BUPIVACAINE HYDROCHLORIDE

Main information

  • Trade name:
  • BUPIVACAINE HYDROCHLORIDE
  • Dosage:
  • 2.5 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BUPIVACAINE HYDROCHLORIDE
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/112/001
  • Authorization date:
  • 02-05-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BupivacaineHydrochloride2.5mg/ml(0.25%w/v)SolutionforInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

BupivacaineHydrochloride2.5mg/ml(0.25%w/v)SolutionforInjectioncontains2.5mgbupivacainehydrochloride

perml(asmonohydrate).

Each5mlampoulecontains12.5mgbupivacainehydrochloride.

Each10mlampoulecontains25mgbupivacainehydrochloride.

Each20mlampoulecontains50mgbupivacainehydrochloride.

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Solutionforinjection

Clearandcolourlesssolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

LocalInfiltration.

PeripheralNerveBlocks.

CentralNerveBlocks(EpiduralandSpinalAnaesthesia).

Forlocalorregionalanaesthesiaand/oranalgesiaforsurgical,diagnosticandobstetricprocedures.

4.2Posologyandmethodofadministration

ADULTS:

Thefollowingrecommendedbupivacainedoses(Table1)serveasaguidelineforanaverageadultwithabodyweight

ofapproximately70kg.

Thedosagevariesanddependsuponthearea(s)tobeanaesthetised,thevascularityofthetissues,thenumberof

neuronalsegmentstobeblocked,individualtoleranceandtheanaesthetictechniquethatistobeused.Thelowest

dosageneededtoprovideeffectiveanaesthesiaand/oranalgesiashouldalwaysbeadministered.

Themaximumdosagemustalwaysbedeterminedbyevaluatingthesizeandphysicalstatusofthepatient,andby

consideringtheusualrateofsystemicabsorptionfromaparticularinjectionsite.Basedonbodyweight,themaximum

recommendeddoseofbupivacainehydrochlorideis2mg/kg,anduptoamaximumof150mgwithina4-hourperiod.

Themaximumrecommendedadultdoseduringa24-hourperiodis400mg.

CHILDREN:

Bupivacainehydrochloridemaybealsousedtoprovideanaesthesiaand/oranalgesiainchildren.Aswithotherlocal

anaesthetics,useofbupivacaineforpaediatricanaesthesiarequiresacarefulassessmentoftherisk/benefitratiobythe

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vascularityofthetissues,thenumberofneuronalsegmentstobeblocked,individualtolerance,theintendedanaesthetic

techniqueand(forpaediatricpatients)thephysiologicalmaturityofthepatient.Thelowestdosageneededtoprovide

effectiveanaesthesiaand/oranalgesiashouldalwaysbeadministered.

Becausethenumberofpossiblevariablesaffectingdosinginchildrenisconsiderable,specificguidanceisnotprovided

inTable1.Reduceddosesshouldalwaysbeused,andtheexactrequirementsforeachpatientshouldbeestablishedby

anexperiencedanaesthetistwithreferencetocurrentprofessionalpracticeguidelinesandrecognisedstandardtexts 1

Themaximumrecommendeddoseofbupivacainehydrochlorideinchildren,baseduponbodyweightis2mg/kg.For

epiduralinfusion,afteraloadingdoseof0.25-0.75mg/Kgthemaximumrateofadministrationinchildren6months

oryoungeris0.2mg/kg/hourandinchildrenolderthan6monthsis0.4mg/kg/hour.Themaximumrecommendeddose

duringa4-hourperiodis1mg/kgforchildren6monthsoryoungerand2mg/kgforchildrenolderthan6months.

Totaldoseduringa24-hourperiodhasnotbeenestablished,recommendedmaximumdoseshouldnotexceed6mg/Kg.

Theuseofbupivacaineover48hoursisnotrecommendedinchildren6monthsofageoryounger.Infusionrates

shouldbereducedinpatientswithriskfactorsforseizures.

ELDERLYPATIENTS:

Elderlyordebilitatedpatientsmightbemoresensitivetothestandarddosage,withanincreasedriskandseverityof

toxicreactionsofthecentralnervousandcardiovascularsystem.Dosereductionshouldbeconsidered,butmusttake

intoaccountthefactthatthismayleadtoinsufficientanaesthesia.

1

MillerRD,“Anesthesia”,ChurchillLivingston,5 th

Edition,1999,ISBN:0443079889,andDalensBJ,“Regional

anaesthesiaininfants,childrenandadolescents”,Waverley,1995,ISBN:0683096523.

TABLE1:RECOMMENDEDDOSINGFORBUPIVACAINE

INCOMMONTYPESOFANAESTHESIA

(FORANAVERAGE70KGADULT)

TypeofBlockade Concentration DoseRange

(minimum-maximum)

mg/ml %w/v ml mg mg/Kg

LOCAL

INFILTRATION 2.5 0.25 Upto60 Upto150 Upto2

Upto30 Upto150 Upto2

PERIPHERALNERVEBLOCKS

Diagnosticor

therapeutic

blocks 2.5 0.25 1-40 2.5-100 0.04-1.4

Digitalblocks 2.5 0.25 1-5

2.5-12.5 0.04-0.18

Intercostal

blocks(per

nerve,uptoa

totalof10

nerves) 5 0.5 2-3

10-15 0.14-0.21

Majornerve

blocks(e.g.

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Ataconcentrationof5mg/mlbupivacainehasadurationofactionof2–5hoursafterasingleepiduralinjectionand

ofmorethan12hoursafteraperipheralnerveblock.Theonsetofanaesthesiaisslowerthanwithlidocaine,especially

whenusedformajornerveblocks,butisgenerallybetween15and30minutesformajornerveblocksandtypically

between2to10minutesforspinalnerveblock.Whenusedatalowerconcentration(2.5mg/ml)themotorblocking

effectwillbelessandthedurationofactionshorter.

Bupivacaineisanisobaricsolution,withbaricitysimilartothatofcerebrospinalfluid(CSF).Thespreadofanaesthesia

dependsonseveralfactorsincludingthevolumeofsolutionandthepositionofthepatientduringandfollowingthe

injection.Itshouldbeunderstoodthatthelevelofspinalanaesthesiaachievedwithanylocalanaestheticcouldbe

CENTRALNERVEBLOCKS

ThoracalEpidural

Surgical

procedures 5 0.5 5-10 25-50 0.36-0.71

Post-operative

painrelief 2.5 0.25 5-15 12.5-37.5 0.18-0.54

Note:Thedoseincludesthetestdose.

ThoracalEpidural–continuousinfusion

Post-operative

painrelief

(thoracaland

upperabdominal

surgery) 2.5 0.25 4-7.5

perhour 10-18.75per

hour 0.14-0.27

Note:Initialbolusdoseof2.5or5mg/mlisneededtoobtainanalgesia.Totalupto400mg

in24hours.

LumbarEpidural

Surgical

procedures

(including

Caesarean

section) 5 0.5 15-30 75-150 1.1-2

Painrelief

duringlabour 2.5 0.25 6-15 15-37.5 0.21-0.54

Note:Thedoseincludesthetestdose.

LumbarEpidural–continuousinfusion

Post-operative

painreliefand

painreliefduring

labour 2.5 0.25 5-7.5

perhour 12.5-18.75

perhour 0.18-0.27

Note:Initialbolusdoseof2.5or5mg/mlisneededtoobtainanalgesia.Totalupto400mg

in24hours.

CaudalEpidural

Surgical

procedures 5 0.5 20-30 100-150 1.43-2

Painrelief

duringlabour 2.5 0.25 6-12 15-30 0.21-0.43

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reducedintheelderlyandinwomeninlatestagesofpregnancy.Theeffectsofadministeringbupivacaine0.5%at

dosesofgreaterthan4mlhavenotbeenstudied;hencedosagesgreaterthan4mlarenotrecommended.

Itisrecommendedthatbupivacaineshouldbewarmedtoroomtemperaturepriortouse,becauseinjectionofacold

solutionmaybepainful.

4.3Contraindications

Knownhypersensitivitytobupivacainehydrochloride,anaestheticsoftheamidetypeoranyoftheexcipients.

Bupivacainehydrochloridemustnotbeusedforintravenousregionalanaesthesia(Bier’sBlock),because

accidentalleakageofbupivacainethroughthetourniquetcancausesystemictoxicreactions.

Bupivacainehydrochloridemustnotbeadministeredtoinflamedorinfectedapplicationsites.

Bupivacainehydrochloridemustnotbeusedforcentralnerveblock(spinalandepidural)ifactivediseaseofthe

centralnervoussystemispresent,suchas:meningitis,poliomyelitis,intracranialhaemorrhage,sub-acutecombined

degenerationofthespinalcordduetoperniciousanaemia,cerebralandspinaltumours,tuberculosisofthespine,in

thecaseofcardiogenicorhypovolaemicshock,orinthepresenceofsignificantcoagulopathyoranticoagulation

therapy,andinobstetricswiththreateningorexistinghaemorrhage.

Bupivacainehydrochloridemustnotbeusedforobstetricparacervicalblock.

4.4Specialwarningsandprecautionsforuse

Withtheexceptionofthesimplestprocedures,allformsoflocalandregionalanaesthesiashouldbeperformedinwell-

equippedfacilitiesandadministeredbystafftrainedandexperiencedintherequiredanaesthetictechniques,andableto

diagnoseandtreatanyunwantedadverseeffectsthatmayoccur.

Adequatemedicalprovisionforresuscitation(suchasinstrumentsforclearingtheairways,resuscitationequipment)

andmanagementofadversereactionsshouldbeavailableforimmediateuse.Wheneverlargerblockadesarerequired

anintravenouscannulashouldbeinsertedbeforethelocalanaestheticisinjected.

Extremecautionshouldbeexercisedtoavoidinadvertentintravascularinjections.Carefulaspirationisrecommended

beforeandduringinjection.Inepiduralanaesthesia,atestdoseof3to5mlbupivacainehydrochlorideis

recommended,preferablywithadrenaline.Intravascularinjectionofadrenalinecanbereadilyidentifiedbyanincrease

inheartfrequency.Continuouscommunicationwiththepatientisrecommended,aswellasmonitoringoftheheartrate

afteradministrationofthetestdose.Re-aspiratebeforeadministrationofthecompletedose.Thecompletedoseshould

beslowlyinjectedbygraduallyincreasingthedoseandbycontinuouslycommunicatingwiththepatient.Ifanytoxic

symptomsoccurtheadministrationshouldbeimmediatelystopped.

Injectionofrepeateddosesofbupivacainehydrochloridemaycausesignificantincreasesinbloodlevelswitheach

repeateddoseduetoslowaccumulationofthedrug.Tolerancevarieswiththestatusofthepatient.

Epiduralorspinalanaesthesiawithanylocalanaestheticcancausehypotensionandbradycardia,whichshouldbe

anticipatedandappropriateprecautionstaken.

Thesemayincludepre-loadingthecirculationwithcrystalloidorcolloidsolution.Ifhypotensiondevelopsitshouldbe

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Particularcareshouldbetakeninthecaseofcertaintypesofanaesthesia,asfollows:

Inordertominimizetheriskofdangeroussideeffectsspecialattentionisalsorequiredinthefollowingpatientgroups:

Elderlypatientsandpatientswithpoorgeneralhealth:acidosisorhypoxiainthepatientincreasestheriskand

severityoftoxicreactionsofthecentralnervoussystemorthecardiovascularsystem.

Patientswithseriousliverand/orkidneyinsufficiency.

PatientswithapartialortotalAVblock:Localanaestheticscancauseaslowingdownofconduction.

Patientsundertreatmentwithbeta-blockers.

Patientswithcoagulationdisordersorongoinganticoagulationtreatment.

IfacentralnerveblockisintendedconcomitanttherapywithNSAIDs(inclusiveacetylsalicylicacid)mustbetaken

intoaccountorbestoppedatanappropriatetimebeforehand.

InobstetricsapossiblecomplicationafteradministrationofBupivacaineisarterialhypotension.

Thepossibilityofcross-hypersensitivitytootheramide-typelocalanaestheticsmustbetakenintoaccount.

Inrarecasescardiacarresthasbeenreportedwithoutpriorcentralnervoussystemsymptoms.Thiswasprobablydueto

overdosecausedbyunintentionalintravascularinjection(seeSection4.9:“Overdose”).

Thereisariskofadditivetoxiceffectsifbupivacaineisadministeredatthesametimeasantiarrhythmicdrugssuchas

tocainideandvolatileanaesthetics.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Bupivacaineshouldbeusedwithcareinpatientsreceivinganti-arrhythmicdrugswithlocalanaestheticactivity,such

aslidocaineandaprindin,sincetheirtoxiceffectsmaybeadditive.

Typeof

Anaesthesia ParticularPrecautionstoNote

Headandneck Cautionisrequiredtoavoidunintentionalintravascularinjection,whichcan

resultincerebraltoxicity,evenatlowdoses.

Retrobulbar

Injection Inrarecasesthelocalanaestheticmayleakintothesubarachnoidspace

resultinginlocalanaesthetictoxicreactionssuchastemporaryblindness,

cardiovascularcollapse,apnoea,convulsionsetc.Thesecomplicationsmust

berecognisedandtreatedimmediately.

Retrobulbarand

peribulbar

injection Withthistypeofinjectionthereisasmallriskofpersistenteyemuscle

dysfunctionarisingfromdamageand/orlocaltoxiceffectsonthemuscles

and/ornerves.Theseverityofdysfunctiondependsuponthedegreeof

damagecaused,theconcentrationofthelocalanaestheticappliedandthe

durationoftissueexposure.

Centralblocks Thepossibilityofserioushypotensionandbradycardiamustbetakeninto

account,particularlyinhypovolaemicpatients.

Cautionisrequiredinpatientswithreducedcardiovascularreservesbecause

theyarepossiblylessabletocompensateforthereducedatrioventricular

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4.6Pregnancyandlactation

Thereisnoevidenceofuntowardeffectsinhumanpregnancy.Studiesinanimalshaveshownreproductivetoxicity

(seesection5.3).Thehumanriskisunknown.Bupivacaineshouldnotthereforebegiveninearlypregnancyunlessthe

benefitsareconsideredtooutweightherisks.

Aswithotherlocalanaestheticsusedforlocalandregionalanaesthesiaduringpregnancy,bupivacainepassesthrough

theplacenta.

Althoughthetotalbupivacaineconcentrationsintheumbilicalcordbloodarelowerthanthemother’sserum

concentrations,thefreebupivacaineconcentrationisthesame.Foetalbradycardiamayoccurfollowingparacervical

block.

Bupivacaineissecretedintobreastmilk.However,theconcentrationsaresolowthatattherapeuticdosesnoharmful

effectsontheneonateareanticipated.

4.7Effectsonabilitytodriveandusemachines

Intherapeuticdoseslocalanaestheticshavenoeffectonmentalfunctions.However,theycanaffectthemotorsystem

inpartsofthebodyinfluencedbythelocalanaestheticblock.Thedoctorshouldalwaysassessthepotentialeffectson

thepatientandadvisethepatientaccordingly.

4.8Undesirableeffects

General

Undesirableeffectsresultingfromoverdoseorunintentionalintravascularinjectionareverysignificantandcanbe

serious(seeSection4.9:“Overdose”).

Bupivacaineismorelikelytoproduceacutecardiactoxicitythanotherlocalanaesthetics.Cardiovascularreactionsare

relatedtodepressionoftheconductionsystemofthenheartandmyocardiumleadingtodecreasedcardiacoutput,heart

block,hypotension,bradycardia,andsometimesventriculararrhythmias,includingventriculartachycardia,ventricular

fibrillationandcardiacarrest.UsuallythesewillbeprecededoraccompaniedbymajorCNStoxicity,suchas

convulsions,butinrarecasescardiacarresthasoccurredwithoutprecedingCNSeffects.Hypoxiaandacidosismodify

thepharmacokineticsandpharmacodynamicsoflocalanaestheticsandmayincreasetheriskofanaesthetictoxicity.

Hypersensitivityreactions

Hypersensitivityreactionstolocalamidetypeanaestheticsrarelyoccur.

Neurologicalcomplications

Neurologicalreactionstolocalamidetypeanaestheticsareveryrare.Inmostcasesthesereactionsareafunctionofthe

totaladministereddoseofthelocalanaesthetic,themannerinwhichtheanaesthetichasbeenadministeredandthe

physicalconditionofthepatient.Manyoftheseeffectsmayberelatedtothetechniquesused,withorwithoutthe

contributionofthemedicationbeingused.Neurologicalreactionsasaresultofregionalanaesthesiaarepersistent

anaesthesia,paraesthesia,paresisorplegiaofthelowerextremitiesandlossofsphinctercontrol.

Acutesystemictoxicity

Seriousreactionscausedbybupivacaineareidenticaltothoseobservedwithotherlocalanaestheticsandtypically

occurasaresultofhighsystemicconcentrations,asinthecaseofoverdose,toorapidabsorptionandthrough

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Frequencytable:

4.9Overdose

Acutesystemictoxicity

Acutesystemictoxicityarisingfromaccidentalintravascularinjectionsoccursrapidly(withinonetothreeminutes).

Withoverdosing,acutetoxicityoccursoveralongerperiod,asthepeakplasmaconcentrationrises;toxiceffects

typicallyoccurupto20-30minutesafteradministrationandrelatetotheeffectofbupivacaineonthecentralnervous

andcardiovascularsystems.

EffectsontheCentralNervousSystem(CNS):

Inoverdosing,thetoxiceffectsofbupivacaineontheCNSoccurgraduallyandinincreasingseriousness.

Theyinclude:

Initially:Circumoralparaesthesia,numbnessofthetongue,dizziness,hyperacusis,andtinnitus.

Visualdisturbanceandmuscletremor:Thesearemoreseriousandmustnotbemistakenfornervousbehaviour

becausetheymayprecedetheoccurrenceofgeneralseizure.

Lossofconsciousnessandgrandmalseizureslastingfromafewsecondstoseveralminutes.

Hypoxiaandhypercapniaoccurringshortlyafterseizures,resultingfromincreasedmuscleactivity,togetherwith

disturbancesofnormalrespiration.Inmoreseriouscases,apneoamayoccur.

Acidosis,whichresultsinexacerbationofthetoxiceffects.

Therateofrecoveryfromthetoxiceffectsofbupivacaineoverdoseisrelatedtotherateofwhichtheblood

concentrationfalls.Whereasmalldosehasbeengiven,recoverycanoccurquitequickly.

EffectsontheCardiovascularSystem:

Incasesofseriousoverdosing,cardiovasculareffectsareseen;includinghypotension,bradycardia,arrhythmiasand(at

highconcentrations)cardiovascularcollapse.

Generally,CNSsymptomsareseenbeforeadversecardiovasculareffectsarise,providingthatthepatientisnotfully

anaesthetizedorheavilysedatedwithdrugssuchasbenzodiazepinesorbarbiturates.

Treatmentofacutetoxicity

Ifsignsofacutesystemictoxicityaresuspected,administrationofbupivacainemustbestoppedimmediately.

Frequency System Symptoms

Common

(>1/100-<1/10) CNS Headache(relatedtotheanaesthetic

technique)

Circulatory Fallinbloodpressureandbradycardia

(primarilywithepiduralanaesthesia)

Rare

(>1/10,000-<1/1,000) General Allergicreactions,inthemostserious

cases–anaphylacticshock.

Circulatory Myocardialdepressionandcardiacarrest

(withabsoluteorrelativeoverdosage)

Unconsciousnessandseizures(with

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Theprincipalaimsoftreatmentare:

Tomaintainoxygenation

Tostabilisethecirculatorysystem,and

Tocontroltheseizures.

Oxygenshouldbeimmediatelyadministered;ifnecessarybybagandmask(assisted)ventilation.

Ifseizuresdonotresolvespontaneouslywithin15–20seconds,ananticonvulsantdrug,suchasthiopental(100to

150mg)shouldbeadministeredintravenously.Benzodiazepines(forexample,Diazepam(5-10mgi.v.))mayalsobe

administered.Succinylcholinemayalsobeusedtoquicklytreatmusclecramps,butadministrationofthisdrugrequires

trachealintubationandartificialventilation,andmustthereforeonlybeadministeredbyexperiencedmedicalstaff,

familiarwiththistechnique.

Ifsignsofcardiovasculardepressionareevident(suchashypotensionandbradycardia),ephedrine(5–10mg)should

beadministeredintravenously,andaseconddoseprovided,ifnecessary,aftertwotothreeminutes.

Ifcirculatoryarrestoccurs,cardiopulmonaryresuscitationshouldbeimmediatelyinitiated:Adrenaline(0.1-0.2mg)

shouldbeimmediatelyadministeredintravenouslyorintracardiallyandifnecessaryrepeated.Optimaloxygenation,

ventilation,circulatorymaintenanceandtreatmentofacidosismustalsobeprovided,becausehypoxiaandacidosiscan

exacerbatetheacutetoxiceffects.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:LocalAnaesthetic.ATCCode:N01BB01

Bupivacaineisalocalamidetypeanaestheticwithalong-termeffectivenessandahighanaestheticactivity.

Themechanismofactionisbasedonreducedsodiumionpermeabilityofthenervecellmembrane.Asaresultofthis,

thedepolarisationrateisreducedandtheexcitationthresholdisincreased,whichleadstoareversiblelossoffeeling.

Ataconcentrationof5mg/mlbupivacainehasadurationofactionof2–5hoursafterasingleepiduralinjectionand

ofmorethan12hoursafteraperipheralnerveblock.Theonsetofanaesthesiaisslowerthanwithlidocaine,especially

whenusedformajornerveblocks,butisgenerallybetween15and30minutesformajornerveblocksandtypically2

to10minutesforspinalnerveblock.Whenusedatalowerconcentration(2.5mg/ml)themotorblockingeffectwillbe

lessandthedurationofactionshorter.

Itshouldbenotedthattheindividualvariationsinmotorblockresponsestobupivacainearelarge.

5.2Pharmacokineticproperties

Absorptionanddistribution

Theextentofsystemicabsorptionofbupivacainedependsuponthedose,themannerofadministrationandtheextent

ofvascularisationofthesiteofinjection.Increasedlevelsofalphaacidglycoproteins,ascanoccuraftermajorsurgery,

cangiverisetoanincreaseinthetotalbupivacaineplasmaconcentrations.However,thefreebupivacaine

concentrationremainsthesameandthisexplainswhytotalbupivacaineconcentrationshigherthanthelimitof2.6to3

mg/l(whichisconsideredtoxic)areusuallywelltoleratedbypatients.

Metabolismandexcretion

Bupivacaineislargelymetabolisedintheliverandeliminatedthroughthekidneys.Aswithotherlocalamidetype

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5.3Preclinicalsafetydata

Atsupratherapeuticdosesthereisevidenceofdecreasedpupsurvivalinratsandembryologicaleffectsinrabbitsif

bupivacaineisadministeredduringpregnancy.Furtherpreclinicaldataareofnomorerelevancetotheprescriberthan

thatstatedinothersectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

Sodiumhydroxide

Waterforinjections

6.2Incompatibilities

Theadditionofbupivacainetoalkalinesolutionscausesprecipitationofbupivacainebecausethesolubilityof

bupivacaineislimitedatpHlevelsgreaterthan6.5.

Thesolutionsshouldnotcomeincontactwithmetals,forexampleneedles,orwithpartsofthesyringeforalong

periodoftime,sincemetalionsinthesolutionmayleadtoswellingattheinjectionsite.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

5ml,10ml,or20mlType1colourlessglassampoules,eachofwhichissuppliedinpacksof10ampoules.

Notallpresentationsmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Eachampouleisintendedforsingleuseonly.

Thesolutionshouldbeimmediatelyusedafteropeningtheampoule.

Anyunusedproductshouldbedisposedofafterfirstuseinaccordancewithlocalrequirements.

Onlyusebupivacaineifthesolutionintheampouleiscompletelyclearandtheampouleisundamaged.

7MARKETINGAUTHORISATIONHOLDER

BaxterHealtcareLtd.

CaxtonWay

Thetford,Norfolk

IP243SE

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8MARKETINGAUTHORISATIONNUMBER

PA167/112/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:02May2003

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