloodpressureand,inisolatedcases,anaphylacticshock,

evenwhenthepatienthasshownnohypersensitivitytopreviousadministration.

Increaseinserumcreatinineleveland/oracuterenalfailurehavebeenobserved.

Thromboembolicreactionssuchasmyocardialinfarction,stroke,pulmonaryembolism,deepveinthrombosishave

beenobserved.

ThereisclinicalevidenceofapossibleassociationbetweenIVIgadministrationandthepotentialforthedevelopment

ofthromboticevents.Theexactcauseofthisisunknown;therefore,cautionshouldbeexercisedintheprescribingand

infusionofIVIginpatientswithahistoryofandpredisposingfactorstowardscardiovasculardiseaseorthrombotic

episodes.Analysisofadverseeventreportshasindicatedthatarapidrateofinfusionmaybeariskfactorforvascular

occlusiveevents.

AdversereactionswerepooledfromapivotalclinicalstudyofGammagardS/Dandphase4studyassessingtheacute

andmid-termsafetyofgammagardS/D.ADRsreportedinthetwostudiesandpost-marketingaresummarizedand

categorizedaccordingtotheMedDRASystemorganclassandfrequencyinthetablebelow.

Frequencyhasbeenevaluatedusingthefollowingcriteria:verycommon( ≥1/10),common(≥1/100to<1/10),

uncommon( ≥1/1,000to<1/100),rare(≥1/10,000to<1/1,000),veryrare(<1/10,000),notknown(cannotbeestimated

fromavailabledata).

Adversedrugreactions(ADRs)withGammagardS/D

MedDRA

systemorganclass MedDRApreferredterm ADRfrequency

category*

Infectionsandinfestations Influenza Uncommon

Meningitisaseptic Notknown

Bloodandlymphatic

systemdisorders Haemolysis,anaemia,thrombocytopenia,

lymphadenopathy. Notknown

Immunesystemdisorders Hypersensitivity,anaphylacticoranaphylactoid

reaction,anaphylacticshock Notknown

Psychiatricdisorders Anxiety,Agitation Uncommon

Restlessness Notknown

Nervoussystemdisorders Headache Common

Lethargy Uncommon

Dizziness,paraesthesiaanddysaesthesia,tremor,

convulsions,centralnervoussystemhaemorrhages

andcerebrovascularaccidents,transientischemic

attack,migraine,syncope Notknown

Eyedisorders Visionblurred Uncommon

Photophobia,visualdisturbance,eyepain,retinal

veinthrombosis Notknown

Cardiacdisorders Palpitations Uncommon

Myocardialinfarction,cyanosis,tachycardia,

bradycardia Notknown

Vasculardisorders Flushing Common

Hypertension,pallor,hypotension,

thrombophlebitis,deepveinthrombosis,venacava

thrombosis,arterialthrombosis, Notknown

Respiratory,thoracicand

mediastinaldisorders Dyspnea,epistaxis Uncommon

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*Basedonpercentageperinfusions

Anasepticmeningitissyndrome(AMS)hasbeenreportedtooccurinassociationwithIVIG(includingGGSD)treatment.

DiscontinuationofIVIGtreatmenthasresultedinremissionofAMSwithinseveraldayswithoutsequelae.Thesyndromeusually

beginswithinseveralhoursto2daysfollowingIVIGtreatment.

-Cerebrospinalfluidstudiesarefrequentlypositivewithpleocytosisuptoseveralthousandcellspermm3,predominantlyfrom

thegranulocyticseries,andelevatedproteinlevelsuptoseveralhundredmg/dL.

-AMSmayoccurmorefrequentlyinassociationwithhighdose(2g/kg)IVIGtreatment

HemolyticanemiacandevelopsubsequenttoIVIG(includingGGSD)therapy.IVIGproductscancontainbloodgroup

antibodiesthatmayactashemolysinsandinduceinvivocoatingofredbloodcellswithimmunoglobulin,causinga

positivedirectantiglobulinreactionand,rarely,hemolysis.

Forsafetywithrespecttotransmissibleagentsseesection4.4.

4.9Overdose

Overdosagemayleadtofluidoverloadandhyperviscosity,particularlyintheelderlyandorpatientswithrenal

impairment.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:immuneseraandimmunoglobulins:immunoglobulins,normalhuman,forintravascular

administration,ATCcode:J06BA02

wheezing,bronchospasm,pulmonaryembolism,

pulmonaryedema

Gastrointestinaldisorders Nausea,vomiting Common

Diarrhea,abdominalpainupper,stomach

discomfort,stomatitis Uncommon

Dyspepsia,abdominalpain Notknown

HepatobiliaryDisorders Hepatitis(non-infectioushepatitis) Notknown

Skinandsubcutaneous

tissuedisorders Pruritus,urticaria,coldsweat,hyperhidrosis Uncommon

Erythema,rash,dermatitis,angioedema Notknown

Musculoskeletaland

connectivetissuedisorders Backpain,musclespasm,paininextremity Uncommon

Arthralgia,myalgia Notknown

Renalandurinarydisorders Renalfailure Notknown

Generaldisordersand

administrationsite

conditions Fatigue,chills,pyrexia Common

Chestpain,chestdiscomfort,feelingabnormal,

feelingcold,feelinghot,influenza-likeillness,

infusionsiteerythema,infusionsiteextravasation,

infusionsitepain,malaise,pain Uncommon

Asthenia,edema,injectionandinfusionsite

reactions,rigors Notknown

Investigations Bloodpressureincreased,

bloodpressurefluctuation Uncommon

Coombsdirecttestpositive Notknown

MetabolismandNutritional

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infectiousagents.

HumannormalimmunoglobulincontainstheIgGantibodiespresentinthenormalpopulation.Itispreparedfrom

pooledmaterialfromnotfewerthan1000donations.ItshouldhaveadistributionofimmunoglobulinGsubclasses

closelyproportionaltothatinnativehumanplasma.Adequatedosesofthismedicinalproductmayrestoreabnormally

lowimmunoglobulinGlevelstothenormalrange.

Themechanismofactioninindicationsotherthanreplacementtherapyisnotfullyelucidated,butincludesimmune

modulatoryeffects.

5.2Pharmacokineticproperties

Humannormalimmunoglobulinisimmediatelyandcompletelybioavailableinthereceipient’scirculationafter

intravenousadministration.Itisdistributedrelativelyrapidlybetweenplasmaandextravascularfluid,after

approximately3-5daysequilibriumisreachedbetweentheintra-andextra-vascularcompartments.

Humannormalimmunoglobulinhasahalf-lifeapproximately37.5+15days.Thishalf-lifemayvaryfrompatientto

patient,inparticularinprimaryimmunodeficiency.

IgGandIgG–complexesarebrokendownincellsofthereticuloendothelialsystem.

5.3Preclinicalsafetydata

ToxicologicalProperties

Immunoglobulinsarenormalconstituentsofthehumanbody.

Inanimals,singledosetoxicitytestingisofnorelevanceandhigherdosesresultinoverloading.Repeateddosetoxicity

testingandembryo-foetaltoxicitystudiesareimpracticalduetoinductionof,andinterferencewithantibodies.Effects

oftheproductontheimmunesystemofthenewbornhavenotbeenstudied.

Sinceclinicalexperienceprovidesnohintfortumorigenicormutageniceffectsofimmunoglobulins,experimental

studies,particularlyinheterogolousspecies,arenotconsiderednecessary.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

SodiumChloride

GlucoseMonohydrate

HumanAlbumin(asstabiliser:1.5-3mg/mlfora5%solution)

Glycine

Macrogol

HydrochloricAcid(forpHadjustment)

SodiumHydroxide(forpHadjustment)

Solvent

Waterforinjections

6.2Incompatibilities

Thismedicinalproductmustnotbemixedwithothermedicinalproducts.

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administeredseparatelyfromothermedicinalproductsthatthepatientsmaybereceiving.

6.3ShelfLife

Unopened:2years.

Oncereconstituted:Productshouldbeusedwithin2hoursofreconstitutionwiththesolventifkeptatatemperatureof

≤25 o

C.Whenreconstitutionhastakenplaceincontrolledandvalidatedascepticconditionsthereconstitutedproduct

maybestorednolongerthan24hoursat2to8 o

6.4Specialprecautionsforstorage

Unopenedpack:Donotstoreabove25 o

C.Donotfreeze.Forstorageafterreconstitutionrefertosection6.3,Shelf

life.

6.5Natureandcontentsofcontainer

HumanNormalImmunoglobulinforIntravenousAdministration,GammagardS/Disavailableinvialsof0.5g,2.5g,

5.0gand10.0g.

Eachpackageof0.5gcontainsthesolvent(10ml),asteriledouble-endedneedle,asterilefilterneedle,a10mlsterile

plasticsyringeandasterilemini-infusionset.

Eachpackageof2.5g,5.0gand10.0gcontainsthesolvent(50ml,96ml,192mlrespectively)asteriletransferdevice

andasterileadministrationsetwithfilter.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Theproductshouldbebroughttoroomorbodytemperaturebeforeuse.

Totalreconstitutionshouldbeobtainedwithin30minutes.

Reconstitutedmaterialshouldbeacleartoslightlyopalescentandcolourlesstopaleyellowsolution.Donotuse

solutionsthatarecloudyorhavedeposits.Reconstitutedproductsshouldbeinspectedvisuallyforparticulatematter

anddiscolorationpriortoadministration.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

Reconstitution-useaseptictechnique:

0.5gSize

BringGAMMAGARDS/DandSterilizedWaterforInjections(solvent)toroomtemperature.Thistemperatureneeds

tobemaintaineduntildissolutioniscomplete.

A.5%Solution:

1.Removebottlecapsandcleanstopperswithgermicidalsolution.

2.Removeprotectivecoverfromoneendofthedouble-endedneedle.Donottouchtheneedle.

3.Placesolventbottleonaflatsurface.Useexposedneedletospikesolventbottlethroughcentreofthestopper.

4.Removeprotectivecoverfromotherendofthedouble-endedneedle.Donottouchtheneedle.

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solvent.

6.Spikeconcentratebottlethroughcentreofthestopperwhilequicklyinvertingthesolventvialtoavoidspillingout

solvent.

CAUTION:Failuretoinsertthespikeintothecenterofthestoppermayresultindislodgingofthestopperand

lossofvacuum.

7.Aftertransferofsolventiscomplete,removedouble-endedneedleandemptysolventbottle.Immediatelyswirlthe

concentratebottlegentlytothoroughlymixcontents.

CAUTION:Donotshake.Avoidfoaming.

8.Discarddouble-endedneedleaftersingleuse.

B.10%Solution:

1.Removebottlecapsandcleanstopperswithgermicidalsolution.

2.Topreparea10%solution,itisnecessarytoremovehalfofthevolumeofsolvent.Thevolumeofsolventrequired

fora10%solutionis5mLfor0.5gsize.

3.Usingaseptictechnique,drawrequiredvolumeofwaterintoasterilehypodermicneedleandsyringe.Donottouch

theneedle.

4.Injectthe5mlsolventinthesyringeintotheconcentratevial.

5.Aftertransferofsolventiscomplete,removeneedleandsyringefromconcentratevial.

Immediatelyswirltheconcentratebottlegentlytothoroughlymixcontents.

CAUTION:Donotshake.Avoidfoaming.

6.Discardneedleandsyringeandanyunusedsolventaftersingleuse.

2.5g,5.0g,10.0gSizes

BringGAMMAGARDS/DandSterilizedWaterforInjections(solvent)toroomtemperature.Thistemperatureneeds

tobemaintaineduntildissolutioniscomplete.

A.5%Solution:

1.Removebottlecapsandcleanstopperswithgermicidalsolution.

2.Removespikecapfromoneendofthetransferdevice.

Donottouchspike.

3a.Placethesolventvialonaflatsurface.Useexposed

endoftransferdevicetospikesolventvialthrough

centreofthestopper

CAUTION:Failuretoinsertspikeintocentreof

thestoppermayresultindislodgingofthestopper.

3b.Ensurethatthecollarcollapsesfullyintothedevicebypushingdownonthetransferdevice

firmly.

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4.Holdsolventbottlewithattachedtransferdeviceatanangletotheconcentratebottletopreventspillingthesolvent.

Note:Donotholdsolventbottleupsidedown,

forthiscanleadtosolventspillage.

5a.Spikeconcentratebottlethroughthecentreofthestopperwhilequicklyinvertingthesolventvialtoavoid

spillingoutsolvent.

CAUTION:Failuretoinsertthespikeintothecentreofthestoppermayresultin

dislodgingofthestopperandlossofvacuum.

5b.Ensurethatthecollarcollapsesfullyintothedevicebypushingdownonthesolventbottlefirmly.

6.Aftertransferofsolventiscomplete,removetransferdeviceandemptysolventbottle.Immediatelyswirlthe

concentratebottlegentlytothoroughlymixcontents.

CAUTION:Donotshake.Avoidfoaming.

Discardtransferdeviceaftersingleuse.

B.10%Solution:

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2.Topreparea10%solution,itisnecessarytoremovehalfofthevolumeofsolvent.Table2indicatesthevolumeof

solventthatshouldberemovedfromthevialbeforeattachingthetransferdevicetoproducea10%concentration.

Usingaseptictechnique,withdrawtheunnecessaryvolumeofsolventusingasterilehypodermicsyringeandneedle.

Discardthefilledsyringeandtheneedle.

3.Usingtheresidualsolventinthesolventvial,followsteps2-6aspreviouslydescribedinA.

TABLE2

RequiredSolventVolumetobeRemoved

2.5g 5.0g 10.0g

Concentration bottle bottle bottle

Donotremoveanysolventforreconstitutionof5%Solution

25mL 48mL 96mL

Administration-useaseptictechnique

0.5gSize

1.Attachthefilterneedletoanemptyplasticsyringe.

2.Drawbacktheplungertoadmitairintothesyringe.

3.PlacethereconstitutedGAMMAGARDS/Dvialonaflatsurfaceand,whileholdingthebottlefirmlytoprevent

slipping,inserttheneedleperpendicularlythroughthecentreofthevialstopper.

4.Injectairintovialandthenwithdrawthereconstitutedmaterialintothesyringe.

5.Removesyringeandinjectsolutionintravenouslythroughthemini-infusionset.

2.5g,5.0g,10.0gSizes

Followthedirectioninsertforuse,whichaccompaniestheadministrationsetprovidedineachpackage.Ifanother

administrationsetisused,ensurethatthesetcontainsasimilarfilter.

7MARKETINGAUTHORISATIONHOLDER

BaxterHealthcareLimited

CaxtonWay

Thetford

Norfolk

IP243SE

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0167/079/004

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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Dateoflastrenewal:01May2008

10DATEOFREVISIONOFTHETEXT

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