EPAXAL

Main information

  • Trade name:
  • EPAXAL Suspension for Injection
  • Pharmaceutical form:
  • Suspension for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • EPAXAL Suspension for Injection
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0941/001/001
  • Authorization date:
  • 21-01-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Epaxalsuspensionforinjectioninaprefilledsyringe

HepatitisAvaccine(inactivated,virosome).

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1vaccinedose(0.5ml)containsatleast24IUofinactivatedhepatitisAvirus(strainRG-SB),propagatedinhuman

diploid(MRC-5)cells.

Thevirusparticlesareadsorbedonvirosomesastheadjuvantsystem,composedofhighlypurifiedinfluenzavirus

surfaceantigens(10microgramshaemagglutinin)oftheA/Singapore/6/86(H1N1)strainandthephospholipidslecithin

(80micrograms)andcephalin(20micrograms).

Formoreinformationontheadjuvant,seesection5.1.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Suspensionforinjectioninaprefilledsyringe.Clear,colourlessliquid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ActiveimmunisationagainsthepatitisAofchildrenfrom1yearofageandadults.

4.2Posologyandmethodofadministration

Onedoseof0.5mlisinjectedintramuscularly.Toensureoptimalimmuneresponse,thevaccineshouldbeinjectedinto

thedeltoidmuscle.Inpatientswithcoagulationdisorders,thevaccinemaybeadministeredsubcutaneouslyintheupper

arm.

Inordertoprovidelong-termprotection,asecond(booster)doseof0.5mlshouldbeadministered.Thisispreferably

givenbetween6-12monthsafterthefirstdosebutmaybegivenupto10yearslaterbasedonlimitedexperiencein

healthyadulttravellers(seesection5.1).

EpaxalcanbeusedinterchangeablywithotherinactivatedhepatitisAvaccinesforthefirstandsecond(booster)dose.

Simultaneousactiveandpassiveimmunisation

IfimmediateprotectionagainsthepatitisAisnecessary,Epaxalcanbeadministeredconcomitantlywithhumangamma

globulinatseparateinjectionsites.

Postexposurevaccination

Post-exposurevaccinationshouldbegivenaccordingtoofficialrecommendations.

4.3Contraindications

Hypersensitivitytoanyconstituentofthevaccine.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/02/2012 CRN 2111583 page number: 1

Incasesofacuteinfectiousdiseasewithfever,vaccinationwithEpaxalshouldbepostponed.

4.4Specialwarningsandprecautionsforuse

Aswithallinjectablevaccines,suitabletreatmentandmedicalsupervisionmustalwaysbepromptlyavailableincase

thereisarareanaphylacticreactionfollowingadministrationofthevaccine

InfluenzahaemagglutininascontainedinEpaxaldoesnotprovideanalternativeforinfluenzavaccination.

Immunodeficiencydisordersmayimpairtheimmuneresponse.Insplenectomisedpatients,theboostervaccination

shouldbeadministered1to6monthsafterprimaryimmunisation,owingtothelowertitresachievedinthesesubjects.

Thisalsoappliestoothercategoriesofimmunocompromisedpatients.

Experienceofthevaccinationofchildrenunder1yearofageandinadultsover60yearsofageislimited.

EpaxalmaycontaintracesofpolymyxinB

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Aprospectivelyplannedinteractionstudywasperformedwithyellowfevervaccinein55subjects.Inaddition,

concomitantvaccinationagainstyellowfever,typhoidfever,poliomyelitis,diphtheria,tetanus,meningococciA+C,as

wellasconcomitantmalariaprophylaxiswasstudiedaspartofatravelprophylaxisprogramin38subjects.

Aprospectivelyplannedinteractionstudywasperformedwithconcomitantwholecellinfluenzavaccinein163

subjects.ConcomitantadministrationdoesnotimpairimmuneresponsetohepatitisAorinfluenza.Inaddition,the

immuneresponsetohepatitisAisindependentofthelevelofinfluenzapre-immunisationtiters.

TheresultsindicatedthatEpaxalcanbeadministeredsimultaneouslywiththeabovevaccinesbutinseparatesyringes,

aswellaswithmalariaprophylaxis.

4.6Fertility,pregnancyandlactation

TherearenoadequatedatafromtheuseofEpaxalinpregnantwomen.TheeffectofEpaxalonfoetaldevelopmenthas

notbeenassessed.Aswithallinactivatedvaccines,noharmtothefoetusisexpected.Thevaccineshouldnotbegiven

topregnantwomenunlesstheriskofhepatitisAisincreased.

Whetherthevaccinepassesintothemilkofalactatingmotherisunknown.Breast-feedingwomenshoulduseEpaxal

withcaution.

4.7Effectsonabilitytodriveandusemachines

Thereisnoevidenceofanyvaccine-relatedreductioninreactiontimes.

However,theoccasionaloccurrenceofdizzinessorheadache,asalsoobservedoccasionallywithothervaccines,needs

tobeconsidered.

4.8Undesirableeffects

Possibleundesirableeffectsaremildinnatureandofshortduration.Thefrequenciesofadverseeventsprovidedbelow

arederivedfromclinicalstudies.Themostcommonadversereactionsarefatigue,injectionsitepainandheadache,

whichhavebeenshowninclinicalstudiestooccuratfrequenciesof6-32%,5–25%and6–25%respectively.

Verycommon(1/10):

Nervoussystemdisorders:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/02/2012 CRN 2111583 page number: 2

Generaldisordersandadministrationsiteconditions:

Fatigue,injectionsitepain.

Common(1/100and<1/10):

Metabolismandnutritiondisorders:

Anorexia

Gastrointestinaldisorders:

Diarrhoea,nausea

Generaldisordersandadministrationsiteconditions:

Injectionsitereaction,injectionsiteinduration,injectionsiteerythema,injectionsiteswelling,malaise,pyrexia

Uncommon(1/1000and<1/100):

Nervoussystemdisorders:

Dizziness

Skinandsubcutaneoustissuedisorders:

Rash,pruritus

Gastrointestinaldisorders:

Vomiting

Musculosceletalandconnectivetissuedisorders:

Arthralgia

Thedegreeofdizzinessisnotmorepronouncedascomparedtoothervaccinesincomparativetrials.

Atransientandmildriseinlevelsofliverenzymeswasobservedonsingleoccasionsatthetimeofvaccination.

Asobservedwithothervaccines,occasionalinflammatorydiseasesofthecentralandperipheralnervoussystemmay

occur,includingascendingparalysisuptorespiratoryparalysis,e.g.Guillain-BarréSyndrome.

Inveryrarecases,anaphylacticshockmayoccur.

4.9Overdose

Therearenoreportsofoverdosage.Inadvertentadministrationofaseconddoseof0.5mlEpaxalhasnoadverse

effects.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmaceuticalgroup:VaccineagainsthepatitisA

ATC-codeJ07BC02.

EpaxalcontainshepatitisAvirus,strainRG-SB,propagatedinMRC-5humandiploidcellsandinactivatedwith

formaldehyde.Theisolatedvirusparticlesareboundtoanewimmunoadjuvantconsistingofsynthetic,spherical

virosomescalledIRIVs(IRIV=ImmunopotentiatingReconstitutedInfluenzaVirosome).IRIVsconsistofadouble

membranecomposedofthephospholipidslecithin(phosphatidylcholine)andcephalin(phosphatidylethanolamine)and

ofviralphospholipids.Thedoublemembranecontainstheviralglycoproteinshaemagglutininandneuraminidase

whichhavebeenisolatedfrominactivatedinfluenzavirus(A/Singapore/6/86(H1N1)).

PresenceofantibodiesagainstthephospholipidoftheIRIVs(i.e.antibodiesagainstlecithinandcephalin)couldnotbe

detectedbyspecificenzyme-linkedimmuno-sorbentassays(ELISAs)inseraofsubjectvaccinatedandboostedwith

Epaxal.

AfteradministrationofEpaxal,thecomplexesofIRIVandhepatitisAvirusactivelybindtospecialreceptorson

macrophagesandarethenphagocytosed.Simultaneously,complexesofIRIVandhepatitisAvirusbindtoB

lymphocytes,whicharestimulatedtoproliferate.Themembranesofthephagocytosedliposomesfusewiththe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/02/2012 CRN 2111583 page number: 3

themacrophages.ThispotentiatesthepresentationofantigenandthestimulationofTlymphocyteswhich,inturn,

stimulatetheproductionofanti-hepatitisAantibodiesbytheBlymphocytes.

Immunogenicityandprotectiveefficacy

Vaccinationwithonedoseof0.5mlEpaxalresultsinprotectiveantibodytitres(min.20mIU/ml)in80-97%of

vaccinatedsubjectsafter2weeks,in92-100%after4weeks,andin78-100%after12months.Morethan1,600adults

andchildren(>10yearsofage),morethan320children(2-10yearsofage),61children(1-2yearsofage)and30

children(6months-1yearofage)havebeenfollowedinclinicaltrials.Thisincludesadouble-blind,placebocontrolled

fieldtrialin137children(18months-6yearsofage)inahighlyendemicareawhichshoweda96%protectionrate

againstacutehepatitisAinfection,basedonIgMandIgGantibodytitres,aswellasclinicalsigns.

Durationofprotection

Thefirstvaccinedosewith0.5mlEpaxalresultsinprotectiveantibodytitres(min.20mIU/ml)in78-100%of

vaccinatedsubjectsforatleast12months.Asecond(booster)vaccinationwith0.5mlEpaxalisestimatedtoprolong

theprotectiveefficacytoatleast30yearsforatleast95%ofthevaccinatedsubjectswhenconsideringanantibodytitre

thresholdof10mIU/mL.Thisestimateisbasedonmathematicalmodellingandextrapolationof10-12yearsfollowup

datafromsubjectsintheagerange16to45years.Ananalysisoftheseraof26adulthealthytravellers24to73years

oldwhoreceivedasecond(booster)dosebetween98to128monthsafterthefirstdosedemonstratedthatadelayup

to10yearsbetweenthefirstandsecondvaccinedosehadnoeffectonthemagnitudeoftheboosterresponse.However,

prescribers/physiciansshouldnotroutinelyadoptalongergapbetweenprimaryandsecondvaccinations(seesection

4.2).

5.2Pharmacokineticproperties

Pharmacokineticstudiesarenotrequiredforvaccines.

5.3Preclinicalsafetydata

Preclinicalsafetydatashownosignsoftoxicityafterasingledoseorafterrepeateddoses.Notissueintolerancewas

observedafteradministrationtorabbits.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

Waterforinjections

Forinformationontheadjuvant,seesection2.

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Storeinarefrigerator(2 o

C-8 o

Storeintheoriginalpackageinordertoprotectfromlight.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/02/2012 CRN 2111583 page number: 4

6.5Natureandcontentsofcontainer

Single-dosesyringe

0.5mLsuspensioninapre-filledsyringe(TypeIglass)withrubberplungerstopper(chlorobutyl)andwithneedleof

stainlesssteeltype304.

Packagesizes: 1x0.5mL

10x0.5mL

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Shakebeforeuse.Thesyringeshouldbecheckedvisuallyforintegrityandanyparticulatematterinthesyringe

content.Thevaccineshouldbeclearandcolourless.Anyunusedproductorwastematerialshouldbedisposedofin

accordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

CrucellItalyS.r.l.

ViaZambeletti25

20021Baranzate(MI)

Italy

8MARKETINGAUTHORISATIONNUMBER

PA0941/001/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21January2000

Dateoflastrenewal:25April2007

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/02/2012 CRN 2111583 page number: 5