GAMMABULIN

Main information

  • Trade name:
  • GAMMABULIN Solution for Injection 0.8g/ 5ml %w/ v
  • Dosage:
  • 0.8g/ 5ml %w/ v
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • GAMMABULIN Solution for Injection 0.8g/5ml %w/v
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/116/002
  • Authorization date:
  • 14-08-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

GammabulinS/D160mg/mlSolutionforinjection,5ml

2QUALITATIVEANDQUANTITATIVECOMPOSITION

HumanNormalImmunoglobulin(SC/IMIg).

1mlsolutioncontains:

humanprotein160mg

(ofwhichatleast90%areimmunoglobulin)

DistributionofIgGsubclasses:

MaximumIgAcontent:4.8mg/ml.

1vialof5mlcontains800mghumanprotein(ofwhichatleast90%areimmunoglobulin).

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

SolutionforInjection

Theproductisaclearorslightlyopalescent,colourlesstopaleyellowsolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Replacementtherapyinpatientswithprimaryorsecondaryimmunodeficiency.

Congenitalagammagloculinaemiaandhypogammaglobulinaemia.

Commonvariableimmunodeficiency.

Severecombinedimmunodeficiency.

IgGsubclassdeficiencieswithorwithoutconcomitantIgAdeficiency.

Specificantibodydeficiencies.

ReplacementtherapyinsecondaryimmunodeficiencydisorderssuchashypogammaglobulinaemiaorlowlevelsifIgG

duetolowgradeB-celltumours.

4.2Posologyandmethodofadministration

Replacementtherapy:humannormalimmunoglobulini.m.maypreventseriousinfectioninpatientswith

immunoglobulindeficiency.Thedosageshouldbeadjustedtomaintainanapproximatelevelof2g/Iofcirculating

IgG145-75%

IgG220-45%

IgG3 3-10%

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Theusualposologyconsistsof0.66ml/kgbodyweight(100mg/kg)givenevery3to4weeks,withadoubledose

givenatonsetoftherapy.

4.2.1Posology

Thedoseanddosageregimenisdependentontheindication.Inreplacementtherapythedosagemayneedtobe

individualisedforeachpatientdependentonthepharmacokineticandclinicalresponse.Thefollowingdosageregimens

aregivenasaguideline.

Allrecommendationsanddosesgivenbelowrefertothe16%solutionandareexpressedinml.

Antibodydeficiencysyndromeindys-,hypo-andagammaglobulinaemia:

ByintramuscularadministrationofGammabulinS/Dantibodyconcentratethefrequencyandseverityofrecurring

bacterialinfectionscanbereduced.Fortreatmentofimmunoglobulindeficiency,itisnecessarytoachieveand

maintainanimmunoglobulinlevelofapproximately200mgper100mlserum.

Initialdosage:1.8mlperkgbodyweight,e.g.inthreesingleadministrationsof0.6ml/kgbodyweighteachatintervals

of24hours.

Maintenancedose:0.6mlperkgbodyweightmonthly.

ThedosageregimenusingthesubcutaneousrouteshouldachieveasustainedtroughlevelofIgG(measuredbeforethe

nextinfusion).Dependingontheseverityandnumberofinfections,loadingviathesubcutaneousorintravenousroute

mayberequired.

AftersteadystateofIgGlevelshavebeenattained,therecommendedmaintenancedoseisintheorderofatleast0.1

g/kg/week(0.625ml/kg/week)or0.2g/kg(1.25ml/kg)atintervalsof14daysor0.4–0.6g/kg/month(2.5–3.75

ml/kg/month).

IfasteadystateofIgGserumlevelhasnotbeenreachedpriortosubcutaneoustreatment,aloadingdoseofdaily

subcutaneousinfusion(0.1g/kg)(0.625ml/kg/week)forapprox.5dayswillsufficetoachieveasteadystate,after

whichweeklydosescanbeapplied.

Incasesofantibodydeficiencysyndromes,thetherapeuticaimistoreachandmaintainaserumIgGlevelofatleast4-

6g/l.

Inexceptionalcases,wheresubcutaneousadministrationsnotapplicable,theproductcanbeadministered

intramuscularly.

4.2.2Methodofadministration

Subcutaneous

GammabulinS/Dshouldbeadministeredviasubcutaneousinfusion.

Subcutaneousinfusionforhometreatmentshouldbeinitiatedafterthoroughtrainingbyaphysicianexperiencedinthe

guidanceofpatientsforhometreatment.InordertoobtainsteadystateImmunoglobulinGserumlevelsthetreatment

canthenbecontinuedbythepatientorguardian.Oncethepatientisfamiliarwiththemethodandnounacceptableside

effectswereobservedduringthetrainingphasethetreatmentcanbecontinuedbythepatientortheguardianinorderto

reachthesteadystateoftheserumlevel.

Itisrecommendedtouseabatteryoperatedsyringedriverfortheinfusionwithaninitialadministrationspeedof10

ml/h/pump.

Theinfusionspeedcanbeenhancedby1ml/h/pumpeverysubsequentinfusion.Therecommendedmaximumspeedis

20ml/h/pump.Morethanonepumpcanbeusedsimultaneously.Theinfusionsiteshouldbechangedevery5-15ml.

Intramuscular

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Iflargedosesaretobeadministered,itisadvisabletosplitthedoseandadministerittovariousregions.Asageneral

rule,nomorethan5mlinadultsand3mlinchildrenshouldbeinjectedinthesameanatomicalareaandnomorethan

25mlperdayshouldbeadministered.Largerdoseshavebeenadministeredsafely.

4.3Contraindications

Hypersensitivitytoanyofthecomponents.

Injectionsmustnotbegivenintravenously.GammabulinS/Dmustnotbeadministeredintramuscularlytopatients

sufferingfromseverethrombocytopeniaoranydisorderofhaemostasis.

4.4Specialwarningsandprecautionsforuse

4.4.1Precautions

WhenGammabulinS/Disadministeredintoabloodvessel,patientscouldreactwithshocksymptoms.Therefore,it

mustbeensuredthatGammabulinisnotadministeredintoabloodvessel.

Precautionsshouldbetakentoavoidanysciaticnerveinjury,whenadministeringintramuscularinjections.

Therecommendedinfusionrategivenunder“4.2.2MethodofAdministration”mustbecloselyfollowed.Patientsmust

becarefullyobservedforanysymptomsthroughouttheinfusionperiod.

Patientsinself-hometreatmentandtheguardianmustbetrainedtobeabletodetecttheearlysignsofhypotensive

reactionsthatoccurveryseldom.Ifsevereanaphylactoidreactionsoccur,theuseofanadrenalinpenmayprevent

furtherdevelopmentofanaphylacticreaction.Inanycase,thepatientorguardianshouldcontactadoctorimmediately.

Certainadversereactionsmayoccurmorefrequentlyinpatientswhoreceivehumannormalimmunoglobulinforthe

firsttimeor,inrarecases,whenthehumannormalimmunoglobulinproductisswitchedorwhentreatmenthasbeen

stoppedformorethaneightweeks.

Trueanaphylacticreactionsarerare.TheycanoccurintheseldomcasesofIgAdeficiencywithanti-IgAantibodies.

ForthetreatmentofpatientswithIgAdeficiencyandanti-IgAantibodiesappropriateprecautionsmustbetakenasa

riskofintolerance,thoughlowerthanwiththeintravenousadministrationofimmunoglobulin,cannotberuledout.

Rarely,humannormalimmunoglobulincaninduceafallinbloodpressurewithanaphylacticreaction,eveninpatients

whohadtoleratedprevioustreatmentwithhumannormalimmunoglobulin.

Potentialcomplicationscanoftenbeavoidedbyensuring:

thatpatientsarenotsensitivetohumannormalimmunoglobulinbyfirstinjectingtheproductslowly.

thatpatientsarecarefullyobservedforanysymptomsthroughouttheinfusionperiod.Inparticular,patientsnaïve

tohumannormalimmunoglobulin,patientsswitchedfromanalternativeproductorwhentherehasbeenalonginterval

sincethepreviousinfusionshouldbeobservedduringthefirstinfusionandforthefirsthourafterthefirstinfusion

shouldbeobservedduringthefirstinfusionandforthefirsthourafterthefirstinfusion,inordertodetectpotential

adversesigns.Allotherpatientsshouldbeobservedforatleast20minutesafteradministration.

Suspicionofsystemicreactionslikehighpulserate,nauseaandcoldsweatsrequiresimmediatediscontinuationofthe

injection.Incaseofshock,thecurrentmedicalstandardsforshocktreatmentaretobeobserved.

Inpatientsatrisk,theproductshouldbeadministeredattheminimuminfusion-ratepracticable.

Nospecificclinicalstudiesforthetreatmentofchildrenwereconductedwiththisproduct.However,datafromthe

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4.4.2SpecialWarnings

Gammabulinismadefromhumanplasma.Standardmeasurestopreventinfectionsresultingfromtheuseofmedicinal

productspreparedfromhumanbloodorplasmaincludeselectionofdonors,screeningofindividualdonationsand

plasmapoolsforspecificmarketsinfectionandtheinclusion/removalofviruses.Despitethis,whenmedicinalproducts

preparedfromhumanbloodorplasmaareadministered,thepossibilityoftransmittinginfectiveagentscannotbe

totallyexcluded.Thisalsoappliestounknownoremergingvirusesandotherpathogens.

ThemeasurestakenareconsideredeffectiveforenvelopedvirusessuchasHIV,HBVandHCV.

Themeasurestakenmaybeoflimitedvalueagainstnon-envelopedvirusessuchasHAVandparvovirusB19.

ThereisreassuringclinicalexperienceregardingthelackofhepatitisAorparvovirusB19transmissionwith

immunoglobulinanditisalsoassumedthattheantibodycontentmakesanimportantcontributiontotheviralsafety.

ItisstronglyrecommendedthateverytimethatGammabulinisadministeredtoapatient,thenameandbatchnumber

oftheproductarerecordedinordertomaintainalinkbetweenthepatientandthebatchoftheproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

4.5.1 Liveattenuatedvirusvaccines

Immunoglobulinadministrationmayimpairforaperiodofatleast6weeksandupto3monthstheefficacyoflive

attenuatedvirusvaccinessuchasmeasles,rubella,mumpsandvaricella.Afteradministrationofthisproduct,an

intervalof3monthsshouldelapsebeforevaccinationwithliveattenuatedvirusvaccines.Inthecaseofmeasles,this

impairmentmaypersistforupto1year.

Thereforepatientsreceivingmeaslesvaccineshouldhavetheirantibodystatuschecked.

4.5.2 Interferencewithserologicaltesting

Afterinjectionofimmunoglobulinthetransitoryriseofthevariouspassivelytransferredantibodiesinthepatient’s

bloodmayresultinmisleadingpositiveresultsinserologicaltesting.

Passivetransmissionofantibodiestoerythrocyteantigens,e.g.A,B,Dmayinterferewithsomeserologicaltests

(Coombstest).

4.6Pregnancyandlactation

Thesafetyofthismedicinalproductforuseinhumanpregnancyhasnotbeenestablishedincontrolledclinicaltrials

andthereforeshouldonlybegivenwithcautiontopregnantwomenorbreast-feedingmothers.However,clinical

experiencewithimmunoglobulinsuggeststhatnoharmfuleffectsonthecourseofpregnancy,onthefoetusandthe

neonatearetobeexpected.

Continuedtreatmentofthepregnantwomanisimportanttoensurethattheneonateisbornwithappropriatepassive

immunity.

4.7Effectsonabilitytodriveandusemachines

Noeffectsontheabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

Rarelyhumannormalimmunoglobulinsmaycauseasuddenfallinbloodpressureand,inisolatedcases,anaphylactic

shock,evenwhenthepatienthasshownnohypersensitivitytopreviousadministration.However,comparedtothe

intravenousroute,veryfewadversesystemicreactionshaveoccurredwiththesubcutaneousadministration.

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andmoderatelowbackpainmayoccuroccasionally.

Occasionally,localpain,soreness,induration,redness,swellingortendernessmayoccurattheinjection/infusionsite.

Toalargeextent,thesecanbepreventedbysplittinglargerdosesintoseveralsmallerdosesandbyinjecting/infusing

thesesmallerdosesatdifferentinjection/infusionsites.

Inrarecasesitching,bruising,rush,erythema,fever,nausea,vomiting,hypotension,dizziness,andtachycardiahave

beenobserved.

Inveryrarecasesanaphylactic/anaphylactoidreactions,suchasdyspnea,chesttightness,flushingofthefaceandskin,

feelingofheat,andurticaria,mayoccur.

Forinformationonviralsafety,see“4.4.2SpecialWarnings”.

4.9Overdose

Noundesirableeffectsspecificallyresultingfromoverdoseareknown.

5PHARMACOLOGICALPROPERTIES

GammabulinS/Disaliquidimmunoglobulinconcentrateforsubcutaneousorintramuscularadministration,whichis

manufacturedfrompooledhumanplasma.

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:immuneseraandimmunoglobulins:immunoglobulins,normalhuman,forextravascular

administration.ATC-code:JO6BA01.

HumannormalimmunoglobulincontainsmainlyIgG(ImmunoglobulinG)withabroadspectrumofantibodiesagainst

infectiousagents.

HumannormalimmunoglobulincontainstheIgGantibodiespresentinthenormalpopulation.Itisusuallyprepared

frompooledmaterialfromnotfewerthan1000donations.IthasadistributionofIgGsubclassescloselyproportionalto

thatinnativehumanplasma.

AdequatedosesofthismedicinalproductmayrestoreabnormallylowIgGlevelstothenormalrange.

5.2Pharmacokineticproperties

Forsubcutaneousadministrationpeaklevelsofhumannormalimmunoglobulinareachievedintherecipient’s

circulationafteramediandelayofabout4days.Thishalf-lifemayvaryfrompatienttopatient,inparticularinprimary

immunodeficiency.

Forintramuscularadministrationpeaklevelsofhumannormalimmunoglobulinareachievedintherecipient’s

circulationafteradelayofabout2-3days.

5.3Preclinicalsafetydata

Singledosetoxicitytestingstudiesdemonstratethatthedosesseveraltimeshigherthanthemaximumrecommended

humandosehadnotoxiceffectsonlaboratoryanimals.Repeateddosetoxicitytestinginanimalsisimpracticabledue

tointerferencewithdevelopingantibodiestoheterologousprotein.

Sincehumanproteinshavenotbeenseentocausetumourigenicormutageniceffects,experimentalstudiesparticularly

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Glycine

SodiumChloride

WaterforInjection

6.2Incompatibilities

Thismedicinalproductmustnotbemixedwithothermedicinalproductsandistobeadministeredasaseparate

injection/infusion.

6.3ShelfLife

Threeyears.

6.4Specialprecautionsforstorage

Storeinarefrigerator(2ºC–8ºC).

Donotfreeze.

Keepthevialintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

ThenatureoftheproductissuppliedinvialsmadeofglasshydrolyticclassTypeIthatareclosedwithbromobutyl

rubberstopper.

GammabulinS/Disavailableinpackagescontainingeither:

1vialwith5mlsolutionforinjection/infusion.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Theproductshouldbebroughttoroomorbodytemperaturebeforeuse.

Theliquidpreparationisclearandpaleyellowtolightbrown;duringstorageitmayshowformationofslightturbidity

orasmallamountofparticulatematter.Donotusesolutionthataremorethanjustslightturbid.

Enteredvialsmustnotbereused.

Afteropeningofthevialtheproductmustbeusedimmediately.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

BaxterHealthcareLimited

Caxtonway

Thetford

Norfolk

IP243SE

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8MARKETINGAUTHORISATIONNUMBER

PA167/116/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14August1984

Dateoflastrenewal:14August2004

10DATEOFREVISIONOFTHETEXT

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