FLEBOGAMMA

Main information

  • Trade name:
  • FLEBOGAMMA Solution for Infusion 50 g/l
  • Dosage:
  • 50 g/l
  • Pharmaceutical form:
  • Solution for Infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLEBOGAMMA Solution for Infusion 50 g/l
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0849/004/001
  • Authorization date:
  • 08-03-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0849/004/001

CaseNo:2070717

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

InstitutoGrifolsS.A.

CANGuasch2,ParetsdelValles08150,Barcelona,Spain

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Flebogamma5%SolutionforInfusion.HumanNormalImmunoglobulinforIntravenousAdministration.

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom08/03/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Flebogamma5%.

SolutionforInfusion.

HumanNormalImmunoglobulinforIntravenousAdministration.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Humannormalimmunoglobulin(IVIg)

ThepercentageofIgGsubclassesisapproximately68.7%IgG

,25.9%IgG

,3.7%IgG

and1.78%IgG

Humanproteincontentis50g/lofwhichatleast97%isIgG.

IgAcontentislowerthan0.05mg/ml.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Solutionforinfusion

Solutionisclearorslightlyopalescentandcolourlessorpaleyellow.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Flebogamma5%isindicatedfor:

Replacementtherapyin:

Primaryimmunodeficiencysyndromessuchas:

Congenitalagammaglobulinaemiaandhypogammaglobulinaemia

Commonvariableimmunodeficiency

Severecombinedimmunodeficiency

WiskottAldrichsyndrome

Myelomaorchroniclymphocyticleukaemiawithseveresecondaryhypogammaglobulinaemiaandrecurrentinfections.

ChildrenwithcongenitalAIDSandrecurrentinfections.

Immunomodulation:

Idiopathicthrombocytopenicpurpura(ITP),inchildrenoradultsathighriskofbleedingorpriortosurgerytocorrect

theplateletcount.

GuillainBarréSyndrome.

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Allogeneicbonemarrowtransplantation.

4.2Posologyandmethodofadministration

4.2.1.Posology

Thedoseanddosageregimenisdependentontheindication.

Inreplacementtherapythedosagemayneedtobeindividualisedforeachpatientdependentonthepharmacokinetic

andclinicalresponse.Thefollowingdosageregimensaregivenasaguideline.

Replacementtherapyinprimaryimmunodeficiencysyndromes

ThedosageregimenshouldachieveatroughlevelofIgG(measuredbeforethenextinfusion)ofatleast4-6g/l.

Threetosixmonthsarerequiredaftertheinitiationoftherapyforequilibrationtooccur.

Therecommendedstartingdoseis0.4-0.8g/kgfollowedbyatleast0.2g/kgeverythreeweeks.

Thedoserequiredtoachieveatroughlevelof6g/lisoftheorderof0.2-0.8g/kg/month.

Thedosageintervalwhensteadystatehasbeenreachedvariesfrom2-4weeks.

Troughlevelsshouldbemeasuredinordertoadjustthedoseanddosageinterval.

Replacementtherapyinmyelomaorchroniclymphocyticleukaemiawithseveresecondaryhypogammaglobulinemia

andrecurrentinfections;replacementtherapyinchildrenwithAIDSandrecurrentinfections

Therecommendeddoseis0.2-0.4g/kgeverythreetofourweeks.

IdiopathicThrombocytopenicPurpura

Forthetreatmentofanacuteepisode,0.8-1g/kgondayone,thismayberepeatedoncewithin3days,or0.4g/kgdaily

fortwotofivedays.Thetreatmentcanberepeatedifrelapseoccurs.

GuillainBarrésyndrome

0.4g/kg/dayfor3to7days.

Experienceinchildrenislimited.

KawasakiDisease

1.6-2.0g/kgshouldbeadministeredindivideddosesovertwotofivedaysor2.0g/kgasasingledose.

Patientsshouldreceiveconcomitanttreatmentwithacetylsalicylicacid.

AllogeneicBoneMarrowTransplantation

Humannormalimmunoglobulintreatmentcanbeusedaspartoftheconditioningregimenandafterthetransplant.

Forthetreatmentofinfectionsandprophylaxisofgraftversushostdisease,dosageisindividuallytailored.

Thestartingdoseisnormally0.5g/kg/week,startingsevendaysbeforetransplantationandforupto3monthsafter

transplantation.

Incaseofpersistentlackofantibodyproduction,dosageof0.5g/kg/monthisrecommendeduntilantibodylevelreturns

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Thedosagerecommendationsaresummarisedinthefollowingtable:

4.2.2.Methodofadministration

Flebogamma5%shouldbeinfusedintravenouslyataninitialrateof0.6-1.2ml/kg/hourforthefirstthirtyminutes.If

welltolerated,therateofadministrationmaygraduallybeincreasedtoamaximumof4.2ml/kg/hour.

4.3Contraindications

Hypersensitivitytoanyofthecomponents.

(Seespecialwarningsaboutexcipients,section4.4.).

Hypersensitivitytohomologousimmunoglobulins,especiallyinveryrarecasesofIgAdeficiency,whenthepatienthas

Indication Dose Frequency

Replacementtherapyinprimary

immunodeficiency

Replacementtherapyinsecondary

immunodeficiency

-startingdose:

0.4–0.8g/kg

-thereafter:

0.2–0.8g/kg

0.2–0.4g/kg

0.2–0.4g/kg every2–4weekstoobtainIgG

troughlevelofatleast4–6g/l

every3–4weekstoobtainIgG

troughlevelofatleast4–6g/l

every3–4weeks

Immunomodulation:

IdiopathicThrombocytopenic

Purpura

GuillainBarrésyndrome

0.8–1g/kg

0.4g/kg/d

0.4g/kg/d

1.6–2g/kg

onday1,possiblyrepeatedonce

within3days

for2–5days

for3–7days

inseveraldosesfor2–5daysin

associationwithacetylsalicylic

acid

inonedoseinassociationwith

acetylsalicylicacid

Allogeneicbonemarrow

transplantation:

treatmentofinfectionsand

prophylaxisofgraftversushost

disease

persistentlackofantibody

production 0.5g/kg

0.5g/kg everyweekfromday–7upto3

monthsaftertransplantation

everymonthuntilantibodylevels

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4.4Specialwarningsandprecautionsforuse

Certainsevereadversedrugreactionsmayberelatedtotherateofinfusion.Therecommendedinfusionrategiven

under“section4.2.Posologyandmethodofadministration”mustbecloselyfollowed.Patientsmustbeclosely

monitoredandcarefullyobservedforanysymptomsthroughouttheinfusionperiod.

Certainadversereactionsmayoccurmorefrequently:

Incaseofhighrateofinfusion,

Inpatientswithhypo-oragammaglobulinemiawithorwithoutIgAdeficiency,

Inpatientswhoreceivehumannormalimmunoglobulinforthefirsttime,orinrarecases,

Whenthehumannormalimmunoglobulinproductisswitchedorwhentherehasbeenalongintervalsincethe

previousinfusion.

Truehypersensitivityreactionsarerare.TheycanoccurintheveryseldomcasesofIgAdeficiencywithanti-IgA

antibodies.

Rarely,humannormalimmunoglobulincaninduceafallinbloodpressurewithanaphylacticreaction,eveninpatients

whohadtoleratedprevioustreatmentwithhumannormalimmunoglobulin.

Potentialcomplicationscanoftenbeavoidedbyensuring:

Thatpatientsarenotsensitivetohumannormalimmunoglobulinbyfirstinjectingtheproductslowlyataninitial

rateof0.6-1.2ml/kg/hour,

Thatpatientsarecarefullymonitoredforanysymptomsthroughouttheinfusionperiod.Inparticular,patients

naivetohumannormalimmunoglobulin,patientsswitchedfromanalternativeIVIgproductorwhentherehas

beenalongintervalsincethepreviousinfusionshouldbemonitoredduringthefirstinfusionandforthefirsthour

afterthefirstinfusion,inordertodetectpotentialadversesigns.Allotherpatientsshouldbeobservedforatleast

20minutesafteradministration.

ThereisclinicalevidenceofanassociationbetweenIVIgadministrationandthromboemboliceventssuchas

myocardialinfarction,stroke,pulmonaryembolismanddeepveinthromboseswhichisassumedtoberelatedtoa

relativeincreaseinbloodviscositythroughthehighinfluxofimmunoglobulininat-riskpatients.Cautionshouldbe

exercisedinprescribingandinfusingIVIginobesepatientsandinpatientswithpre-existingriskfactorsforthrombotic

events(suchasadvancedage,hypertension,diabetesmellitusandahistoryofvasculardiseaseorthromboticepisodes,

patientswithacquiredorinheritedthrombophilicdisorders,patientswithprolongedperiodsofimmobilisation,severely

hypovolemicpatients,patientswithdiseaseswhichincreasebloodviscosity).

CasesofacuterenalfailurehavebeenreportedinpatientsreceivingIVIgtherapy.Inmostcases,riskfactorshavebeen

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

nephrotoxicmedicinalproductsorageover65.

Incaseofrenalimpairment,IVIgdiscontinuationshouldbeconsidered.

Whilethesereportsofrenaldysfunctionandacuterenalfailurehavebeenassociatedwiththeuseofmanyofthe

licensedIVIgproducts,thosecontainingsucroseasastabiliseraccountedforadisproportionateshareofthetotal

number.Flebogamma5%doesnotcontainsucrose.Inpatientsatrisk,theuseofIVIgproductsthatdonotcontain

sucrosemaybeconsidered.

Inpatientsatriskforacuterenalfailureorthromboembolicadversereactions,IVIgproductsshouldbeadministeredat

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Inallpatients,IVIgadministrationrequires:

adequatehydrationpriortotheinitiationoftheinfusionofIVIg

monitoringofurineoutput

monitoringofserumcreatininelevels

avoidanceofconcomitantuseofloopdiuretics

Incaseofadversereaction,eithertherateofadministrationmustbereducedortheinfusionstopped.

Thetreatmentrequireddependsonthenatureandseverityofthesideeffect.

Incaseofshock,standardmedicaltreatmentforshockshouldbeimplemented.

Standardmeasurestopreventinfectionsresultingfromtheuseofmedicinalproductspreparedfromhumanbloodor

plasmaincludeselectionofdonors,screeningofindividualdonationsandplasmapoolsforspecificmarkersof

infectionandtheinclusionofeffectivemanufacturingstepsfortheinactivation/removalofviruses.Despitethis,when

medicinalproductspreparedfromhumanbloodorplasmaareadministered,thepossibilityoftransmittinginfective

agentscannotbetotallyexcluded.Thisalsoappliestounknownoremergingvirusesandotherpathogens.

ThemeasurestakenareconsideredeffectiveforenvelopedvirusessuchasHIV,HBVandHCV,andforthenon-

envelopedvirusHAV.

Themeasurestakenmaybeoflimitedvalueagainstnon-envelopedvirusessuchasparvovirusB19.

ThereisreassuringclinicalexperienceregardingthelackofhepatitisAorparvovirusB19transmissionwith

immunoglobulinsanditisalsoassumedthattheantibodycontentmakesanimportantcontributiontotheviralsafety.

ItisstronglyrecommendedthateverytimethatFlebogamma5%isadministeredtoapatient,thenameandbatch

numberoftheproductarerecordedinordertomaintainalinkbetweenthepatientandthebatchoftheproduct.

Specialwarningsaboutexcipients:thismedicinalproductcontains5gofsorbitolper100mlasexcipient.Incaseof

fructosehereditaryintolerancethisproductshouldnotbeused.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Liveattenuatedvirusvaccines

Immunoglobulinadministrationmayimpairforaperiodofatleast6weeksandupto3monthstheefficacyoflive

attenuatedvirusvaccinessuchasmeasles,rubella,mumpsandvaricella.Afteradministrationofthisproduct,an

intervalof3monthsshouldelapsebeforevaccinationwithliveattenuatedvirusvaccines.Inthecaseofmeasles,this

impairmentmaypersistforupto1year.Thereforepatientsreceivingmeaslesvaccineshouldhavetheirantibodystatus

checked.

Interferencewithserologicaltesting

Afterinjectionofimmunoglobulinthetransitoryriseofthevariouspassivelytransferredantibodiesinthepatient’s

bloodmayresultinmisleadingpositiveresultsinserologicaltesting.

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

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4.6Pregnancyandlactation

Thesafetyofthismedicinalproductforuseinhumanpregnancyhasnotbeenestablishedincontrolledclinicaltrials

andthereforeshouldonlybegivenwithcautiontopregnantwomenandbreast-feedingmothers.Clinicalexperience

withimmunoglobulinssuggeststhatnoharmfuleffectsonthecourseofpregnancy,oronthefoetusandtheneonateare

tobeexpected.

Immunoglobulinsareexcretedintothemilkandmaycontributetothetransferofprotectiveantibodiestotheneonate.

4.7Effectsonabilitytodriveandusemachines

Noeffectsonabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

Adversereactionssuchaschills,headache,fever,vomiting,allergicreactions,nausea,arthralgia,lowbloodpressure

andmoderatelowbackpainmayoccuroccasionally.

Rarelyhumannormalimmunoglobulinsmaycauseasuddenfallinbloodpressureand,inisolatedcases,anaphylactic

shock,evenwhenthepatienthasshownnohypersensitivitytopreviousadministration.

Casesofreversibleasepticmeningitis,isolatedcasesofreversiblehaemolyticanaemia/haemolysisandrarecasesof

transientcutaneousreactions,havebeenobservedwithhumannormalimmunoglobulin.

Increaseinserumcreatinineleveland/oracuterenalfailurehavebeenobserved.

Veryrarely:Thromboembolicreactionssuchasmyocardialinfarction,stroke,pulmonaryembolism,deepvein

thromboses.

Forsafetywithrespecttotransmissibleagents,SeeSection4.4,Specialwarningsandprecautionsforuse.

4.9Overdose

Overdosemayleadtofluidoverloadandhyperviscosity,particularlyinpatientsatrisk,includingelderlypatientsor

patientswithrenalimpairment.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:immuneseraandimmunoglobulins:immunoglobulins,normalhuman,forintravascular

administration,ATCcode:J06BA02.

HumannormalimmunoglobulincontainsmainlyimmunoglobulinG(IgG)withabroadspectrumofantibodiesagainst

infectiousagents.

HumannormalimmunoglobulincontainstheIgGantibodiespresentinthenormalpopulation.Itisusuallyprepared

frompooledplasmafromnotfewerthan1000donors.IthasadistributionofimmunoglobulinGsubclassesclosely

proportionaltothatinnativehumanplasma.

AdequatedosesofthismedicinalproductmayrestoreabnormallylowimmunoglobulinGlevelstothenormalrange.

Themechanismofactioninindicationsotherthanreplacementtherapyisnotfullyelucidated,butincludes

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5.2Pharmacokineticproperties

Humannormalimmunoglobulinisimmediatelyandcompletelybioavailableintherecipient’scirculationafter

intravenousadministration.Itisdistributedrelativelyrapidlybetweenplasmaandextravascularfluid,after

approximately3-5daysequilibriumisreachedbetweentheintra-andextravascularcompartments.

Humannormalimmunoglobulinhasahalf-lifeofabout36-65days.Thishalf-lifemayvaryfrompatienttopatient,in

particularinprimaryimmunodeficiency.

IgGandIgG-complexesarebrokendownincellsofthereticuloendothelialsystem.

5.3Preclinicalsafetydata

Immunoglobulinsarenormalconstituentsofthehumanbody.Inanimals,singledosetoxicitytestingisofnorelevance

sincehigherdosesresultinoverloading.

Repeateddosetoxicitytestingandembryo-foetaltoxicitystudiesareimpracticableduetoinductionof,andinterference

withantibodies.Effectsoftheproductontheimmunesystemofthenewbornhavenotbeenstudied.

Sinceclinicalexperienceprovidesnohintfortumorigenicandmutageniceffectsofimmunoglobulins,experimental

studies,particularlyinheterologousspecies,arenotconsiderednecessary.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

D-sorbitol

WaterforInjection

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

Itshouldbeadministeredbyaseparateintravenousline.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Storebelow25°C

Donotfreeze.

Storeintheoriginalpackagetoprotectfromlight.

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Theproductshouldbebroughttoroomorbodytemperaturebeforeuse.

Thesolutionshouldbeclearorslightlyopalescent.Donotusesolutionsthatarecloudyorhavedeposits.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

InstitutoGrifols,S.A.

CanGuasch,2-ParetsdelVallès

08150Barcelona-SPAIN

8MARKETINGAUTHORISATIONNUMBER

PA849/4/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:08March1995

Dateoflastrenewal:08March2010

10DATEOFREVISIONOFTHETEXT

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