CLINOLEIC

Main information

  • Trade name:
  • CLINOLEIC Emulsion for Infusion 20 %w/ v
  • Dosage:
  • 20 %w/ v
  • Pharmaceutical form:
  • Emulsion for Infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLINOLEIC Emulsion for Infusion 20 %w/v
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/141/001
  • Authorization date:
  • 15-01-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0167/141/001

CaseNo:2075471

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

TransferredfromPA0854/001/001.

BaxterHealthcareLimited

CaxtonWay,Thetford,NorfolkIP243SE,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Clinoleic20%,emulsionforinfusion,glassbottles

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom15/01/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ClinOleic20%,emulsionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Per100ml

Refinedoliveoilandrefinedsoyabeanoil*.20.00g

correspondingtoacontentofessentialfattyacids.4.00g

*Mixtureofrefinedoliveoil(approximately80%)andrefinedsoyabeanoil(approximately20%)

Energycontent.2000kcal/l(8.36MJ/l)

Lipidcontent(oliveandsoyabeanoil).200g/l

Osmolarity.270mOsm/l

pH.6-8

Density.0.986

Phospholipidsprovide47milligramsor1.5mmolofphosphorusper100ml

Forexcipients,seesection6.1

3PHARMACEUTICALFORM

Emulsionforinfusion

Milk-likehomogeneousliquid

4CLINICALPARTICULARS

4.1TherapeuticIndications

Indicatedasasourceoflipidsforpatientsrequiringparenteralnutrition,whenoralorenteralnutritionisimpossible,

insufficientorcontraindicated.

4.2Posologyandmethodofadministration

Clinoleic20%contains200g/loflipidscorrespondingto200mg/ml.

Routeofadministration

Intravenousinfusion:

whenadministeredaspartofacompletenutritionadmixture(withglucoseandaminoacids)thecentralor

peripheralvenousrouteshouldbechosendependingontheosmolarityofthefinaladmixture.

inrarecases,wheninfusedaloneasacomplementarysupporttooralorenteralnutrition,ClinOleic20%canbe

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Dosage

INADULTS:

Thedosageis1toamaximumof2glipids/kg/day.Theinitialinfusionratemustbeslowandnotexceed0.1glipidsor

0.5ml(10drops)perminutefor10minutesthengraduallyincreaseduntilreachingtherequiredrateafterhalfanhour.

Neverexceed0.15glipids/kg/hour(0.75ml/kg/hour

INCHILDREN:

ClinOleic20%shouldbeadministeredasacontinuous24h/dayinfusion.

Itisrecommendednottoexceedadailydoseof3g-lipids/kgb.w.andaninfusionrateof0.15glipids/kgb.w./h.

Dailydoseshouldbeincreasedgraduallyduringthefirstweekofadministration.

INPREMATURENEWBORNSANDLOWBIRTHWEIGHTINFANTS:

TheuseofClinOleic20%isrestrictedtoprematureinfantsof28weeksofgestationalageormore.

ClinOleic20%shouldbeadministeredasacontinuous24h/dayinfusion.

Theinitialdailydoseshouldbe0.5-1.0glipids/kgb.w.Thedosemaybeincreasedby0.5-1.0glipids/kgb.w.every24

hoursuptoadailydoseof2.0glipids/kgb.w.

Usageinnutritiveadmixtures(withglucoseandaminoacids)

Lipidspresentonlyonecomponentinparenteralnutrition.Foracompleteparenteralnutritiontheconcomitant

substitutionwithaminoacids,carbohydrates,electrolytes,vitamins,andtraceelementsisnecessary.Before

administrationtothepatient,thecompatibilityofthecomponentsandstabilityoftheadmixturemustbechecked.

Admixingshouldbeaccompaniedbygentleagitationduringpreparationunderstrictasepticconditions.

“Breaking”or“oilingout”oftheemulsioncanbevisiblyidentifiedbyaccumulationofyellowishdropletsorparticles

intheadmixture.

4.3Contraindications

TheuseofClinOleiciscontra-indicatedinthefollowingsituations:

hypersensitivitytoeggprotein,soyaproteinorpeanutproteinortoanyoftheactivesubstancesorexcipients

severedyslipidemiaandnoncorrectedmetabolismdisordersincludinglacticacidosisanduncompensated

diabetes,

severesepsis

severeliverdisease,

bloodcoagulationdisorders,thrombophlebitis,

myocardialinfarction

4.4Specialwarningsandprecautionsforuse

Specialclinicalmonitoringisrequiredatthebeginningofanyintravenousinfusion.Shouldanyabnormalitiesoccur,

Adultsperkg

ofbodyweight Adultsfor70kg

Usuallipiddosage 1to2g/kg/day 70to140g/day

InfusedvolumeofClinOleic

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Theinfusionmustbestoppedimmediatelyifanyabnormalsignsorsymptomsofanallergicreaction(suchassweating,

fever,shivering,headache,skinrashesordyspnoea)develop.Thismedicinalproductcontainssoya-beanoilandegg

phospholipids,whichmayrarelycausehypersensitivityreactions.Cross-allergicreactionsbetweensoyaproteinsand

peanutproteinshavebeenobserved.

Plasmatriglyceridelevelsandclearanceshouldbemonitoreddaily.Thetriglycerideconcentrationinserumunder

infusionshouldnotexceed3mmol/l.Infusionshouldonlybestartedwhenserumtriglyceridelevelshavereturnedto

baselinelevel.

Reducedabilitytoremovelipidsmayresultina“fatoverloadsyndrome”whichmaybecausedbyoverdosebutmay

alsooccuratthestartofaninfusionaccordingtoinstruction,theeffectsofwhichareusuallyreversibleafterthelipid

infusionisstopped(seealsoSection4.8).

Elevatedliverenzymesandcholestasishavebeenreportedwithlipidproducts.

Duringshort-termorlong-termintravenousnutrition,alkalinephosphatasesandtotalbilirubinshouldbecheckedat

regularintervals,dependingonthehealthstatusofthepatient.

HydroelectrolyticormetabolismdisordersshouldbecorrectedbeforeClinOleic20%administration.

Fatemulsionsshouldbeadministeredsimultaneouslywithcarbohydratesandaminoacidstoavoidoccurrenceof

metabolicacidosis.

Thebloodsugar,theacid-basebalance,electrolytes,andthebloodcountmustbecheckedatregularintervals.

Asforanyparenteralinfusion,particularattentionshouldbegivenonwaterbalance,especiallyinpatientswithacute

oliguriaoranuria.

Asotherlipidemulsions,ClinOleic20%shouldbeusedinextremelyprematureand/orverylowbirth-weightinfant

undertheclosesupervisionofaneonatologist.ThereisclinicalexperienceforClinOleic20%infusiontime,upto7

daysinneonatesandupto2monthsinchildren.

ClinOleic20%shouldbeadministeredwithcautionincaseofneonatalhyperbilirubinemia(totalserumbilirubin>200

µmol/l).Totalbilirubinlevelsshouldbemonitoredclosely.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Completeinformationaboutincompatibilitiesisnotavailable.

Neveraddmedicationorelectrolytesdirectlytothelipidemulsion.Ifitisnecessarytointroduceadditives,verifythe

compatibilityandmixthoroughlybeforeadministrationtothepatient.Thecompatibilitywithsolutionsadministered

simultaneouslyviaacommonendsectionmustbeensured.

4.6Pregnancyandlactation

ThesafetyofadministrationofClinOleic20%duringpregnancyandlactationhasnotbeenestablished.Therefore,

ClinOleic20%shouldnotbeusedduringpregnancyandlactationexceptafterspecialconsideration.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

Adversedrugreactions(ADRs)thatoccurredafteradministrationofClinOleic20%arepresentedwiththeirrelative

frequencies;theseincludeADRsdocumentedinclinicaltrialsandthosefrompost-marketingreports.ClinOleicwas

administeredto274adultpatientsintheclinicaltrialsandthereforethefrequenciesofARsarelimitedtoverycommon

touncommon,usingthefollowingconvention:verycommon( ≥1/10);common(≥1/100to<1/10);uncommon(≥1/100

to<1/1,000);rare( ≥1/10,000to<1/1,000);veryrare(≥1/10,000);andunknown(cannotbeestimatedfromthe

availabledata).

ThemostfrequentADRsnotedforClinOleic20%inclinicaltrialswerenausea/vomiting,whichoccurredinmorethat

2%ofthepatients.

ClinicalTrialandPost-MarketingAdverseDrugReactionsReportedforClinOleic20%

Fatoverloadsyndrome:

Reducedabilitytoremovethelipidsmayresultina"fatoverloadsyndrome"whichmaybecausedbyoverdosebut

mayalsooccuratthestartofaninfusionaccordingtoinstructions,andisassociatedwithasuddendeteriorationinthe

patient'sclinicalcondition.Itischaracterizedbyhyperlipidaemia,fever,liverfattyinfiltration,hepatomegaly,anaemia,

leucopaenia,thrombocytopaenia,coagulationdisordersandcoma,requiringhospitalisation.Allofthesesymptomsare

usuallyreversiblewhenthelipidemulsioninfusionisstopped.

4.9Overdose

Incaseofoverdosing(anabnormaltriglycerideriseunderinfusionoffat)causingspecialreactions(generalsymptoms

suchasfeverorevocatinganhemodynamicinstability,emesis,algia,liverfunctionabnormalities,hepatoor

splenomegalia,hemostasisdisorders,hyperlipidemia,hypersensitivity)fatinfusionshouldbestoppedorifnecessary,

SystemOrganClass(SOC) Frequency MedDRAPreferredTerm

Bloodandlymphaticsystem

disorders Uncommon Leukopaenia

Unknown 1 Thrombocytopaenia

Gastrointestinaldisorders Common Nausea,Vomiting

Uncommon Abdominaldistension,

Abdominalpain,Epigastric

discomfort

Generaldisordersand

administrationsiteconditions Unknown 1 Chills

Hepatobiliarydisorders Uncommon Cholestasis

Immunesystemdisorders Unknown 1 Hypersensitivity

Investigations Common Meanarterialpressuredecreased

Uncommon Bilirubinconjugatedincreased,

Bloodbilirubinincreased,

Hepaticenzymeincreased,Blood

triglyceridesincreased

Metabolismandnutrition

disorders Common Hyperglycaemia

Skinandsubcutaneousdisorders Unknown 1 Urticaria

Adversereactionobservedduringpost-marketingexperience:Thefrequencyofpost-

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:B05BA02

Thecombinationofoliveandsoybeanoilsallowsacontentoffattyacidsinanapproximateratioof:

Saturatedfattyacids:15%(SFA)

Mono-unsaturatedfattyacids:65%(MUFA)

EssentialPoly-unsaturatedfattyacids:20%(EPUFA)

Themoderatelevelofessentialfattyacids(EFA)probablyfacilitatestheirutilisation,enablesacorrectstatusofEFA

upperderivativesandcorrectsEFAdeficiency.

Incomparisonwithsoybeanoil:

–inpreterminfantsabove28weeksofgestationalage,treatedfor7days,thehighercontentin tocopherolrelatedto

thepresenceofoliveoil,resultsinanimprovedvitaminEstatus.

–inchildren(8pertreatmentgroup)underlong-termparenteralnutrition,for2months,abettervitaminE/EPUFA

ratioresultsinreducedlipidperoxydation.

Thesepropertieshavebeenverifiedfordosesrangingfrom1to3g/kg/day.

Thehigh-energycontentoftheemulsionenablestheadministrationofalargequantityofcaloriesinasmallvolume.

5.2Pharmacokineticproperties

Clearancerateoflipidemulsionsisdependentonparticlesize:

Smalllipiddropletsizetendstodelaytheclearance,whileitimproveslipolysisbyliproteinlipase.

Clinoleic20%,whichhasdropletsizeclosetothatofchylomicronshasasimilareliminationrate.

5.3Preclinicalsafetydata

Toxicologicalstudiesshowedthattheproductiswelltolerated.

Toxicitystudiesshowedtheusualmodificationsduetohighintakeoflipidemulsions:fatandpigmentsdepositsinthe

liver,thrombocytopenia,andhypercholesterolemia.

AdecreaseoflipidperoxidationandimprovedvitaminEstatushasbeenexperimentallyshowedforhighintakeof

Clinoleic20%comparedtosoybeanemulsions.

Oneinvitrostudyperformedonhumancells,andoneinvivostudyperformedinratsincomparisonwithsoybeanoil-

basedemulsions,haveshownthatClinOleic20%,emulsionforinfusion,maintainslymphocyteproliferation,cell

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Eggphosphatides

Glycerol

Sodiumoleate

Sodiumhydroxide

WaterforInjections

6.2Incompatibilities

Completeinformationaboutincompatibilitiesisnotavailable.

Neveraddmedicationorelectrolytesdirectlytothelipidemulsion.Ifitisnecessarytointroduceadditives,verifythe

compatibilityandmixthoroughlybeforeadministrationtothepatient.

6.3ShelfLife

18monthsinglassbottle.

6.4Specialprecautionsforstorage

Donotstoreabove25°C

Donotfreeze

Keepthecontainerintheoutercarton.

6.5Natureandcontentsofcontainer

ClinOleic20%canbepackaged:

inglassbottle(typeII),

Presentations:

Inbottle:

100mlinbottle-Packagesizes:24or10units.

125mlinbottle-Packagesizes:24or10units.

250mlinbottle-Packagesizes:12or10units.

500mlinbottle-Packagesizes:12or10units.

1000mlinbottle-Packagesize:6units.

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Onceopened,useimmediatelyanddiscardpartlyusedcontainers.

Forsingleuseonly

BOTTLE

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7MARKETINGAUTHORISATIONHOLDER

BaxterHealthcareLimited

CaxtonWay

Thetford

NorfolkIP243SE

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA167/141/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorization:09January1998

Dateoflastrenewal:28November2005

10DATEOFREVISIONOFTHETEXT

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