ABELCET

Main information

  • Trade name:
  • ABELCET Suspension for Injection 5 mg/ml
  • Dosage:
  • 5 mg/ml
  • Pharmaceutical form:
  • Suspension for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ABELCET Suspension for Injection 5 mg/ml
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0827/005/001
  • Authorization date:
  • 21-05-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Abelcet5mg/mlConcentrateforSuspensionforInfusion.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

AmphotericinBLiquidComplex.Eachmlcontains5mgAmphotericinB.

Eachvialcontains20ml(100mg,100,000IUofamphotericinB)whichmustbedilutedbeforeintravenousinfusion.

Abelcetcontains3.6mg/mlofsodium(0.156mmol);thisrepresents71.8mgofsodium(3.12mmol)per20mlvial.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

ConcentrateforsuspensionforInfusion

Abelcetisasterile,pyrogenfreeyellowsuspension.

4CLINICALPARTICULARS

4.1TherapeuticIndications

First-linetreatmentofaspergillosis

Abelcetisindicatedforthefirst-linetreatmentofaspergillosisinimmunocompromisedandimmunocompetentpatients.

First-linetreatmentofsystemiccandidalinfections

Abelcetisindicatedforfirst-linetreatmentofsystemiccandidalinfectionsinneutropenicandnon-neutropenicpatients.

Inarandomised,comparativestudyagainstconventionalamphotericinB,thetwotreatmentswereequallyefficacious

intermsofclinicalimprovementandintheeradicationoffungalpathogens.However,acomparisonofpatients’renal

functionshowedthatAbelcetwassignificantlybettertoleratedthanconventionalamphotericinB.

AstatisticallysignificantdelayindeteriorationofrenalfunctionwasobservedintheAbelcetpatientscomparedto

thosetreatedwithconventionalamphotericinB.

Firstlinetreatmentofcryptococcalmeningitis

Abelcetisalsoindicatedforfirstlinetreatmentofcryptococcalmeningitisandsystemiccryptococcosisinpatientswith

acquiredimmunodeficiencysyndrome(AIDS).InacomparativeclinicalstudyinAIDSpatientswithcryptococcal

meningitis,theefficacyofAbelcetwascomparabletothatofconventionalamphotericinB.However,thetoxicity,

particularlythenephrotoxicity,ofAbelcetwasmarkedlyless,allowingadministrationofconsiderablyhigherdosesfor

aprolongedperiod.

Severesystemicfungalinfections

Abelcetisindicatedforthetreatmentofseveresystemicfungalinfectionsinpatientswhohavenotrespondedto

conventionalamphotericinBorothersystemicantifungalagents,inthosewhohaverenalimpairmentorother

contraindicationstoconventionalamphotericinB,orinpatientswhohavedevelopedamphotericinBnephrotoxicity.

Inanopen-labelemergencyusestudyofAbelcetinthesepatientgroups,74/111(67%)patientsexperiencedclinical

cureorimprovement,andin37/67(55%)wherefungalpathogenswereisolated,mycologicaleradicationwas

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FungalinfectionsthathaverespondedtoAbelcettreatmentincludesystemiccandidiasis,aspergillosis,cryptococcal

meningitisanddisseminatedcryptococcosis,fusariosis,zygomycosis,blastomycosisandcoccidioidomycosis.Abelcet

mayalsobeeffectiveinthetreatmentofhistoplasmosis,chronicmycetoma,pseudallescheriasis,sporotrichosisand

trichosporosis.

Abelcethasbeenusedsuccessfullytotreatsystemicfungalinfectionsinpatientswhoareseverelyneutropenicasa

consequenceofhaematologicmalignancyortheuseofcytotoxicorimmunosuppressivedrugs.

4.2Posologyandmethodofadministration

Abelcetisasterile,pyrogen-freesuspensiontobedilutedforintravenousinfusiononly.Therecommendeddailydose

is5.0mg/kggivenasasingleinfusion.

Abelcetshouldbeadministeredbyintravenousinfusionatarateof2.5mg/kg/hr.Whencommencingtreatmentwith

Abelcetforthefirsttimeitisrecommendedtoadministeratestdoseimmediatelypriortothefirstinfusion.Thefirst

infusionshouldbepreparedaccordingtotheinstructionsthenoveraperiodof15minutesapprox.1mgoftheinfusion

shouldbeadministeredtothepatient.Afterthisamounthasbeenadministeredtheinfusionshouldbestoppedandthe

patientobservedcarefullyfor30minutes.Ifthepatientshowsnosignsofhypersensitivitytheinfusionmaybe

continued.AsforusewithallamphotericinBproducts,facilitiesforresuscitationshouldbereadilyathandwhen

administeredAbelcet®forthefirsttime,duetothepossibleoccurrenceofanaphylactoidreactions.Dataarepresently

insufficienttodefinethetotaldoseandtreatmentdurationnecessaryforsuccessfultreatment.However,forsevere

systemicinfectionstreatmentdurationshouldbeatleast14days.Abelcethasbeenadministeredforaslongas11

months,andcumulativedoseshavebeenashighas56.6gwithoutsignificanttoxicity.

Anin-linefiltermaybeusedforintravenousinfusionofAbelcet.Themeanporediameterofthefiltershouldnotbe

lessthan15.0microns.

Useindiabeticpatients

Abelcetcanbeadministeredtodiabeticpatientsatdosescomparabletotherecommendeddoseonabodyweightbasis.

Paediatricuse

Systemicfungalinfectionsinchildren(rangingfrom1monthto16yearsofage)havebeentreatedsuccessfullywith

Abelcetatdosescomparabletotherecommendedadultdoseonabodyweightbasis.

Useinelderlypatients

SystemicfungalinfectionsinelderlypatientshavebeentreatedsuccessfullywithAbelcetatdosescomparabletothe

recommendedadultdoseonabodyweightbasis.

Useinpatientswithseriousconcomitantillnesses,renalimpairmentorhepaticinsufficiency

Therecommendeddoseis5.0mg/kg/dayinthesepatients.Seesection4.4Specialwarningsandprecautionsforuse.

Useinrenaldialysispatientsandinpatientswithrenalfailure

Abelcetshouldbeadministeredtorenaldialysispatientsonlyafterthecompletionofdialysis.Abelcetmaybegivento

patientswithrenalfailureattherecommendedadultdose.

4.3Contraindications

Abelcetiscontraindicatedinpatientswithknownhypersensitivitytoanyofitsconstituents,unlessintheopinionofthe

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4.4Specialwarningsandprecautionsforuse

Adversereactionsmayoccur,andarelikelytobesimilartothoseassociatedwithconventionalamphotericinB.To

detectidiosyncraticanaphylacticreactionsandtominimisethedoseadministeredifsuchareactionoccurs,atestdose

shouldbeadministeredinitially.Particularattentionshouldbepaidtopatientsreceivingnephrotoxicdrugs

concomitantlywithAbelcet.Renalfunctionshouldbecloselymonitoredinthesepatients.

SinceAbelcetisapotentiallynephrotoxicdrug,monitoringofrenalfunctionshouldbeperformedbeforeinitiating

treatmentinpatientswithpre-existingrenaldiseaseorwhohavealreadyexperiencedrenalfailureandregularlyduring

therapy.

Serumpotassiumandmagnesiumlevelsshouldbemonitoredregularly.

AnalysisofrenalfunctiontestresultshasshownthatduringAbelcettreatmentrenalfunctionremainsstableor

improves,ratherthandeclines.Inpatientswithserioussystemicfungalinfectionsandcontraindicationsto

conventionalamphotericinB,themeanserumcreatininedecreasedfrom174.4µmol/latbaselineto130.0µmol/lafter

6weeksoftreatment.Inthesubpopulationofcaseswithbaselineserumcreatininelevelsof221.0µmol/lorgreater,

themeanserumcreatininedecreasedfrom341.2µmol/latthestartoftreatmentto192.7µmol/lafter6weeksof

treatment.RenaldysfunctionthatdevelopedduringtreatmentwithconventionalamphotericinBhasbeenshownto

stabilizeorimproveduringsubsequentAbelcettreatment.

Aswithalltreatmentsinthiscase,hepaticimpairmentmayoccur.Hepaticmonitoringisrecommended.However,

patientswithconcurrenthepaticimpairmentduetoinfection,graftversus-hostdisease,otherliverdiseaseor

administrationofhepatotoxicdrugshavebeensuccessfullytreatedwithAbelcet.

Abelcethasbeenusedsuccessfullytotreatsystemicfungalinfectionsinpatientswhoareseverelyneutropenicasa

consequenceofhaematologicmalignancyortheuseofcytotoxicorimmunosuppressivedrugs.

InfusionHypersensitivityReactions

Premedicationmaybeconsideredforthepreventionofinfusionrelatedreactions(seesection4.8).Paracetamol,

diphenydramine,pethidine,and/orhydrocortisonehavebeenreportedassuccessfulinthepreventionandtreatmentof

suchreactions.

Systemicfungalinfections

Abelcetshouldnotbeusedfortreatmentofcommonorsuperficial,clinicallyunapparentfungalinfectionsthatare

detectableonlybypositiveskinorserologictests.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

TheinteractionofAbelcetwithotherdrugshasnotbeenstudiedtodate.Patientsrequiringconcomitantmedications

shouldbecloselyobserved.Specifically,inpatientsreceivingnephrotoxicdrugs,renalfunctionshouldbeclosely

monitored.ConventionalamphotericinBhasbeenreportedtointeractwithantineoplasticagents,corticosteroidsand

corticotropin(ACTH),digitalisglycosides.flucytosineandskeletalmusclerelaxants.

AcutepulmonarytoxicityhasbeenreportedinpatientsreceivingintravenousconventionalamphotericinBand

leukocytetransfusions.ItisnotrecommendedtoadministerAbelcetwithleukocytetransfusions.

Indogs,exacerbatedmyelotoxicityandnephrotoxicitywereobservedwhenAbelcet(1.5or5.0mg/kg/day)was

administeredconcomitantlywithzidovudinefor30days.Thispossibleinteractionhasnotbeeninvestigatedin

humans.Ifconcomitanttreatmentwithbothagentsisrequired,renalandhaematologicfunctionshouldbeclosely

monitored.

PreliminarydatasuggestthatpatientsreceivingAbelcetconcomitantlywithhighdosecyclosporinexperiencean

increaseinserumcreatinine.Thedataalsoindicatethattheincreaseinserumcreatinineiscausedbycyclosporinand

notAbelcet.Untilfurtherinformationisavailable,renalfunctionshouldbemonitoredcloselyinpatientswhoreceive

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4.6Fertility,pregnancyandlactation

ConventionalamphotericinBhasbeenusedsuccessfullytotreatsystemicfungalinfectionsinpregnantwomenwithno

obviouseffectsonthefoetus,butonlyasmallnumberofcaseshavebeenreported.Reproductivetoxicitystudiesof

Abelcetinratsandrabbitsshowednoevidenceofembryotoxicity,foetotoxicityorteratogenicity.However,safetyfor

useinpregnantwomenhasnotbeenestablishedforAbelcet.Therefore,Abelcetshouldbeadministeredtopregnant

womenonlyforlife-threateningdiseasewhenthelikelybenefitexceedstherisktothemotherandfoetus.

ItisunknownwhetherAbelcetpassesintobreastmilk.Adecisiononwhethertocontinue/discontinuenursingor

whethertocontinue/discontinueAbelcetshouldbemadetakingintoaccountthebenefitofbreast-feedingtothechild

andthebenefitofAbelcettothewoman.

4.7Effectsonabilitytodriveandusemachines

TheeffectsofAbelcetontheabilitytodriveand/orusemachineshavenotbeeninvestigated.Someoftheundesirable

effectsofAbelcetpresentedinSection4.8mayimpacttheabilitytodriveandusemachines.However,theclinical

conditionofpatientswhorequireAbelcetgenerallyprecludesdrivingoroperatingmachinery.

4.8Undesirableeffects

Themostcommonclinicaladversereactionsinrandomisedcontrolledandopenlabelclinicaltrialshavebeenchills,

increasedcreatinine,pyrexia,hypokalaemia,nauseaandvomitingatlevelsof16,13,10,9,7and6%respectively.

ThefollowingundesirableeffectshavebeenreportedwithAbelcetduringclinicaltrialsand/orpost-marketinguse.

Theincidenceisbasedonanalysisfrompooledclinicaltrialsof709Abelcettreatedpatients(556fromemergencyuse

studiesand153fromarandomisedcontrolledtrialincandidiasis).

AdversereactionsarelistedbelowasMedDRApreferredtermbysystemorganclassandfrequency.Frequenciesare

definedas:verycommon(>1/10),common(1/100and<1/10),uncommon(1/1000and<1/100)andnotknown(can

notbeestimatedfromtheavailabledata).

SystemOrgan

class Adversereaction Frequency

Infectionsandinfestations

Infection,Sepsis Uncommon

Bloodandlymphaticsystemdisorders

Anaemia,Leukopenia,Thrombocytopenia Common

Coagulopathy,Eosinophilia,Haemolyticanaemia,

Leukaemoidreaction,Pancytopenia Uncommon

Immunesystemdisorders

Anaphylactoidreaction,Hypersensitivity,Transplant

rejection Uncommon

Metabolismandnutritiondisorders

Acidosis,Hyperbilirubinaemia,Hypokalaemia,

Hypomagnesaemia,Electrolyteimbalanceincluding

hyperkalaemia,disturbanceofserumcalcium,

chloride,phosphate. Common

Alkalosis,Anorexia,Hyperlipidaemia,

Hypernatraemia,Hyperuricaemia Uncommon

Psychiatricdisorders

Anxiety,Nervousness Uncommon

Nervoussystemdisorders

Headache,Tremor Common

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Convulsion,Dizziness,Hypertonia,Hypoaesthesia,

Neuropathy,Nuchalrigidity,Paraesthesia,Peroneal

nervepalsy,Somnolence,Speechdisorder,Stupor,

Thinkingabnormal

Earandlabyrinthdisorders

Deafness,Tinnitus Uncommon

Cardiacdisorders

Tachycardia,ArrythmiasincludingSupraventricular

tachycardia,Bradycardia,Atrialfibrillation,

AtrioventricularblockseconddegreeandVentricular

extrasystoles Common

Cardiacfailure,Cyanosis,Palpitations,Cardiacarrest Uncommon

Vasculardisorders

Hypertension,Hypotension Common

Angiopathy,Pallor,Phlebitis,Pulmonaryembolism,

Shock,Vasodilatation,Venoocclusiveliverdisease Uncommon

Respiratory,thoracicandmediastinaldisorders

Asthma,Dyspnoea,Hyperventilation,Respiratory

disorder Common

Cough,Hypoxia,Pulmonaryoedema,Respiratory

failure,Rhinitis Uncommon

Bronchospasm Notknown

Gastrointestinaldisorders

Diarrhoea,Nausea,Vomiting,Abdominalpain Common

Abnormalfaeces,Constipation,Drymouth,

Dysgeusia,Dyspepsia,Dysphagia,Flatulence,

Gastrointestinalhaemorrhageincludingrectaland

gingival,Pancreatitis,Stomatitis,Tongue

discolouration Uncommon

Hepatobiliarydisorders

Liverfunctiontestsabnormal Common

Cholelithiasis,Hepatitis,Hepatocellulardamage,

Hepatorenalsyndrome,Jaundice Uncommon

Skinandsubcutaneoustissuedisorders

Rash Common

Ecchymosis,Hyperhidrosis,Petechiae,Pruritus,Rash

maculo-papular,Skindiscolouration,Skinulcer,

Urticaria Uncommon

Dermatitisexfoliative Notknown

Musculoskeletal,connectivetissueandbonedisorders

Arthalgia,Bonepain,Musclespasms,Myalgia Uncommon

Renalandurinarydisorders

Renalimpairmentincludingrenalfailure Common

Anuria,Haematuria,Nephropathytoxic,Oliguria,

Urineabnormality Uncommon

Hyposthenuria,Renaltubularacidosis Notknown

Generaldisordersandadministrationsiteconditions

Chills,Pyrexia Verycommon

Asthenia,Generalisedoedema Common

Backpain,Chestpain,Injectionsite

hypersensitivity,Malaise,Multi-organfailure,

Injectionsitereaction Uncommon

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Afurther178patientsfromclinicaltrialsinvolvingnon-homogenouspatientpopulationsyieldedanadversereaction

profilesimilartothatdescribedabove.

Infusionrelatedreactions(suchaschillsandpyrexia)recordedfollowingtheadministrationofAbelcethavegenerally

beenmoderate,andhavemainlybeenrecordedduringthefirst2daysofadministration.Thesereactionsmaybe

relievedusingappropriatepre-medication,seeSection4.4SpecialWarningsandPrecautionsforUse.

Infusionhypersensitivityreactionshavebeenassociatedwithabdominalpain,nauseas,vomiting,myalgia,pruritus,

maculopularrash,fever,hypotension,shock,bronchospasm,respiratoryfailure.

Renaltubularacidosishasbeenreportedincludinghyposthenuriaandelectrolyteimbalancesuchasincreased

potassiumanddecreasedmagnesium.

ThemajorityofadversereactionsseencommonlywithAbelcet(i.e.inthe"verycommon"and"common"frequency

categories)havealsobeenobservedwithotherdrugproductsinthisclass.

AbnormalliverfunctiontestshavebeenreportedwithAbelcetandotheramphotericinBproducts.Althoughother

factorssuchasinfection,hyperalimentation,concomitanthepatotoxicdrugsandgraft-versus-hostdiseasemaybe

contributory,acausalrelationshipwithAbelcetcannotbeexcluded.Inrandomised,controlled,comparativestudies

againstconventionalamphotericinB,patientswithhepaticdysfunctionatentrytothestudieshadrelativelyless

deteriorationinhepaticimpairmentintheAbelcetarmscomparedtopatientstreatedwithconventionalamphotericinB.

Datafromarandomised,controlled,comparativestudydemonstratedthatrenalfunctionremainedstableinthe

majorityofpatientswhohadnormalrenalfunctionandwhohadnotpreviouslybeentreatedwithconventional

amphotericinB.

RenaldysfunctionthatdevelopedduringtreatmentwithconventionalamphotericinBhasbeenshowntostabilizeor

improveduringsubsequentAbelcettreatment.Diminishedrenalfunctionresultedinthewithdrawalof15%ofpatients

treatedwithconventionalamphotericinBascomparedto6%ofpatientstreatedwithAbelcetinrandomised

comparativestudies.Anincreaseinserumcreatinineresultedindrugdiscontinuationmorethanfourtimesas

frequentlyintheconventionalamphotericinBpatients(10%)thenintheAbelcettreatedpatients(2%).

Inanopenlabelstudyincludingpaediatricpatients,theadversereactionprofilereportedwassimilartothatinadults

withchillsandpyrexiabeingthemostcommonlyobservedreactions.

Inarandomisedcontrolledstudyincludingpatients65years,theadversereactionprofilewassimilartothatseenin

youngeradults,withtheimportantexceptionsthatincreasesinserumcreatinineanddyspnoeawerereportedforboth

Bloodcreatinineincreased Verycommon

Bloodalkalinephosphataseincreased,Bloodurea

increased Common

Alanineaminotransferaseincreased,Aspartate

aminotransferaseincreased,Bloodcreatine

phosphokinaseincreased,Bloodlactate

dehydrogenaseincreased,Creatininerenalclearance

decreased,Electrocardiogramabnormal,Pulmonary

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4.9Overdose

Dosagesupto10mg/kg/dayhavebeenadministeredinclinicalstudieswithnoapparentdose-dependenttoxicity.

InstancesofoverdosereportedwithAbelcethavebeenconsistentwiththosereportedinclinicaltrialswithtreatmentat

standarddoses(seesection4.8).Inaddition,seizuresandbradycardiawereexperiencedbyonepaediatricpatientwho

receivedadoseof25mg/kg.

Incaseofoverdose,thestatusofthepatient(inparticularthecardio-pulmonary,renalandhepaticfunctionaswellas

thebloodcountandserumelectrolytes)shouldbemonitoredandsupportivemeasuresinitiated.Nospecificantidoteto

amphotericinBisknown.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Abelcetconsistsoftheantifungalagent,amphotericinB,complexedtotwophospholipids.AmphotericinBisa

macrocyclic,polyene,broad-spectrumantifungalantibioticproducedbyStreptomycesnodosus.Thelipophilicmoiety

ofamphotericinBallowsmoleculesofthedrugtobecomplexedinaribbon-likestructurewiththephospholipids.

ATCCode

J02AA01

Mechanismofaction

AmphotericinB,theactiveantifungalagentinAbelcet,maybefungistaticorfungicidal,dependingonits

concentrationandonfungalsusceptibility.Thedrugprobablyactsbybindingtoergosterolinthefungalcell

membranecausingsubsequentmembranedamage.Asaresult,cellcontentsleakfromthefungalcell,and,ultimately,

celldeathoccurs.

Bindingofthedrugtosterolsinhumancellmembranesmayresultintoxicity,althoughamphotericinBhasgreater

affinityforfungalergosterolthanforthecholesterolofhumancells.

Microbiologicalactivity

AmphotericinBisactiveagainstmanyfungalpathogensinvitro,includingCandidaspp.,Cryptococcusneoformans,

Aspergillusspp.,Mucorspp.,Sporothrixschenckii,Blastomycesdermatitidis,CoccidioidesimmitisandHistoplasma

capsulatum.MoststrainsareinhibitedbyamphotericinBconcentrationsof0.03-1.0g/ml.AmphotericinBhaslittle

ornoactivityagainstbacteriaorviruses.TheactivityofAbelcetagainstfungalpathogensinvitroiscomparabletothat

ofamphotericinB.However,activityofAbelcetinvitromaynotpredictactivityintheinfectedhost.

5.2Pharmacokineticproperties

AmphotericinBiscomplexedtophospholipidsinAbelcet.ThepharmacokineticpropertiesofAbelcetand

conventionalamphotericinBaredifferent.Pharmacokineticstudiesinanimalsshowedthat,afteradministrationof

Abelcet,amphotericinBlevelswerehighestintheliver,spleenandlung.AmphotericinBinAbelcetwasrapidly

distributedtotissues.Theratioofdrugconcentrationsintissuestothoseinbloodincreaseddisproportionatelywith

increasingdose,suggestingthateliminationofthedrugfromthetissueswasdelayed.Peakbloodlevelsof

amphotericinBwerelowerafteradministrationofAbelcetthanafteradministrationofequivalentamountsof

conventionaldrug.AdministrationofconventionalamphotericinBresultedinmuchlowertissuelevelsthandiddosing

withAbelcet.However,indogsamphotericinBproduced20-foldhigherkidneyconcentrationsthandidAbelcetgiven

atcomparabledoses.

ThepharmacokineticsofAbelcetinwholebloodweredeterminedinpatientswithmucocutaneousleishmaniasis.

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TherapidclearanceandlargevolumeofdistributionofAbelcetresultinarelativelylowAUCandareconsistentwith

preclinicaldatashowinghightissueconcentrations.ThekineticsofAbelcetarelinearandtheAUCincreases

proportionatelywithdose.

DetailsofthetissuedistributionandmetabolismofAbelcetinhumans,andthemechanismsresponsibleforreduced

toxicity,arenotwellunderstood.Thefollowingdataareavailablefromnecropsyinahearttransplantpatientwho

receivedAbelcetatadoseof5.3mg/kgfor3consecutivedaysimmediatelybeforedeath:

5.3Preclinicalsafetydata

AcutetoxicitystudiesinrodentsshowedthatAbelcetwas10-foldto20-foldlesstoxicthanconventionalamphotericin

B.Multiple-dosetoxicitystudiesindogslasting2-4weeksshowedthatonamg/kgbasis,Abelcetwas8-foldto10-

foldlessnephrotoxicthanconventionalamphotericinB.Thisdecreasednephrotoxicitywaspresumablyaresultof

lowerdrugconcentrationsinthekidney.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

L--dimyristoylphosphatidylcholine(DMPC)

L--dimyristoylphosphatidylglycerol(sodiumandammoniumsalts)(DMPG)

Sodiumchloride

Waterforinjections

6.2Incompatibilities

Abelcetshouldnotbedilutedinsodiumchloridesolution,ormixedwithotherdrugsorelectrolytes.Itisincompatible

withSalineSolution.

6.3Shelflife

Abelcet™

Dose:(mg/kg/day) 5.0

PeakbloodlevelC

:(g/ml) 1.7

Areaundertime-concentration

curveAUC (ghr/ml) 9.5

Clearance:(ml/hr/kg) 211.0

VolumeofdistributionVd:(l) 2286.0

Half-lifeT

:(hr) 173.4

Organ Abelcettissueconcentration

expressedasAmphotericinB

content(mg/kg)

Spleen 290.0

Lung 222.0

Liver 196.0

Kidney 6.9

Lymphnode 7.6

Heart 5.0

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Chemicalandphysicalin-usestabilityofpreparedintravenoussolutionsin5%DextroseInjectionhasbeen

demonstratedfor48hoursat2°to8°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2°

C–8°C,unlessreconstitutionanddilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Storeat2°C–8°C.Donotfreeze.Keepthevialintheoutercarton.

6.5Natureandcontentsofcontainer

Abelcetisasterile,pyrogen-freeyellowsuspensioninaTypeIglasssingleusevialcontaining20ml(100mg

amphotericinB).Thevialissealedwitharubberstopperandaluminiumsealandpackagedincartonsof10vials.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Abelcetisasterile,pyrogen-freesuspensiontobedilutedforintravenousInfusiononly.

Preparationofthesuspensionforinfusion

Allowthesuspensiontocometoroomtemperature.Shakegentlyuntilthereisnoevidenceofanyyellowsettlementat

thebottomofthevial.WithdrawtheappropriatedoseofAbelcetfromtherequirednumberofvialsintooneormore

sterilesyringes.RemovetheneedlefromeachsyringefilledwithAbelcetandreplacewiththe5micronfilterhigh

flowneedle(suppliedbyB.BraunMedical,Inc.)providedwitheachvial.Insertthefilterneedleofthesyringeintoan

IVbagcontaining5.0%DextroseforInjectionandemptythecontentofthesyringeintothebag.Eachfilterneedle

mustonlybeusedtofilterthecontentsofonevial,andanewfilterneedleshouldbeusedforeachsubsequentvial.The

finalinfusionconcentrationshouldbe1mg/ml.Forpaediatricpatientsandpatientswithcardiovasculardiseasethe

drugmaybedilutedwith5.0%DextroseforInjectiontoafinalinfusionconcentrationof2mg/ml.Donotusethe

agentafterdilutionwith5.0%DextroseforInjectionifthereisanyevidenceofforeignmatter.

AseptictechniquemustbestrictlyobservedthroughouthandlingofAbelcet,sincenobacteriostaticagentor

preservativeispresent.Theinfusionisbestadministeredbymeansofaninfusionpump.

DONOTDILUTEWITHSALINESOLUTIONSORMIXWITHOTHERDRUGSORELECTROLYTES.The

compatibilityofAbelcetwiththesematerialshasnotbeenestablished.Anexistingintravenouslineshouldbeflushed

with5.0%DextroseforInjectionbeforeinfusionofAbelcetoraseparateinfusionlineshouldbeused.

Singleusevial.Discardunusedcontents.Donotstoreforlateruse.

7MARKETINGAUTHORISATIONHOLDER

CephalonUKLimited

RidingsPoint

WhistlerDrive

Castleford

WestYorkshireWF105HX

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01May1996

Dateoflastrenewal:01May2006

10DATEOFREVISIONOFTHETEXT

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There are no safety alerts related to this product.

16-5-2018

EU/3/06/391 (Novartis Europharm Limited)

EU/3/06/391 (Novartis Europharm Limited)

EU/3/06/391 (Active substance: Amphotericin B (for inhalation use)) - Transfer of orphan designation - Commission Decision (2018)3034 of Wed, 16 May 2018 European Medicines Agency (EMA) procedure number: EMA/OD/027/06/T/03

Europe -DG Health and Food Safety