CHIROCAINE

Main information

  • Trade name:
  • CHIROCAINE Solution for Infusion 0.625
  • Dosage:
  • 0.625
  • Pharmaceutical form:
  • Solution for Infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CHIROCAINE Solution for Infusion 0.625
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0038/071/004
  • Authorization date:
  • 18-11-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Chirocaine0.625mg/mlsolutionforinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Levobupivacainehydrochloridecorrespondingto0.625mg/mlLevobupivacaine.

Excipients:3.6mg/mlofsodiumperbag.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Solutionforinfusion

Clearsolution

4CLINICALPARTICULARS

4.1TherapeuticIndications

Adults

Painmanagement

Continuousepiduralinfusion,forthemanagementofpostoperativepainandlabouranalgesia.

4.2Posologyandmethodofadministration

Levobupivacaineshouldbeadministeredonlyby,orunderthesupervisionof,aclinicianhavingthenecessarytraining

andexperience.

ChirocaineSolutionforInfusionisforepiduraluseonly.Itmustnotbeusedforintravenousadministration.

Carefulaspirationbeforeinfusionisrecommendedtopreventintravascularinjection.Iftoxicsymptomsoccur,the

injectionshouldbestoppedimmediately.

Maximumdose

Themaximumdosagemustbedeterminedbyevaluatingthesizeandphysicalstatusofthepatient.Themaximum

TypeofBlock Concentration

mg/ml InfusionRatePerHour

ContinuousInfusion:

Postoperativepain

management

Lumbarepidural

(analgesiainlabour) 0.625

0.625 20-30

8-20 12.5-18.75

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

24hourperiodshouldnotexceed400mg.Forlabouranalgesiabyepiduralinfusion,thedoseshouldnotexceed

12.5mg/hour.

Children

Thesafetyandefficacyoflevobupivacaineinchildrenforpainmanagementhasnotbeenestablished.

SpecialPopulations

Debilitated,elderlyoracutelyillpatientsshouldbegivenreduceddosesoflevobupivacainecommensuratewiththeir

physicalstatus.

Inthemanagementofpost-operativepain,thedosegivenduringsurgerymustbetakenintoaccount.

Therearenorelevantdatainpatientswithhepaticimpairment(seesections4.4and5.2).

4.3Contraindications

Generalcontraindicationsrelatedtoregionalanaesthesia,regardlessofthelocalanaestheticused,shouldbetakeninto

account.

Levobupivacainesolutionsarecontraindicatedinpatientswithaknownhypersensitivitytolevobupivacaine,local

anaestheticsoftheamidetypeoranyoftheexcipients(seesection4.8).

Levobupivacainesolutionsarecontraindicatedforintravenousregionalanaesthesia(Bier'sblock).

Levobupivacainesolutionsarecontraindicatedinpatientswithseverehypotensionsuchascardiogenicor

hypovolaemicshock.

Levobupivacainesolutionsarecontraindicatedforuseinparacervicalblockinobstetrics(seesection4.6).

4.4Specialwarningsandprecautionsforuse

Allformsoflocalandregionalanaesthesiawithlevobupivacaineshouldbeperformedinwell-equippedfacilitiesand

administeredbystafftrainedandexperiencedintherequiredanaesthetictechniquesandabletodiagnoseandtreatany

unwantedadverseeffectsthatmayoccur.

Levobupivacainecancauseacuteallergicreactions,cardiovasculareffectsandneurologicaldamage(seesection4.8).

Theintroductionoflocalanestheticsviaepiduraladministrationintothecentralnervoussysteminpatientswith

preexistingCNSdiseasesmaypotentiallyexacerbatesomeofthesediseasestates.Therefore,clinicaljudgmentshould

beexercisedwhencontemplatingepiduralanesthesiainsuchpatients.

Thismedicinalproductcontains3.6mg/mlsodiuminthebagorampoulesolutiontobetakenintoconsiderationby

patientsonacontrolledsodiumdiet.

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.Syringeaspirationsshouldalsobeperformed

beforeandduringeachsupplementalinjectionincontinuous(intermittent)cathetertechniques.Anintravascular

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isrecommendedthatatestdosebeadministeredinitiallyandtheeffectsmonitoredbeforethefulldoseisgiven.

Epiduralanaesthesiawithanylocalanaestheticmaycausehypotensionandbradycardia.Allpatientsmusthave

intravenousaccessestablished.Theavailabilityofappropriatefluids,vasopressors,anaestheticswithanticonvulsant

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

Specialpopulations

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).

Forlevobupivacaine,therearenoclinicaldataonfirsttrimester-exposedpregnancies.Animalstudiesdonotindicate

teratogeniceffectsbuthaveshownembryo-foetaltoxicityatsystemicexposurelevelsinthesamerangeasthose

obtainedinclinicaluse(seesection5.3).Thepotentialriskforhumanisunknown.Levobupivacaineshouldtherefore

notbegivenduringearlypregnancyunlessclearlynecessary.

Nevertheless,todate,theclinicalexperienceofbupivacaineforobstetricalsurgery(atthetermofpregnancyorfor

delivery)isextensiveandhasnotshownafoetotoxiceffect.

Lactation

Levobupivacaineexcretioninbreastmilkisunknown.However,levobupivacaineislikelytobepoorlytransmittedin

thebreastmilk,asforbupivacaine.Thusbreastfeedingispossibleafterlocalanaesthesia.

4.7Effectsonabilitytodriveandusemachines

Levobupivacainecanhaveamajorinfluenceontheabilitytodriveorusemachines.Patientsshouldbewarnednotto

driveoroperatemachineryuntilalltheeffectsoftheanaesthesiaandtheimmediateeffectsofsurgeryarepassed.

4.8Undesirableeffects

Theadversedrugreactionsforlevobupivacaineareconsistentwiththoseknownforitsrespectiveclassofmedicinal

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

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Adversereactionsreportedeitherspontaneouslyorobservedinclinicaltrialsaredepictedinthefollowingtable.Within

eachsystemorganclass,theadversedrugreactionsarerankedunderheadingsoffrequency,usingthefollowing

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

estimatedfromtheavailabledata).

SystemOrganClass Frequency Adverse

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

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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.

Pregnancy,puerperiumand

perinatalconditions Common Foetaldistresssyndrome

Reproductivesystemandbreast

disorder Notknown Priapism 1

Generaldisordersand

administrationsiteconditions Common Pyrexia

Investigations Notknown

Notknown Cardiacoutputdecreased

Electrocardiogramchange

Injury,poisoningand

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Convulsionsshouldbetreatedimmediatelywithintravenousthiopentoneordiazepamtitratedasnecessary.

Thiopentoneanddiazepamalsodepresscentralnervoussystem,respiratoryandcardiacfunction.Therefore,theiruse

mayresultinapnoea.Neuro-muscularblockersmaybeusedonlyiftheclinicianisconfidentofmaintainingapatent

airwayandmanagingafullyparalysedpatient.

Ifnottreatedpromptly,convulsionswithsubsequenthypoxiaandhypercarbiaplusmyocardialdepressionfromthe

effectsofthelocalanaestheticontheheart,mayresultincardiacarrhythmias,ventricularfibrillationorcardiacarrest.

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.

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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

valueswere0.58µg/mland3.56µgh/mlrespectively.

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

mentionedinsection6.3.

6.3Shelflife

Shelflifeaspackagedforsale:3years

Shelflifeafterfirstopening:Theproductshouldbeusedimmediately.

Shelflifeafterdilutioninsodiumchloridesolution0.9%:

Chemicalandphysicalin-usestabilityhasbeendemonstratedforbothlevobupivacaine0.625mg/mland1.25mg/ml

with8.3-8,4µg/mlclonidine,50µg/mlmorphineand2µg/mlfentanyl,respectively,storedfor30daysateither2-8ºC

or20–22 °

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1.25mg/mlwithsufentaniladdedintheconcentrationof0.4µg/mlandstoredfor30daysat2-8ºCor7daysat20–22 °

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2-

8ºC,unlesstheadmixhasbeenpreparedincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

6.5Natureandcontentsofcontainer

Chirocaineisavailableintwopresentations;

100mlsolutionina100mlflexiblepolyesterbagwithanaluminiumfoiloverpouch.

200mlsolutionina250mlflexiblepolyesterbagwithanaluminiumfoiloverpouch.

EachpolyesterbagcontainsonePVCadmixtureportandonePVCadministrationport.

Packsizes: 5bagsofthe100mlsolution.

5bagsofthe200mlsolution.

24bagsofthe100mlsolution.

12bagsofthe200mlsolution.

60bagsofthe100mlsolution.

32bagsofthe200mlsolution.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Forsingleepiduraluseonly.Donotuseunlessthesolutionisclearandcontainerisundamaged.Discardanyunused

solution.

Thesolution/dilutionshouldbeinspectedvisuallypriortouse.Onlyclearsolutionswithoutvisibleparticlesshouldbe

used.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratoriesIrelandLtd

4051KingswoodDrive

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18November2003

Dateoflastrenewal:18December2008

10DATEOFREVISIONOFTHETEXT

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