CHIROCAINE

Main information

  • Trade name:
  • CHIROCAINE Solution injection or concentrate for solution infusion 7.5
  • Dosage:
  • 7.5
  • Pharmaceutical form:
  • Solution injection or concentrate for solution infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CHIROCAINE Solution injection or concentrate for solution infusion 7.5
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0038/071/008
  • Authorization date:
  • 08-06-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Chirocaine7.5mg/mlsolutionforinjection/concentrateforsolutionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onemlcontains7.5mglevobupivacaineaslevobupivacainehydrochloride.

Eachampoulecontains75mgin10ml.

Excipients:3.6mg/mlofsodiumperampoule.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Solutionforinjection/concentrateforsolutionforinfusion.

Clearcolourlesssolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Adults

Surgicalanaesthesia

-Major,e.g.epidural,intrathecal,peripheralnerveblock.

-Minor,e.g.localinfiltration,peribulbarblockinophthalmicsurgery.

Painmanagement

-Continuousepiduralinfusion,singleormultiplebolusepiduraladministrationforthemanagementofpain

especiallypost-operativepainorlabouranalgesia.

Children

Analgesia(ilioinguinal/iliohypogastricblocks).

4.2Posologyandmethodofadministration

Levobupivacaineshouldbeadministeredonlyby,orunderthesupervisionof,aclinicianhavingthenecessarytraining

andexperience.

Thetablebelowisaguidetodosageforthemorecommonlyusedblocks.Foranalgesia(e.g.epiduraladministration

forpainmanagement),thelowerconcentrationsanddosesarerecommended.Whereprofoundorprolongedanaesthesia

isrequiredwithdensemotorblock(e.g.epiduralorperibulbarblock),thehigherconcentrationsmaybeused.Careful

aspirationbeforeandduringinjectionisrecommendedtopreventintravascularinjection.

Aspirationshouldberepeatedbeforeandduringadministrationofabolusdose,whichshouldbeinjectedslowlyandin

incrementaldoses,atarateof7.5–30mg/min,whilecloselyobservingthepatient’svitalfunctionsandmaintaining

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Iftoxicsymptomsoccur,theinjectionshouldbestoppedimmediately.

Maximumdose

Themaximumdosagemustbedeterminedbyevaluatingthesizeandphysicalstatusofthepatient,togetherwiththe

concentrationoftheagentandtheareaandrouteofadministration.Individualvariationinonsetanddurationofblock

doesoccur.Experiencefromclinicalstudiesshowsonsetofsensoryblockadequateforsurgeryin10-15minutes

followingepiduraladministration,withatimetoregressionintherangeof6-9hours.

Therecommendedmaximumsingledoseis150mg.Wheresustainedmotorandsensoryblockarerequiredfora

prolongedprocedure,additionaldosesmayberequired.Themaximumrecommendeddoseduringa24hourperiodis

400mg.Forpost-operativepainmanagement,thedoseshouldnotexceed18.75mg/hour.

Obstetrics

Forcaesareansection,higherconcentrationsthanthe5.0mg/mlsolutionshouldnotbeused(seesection4.3).The

maximumrecommendeddoseis150mg.

Forlabouranalgesiabyepiduralinfusion,thedoseshouldnotexceed12.5mg/hour.

Children

Inchildren,themaximumrecommendeddoseforanalgesia(ilioinguinal/iliohypogastricblocks)is1.25mg/kg/side.

Thesafetyandefficacyoflevobupivacaineinchildrenforotherindicationshavenotbeenestablished.

Specialpopulations

Debilitated,elderlyoracutelyillpatientsshouldbegivenreduceddosesoflevobupivacainecommensuratewiththeir

physicalstatus.

Inthemanagementofpost-operativepain,thedosegivenduringsurgerymustbetakenintoaccount.

Therearenorelevantdatainpatientswithhepaticimpairment(seesections4.4and5.2).

TableofDoses

Concentration

(mg/ml) 1 Dose MotorBlock

SurgicalAnaesthesia

Epidural(slow)bolus 2

forsurgery

-Adults 5.0-7.5 10-20ml(50-150mg) Moderateto

complete

Epiduralslow

injection 3

CaesareanSection 5.0 15-30ml(75-150mg) Moderateto

complete

Intrathecal 5.0 3ml(15mg) Moderateto

complete

PeripheralNerve

Ilioinguinal/

Iliohypogastricblocks

inchildren<12years 2.5-5.0

2.5-5.0 1-40ml(2.5-150mgmax

0.25-0.5ml/kg(0.625-

2.5mg/kg) Moderateto

complete

Notapplicable

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Levobupivacainesolutionforinjection/concentrationforsolutionforinfusionisavailablein2.5,5.0and7.5mg/ml

solutions.

Spreadover5minutes(seealsotext).

Givenover15-20minutes.

Incaseswherelevobupivacaineiscombinedwithotheragentse.g.opioidsinpainmanagement,thelevobupivacaine

doseshouldbereducedanduseofalowerconcentration(e.g.1.25mg/ml)ispreferable.

Theminimumrecommendedintervalbetweenintermittentinjectionsis15minutes.

Forinformationondilution,seesection6.6.

4.3Contraindications

Generalcontraindicationsrelatedtoregionalanaesthesia,regardlessofthelocalanaestheticused,shouldbetakeninto

account.

Levobupivacainesolutionsarecontraindicatedinpatientswithaknownhypersensitivitytolevobupivacaine,local

anaestheticsoftheamidetypeoranyoftheexcipients(seesection4.8).

Levobupivacainesolutionsarecontraindicatedforintravenousregionalanaesthesia(Bier'sblock).

Levobupivacainesolutionsarecontraindicatedinpatientswithseverehypotensionsuchascardiogenicor

hypovolaemicshock.

The7.5mg/mlsolutioniscontraindicatedforobstetricuseduetoanenhancedriskforcardiotoxiceventsbasedon

experiencewithbupivacaine(seesection4.6).

Levobupivacainesolutionsarecontraindicatedforuseinparacervicalblockinobstetrics(seesection4.6).

4.4Specialwarningsandprecautionsforuse

Allformsoflocalandregionalanaesthesiawithlevobupivacaineshouldbeperformedinwell-equippedfacilitiesand

administeredbystafftrainedandexperiencedintherequiredanaesthetictechniquesandabletodiagnoseandtreatany

unwantedadverseeffectsthatmayoccur.

block) complete

LocalInfiltration

-Adults 2.5 1-60ml(2.5-150mgmax) Notapplicable

PainManagement 4

LabourAnalgesia

(epiduralbolus 5

6-10ml(15-25mg) Minimalto

moderate

LabourAnalgesia

(epiduralinfusion) 1.25 6 4-10ml/h(5-12.5mg/h) Minimalto

moderate

Post-operativepain

1.25 6

10-15ml/h(12.5-

18.75mg/h)

5-7.5ml/h(12.5–

18.75mg/h) Minimalto

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Levobupivacaineshouldbeusedwithcautionforregionalanaesthesiainpatientswithimpairedcardiovascularfunction

e.g.seriouscardiacarrhythmias(seesection4.3).

Theintroductionoflocalanestheticsviaeitherintrathecalorepiduraladministrationintothecentralnervoussystemin

patientswithpreexistingCNSdiseasesmaypotentiallyexacerbatesomeofthesediseasestates.Therefore,clinical

judgmentshouldbeexercisedwhencontemplatingepiduralorintrathecalanesthesiainsuchpatients.

Thismedicinalproductcontains3.6mg/mlsodiuminthebagorampoulesolutiontobetakenintoconsiderationby

patientsonacontrolledsodiumdiet.

EpiduralAnesthesia

Duringepiduraladministrationoflevobupivacaine,concentratedsolutions(0.5-0.75%)shouldbeadministeredin

incrementaldosesof3to5mlwithsufficienttimebetweendosestodetecttoxicmanifestationsofunintentional

intravascularorintrathecalinjection.Casesofseverebradycardia,hypotensionandrespiratorycompromisewith

cardiacarrest(someofthemfatal),havebeenreportedinconjunctionwithlocalanesthetics,including

levobupivacaine.Whenalargedoseistobeinjected,e.g.inepiduralblock,atestdoseof3-5mllidocainewith

adrenalineisrecommended.Aninadvertentintravascularinjectionmaythenberecognisedbyatemporaryincreasein

heartrateandaccidentalintrathecalinjectionbysignsofaspinalblock.

Syringeaspirationsshouldalsobeperformedbeforeandduringeachsupplementalinjectionincontinuous

(intermittent)cathetertechniques.Anintravascularinjectionisstillpossibleevenifaspirationsforbloodarenegative.

Duringtheadministrationofepiduralanesthesia,itisrecommendedthatatestdosebeadministeredinitiallyandthe

effectsmonitoredbeforethefulldoseisgiven.

Epiduralanaesthesiawithanylocalanaestheticmaycausehypotensionandbradycardia.Allpatientsmusthave

intravenousaccessestablished.Theavailabilityofappropriatefluids,vasopressors,anaestheticswithanticonvulsant

properties,myorelaxants,andatropine,resuscitationequipmentandexpertisemustbeensured(seesection4.9).

Majorregionalnerveblocks

ThepatientshouldhaveI.V.fluidsrunningviaanindwellingcathetertoassureafunctioningintravenouspathway.

Thelowestdosageoflocalanestheticthatresultsineffectiveanesthesiashouldbeusedtoavoidhighplasmalevelsand

seriousadverseeffects.Therapidinjectionofalargevolumeoflocalanestheticsolutionshouldbeavoidedand

fractional(incremental)dosesshouldbeusedwhenfeasible.

UseinHeadandNeckArea

Smalldosesoflocalanestheticsinjectedintotheheadandneckarea,includingretrobulbar,dentalandstellateganglion

blocks,mayproduceadversereactionssimilartosystemictoxicityseenwithunintentionalintravascularinjectionsof

largerdoses.Theinjectionproceduresrequiretheutmostcare.Reactionsmaybeduetointraarterialinjectionofthe

localanestheticwithretrogradeflowtothecerebralcirculation.Theymayalsobeduetopunctureoftheduralsheathof

theopticnerveduringretrobulbarblockwithdiffusionofanylocalanestheticalongthesubduralspacetothe

midbrain.Patientsreceivingtheseblocksshouldhavetheircirculationandrespirationmonitoredandbeconstantly

observed.Resuscitativeequipmentandpersonnelfortreatingadversereactionsshouldbeimmediatelyavailable.

UseinOphthalmicSurgery

Clinicianswhoperformretrobulbarblocksshouldbeawarethattherehavebeenreportsofrespiratoryarrestfollowing

localanaestheticinjection.Priortoretrobulbarblock,aswithallotherregionalprocedures,theimmediateavailability

ofequipment,drugs,andpersonneltomanagerespiratoryarrestordepression,convulsions,andcardiacstimulationor

depressionshouldbeassured.Aswithotheranestheticprocedures,patientsshouldbeconstantlymonitoredfollowing

ophthalmicblocksforsignsoftheseadversereactions.

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Debilitated,elderlyoracutelyillpatients:levobupivacaineshouldbeusedwithcautionindebilitated,elderlyor

acutelyillpatients(seesection4.2).

Hepaticimpairment:sincelevobupivacaineismetabolisedintheliver,itshouldbeusedcautiouslyinpatientswith

liverdiseaseorwithreducedliverbloodflowe.g.alcoholicsorcirrhotics(seesection5.2).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

InvitrostudiesindicatethattheCYP3A4isoformandCYP1A2isoformmediatethemetabolismoflevobupivacaine.

Althoughnoclinicalstudieshavebeenconducted,metabolismoflevobupivacainemaybeaffectedbyCYP3A4

inhibitorseg:ketoconazole,andCYP1A2inhibitorseg:methylxanthines.

Levobupivacaineshouldbeusedwithcautioninpatientsreceivinganti-arrhythmicagentswithlocalanaesthetic

activity,e.g.,mexiletine,orclassIIIanti-arrhythmicagentssincetheirtoxiceffectsmaybeadditive.

Noclinicalstudieshavebeencompletedtoassesslevobupivacaineincombinationwithadrenaline.

4.6Fertility,pregnancyandlactation

Pregnancy

Levobupivacainesolutionsarecontraindicatedforuseinparacervicalblockinobstetrics.Basedonexperiencewith

bupivacainefoetalbradycardiamayoccurfollowingparacervicalblock(seesection4.3).

The7.5mg/mlsolutioniscontra-indicatedforobstetricuseduetoenhancedriskforcardiotoxiceventsbasedon

experiencewithbupivacaine(seesection4.3).

Forlevobupivacaine,therearenoclinicaldataonfirsttrimester-exposedpregnancies.Animalstudiesdonotindicate

teratogeniceffectsbuthaveshownembryo-foetaltoxicityatsystemicexposurelevelsinthesamerangeasthose

obtainedinclinicaluse(seesection5.3).Thepotentialriskforhumanisunknown.Levobupivacaineshouldtherefore

notbegivenduringearlypregnancyunlessclearlynecessary.

Lactation

Levobupivacaineexcretioninbreastmilkisunknown.However,levobupivacaineislikelytobepoorlytransmittedin

thebreastmilk,asforbupivacaine.Thusbreastfeedingispossibleafterlocalanaesthesia.

4.7Effectsonabilitytodriveandusemachines

Levobupivacainecanhaveamajorinfluenceontheabilitytodriveorusemachines.Patientsshouldbewarnednotto

driveoroperatemachineryuntilalltheeffectsoftheanaesthesiaandtheimmediateeffectsofsurgeryarepassed.

4.8Undesirableeffects

Theadversedrugreactionsforlevobupivacaineareconsistentwiththoseknownforitsrespectiveclassofmedicinal

products.Themostcommonlyreportedadversedrugreactionsarehypotension,nausea,anaemia,vomiting,dizziness,

headache,pyrexia,proceduralpain,backpainandfoetaldistresssyndromeinobstetricuse(seetablebelow).

Adversereactionsreportedeitherspontaneouslyorobservedinclinicaltrialsaredepictedinthefollowingtable.Within

eachsystemorganclass,theadversedrugreactionsarerankedunderheadingsoffrequency,usingthefollowing

convention:verycommon(1/10),common(1/100,<1/10),uncommon(1/1000,<1/100),notknown(cannotbe

estimatedfromtheavailabledata).

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Reaction

Bloodandlymphaticsystem

disorders VeryCommon Anaemia

Immunesystemdisorders Notknown

Notknown Allergicreactions(inserious

casesanaphylacticshock)

Hypersensitivity

Nervoussystemdisorders Common

Common

Notknown

Notknown

Notknown

Notknown

Notknown

Notknown

Dizziness

Headache

Convulsion

Lossofconsciousness

Somnolence

Syncope

Paraesthesia

Paraplegia

Paralysis 1

Eyedisorders Notknown

Notknown

Notknown

Notknown Visionblurred

Ptosis 2

Miosis 2

Enophthalmos 2

Cardiacdisorders Notknown

Notknown

Notknown

Notknown

Notknown Atrioventricularblock

Cardiacarrest

Ventriculartachyarrhythmia

Tachycardia

Bradycardia

Vasculardisorders Verycommon

Notknown Hypotension

Flushing 2

Respiratory,thoracicand

mediastinaldisorders Notknown

Notknown

Notknown

Notknown Respiratoryarrest

Laryngealoedema

Apnoea

Sneezing

Gastrointestinaldisorders VeryCommon

Common

Notknown

Notknown Nausea

Vomiting

Hypoaesthesiaoral

Lossofsphinctercontrol 1

Skinandsubcutaneoustissue

disorders Notknown

Notknown

Notknown

Notknown

Notknown

Notknown Angioedema

Urticaria

Pruritus

Hyperhidrosis

Anhidrosis 2

Erythema

Musculoskeletalandconnective

tissuedisorders Common

Notknown

Notknown Backpain

Muscletwitching

Muscularweakness

Renalandurinarydisorders Notknown

Bladderdysfunction 1

Pregnancy,puerperiumand

perinatalconditions Common Foetaldistresssyndrome

Reproductivesystemandbreast

disorders Notknown

Priapism 1

Generaldisordersand

administrationsiteconditions Common Pyrexia

Investigations Notknown

Notknown Cardiacoutputdecreased

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Thismaybeasignorsymptomofcaudaequinasyndrome(seeadditionalsection4.8textbelow).

ThismaybeasignorsymptomoftransientHorner’ssyndrome(seeadditionalsection4.8textbelow).

Adversereactionswithlocalanaestheticsoftheamidetypearerare,buttheymayoccurasaresultofoverdosageor

unintentionalintravascularinjectionandmaybeserious.

Cross-sensitivityamongmembersoftheamide-typelocalanestheticgrouphavebeenreported(seesection4.3).

Accidentalintrathecalinjectionoflocalanaestheticscanleadtoveryhighspinalanaesthesia.

Cardiovasculareffectsarerelatedtodepressionoftheconductionsystemoftheheartandareductioninmyocardial

excitabilityandcontractility.UsuallythesewillbeprecededbymajorCNStoxicity,i.e.convulsions,butinrarecases,

cardiacarrestmayoccurwithoutprodromalCNSeffects.

Neurologicaldamageisararebutwellrecognisedconsequenceofregionalandparticularlyepiduralandspinal

anaesthesia.Itmaybeduetodirectinjurytothespinalcordorspinalnerves,anteriorspinalarterysyndrome,injection

ofanirritantsubstanceoraninjectionofanon-sterilesolution.Rarely,thesemaybepermanent.

Therehavebeenreportsofprolongedweaknessorsensorydisturbance,someofwhichmayhavebeenpermanent,in

associationwithlevobupivacainetherapy.Itisdifficulttodeterminewhetherthelong-termeffectswheretheresultof

medicationtoxicityorunrecognizedtraumaduringsurgeryorothermechanicalfactors,suchascatheterinsertionand

manipulation.

Rarereportshavebeenreceivedofcaudaequinasyndromeorsignsandsymptomsofpotentialinjurytothebaseofthe

spinalcordorspinalnerveroots(includinglowerextremityweaknessorparalysis,lossofbowelcontroland/orbladder

controlandpriapism)associatedwithbupivacaineorlevobupivacainetherapy.However,itcannotbedetermined

whethertheseeventsareduetoaneffectoflevobupivacaine,mechanicaltraumatothespinalcordorspinalnerve

roots,orbloodcollectionatthebaseofthespine.

TherehavealsobeenrarereportsoftransientHorner’ssyndrome(ptosis,miosis,enophthalmos,unilateralsweating

and/orflushing)inassociationwithuseofregionalanaesthetics,includinglevobupivacaine.Thiseventresolveswith

discontinuationoftherapy.

4.9Overdose

Accidentalintravascularinjectionoflocalanaestheticsmaycauseimmediatetoxicreactions.Intheeventofoverdose,

peakplasmaconcentrationsmaynotbereacheduntil2hoursafteradministrationdependingupontheinjectionsiteand,

therefore,signsoftoxicitymaybedelayed.Theeffectsofthedrugmaybeprolonged.

Systemicadversereactionsfollowingoverdoseoraccidentalintravascularinjectionreportedwithlongactinglocal

anaestheticagentsinvolvebothCNSandcardiovasculareffects.

CNSEffects

Convulsionsshouldbetreatedimmediatelywithintravenousthiopentoneordiazepamtitratedasnecessary.

Thiopentoneanddiazepamalsodepresscentralnervoussystem,respiratoryandcardiacfunction.Thereforetheiruse

mayresultinapnoea.Neuro-muscularblockersmaybeusedonlyiftheclinicianisconfidentofmaintainingapatent

airwayandmanagingafullyparalysedpatient.

Ifnottreatedpromptly,convulsionswithsubsequenthypoxiaandhypercarbiaplusmyocardialdepressionfromthe

Injury,poisoningand

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CardiovascularEffects

Hypotensionmaybepreventedorattenuatedbypre-treatmentwithafluidloadand/ortheuseofvasopressors.If

hypotensionoccursitshouldbetreatedwithintravenouscrystalloidsorcolloidsand/orincrementaldosesofa

vasopressorsuchasephedrine5-10mg.Anycoexistingcausesofhypotensionshouldberapidlytreated.

Ifseverebradycardiaoccurs,treatmentwithatropine0.3-1.0mgwillnormallyrestoretheheartratetoanacceptable

level.

Cardiacarrhythmiashouldbetreatedasrequiredandventricularfibrillationshouldbetreatedbycardioversion.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Localanaesthetics,amide

ATCCode N01BB10

Levobupivacaineisalongactinglocalanaestheticandanalgesic.Itblocksnerveconductioninsensoryandmotor

nerveslargelybyinteractingwithvoltagesensitivesodiumchannelsonthecellmembrane,butalsopotassiumand

calciumchannelsareblocked.Inaddition,levobupivacaineinterfereswithimpulsetransmissionandconductionin

othertissueswhereeffectsonthecardiovascularandcentralnervoussystemsaremostimportantfortheoccurrenceof

clinicaladversereactions.

Thedoseoflevobupivacaineisexpressedasbase,whereas,intheracematebupivacainethedoseisexpressedas

hydrochloridesalt.Thisgivesrisetoapproximately13%moreactivesubstanceinlevobupivacainesolutionscompared

tobupivacaine.Inclinicalstudiesatthesamenominalconcentrationslevobupivacaineshowedsimilarclinicaleffectto

bupivacaine.

Inaclinicalpharmacologystudyusingtheulnarnerveblockmodel,levobupivacainewasequipotentwithbupivacaine.

Thereislimitedsafetyexperiencewithlevobupivacainetherapyforperiodsexceeding24hours.

5.2Pharmacokineticproperties

Inhumanstudies,thedistributionkineticsoflevobupivacainefollowingi.v.administrationareessentiallythesameas

bupivacaine.Theplasmaconcentrationoflevobupivacainefollowingtherapeuticadministrationdependsondoseand,

asabsorptionfromthesiteofadministrationisaffectedbythevascularityofthetissue,onrouteofadministration.

Therearenorelevantdatainpatientswithhepaticimpairment(seesection4.4).

Therearenodatainpatientswithrenalimpairment.Levobupivacaineisextensivelymetabolisedandunchanged

levobupivacaineisnotexcretedinurine.

Plasmaproteinbindingoflevobupivacaineinmanwasevaluatedinvitroandwasfoundtobe>97%atconcentrations

between0.1and1.0µg/ml.

Inaclinicalpharmacologystudywhere40mglevobupivacainewasgivenbyintravenousadministration,themean

half-lifewasapproximately80+22minutes,C

1.4+0.2µg/mlandAUC70+27µgmin/ml.

ThemeanC

andAUC(0-24h)oflevobupivacainewereapproximatelydose-proportionalfollowingepidural

administrationof75mg(0.5%)and112.5mg(0.75%)andfollowingdosesof1mg/kg(0.25%)and2mg/kg(0.5%)

usedforbrachialplexusblock.Followingepiduraladministrationof112.5mg(0.75%)themeanC

andAUC

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Themeantotalplasmaclearanceandterminalhalf-lifeoflevobupivacaineafterintravenousinfusionwere39

litres/hourand1.3hours,respectively.Thevolumeofdistributionafterintravenousadministrationwas67litres.

Levobupivacaineisextensivelymetabolisedwithnounchangedlevobupivacainedetectedinurineorfaeces.3-

hydroxylevobupivacaine,amajormetaboliteoflevobupivacaine,isexcretedintheurineasglucuronicacidand

sulphateesterconjugates.InvitrostudiesshowedthatCYP3A4isoformandCYP1A2isoformmediatethemetabolism

oflevobupivacainetodesbutyl-levobupivacaineand3-hydroxylevobupivacainerespectively.Thesestudiesindicate

thatthemetabolismoflevobupivacaineandbupivacainearesimilar.

Followingintravenousadministration,recoveryoflevobupivacainewasquantitativewithameantotalofabout95%

beingrecoveredinurine(71%)andfaeces(24%)in48hours.

Thereisnoevidenceofinvivoracemisationoflevobupivacaine.

5.3Preclinicalsafetydata

Inanembryo-foetaltoxicitystudyinrats,anincreasedincidenceofdilatedrenalpelvis,dilatedureters,olfactory

ventricledilatationandextrathoraco-lumbarribswasobservedatsystemicexposurelevelsinthesamerangeasthose

obtainedatclinicaluse.Therewerenotreatment-relatedmalformations.

Levobupivacainewasnotgenotoxicinastandardbatteryofassaysformutagenicityandclastogenicity.No

carcinogenicitytestinghasbeenconducted.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

SodiumChloride

SodiumHydroxide

Hydrochloricacid

WaterforInjections

6.2Incompatibilities

Levobupivacainemayprecipitateifdilutedwithalkalinesolutionsandshouldnotbedilutedorco-administeredwith

sodiumbicarbonateinjections.Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthose

mentionedinsection6.6.

6.3Shelflife

Shelflifeaspackagedforsale:3years

Shelflifeafterfirstopening:Theproductshouldbeusedimmediately

Shelflifeafterdilutioninsodiumchloridesolution0,9%:

Chemicalandphysicalin-usestabilityhasbeendemonstratedfor7daysat20-22°C.Chemicalandphysicalin-use

stabilitywithclonidine,morphineorfentanylhasbeendemonstratedfor40hoursat20-22°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuser.

6.4Specialprecautionsforstorage

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Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

6.5Natureandcontentsofcontainer

Chirocaineisavailableintwopresentations;

10mlpolypropyleneampouleinpacksof5,10&20

10mlpolypropyleneampoule,insterileblisterpacksof5,10&20

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Forsingleuseonly.Discardanyunusedsolution.

Thesolution/dilutionshouldbeinspectedvisuallypriortouse.Onlyclearsolutionswithoutvisibleparticlesshouldbe

used.

Asterileblistercontainershouldbechosenwhenasterileampoulesurfaceisrequired.Ampoulesurfaceisnotsterile

ifsterileblisterispierced.

Dilutionsoflevobupivacainestandardsolutionsshouldbemadewithsodiumchloride9mg/ml(0.9%)solutionfor

injectionusingaseptictechniques.

Clonidine8.4µg/ml,morphine0.05mg/mlandfentanyl4µg/mlhavebeenshowntobecompatiblewith

levobupivacaineinsodiumchloride9mg/ml(0.9%)solutionforinjection.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratoriesIrelandLtd

4051KingswoodDrive

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA38/71/8

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8 th

June2007

Dateoflastrenewal:18 th

December2008

10DATEOFREVISIONOFTHETEXT

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