DOTAREM

Main information

  • Trade name:
  • DOTAREM Solution for Injection 279.32 Mg/Ml
  • Dosage:
  • 279.32 Mg/Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOTAREM Solution for Injection 279.32 Mg/Ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0686/003/002A
  • Authorization date:
  • 10-06-1996
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dotarem279.32mg/mlSolutionforInjection,glassvials.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

*GadotericacidisformedinsituduringmanufacturefromDOTAandgadoliniumoxide.

Gadotericacid:1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’tetraaceticacid(orDOTA)gadoliniumcomplex

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Solutionforinjection.

Clearcolourlessorslightlyyellowsolution.

Osmolality: 1350mOsm/kg -1

Viscosityat20°C: 3.2mPa.s

Viscosityat37°C: 2.0mPa.s

6.5to8.0

4CLINICALPARTICULARS

4.1TherapeuticIndications

EnhancementofcontrastinMagneticResonanceImaging:

*MRIofthebrainandspine:

braintumours,tumoursofthespineandthesurroundingtissue,intervertebraldiskprolapse,infectiousdiseases.

*WholebodyMRI:

Abdominaldiseases:primaryandsecondaryhepatictumours,pancreatictumours.

Renaldiseases:renaltumoursandcysts,follow-upofkidneytransplants.

Pelvicdiseases:uterineandovariantumours.

Cardiacdiseases:follow-upofinfarctionandhearttransplants.

Breastdiseases:breasttumours,follow-upofimplants.

Osteo-articulardiseases:boneandsofttissuetumours.

*Vascularpathology(angiography)

4.2Posologyandmethodofadministration

Posology

EncephalicandspinalMRI:inmostcases,therecommendeddoseis0.1mmol/kgbodyweighti.e.0.2ml/kg,

whichissufficienttoprovidediagnosticallyadequatecontrast.Ifastrongclinicalsuspicionofalesionpersistsdespite

anormalMRIexamination,afurtherinjectionof0.2mmol/kg,i.e.0.4ml/kg,within30minutes,mayimprovetumour

characterisationandfacilitatetherapeuticdecision-making.

Nameofingredient Formulaperml

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diagnosticallyadequatecontrastinadultsandchildren.

Asecondinjectionof0.1mmol/kgmayalsobejustifiedforangiographyofcertainregions.

SpecialPopulations

Impairedrenalfunction

Dotaremshouldonlybeusedinpatientswithsevererenalimpairment(GFR<30ml/min/1.73m 2

)andinpatientsinthe

perioperativelivertransplantationperiodaftercarefulrisk/benefitassessmentandifthediagnosticinformationis

essentialandnotavailablewithnon-contrastenhancedMRI(seesection4.4).IfitisnecessarytouseDotarem,thedose

shouldnotexceed0.1mmol/kgbodyweight.Morethanonedoseshouldnotbeusedduringascan.Becauseofthelack

ofinformationonrepeatedadministration,Dotareminjectionsshouldnotberepeatedunlesstheintervalbetween

injectionsisatleast7days.

Elderly(aged65yearsandabove)

Nodosageadjustmentisconsiderednecessary.Cautionshouldbeexercisedinelderlypatients(seesection4.4).

Impairedhepaticfunction

Theadultdoseappliestothesepatients.Cautionisrecommended,especiallyinthecaseofperioperativeliver

transplantationperiod(seeaboveimpairedrenalfunction).

Pediatricpopulation

Neonatesupto4weeksofage,infantsupto1yearofageandchildren

Duetoimmaturerenalfunctioninneonatesupto4weeksofageandinfantsupto1yearofage,Dotaremshouldonly

beusedinthesepatientsaftercarefulconsiderationatadosenotexceeding0.1mmol/kgbodyweight.Morethanone

doseshouldnotbeusedduringascan.Becauseofthelackofinformationonrepeatedadministration,Dotarem

injectionsshouldnotberepeatedunlesstheintervalbetweeninjectionsisatleast7days.

Dotaremisnotrecommendedforangiographyinchildrenlessthan18yearsofageduetoinsufficientdataonefficacy

andsafetyinthisindication.

Methodofadministration

Theproductisintendedforintravenousadministrationonly.

4.3Contraindications

ContraindicationsrelatedtoMRI:

Patientswithpace-makers,vascularclips,infusionpumps,nervestimulators,cochlearimplants,orsuspectedintra-

corporealmetallicforeignbodies,particularlyintheeye.

4.4Specialwarningsandprecautionsforuse

Tobeadministeredintravenouslyonly.Intheeventofextravasation,localintolerancereactionsmaybeobserved

necessitatingshort-termlocaltreatment.

Neverinjectbythesub-arachnoidroute.Dotaremmustnotbeadministeredbysubarachnoid(orepidural)

injections.

Hypersensitivity

-Aswithothergadoliniumcontainingcontrastmedia,hypersensitivityreactionscanoccur(see”4.8Undesirable

effects“).Mostofthesereactionsappearwithinatleasthalfanhourafterinjectionofthecontrastmedium.However,as

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-Patientswithhypersensitivityorapreviousreactiontocontrastmediaareatincreasedriskofhavingaseverereaction.

Patientsshouldbequestionedforahistoryofallergy(e.g.hayfever,hives,asthma..)beforeanycontrastmediumis

injected.Insuchpatients,thedecisiontouseDotaremmustbemadeaftercarefulevaluationoftherisk-benefitratio.

-Asknownfromtheuseofiodinatedcontrastmedia,hypersensitivityreactionscanbeaggravatedinpatientsonbeta-

blockers,andparticularlyinthepresenceofbronchialasthma.Thesepatientsmayberefractorytostandardtreatment

ofhypersensitivityreactionswithbeta-agonists.

-Duringtheexamination,supervisionbyaphysicianisnecessary.Ifhypersensitivityreactionsoccur,administrationof

thecontrastmediummustbediscontinuedimmediatelyand-ifnecessary-specifictherapyinstituted.Avenousaccess

shouldthusbekeptduringtheentireexamination.Topermitimmediateemergencycountermeasures,appropriatedrugs

(e.g.epinephrineandantihistamines),anendotrachealtubeandarespiratorshouldbereadyathand.

Impairedrenalfunction

PriortoadministrationofDotarem,itisrecommendedthatallpatientsarescreenedforrenaldysfunctionby

obtaininglaboratorytests.

Therehavebeenreportsofnephrogenicsystemicfibrosis(NSF)associatedwithuseofsomegadolinium-containing

contrastagentsinpatientswithacuteorchronicsevererenalimpairment(GFR<30ml/min/1.73m 2

).Patients

undergoinglivertransplantationareatparticularrisksincetheincidenceofacuterenalfailureishighinthisgroup.As

thereisapossibilitythatNSFmayoccurwithDotarem,itshouldthereforeonlybeusedinpatientswithsevererenal

impairmentandinpatientsintheperioperativelivertransplantationperiodaftercarefulrisk/benefitassessmentandif

thediagnosticinformationisessentialandnotavailablewithnon-contrastenhancedMRI.

HaemodialysisshortlyafterDotaremadministrationmaybeusefulatremovingDotaremfromthebody.Thereisno

evidencetosupporttheinitiationofhaemodialysisforpreventionortreatmentofNSFinpatientsnotalready

undergoinghaemodialysis.

Pediatricpopulation

Neonatesandinfants

Duetoimmaturerenalfunctioninneonatesupto4weeksofageandinfantsupto1yearofage,Dotaremshouldonly

beusedinthesepatientsaftercarefulconsideration.

Elderly

Astherenalclearanceofgadotericacidmaybeimpairedintheelderly,itisparticularlyimportanttoscreenpatients

aged65yearsandolderforrenaldysfunction.

CNSdisorders

Likewithothergadoliniumcontainingcontrastagentsspecialprecautionisnecessaryinpatientswithalowthreshold

forseizures.Precautionarymeasuresshouldbetaken,e.g.closemonitoring.Allequipmentanddrugsnecessaryto

counteranyconvulsions,whichmayoccur,mustbemadereadyforusebeforehand.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Intheabsenceofspecificstudiesinthisarea,othersubstancesshouldnotbeco-administeredwithDOTAREM®.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenodatafromtheuseofgadotericacidinpregnantwomen.Animalstudiesdonotindicatedirectorindirect

harmfuleffectswithrespecttoreproductivetoxicity(seesection5.3).Dotaremshouldnotbeusedduringpregnancy

unlesstheclinicalconditionofthewomanrequiresuseofgadotericacid.

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Gadoliniumcontainingcontrastagentsareexcretedintobreastmilkinverysmallamounts(seesection5.3).Atclinical

doses,noeffectsontheinfantareanticipatedduetothesmallamountexcretedinmilkandpoorabsorptionfromthe

gut.Continuingordiscontinuingbreastfeedingforaperiodof24hoursafteradministrationofDotarem,shouldbeat

thediscretionofthedoctorandlactatingmother.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

SideeffectsinassociationwiththeuseofDotaremareusuallymildtomoderateinintensityandtransientinnature.A

sensationofheat,coldand/orpainattheinjectionsitearethemostfrequentlyobservedreactions.

Duringclinicaltrialsheadache,paresthesia,wereverycommonly(>10%)observedandnausea,vomitingandskin

reactionssuchaserythematousrashandprurituswerecommonlyobserved(<1/10->1%).

However,rareanaphylactoidreactionshavebeenreportedthatmaybeveryrarelysevere,life-threateningorhavea

fataloutcome,particularlyinpatientswithahistoryofallergy.

Theseallergoidreactionscanoccurirrespectiveoftheamountadministeredandthemodeofadministrationandmay

taketheformofoneormoreofthefollowingsymptoms:Angioedema,anaphylacticshock,circulatoryandcardiac

arrest,hypotension,larynxoedema,bronchospasm,laryngospasm,pulmonaryoedema,dyspnoea,stridor,coughing,

pruritus,rhinitis,sneezing,conjunctivitis,urticariaandrash.

Someofthesesymptomsmaybethefirstsignsofincipientstateofanaphylacticshock.Delayedcontrastmedium

reactionsarepossible(see“4.4.Specialwarnings...“).

Sincepost-marketingthefollowingadversereactionshavebeenveryrarelyreported(<0.01%):

Generaldisordersandadministrationsitesconditions:Chestpain,backpain,malaise,fever,sweatingincreased,

coldness,pallorandsyncope.

WhileinjectingDotaremintoveinswithasmalllumen,thereisthepossibilityofadverseeffectssuchasrednessand

swelling.

Apainfullocalreactionispossibleintheeventofdiffusionofthecontrastmediumoutsidethevein.Casesof

superficialphlebitis,possiblyrelatedtotheinjectiontechnique,havebeenrarelyreported.

Respiratory,thoracicandmediastinaldisorders:Respiratorydisorder.

Gastrointestinaldisorders:Abdominalpain.

Skinandsubcutaneoustissuedisorders:Eczema,erythema,urticaria,pruritusandrash.Isolatedcasesofnephrogenic

systemicfibrosis(NSF)havebeenreportedwithDotarem,mostofwhichwereinpatientsco-administeredother

gadolinium-containingcontrastagents(seesection4.4).

NervousSystemdisorders:Dizziness,generalizedconvulsions,tremor,fatigueandsomnolence.

Musculoskeletal,connectivetissueandbonedisorders:Musclecramps,muscleweakness.

4.9Overdose

ThereisnoexperiencetodateofoverdosewithDotarem.

Dotaremcanberemovedbyhaemodialysis.Howeverthereisnoevidencethathaemodialysisissuitableforprevention

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

GadotericacidhasparamagneticpropertieswhichincreasecontrastenhancementinMRI.Ithasnospecific

pharmacodynamicactivityandishighlybiologicallyinert.

5.2Pharmacokineticproperties

Afterintravenousinjection,Gd-DOTAisdistributedintheextracellularfluidsofthebody.Itdoesnotbindwith

plasmaticalbuminanddoesnotcrossthenormalblood-brainbarrier.

Inpatientswithnormalrenalfunction,theplasmatichalf-lifeisapproximately90minutes.Itiseliminatedby

glomerularfiltrationinunchangedform.Plasmaticclearanceisretardedintheeventofrenalfailure.

Inanimals,Gd-DOTAexcretioninmilkislowandcrossingoftheplacentalbarrierisslow.

Todatenodataexistconcerningkineticsintheelderly,children,pregnantorlactatingwomenorthehepatically

impaired.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityortoxicitytoreproduction.

TheacutetoxicityofDotareminjectedintravenously(2ml/min)wasstudiedinmice(atdosesbetween16and26

ml/kg)andinrats(atadoseof25ml/kg).Manifestationsobservedwereconvulsivesignsandtransientrespiratory

disorders.Deathsoccurredinthetwostudies,fromadoseof18ml/kgupwardsinmice.Necropsyrevealeda

haemorrhagicappearanceinthelungsandsometimesinthekidney.Inanotherspecificstudyinmiceaminor

proconvulsiveeffectwasobservedafterIVadministrationofadoseof4ml/kg.

TheadministrationofGd-DOTAintheratsandindogsadailydosesupto3ml/kg,i.e.15timesthedoselaiddownin

clinicalconditionsandfor28dayscausednoothereffectthanareversiblevacuolisationoftheproximaltubularcellsof

thekidney.

Dotaremisnontoxicforgestatingfemales,nonembryo-toxicandnon-teratogenicforthefoetus.Nopriorperiand

post-nataltoxicityandfertilitystudieshavebeencarriedout.

Dotaremshowednocytotoxicormutagenicactionintheinvivoandinvitrotestsused.

Animalstudieshaveshownnegligible(lessthan1%oftheadministereddose)secretionofgadotericacidinmaternal

milk.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Meglumine

Waterforinjections

6.2Incompatibilities

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6.3ShelfLife

3years.

Theproductisforsingleuseonlyandshouldbeusedimmediatelyafterbeingdrawnupintoasyringefor

administration.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

TypeII,colourlessglassvialsof10ml(filledto5and10ml)and20ml(filledto15and20ml)withelastomer

closures.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forsingleuseonly.Discardanyunusedsolution.

Bottle:prepareasyringeandneedle.Raisetheplasticdisk.Puncturethelatterwiththeneedleaftercleaningthe

stopperwithaclothsoakedinalcohol.Removethequantityofproductnecessaryfortheexaminationandinjectit

intravenously.

Thepeel-offtrackinglabelonthevialsshouldbestuckontothepatientrecordtoenableaccuraterecordingofthe

gadoliniumcontrastagentused.Thedoseusedshouldalsoberecorded.

7MARKETINGAUTHORISATIONHOLDER

GUERBET

B.P.57400

F-95943ROISSYCdGCedex

France

8MARKETINGAUTHORISATIONNUMBER

PA0686/003/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 10June1996

Dateoflastrenewal: 10June2006

10DATEOFREVISIONOFTHETEXT

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