ENDOREM

Main information

  • Trade name:
  • ENDOREM Concentrate for Susp for Inf 11.2 Base mg/ ml
  • Dosage:
  • 11.2 Base mg/ ml
  • Pharmaceutical form:
  • Concentrate for Susp for Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ENDOREM Concentrate for Susp for Inf 11.2 Base mg/ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0686/001/001
  • Authorization date:
  • 14-03-1995
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0686/001/001

CaseNo:2058562

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

Guerbet

BP57400,95943RoissyCdGcedex,France

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

ENDOREM,11.2mgFe/mL,concentrateforsuspensionforinfusion

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom23/08/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 05/09/2009 CRN 2058562 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ENDOREM,11.2mgFe/mL,concentrateforsuspensionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

-Per1mL:

Superparamagneticironoxidenanoparticles 15.8mg

correspondingtoanironcontent 11.2mg

Afterdilutionin100mLof5%isotonicglucosesolution,1mLcontains0.112mgofiron

-Perampoule(8mL):

Superparamagneticironoxidenanoparticles 126.500mg

correspondingtoanironcontent 89.600mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Concentrateforsuspensionforinfusion.

Darkbrowntoblackdispersionofironoxidenanoparticles

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thisproductisfordiagnosticuseonly.

DetectionoflivertumoursbyMRI(MagneticResonanceImaging).

4.2Posologyandmethodofadministration

Therecommendedsingledoseis15µmolesFe/kgofbodyweight,i.e.0.075mL/kgbodyweight.

Theproductmustbeadministeredbyslowinfusionforaperiodofatleast30minutes,afterdilutionin100mLof5%

isotonicglucosesolution.

Goodpracticeofemergencyresuscitationtechniquesisessential,andtheappropriatemedicinalproductsand

equipmentmustbeavailable.

Theimagingisoptimalbetween30minutesand6hoursaftertheadministrationofENDOREM.

Theradiologistwillchoosethemosteffectivemethodofimaging.

Dosageremainsunchangedinsubjectswithliverorrenalinsufficiency.

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4.3Contraindications

Hypersensitivitytoactiveingredient,Dextranortoanytheotherexcipients

4.4Specialwarningsandprecautionsforuse

Neveradministertheproductwithoutfirstdilutingit.

SincetheriskofhypotensionisdecreasedwhentheproductisadministeredbyslowIVinjection,ENDOREM

shouldonlybeadministeredbyslowIVinjection.

Hypotensionmayneverthelessoccurinrareinstances.

Particularattentionmustbepaidtothequalityoftheintravenousinjectionsincelocalirritationfollowing

paravenousadministrationmayoccur.

AdministrationofENDOREMmustnotberepeatedwithinthe14daysfollowingtheexamination,astheactive

ingredient(ironoxide)altersthebiologicalparametersrelatedtoironmetabolismduringthisperiod.

Intheeventoflumbarpain,chestpain,hypotension,ordyspnoea,theinfusionmustbestoppedandthepatientkept

undermedicalsurveillanceuntilthesymptomsdisappear.TheadministrationofENDOREMcanthenbecontinued

undermedicalsupervisionbyreducingtheinfusionrateandspreadingtheinfusionoveratleast60minutes.

AlthoughtheDextrancontainedinENDOREMhasalowmolecularweight,itsadministrationmayinduce

immediateandsevereanaphylactoidreactions.Forthisreason,particularattentionmustbepaidduringthe

administrationoftheproduct(oxygenequipment,adrenaline,antihistaminicmedicationandcorticosteroidsmustbe

availableforimmediatetreatmentofsuchreactions).

TheuseofENDOREMisnotjustifiedinpatientswithhaemochromatosis,duetothenaturalsignalextinctioninthe

liverofthesepatients.

Incaseofblooddiseaseassociatedwithsplenomegaly,thediagnosticefficacymaybereduced.

Theincidenceofadversedrugreactions,particularlylumbarpain,isincreasedforcirrhoticpatients:careisurged

duringtheadministrationinsuchpatients.

Thesafetyandefficacyinpatientsunder18yearsoldhavenotbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Intheabsenceofspecificstudies,noothersubstancesshouldbemixedwithENDOREM.

4.6Pregnancyandlactation

Pregnancy:

StudiesperformedinanimaldemonstratedateratogeniceffectofENDOREMinrabbitatdoses160foldhigherthan

therecommendedtherapeuticdose.

Therearecurrentlynohumanclinicaldatarelevantenoughtoenabletheassessmentofapossiblemalformativeor

foetotoxicriskassociatedwiththeadministrationofENDOREMduringpregnancy.

Therefore,theuseofENDOREMisnotrecommendedduringpregnancy.Thisshouldnotleadtothesystematic

advisingofaninducedabortioninthecaseofinadvertentexposureduringpregnancy,buttoacarefulattitudewith

adaptedprenatalmonitoring.

Lactation:

NodataareavailableonthepassageofENDOREMintobreastmilk.Therefore,breastfeedingshouldbeinterrupted

forafewdaysfollowingEndoremadministration.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

MostsideeffectsinassociationwithENDOREMaretransient.

Thefrequencyoftheadverseeffectsreportedisnotknown:

Immunesystemdisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Anaphylactoidreactionsmayoccur:hypotension,dyspnoea,pruritus,urticaria,facialoedema,skinrash,anaphylactic

shockandbronchospasm.

Nervoussystemdisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Headache

Cardiacdisorders:Notknown(cannotbeestimatedfromtheavailabledata)Tachycardia

Vasculardisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Bloodpressurefluctuation,flushing

Respiratory,thoracicandmediastinaldisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Dyspnoea

Gastrointestinaldisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Nausea,vomiting,abdominalpain.

Musculoskeletalandconnectivetissuedisorders:Notknown(cannotbeestimatedfromtheavailabledata)

Backpain(especiallylumbarpain).

Generaldisordersandadministrationsiteconditions:Notknown(cannotbeestimatedfromtheavailabledata)

Chestpain,feelinghot,chills,hyperhidrosis.

4.9Overdose

Incaseofoverdosage(forexampleaccidentalbolusinjectionofthewholeampoule),vitalsignsshouldbemonitored.

Symptomatictreatmentmaybegivenifnecessary.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:V08CB03superparamagneticironoxidenanoparticles(superparamagneticcontrastagentforMRI).

Thecrystallineconfigurationofthesolidironoxidegivestheproductitssuperparamagneticproperties.Themagnetic

fielddisturbancesgeneratedaroundeachparticlereduceMRIsignalintensityinthetissueswhichcontainit.

Undertherecommendedclinicalconditions,theproducthasshownasatisfactorytoleranceprofileinanimalsandin

humansintermsofeffectstothecardiovascularsystem,thekidneyorthelung.

5.2Pharmacokineticproperties

Pharmacokineticstudieshaveidentifiedtheliverastheorganshowingthemostuptakeoftheproduct.After

intravenousinjection,thebloodisrapidlyclearedoftheproductbytheliver.Theironoxideparticlesdisappearfrom

thestorageorgans(liver,spleen,etc.)overamatterofdays,whichindicatesthattheproductismetabolisedandthe

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5.3Preclinicalsafetydata

Inthepreclinicalplan,ENDOREMhasbeenfoundtohavelowtoxicityaftersingleandrepeateddoseadministration

exceptforeffectsattheinjectionsite.

Incaseofaccidentalperivascularadministration,alocaleffecthasbeenobservedsuchaserythemaandskin

pigmentation,whicheventuallyrevertedtonormal.Thereisnospecificdataconcerningintraarteriallocaltolerance.In

rabbits,theproductwasteratogenicatadoseof11.2mgFe/kgperdayinducingparticularlymalformationsofthe

heart,skull,brain,etc.Inrats,dailydosesof11.2mgFe/kgperdaycausednomalformations.Higherdosesweretoxic

tothemotheranddecreasedgrowthrates(foetusesandneonatesoflowerweight).Nofertilitystudiesorperi-andpost-

nataltoxicitystudieshavebeencarriedout.Theproductwasnotfoundtobemutagenicintheinvivoandinvitrotests

used.Thepassageoftheproductintomilkhasnotbeenstudied.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Dextran

Citricacid

Mannitol

Waterforinjections

6.2Incompatibilities

Basedonthephysico-chemicalstudiescarriedout,ENDOREMmustnotbedilutedwitha0.9%sodiumchloride

solution.

6.3ShelfLife

-Shelflifeofthemedicinalproductaspackagedforsale:3years.

-Shelflifeafterdilution:Chemicalandphysicalin-usestabilityhasbeendemonstratedfor7daysbetween+15°Cand

+25°C.Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-use

storagetimesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24

hoursat2to8°C,unlessdilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Donotfreeze.

6.5Natureandcontentsofcontainer

8mLin10mL-ampoule(typeIneutralglass)accompaniedwithaninfusionset(PVC)includinga5µfilter

(polyamide)andasyringe(polypropylene)withaneedle(stainlesssteel)forinfusionpreparation.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Beforeuse,theampoulemustbeinvertedseveraltimes.

Theproductmustbedilutedbeforeuse.Forsingleuseonly.Discardanyunusedsolution.

Usingthesyringeandneedle(suppliedwiththeampoule),thedosecorrespondingtothepatient’sweightmustbe

dilutedusingaseptictechniquein100mLofa5%glucosesolutionexclusivelybeforeslowintravenousadministration

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Sincethecolouroftheproductpreventsvisualinspection,thefilterguaranteestheabsenceoflargeparticlesduringthe

infusion.

7MARKETINGAUTHORISATIONHOLDER

GUERBET

BP57400

95943RoissyCdGCedex

France

8MARKETINGAUTHORISATIONNUMBER

PA686/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14March1995

Dateoflastrenewal:23August2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 05/09/2009 CRN 2058562 page number: 6