DIPRIVAN 1% W/V EMULSION FOR INTRAVENOUS INJECTION

Main information

  • Trade name:
  • DIPRIVAN 1% W/V EMULSION FOR INTRAVENOUS INJECTION
  • Dosage:
  • 10 Mg/Ml
  • Pharmaceutical form:
  • Emulsion for Inj/Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIPRIVAN 1% W/V EMULSION FOR INTRAVENOUS INJECTION
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0970/005/001
  • Authorization date:
  • 06-11-1997
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0970/005/001

CaseNo:2070848

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

AstraZenecaUKLimited

600CapabilityGreen,Luton,LU13LU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Diprivan1%w/vEmulsionforIntravenousInjectionorInfusion,20mlampoule

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom17/12/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 21/12/2009 CRN 2070848 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Diprivan1%w/vEmulsionforIntravenousInjectionorInfusion,20mlampoule.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

ContainsPropofol10mg/ml(200mgper20mlampoule).

Containssodium0.0018mmol/ml.

ContainsrefinedSoya-beanoil100mg/ml.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Emulsionforinjectionorinfusion.

Awhiteoralmostwhiteemulsionsuppliedin20mlampoules.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Diprivanisashort-actingintravenousanaestheticagentsuitableforinductionandmaintenanceofgeneralanaesthesia

inadultsandchildrenoveronemonthofage.

Diprivanmayalsobeusedforsedationofventilatedpatientsreceivingintensivecareinadults,onlyforaperiodof48

hours,orinrarecasesuptoamaximumof7days.

Diprivanmayalsobeusedforconscioussedationforsurgicalanddiagnosticproceduresinadultsonly.

Diprivanmaybeadministeredbya‘Diprifusor’TCIsystemforinductionandmaintenanceofgeneralanaesthesiaand

conscioussedationforsurgicalanddiagnosticproceduresinadultsonly.AdministrationofDiprivanbya‘Diprifusor’

TCIsystemisnotrecommendedforanyindicationinchildrenoradolescentsunder16yearsold.

AdministrationofDiprivanbya‘Diprifusor’TCIsystemisnotrecommendedforintensivecaresedation.

4.2Posologyandmethodofadministration

SupplementaryanalgesicagentsaregenerallyrequiredinadditiontoDiprivan.

ForspecificguidelinesrelatingtotheadministrationofDiprivanusingtheDiprifusortargetcontrolledinfusion(TCI)

system,whichincorporatesDiprifusorTCIsoftware,seesectionE.Suchuseisrestrictedtoinductionandmaintenance

ofanaesthesiaandconscioussedationforsurgicalanddiagnosticproceduresinadults.TheDiprifusorTCIsystemis

notrecommendedforuseinICUsedation,orinchildrenoradolescentsunder16yearsold.

Theglasspre-filledsyringe(PFS)hasalowerfrictionalresistancethanplasticdisposablesyringesandoperatesmore

easily.Therefore,ifDiprivanisadministeredusingahandheldpre-filledsyringe,thelinebetweenthesyringeandthe

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A)Adults

InductionofGeneralAnaesthesia

Diprivan1%maybeusedtoinduceanaesthesiabyslowbolusinjectionorinfusion.Diprivan2%shouldbeusedto

induceanaesthesiabyinfusionandonlyinthosepatientswhowillreceiveDiprivan2%formaintenanceofanaesthesia.

Inunpremedicatedandpremedicatedpatients,itisrecommendedthatDiprivanshouldbetitrated(approximately40mg

every10secondsinanaveragehealthyadult)againsttheresponseofthepatientuntiltheclinicalsignsshowtheonset

ofanaesthesia.Mostadultpatientsagedlessthanabout55yearsarelikelytorequire1.5to2.5mg/kgofDiprivan.The

totaldoserequiredcanbereducedbylowerratesofadministration(20–50mg/min).Overthisage,therequirementwill

generallybeless.InpatientsofASAgrades3and4,lowerratesofadministrationshouldbeused(approximately

20mgevery10seconds).

MaintenanceofGeneralAnaesthesia

AnaesthesiacanbemaintainedbyadministeringDiprivaneitherbycontinuousinfusionorbyrepeatbolusinjectionsto

maintainthedepthofanaesthesiarequired.

ContinuousInfusion:Diprivan1%orDiprivan2%maybeused.Therequiredrateofadministrationvaries

considerablybetweenpatientsbutratesintheregionof4to12mg/kg/husuallymaintainsatisfactoryanaesthesia.

RepeatBolusInjection:ItisrecommendedthatonlyDiprivan1%isused.Ifatechniqueinvolvingrepeatbolus

injectionisused,incrementsof25mgto50mgmaybeusedaccordingtoclinicalneed.

SedationofVentilatedPatientintheIntensiveCareUnit:

ForsedationduringintensivecareitisadvisedthatDiprivanshouldbeadministeredbycontinuousinfusion.The

infusionrateshouldbedeterminedbythedesireddepthofsedation.Inmostpatientssufficientsedationcanbeobtained

withadosageof0.3–4mg/kg/hofDiprivan(seesection4.4).Diprivanisnotindicatedforsedationinintensivecareof

patientsof16yearsofageoryounger(seesection4.3).AdministrationofDiprivanbyDiprifusorTCIsystemisnot

advisedforsedationintheintensivecareunit.

ConsciousSedationforSurgicalandDiagnosticProcedures

Toprovidesedationforsurgicalanddiagnosticproceduresratesofadministrationshouldbeindividualisedandtitrated

toclinicalresponse.

Mostpatientswillrequire0.5to1mg/kgover1to5minutestoinitiatesedation.

MaintenanceofsedationmaybeaccomplishedbytitratingDiprivaninfusiontothedesiredlevelofsedation–most

patientswillrequire1.5to4.5mg/kg/h.Inadditiontotheinfusion,bolusadministrationof10to20mgmaybeusedif

arapidincreaseinthedepthofsedationisrequired.InpatientsofASAgrades3and4therateofadministrationand

dosagemayneedtobereduced.

B)ElderlyPatients

InelderlypatientsthedoserequirementforinductionofanaesthesiawithDiprivanisreduced.Thereductionshould

takeaccountofthephysicalstatusandageofthepatient.Thereduceddoseshouldbegivenataslowerrateandtitrated

againsttheresponse.WhereDiprivanisusedformaintenanceofanaesthesiaorsedationtherateofinfusionor‘target

concentration’shouldalsobereduced.PatientsofASAgrades3and4willrequirefurtherreductionsindoseanddose

rate.Rapidbolusadministration(singleorrepeated)shouldnotbeusedintheelderlyasthismayleadto

cardiorespiratorydepression.

C)Children

Diprivanisnotrecommendedforuseinchildrenlessthanonemonthofage.Diprivan2%isnotrecommendedfor

inductionandmaintenanceofanaesthesiainchildrenbetween1monthand3yearsofagesincethe2%strengthis

difficulttobeaccuratelytitratedinsmallchildren,duetothesmallvolumesneeded.Forthesepatientsitis

recommendedtouseDiprivan1%.

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InductionofGeneralAnaesthesia:Whenusedtoinduceanaesthesiainchildren,itisrecommendedthatDiprivanis

givenslowlyuntiltheclinicalsignsshowtheonsetofanaesthesia.Thedoseshouldbeadjustedforageand/orweight.

Mostpatientsover8yearsofagearelikelytorequireapproximately2.5mg/kgofDiprivanforinductionof

anaesthesia.Underthisagetherequirementmaybemore.LowerdosageisrecommendedforchildrenofASAgrades3

and4.

MaintenanceofGeneralAnaesthesia:AnaesthesiacanbemaintainedbyadministeringDiprivanbyinfusionorrepeat

bolusinjectiontomaintainthedepthofanaesthesiarequired.ItisrecommendedthatonlyDiprivan1%isusedifrepeat

bolusinjectionsareused.Therequiredrateofadministrationvariesconsiderablybetweenpatientsbutratesinthe

regionof9to15mg/kg/husuallyachievesatisfactoryanaesthesia.Youngerchildren,1monthto3years,mayhave

higherdosagerequirements,withintherangeofrecommendeddosages,whencomparedwitholderpaediatricpatients.

Dosageshouldbeadjustedindividuallyandparticularattentionpaidtotheneedforadequateanalgesia.

ConsciousSedationforSurgicalandDiagnosticProcedures:Diprivanisnotrecommendedforconscioussedationin

childrenassafetyandefficacyhavenotbeendemonstrated.

SedationDuringIntensiveCare:Diprivanisnotrecommendedforsedationinchildrenassafetyandefficacyhavenot

beendemonstrated.Althoughnocausalrelationshiphasbeenestablished,seriousadverseevents(includingfatalities)

havebeenobservedfromspontaneousreportsofunlicenseduseandtheseeventswereseenmostofteninchildrenwith

respiratorytractinfectionsgivendosesinexcessofthoserecommendedforadults.

D)Administration

AdministrationofDiprivan2%bybolusinjectionisnotrecommended.

DiprivancanbeusedforinfusionundilutedfromplasticsyringesorglassinfusionbottlesorDiprivanpre-filled

syringes.WhenDiprivanisusedundilutedtomaintainanaesthesia,itisrecommendedthatequipmentsuchassyringe

pumpsorvolumetricinfusionpumpsshouldalwaysbeusedtocontrolinfusionrates.

Diprivan1%mayalsobeuseddilutedwith5%DextroseIntravenousInfusiononly,inPVCinfusionbagsorglass

infusionbottles.Dilutions,whichmustnotexceed1in5,shouldbepreparedasepticallyimmediatelybefore

administration.Themixtureisstableforupto6hours.

Thedilutionmaybeusedwithavarietyofinfusioncontroltechniquesbutagivingsetusedalonewillnotavoidthe

riskofaccidental,uncontrolledinfusionoflargevolumesofdilutedDiprivan.Aburette,dropcounterorvolumetric

pumpmustbeincludedintheinfusionline.Theriskofuncontrolledinfusionmustbetakenintoaccountwhendeciding

themaximumamountofdilutionintheburette.

DiprivanmaybeadministeredbyaY-piececlosetotheinjectionsite,intoinfusionsofDextrose5%Intravenous

Infusion,SodiumChloride0.9%IntravenousInfusionorDextrose4%withSodiumChloride0.18%Intravenous

Infusion.

Inordertoreducepainoninitialinjection,Diprivan1%usedforinductionmaybemixedwithLidocaineInjectionina

plasticsyringeintheratioof20partsDiprivan1%withuptoonepartof0.5or1%LidocaineInjectionimmediately

priortoadministration.

Diprivan1%maybepremixedwithalfentanilinjectioncontaining500micrograms/mlalfentanil(‘Rapifen’;Janssen

PharmaceuticalsLtd)intheratioof20:1to50:1v/v.Mixturesshouldbepreparedusingsteriletechniqueandused

within6hoursofpreparationatroomtemperatureandundernormallightingconditions.

TheneuromuscularblockingagentsatracuriumandmivacuriumshouldnotbegiventhroughthesameIVlineas

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DilutionandCo-AdministrationofDiprivanwithotherDrugsorInfusionFluids

E)TargetControlledInfusion–AdministrationofDiprivanbyDiprifusorTCISysteminAdults

AdministrationofDiprivanbyaDiprifusorTCIsystemisrestrictedtoinductionandmaintenanceofgeneral

anaesthesiaandconscioussedationforsurgicalanddiagnosticproceduresinadults.Itisnotrecommendedforusein

ICUsedationorinchildrenoradolescentsunder16yearsold.

Toachieveinductionandmaintenanceofanaesthesiaandconscioussedationforsurgicalanddiagnosticproceduresin

adults,DiprivanmaybeadministeredwiththeassistanceofaTarget

ControlledInfusion(TCI)system.Suchsystemsallowtheanaesthetistorintensivisttoachieveandcontroladesired

speedofinductionanddepthofanaesthesiaorconscioussedationbysettingandadjustingtarget(predicted)blood

concentrationsofpropofol.DiprivanmaybeadministeredbyTCIonlywithaDiprifusorTCIsystemincorporating

DiprifusorTCIsoftware.Suchsystemswilloperateonlyonrecognitionofelectronicallytaggedpre-filledsyringes

containingDiprivan1%or2%Injection.TheDiprifusorTCIsystemwillautomaticallyadjusttheinfusionrateforthe

concentrationofDiprivanrecognised.Usersmustbefamiliarwiththeinfusionpumpusersmanual,andwiththe

administrationofDiprivanbyTCIandwiththecorrectuseofthesyringeidentificationsystem,allofwhicharesetout

intheDiprifusortrainingmanual,availablefromAstraZenecaattheaddressbelow.

ThepharmacokineticmodelinDiprifusorTCIsystemassumesthattheinitialbloodpropofolconcentrationinthe

patientiszero.Therefore,inpatientswhohavereceivedpriorpropofol,theremaybeaneedtoselectalowerinitial

targetconcentrationwhencommencingDiprifusorTCI.Similarly,theimmediaterecommencementofDiprifusorTCI

isnotrecommendedifthepumphasbeenswitchedoff;ifthishasoccurred,theDiprifusorTCIsystemindicatesthatit

Co-

administration

Technique Additiveor

Diluent Preparation Precautions

Pre-mixing Dextrose5%

Intravenous

Infusion Mix1partofDiprivan1%withupto4parts

ofDextrose5%IntravenousInfusionineither

PVCinfusionbagsorglassinfusionbottles.

WhendilutedinPVCbags,itisrecommended

thatthebagshouldbefullandthatthedilution

bepreparedbywithdrawingavolumeof

infusionfluidandreplacingitwithanequal

volumeofDiprivan1% Prepareaseptically

beforeadministration.

Themixtureisstablefor

upto6hours

Lidocaine

Hydrochloride

Injection(0.5%

or1%without

preservatives) Mix20partsofDiprivan1%withupto1part

ofeither0.5%or1%LidocaineHydrochloride

Injection Preparemixture

asepticallyimmediately

priortoadministration.

Useforinductiononly

Alfentanil

injection(500

micrograms/ml) MixDiprivan1%withalfentanilinjectionina

ratioof20:1to50:1v/v Preparemixture

aseptically;usewithin

6hoursofpreparation

Co-administration

viaaY-piece

connector Dextrose5%

Intravenous

Infusion Co-administerviaaY-piececonnector PlacetheY-piece

connectorclosetothe

injectionsite

SodiumChloride

0.9%Intravenous

Infusion Asabove Asabove

Dextrose4%

withSodium

Chloride0.18%

Intravenous

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Guidanceonpropofoltargetconcentrationsisgivenbelow.Inviewofinterpatientvariabilityinpropofol

pharmacokineticsandpharmacodynamics,inbothpremedicatedandunpremedicatedpatientsthetargetpropofol

concentrationshouldbetitratedagainsttheresponseofthepatientinordertoachievethedepthofanaesthesiaor

conscioussedationrequired.

Inadultpatientsunder55yearsofage,anaesthesiacanusuallybeinducedwithtargetpropofolconcentrationsinthe

regionof4to8micrograms/ml.

Aninitialtargetof4micrograms/mlisrecommendedinpremedicatedpatientsandinunpremedicatedpatientsaninitial

targetof6micrograms/mlisadvised.Inductiontimewiththeseisgenerallywithintherangeof60–120seconds.

Highertargetswillallowmorerapidinductionofanaesthesiabutmaybeassociatedwithmorepronounced

haemodynamicandrespiratorydepression.

Alowerinitialtargetconcentrationshouldbeusedinpatientsovertheageofabout55yearsandinpatientsofASA

grades3and4.Thetargetconcentrationcanthenbeincreasedinstepsof0.5to1.0microgram/mlatintervalsof

1minutetoachieveagradualinductionofanaesthesia.

Supplementaryanalgesiawillgenerallyberequiredandtheextenttowhichtargetconcentrationsformaintenanceof

anaesthesiacanbereducedwillbeinfluencedbytheamountofconcomitantanalgesiaadministered.Targetpropofol

concentrationsintheregionof3to6micrograms/mlusuallymaintainsatisfactoryanaesthesia.

Thepredictedpropofolconcentrationonwakingisgenerallyintheregionof1.0to2.0micrograms/mlandwillbe

influencedbytheamountofanalgesiagivenduringmaintenance.

ConsciousSedationforSurgicalandDiagnosticProcedures

Targetbloodpropofolconcentrationsettingsintherangeof0.5to2.5micrograms/mlwillgenerallyberequired.The

targetconcentrationsettingshouldbetitratedagainsttheresponseofthepatienttoachievethedepthofconscious

sedationrequired.

Aninitialtargetconcentrationtowardstheupperendofthisrangewillallowmorerapidinductionofconscious

sedation.

Aninitialtargetconcentrationtowardsthelowerendofthisrangeshouldbeusedinelderlypatientsandinpatientsof

ASAgrades3and4.

Routineoxygensupplementationshouldbeprovided.

4.3Contraindications

KnownhypersensitivityforanyofthecomponentsofDiprivan.

Diprivaniscontraindicatedforsedationinintensivecareofpatientsof16yearsofageoryounger(seesection4.4).

Diprivancontainssoyaoilandshouldnotbeusedinpatientswhoarehypersensitivetopeanutorsoya.

4.4Specialwarningsandprecautionsforuse

Diprivanisintendedforuseinhospitalsonly.

Diprivanshouldbegivenbythosetrainedinanaesthesia,orwhereappropriate,doctorstrainedinthecareofpatientsin

IntensiveCare.Patientsshouldbeconstantlymonitoredandfacilitiesformaintenanceofapatentairway,artificial

ventilation,oxygenenrichmentandotherresuscitativefacilitiesshouldbereadilyavailableatalltimes.Diprivan

shouldnotbeadministeredbythepersonconductingthesurgicalordiagnosticprocedure.

WhenDiprivanisadministeredforconscioussedationforsurgicalanddiagnosticprocedures,patientsshouldbe

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Aswithothersedativeagents,whenDiprivanisusedforsedationduringoperativeprocedures,involuntarypatient

movementsmayoccur.Duringproceduresrequiringimmobilitythesemovementsmaybehazardoustotheoperative

site.

Anadequateperiodisneededpriortodischargeofthepatient,toensurefullrecoveryaftergeneralanaesthesia.Very

rarelytheuseofDiprivanmaybeassociatedwiththedevelopmentofaperiodofpostoperativeunconsciousness,which

maybeaccompaniedbyanincreaseinmuscletone.Thismayormaynotbeprecededbyaperiodofwakefulness.

Althoughrecoveryisspontaneous,appropriatecareofanunconsciouspatientshouldbeadministered.

Aswithotherintravenousanaestheticagents,cautionshouldbeappliedinpatientswithcardiac,respiratory,renalor

hepaticimpairmentorinhypovolaemicordebilitatedpatients.

Diprivanlacksvagolyticactivityandhasbeenassociatedwithreportsofbradycardia(occasionallyprofound)andalso

asystole.Theintravenousadministrationofananticholinergicagentbeforeinduction,orduringmaintenanceof

anaesthesiashouldbeconsidered,especiallyinsituationswherevagaltoneislikelytopredominateorwhenDiprivanis

usedinconjunctionwithotheragentslikelytocausebradycardia.

WhenDiprivanisadministeredtoanepilepticpatient,theremaybeariskofconvulsion.

Propofolisnotadvisedforgeneralanaesthesiainchildrenyoungerthan1monthofage.Thesafetyandefficacyof

Diprivanfor(background)sedationinchildrenyoungerthan16yearsofagehavenotbeendemonstrated.Althoughno

causalrelationshiphasbeenestablished,seriousundesirableeffectswith(background)sedationinpatientsyounger

than16yearsofage(includingcaseswithfataloutcome)havebeenreportedduringunlicenseduse.Inparticularthese

effectsconcernedoccurrenceofmetabolicacidosis,hyperlipidemia,rhabdomyolysisand/orcardiacfailure.These

effectsweremostfrequentlyseeninchildrenwithrespiratorytractinfectionswhoreceiveddosagesinexcessofthose

advisedinadultsforsedationintheintensivecareunit.

Similarlyveryrarereportshavebeenreceivedofoccurrenceofmetabolicacidosis,rhabdomyolysis,hyperkalaemia

and/orrapidlyprogressivecardiacfailure(insomecaseswithfataloutcome)inadultswhoweretreatedformorethan

58hourswithdosagesinexcessof5mg/kg/h.Thisexceedsthemaximumdosageof4mg/kg/hcurrentlyadvisedfor

sedationintheintensivecareunit.Thepatientsaffectedweremainly(butnotonly)seriouslyhead-injuredpatientswith

raisedICP.Thecardiacfailureinsuchcaseswasusuallyunresponsivetoinotropicsupportivetreatment.Treating

physiciansareremindedifpossiblenottoexceedthedosageof4mg/kg/h.Prescribersshouldbealerttothesepossible

undesirableeffectsandconsiderdecreasingtheDiprivandosageorswitchingtoanalternativesedativeatthefirstsign

ofoccurrenceofsymptoms.PatientswithraisedICPshouldbegivenappropriatetreatmenttosupportthecerebral

perfusionpressureduringthesetreatmentmodifications.

Appropriatecareshouldbeappliedinpatientswithdisordersoffatmetabolismandinotherconditionswherelipid

emulsionsmustbeusedcautiously.

ItisrecommendedthatbloodlipidlevelsbemonitoredshouldDiprivanbeadministeredtopatientsthoughttobeat

particularriskoffatoverload.AdministrationofDiprivanshouldbeadjustedappropriatelyifthemonitoringindicates

thatfatisbeinginadequatelyclearedfromthebody.Ifthepatientisreceivingotherintravenouslipidconcurrently,a

reductioninquantityshouldbemadeinordertotakeaccountoftheamountoflipidinfusedaspartoftheDiprivan

formulation:1.0mlofDiprivancontainsapproximately0.1goffat.

Diprivanisnotrecommendedforuseinneonatesforinductionandmaintenanceofanaesthesia.Datafromoff-labeluse

haveindicatedthatifthepaediatric(1monthto16yearsofage)doseregimenisappliedinneonates,arelative

overdosecouldoccurwhichmayresultincardiorespiratorydepression(seesections4.2and4.8).

EDTAisachelatorofmetalions,includingzinc.Theneedforsupplementalzincshouldbeconsideredduring

prolongedadministrationofDiprivan,particularlyinpatientswhoarepredisposedtozincdeficiency,suchasthose

withburns,diarrhoeaand/ormajorsepsis.

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AdditionalPrecautions:

Diprivancontainsnoantimicrobialpreservativesandsupportsgrowthofmicro-organisms.WhenDiprivanistobe

aspirated,itmustbedrawnasepticallyintoasterilesyringeorgivingsetimmediatelyafteropeningtheampouleor

breakingthevialseal.Administrationmustcommencewithoutdelay.

AsepsismustbemaintainedforbothDiprivanandinfusionequipmentthroughouttheinfusionperiod.Anyinfusion

fluidsaddedtotheDiprivanlinemustbeadministeredclosetothecannulasite.Diprivanmustnotbeadministeredvia

amicrobiologicalfilter.

DiprivanandanysyringecontainingDiprivanareforsingleuseinanindividualpatient.

Inaccordancewithestablishedguidelinesforotherlipidemulsions,asingleinfusionofDiprivanmustnotexceed12

hours.Attheendoftheprocedureorat12hours,whicheveristhesooner;boththereservoirofDiprivanandthe

infusionlinemustbediscardedandreplacedasappropriate

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Diprivanhasbeenusedinassociationwithspinalandepiduralanaesthesiaandwithcommonlyusedpremedicants,

neuromuscularblockingdrugs,inhalationalagentsandanalgesicagents;nopharmacologicalincompatibilityhasbeen

encountered.LowerdosesofDiprivanmayberequiredwheregeneralanaesthesiaisusedasanadjuncttoregional

anaesthetictechniques.Thehypotensiveeffectofpropofolmaybepotentiatedbytheconcomitantadministrationof

opiateanalgesics.Thiseffectmaybemoremarkedinelderlypatientsandwhenagentssuchasalfentanilaregivenby

infusion.

4.6Pregnancyandlactation

Pregnancy:ThesafetyofDiprivanduringpregnancyhasnotbeenestablished,therefore,Diprivanshouldnotbeusedin

pregnantwomenunlessclearlynecessary.Propofolcrossestheplacentaandmaybeassociatedwithneonatal

depression.Highdoses(morethan2.5mg/kgforinductionor6mg/kg/hformaintenanceofanaesthesia)shouldbe

avoided.

Lactation:SafetytotheneonatefollowingtheuseofDiprivaninmotherswhoarebreast-feedinghasnotbeen

established.Studiesinbreast-feedingwomenshowedthatpropofolisexcretedinsmallamountsintothemilk.

Therefore,mothersshouldstopbreast-feedinganddiscardbreastmilkfor24hoursafteradministrationofpropofol.

4.7Effectsonabilitytodriveandusemachines

Patientsshouldbeadvisedthatperformanceofskilledtasks,suchasdrivingandoperatingmachinery,maybeimpaired

forsometimeaftergeneralanaesthesia.

4.8Undesirableeffects

General

Inductionofanaesthesiaisgenerallysmoothwithminimalevidenceofexcitation,althoughspontaneousmovements

maybeseeninsomepatients.ThemostcommonlyreportedADRsarepharmacologicallypredictablesideeffectsofan

anaestheticagent,suchashypotension.Giventhenatureofanaesthesiaandthosepatientsreceivingintensivecare,

eventsreportedinassociationwithanaesthesiaandintensivecaremayalsoberelatedtotheproceduresbeing

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Maybeminimisedbyusingthelargerveinsoftheforearmandantecubitalfossa.WithDiprivan1%localpain

canalsobeminimisedbytheco-administrationoflidocaine(seesection4.2,partD).

Occasionally,hypotensionmayrequireuseofintravenousfluidsandreductionoftheadministrationrateof

Diprivan.

Seriousbradycardiasarerare.Therehavebeenisolatedreportsofprogressiontoasystole.

VeryrarereportsofrhabdomyolysishavebeenreceivedwhereDiprivanhasbeengivenatdosesgreaterthan

4mg/kg/hrforICUsedation.

Inveryrarecasesrhabdomyolysis,metabolicacidosis,hyperkalaemiaorcardiacfailure,sometimeswithfataloutcome,

havebeenobservedwhenDiprivanwasadministeredatdosagesinexcessof4mg/kg/hforsedationintheintensive

careunit(seesection4.4).

Reportsfromoff-labeluseofDiprivanforinductionofanaesthesiainneonatesindicatethatcardiorespiratory

depressionmayoccurifthepaediatricdoseregimenisapplied(seesections4.2and4.4).

Local

Thelocalpainwhichmayoccurduringtheinductionphasecanbeminimisedbytheuseofthelargerveinsinthe

forearmandantecubitalfossa.WithDiprivan1%localpaincanalsobeminimisedbytheco-administrationof

lidocaine(seesection4.2).Thrombosisandphlebitisarerare.Accidentalclinicalextravasationandanimalstudies

Verycommon

(>1/10) Generaldisordersand

administrationsiteconditions: Localpainoninduction (1)

Common

(>1/100,<1/10) Vasculardisorders:

Hypotension (2)

Cardiacdisorders: Bradycardia (3)

Respiratory,thoracicand

mediastinaldisorders: Transientapnoeaduringinduction

Gastrointestinaldisorders: Nauseaandvomitingduring

recoveryphase

Nervoussystemdisorders: Headacheduringrecoveryphase

Uncommon

(>1/1000,<1/100) Vasculardisorders: Thrombosisandphlebitis

Rare

(>1/10000,<1/1000) Nervoussystemdisorders: Epileptiformmovements,

includingconvulsionsand

opisthotonusduringinduction,

maintenanceandrecovery

Veryrare

(<1/10000) Musculoskeletalandconnective

tissuedisorders: Rhabdomyolysis (4)

Gastrointestinaldisorders: Pancreatitis

Injury,poisoningand

proceduralcomplications: Postoperativefever

Renalandurinarydisorders: Discolourationofurinefollowing

prolongedadministration

Immunesystemdisorders: Anaphylaxis–mayinclude

angioedema,bronchospasm,

erythemaandhypotension

Reproductivesystemandbreast:Sexualdisinhibition

Cardiacdisorders: Pulmonaryoedema

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4.9Overdose

Accidentaloverdosageislikelytocausecardiorespiratorydepression.Respiratorydepressionshouldbetreatedby

artificialventilationwithoxygen.Cardiovasculardepressionwouldrequireloweringofthepatient'sheadand,ifsevere,

useofplasmaexpandersandpressoragents.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Propofol(2,6-diisopropylphenol)isashort-actinggeneralanaestheticagentwitharapidonsetofactionof

approximately30seconds.Recoveryfromanaesthesiaisusuallyrapid.Themechanismofaction,likeallgeneral

anaestheticsispoorlyunderstood.However,propofolisthoughttoproduceitssedative/anaestheticeffectsbythe

positivemodulationoftheinhibitoryfunctionoftheneurotransmitterGABAthroughtheligand-gatedGABA

receptors.

Ingeneral,fallsinmeanarterialbloodpressureandslightchangesinheartrateareobservedwhenDiprivanis

administeredforinductionandmaintenanceofanaesthesia.However,thehaemodynamicparametersnormallyremain

relativelystableduringmaintenanceandtheincidenceofuntowardhaemodynamicchangesislow.

AlthoughventilatorydepressioncanoccurfollowingadministrationofDiprivan,anyeffectsarequantitativelysimilar

tothoseoftheotherintravenousanaestheticagentsandarereadilymanageableinclinicalpractice.

Diprivanreducescerebralbloodflow,intracranialpressureandcerebralmetabolism.Thereductioninintracranial

pressureisgreaterinpatientswithanelevatedbaselineintracranialpressure.

Recoveryfromanaesthesiaisusuallyrapidandclearheadedwithalowincidenceofheadacheandpostoperative

nauseaandvomiting.

Ingeneral,thereislesspostoperativenauseaandvomitingfollowinganaesthesiawithDiprivanthanfollowing

anaesthesiawithinhalationagents.

Diprivan,attheconcentrationslikelytooccurclinically,doesnotinhibitthesynthesisofadrenocorticalhormones.

5.2Pharmacokineticproperties

Thedeclineinpropofolconcentrationsfollowingabolusdoseorfollowingtheterminationofaninfusioncanbe

describedbyathreecompartmentopenmodel.Thefirstphaseischaracterisedbyaveryrapiddistribution(half-life:2-

4minutes)followedbyrapidelimination(half-life:30-60minutes)andaslowerfinalphase,representativeof

redistributionofpropofolfrompoorlyperfusedtissue.Propofolisextensivelydistributedandrapidlyclearedfromthe

body(totalbodyclearance:1.5-2litres/minute).Clearanceoccursbymetabolicprocesses,mainlyintheliver,toform

inactiveconjugatesofpropofolanditscorrespondingquinol,whichareexcretedinurine.

WhenDiprivanisusedtomaintainanaesthesia,bloodconcentrationsofpropofolasymptoticallyapproachthesteady-

statevalueforthegivenadministrationrate.Thepharmacokineticsarelinearovertherecommendedrangeofinfusion

ratesofDiprivan.

5.3Preclinicalsafetydata

Propofolisadrugonwhichextensiveclinicalexperiencehasbeenobtained.Allrelevantinformationfortheprescriber

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Soya-beanOil,refined

PurifiedEggPhosphatide

Glycerol

SodiumHydroxide(foradjustmentofpH)

DisodiumEdetate

WaterforInjections

6.2Incompatibilities

DiprivanshouldnotbemixedpriortoadministrationwithinjectionsorinfusionfluidswiththeexceptionofDiprivan1

%whichcanbemixedwith5%Dextrose,inPVCbagsorglassinfusionbottlesorLidocaineInjectionoralfentanil

injectioninplasticsyringes(seesection4.2).

Theneuromuscularblockingagents,atracuriumandmivacuriumshouldnotbegiventhroughthesameIVlineas

Diprivanwithoutpriorflushing.

6.3ShelfLife

Shelf-lifeoftheproductaspackagedforsale:3years.

Shelf-lifeoftheproductafterfirstopening:Useimmediatelyafteropening.Anyportionofthecontentsremaining

afteruseshouldbediscarded.

Shelf-lifeafterdilutionaccordingtodirections:WhenDiprivanisdilutedwith0.5%or1%Lidocaineinjection

(withoutpreservatives)inplasticsyringes,theresultingdilutionmustbeusedimmediately.

Afterdilutionwith5%DextroseInjectioninPVCbagsorglassinfusionbottlesoralfentanilinjection(containing500

micrograms/mlalfentanil)inplasticsyringes,theshelf-lifeofthedilutedproductwillbenogreaterthan6hourswhen

storedbelow25ºC.Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotused

immediately,in-usestoragetimesandconditionspriortousearetheresponsibilityoftheuser.

6.4Specialprecautionsforstorage

Unopenedampoules:Donotstoreabove25°C.Donotfreeze.

Forstorageprecautionsfordilutedproduct,seesection6.3ShelfLife.

6.5Natureandcontentsofcontainer

TypeIglassampoules(20ml).

Packsize:5ampoules.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

FormoredetailedadministrationinstructionsforDiprivanandmixturesofDiprivan,pleaseseesection4.2Posology

andMethodofAdministration.

In-useprecautions:Containersshouldbeshakenbeforeuse.DiprivanandanysyringecontainingDiprivanarefor

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AsepsisforDiprivanandinfusionequipmentmustbemaintained(seesection4.4SpecialWarningsandPrecautions

forUse).

7MARKETINGAUTHORISATIONHOLDER

AstraZenecaUKLimited

600CapabilityGreen

Luton

LU13LU

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0970/005/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 06November1987

Dateoflastrenewal : 06November2007

10DATEOFREVISIONOFTHETEXT

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