BUPIVACAINE PFIZER 5MG/ML SOLUTION FOR INJECTION

Main information

  • Trade name:
  • BUPIVACAINE PFIZER 5MG/ML SOLUTION FOR INJECTION
  • Dosage:
  • 5.0 Mg/Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BUPIVACAINE PFIZER 5MG/ML SOLUTION FOR INJECTION
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/031/002
  • Authorization date:
  • 01-04-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BupivacainePfizer5mg/mlSolutionforInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmlcontains5mgofBupivacainehydrochloridemonohydrate

Eachvialwith10mlsolutioncontains50mgofbupivacainehydrochloridemonohydrate.

Eachvialwith20mlsolutioncontains100mgofbupivacainehydrochloridemonohydrate.

Excipient:

Eachmlofthesolutioncontains3.15mgofSodium.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Solutionforinjection.

Aclear,colourless,aqueous,sterilesolution.

pHofthesolutionisbetween4.0and6.5andosmolarityis290mOsmol/l.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Fortheproductionoflocalanaesthesiabyperipheralnerveblock(s)andcentralneuralblock(caudalorepidural),that

is,forspecialistuseinsituationswhereprolongedanaesthesiaisrequired.Bupivacaine-Pfizerisalsoindicatedforthe

reliefoflabourpain.

4.2Posologyandmethodofadministration

Thedosagevariesanddependsupontheareatobeanaesthetised,thevascularityofthetissues,thenumberofneuronal

segmentstobeblocked,individualtoleranceandthetechniqueofanaesthesiaused.Thelowestdosageneededto

provideeffectiveanaesthesiashouldbeadministered.Formostindications,thedurationofanaesthesiawith

Bupivacainesolutionsissuchthatasingledoseissufficient.

Themaximumdosagemustbedeterminedbyevaluatingthesizeandphysicalstatusofthepatientandconsideringthe

usualrateofsystemicabsorptionfromaparticularinjectionsite.Experiencetodateindicatesasingledoseofupto

150mgbupivacainehydrochloridemonohydrate.Dosesofupto50mg2-hourlymaysubsequentlybeused.A

maximumdoseof2mg/kgshouldnotbeexceededinanyfour-hourperiod.

Whenprolongedblocksareused,eitherbycontinuousinfusionorbyrepeatedbolusadministration,therisksof

reachingatoxicplasmaconcentrationorinducingalocalneuralinjurymustbeconsidered.

Thedosagesinthefollowingtablearerecommendedasaguideforuseintheaverageadult.Individualvariationsin

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Dosagerecommendationsforadults

Conc

mg/ml Volume

ml Dose

mg Onset

min Duration

hours

SURGICALANAESTHESIA

LumbarEpiduralAdministration 1)

Surgery 5.0 15-30 75-150 15-30 2-3

LumbarEpiduralAdministration 1)

CaesareanSection 5.0 15-30 75-150 15-30 2-3

ThoracicEpiduralAdministration 1)

Surgery 2.5

5-15

5-10 12.5-37.5

25-50 10-15

10-15 1.5-2

CaudalEpiduralBlock 1) 2.5

20-30

20-30 50-75

100-150 20-30

15-30 1-2

MajorNerveBlock 2)

(eg,brachial

plexus,femoral,sciatic) 5.0 10-30 50-150 15-30 4-8

Fieldblock(eg,minornerveblocks

andinfiltration) 2.5

<60

≤30 <150

≤150 1-3

1-10 3-4

ACUTEPAINMANAGEMENT

LumbarEpiduralAdministration

Intermittentinjections 3)

(e.g.post-operativepainrelief) 2.5 6-15;

minimum

interval30

minutes 15-37.5;

minimum

interval30

minutes 2-5 1-2

Continuousinfusion 4) 1.25

10-15/h

5-7.5/h 12.5-18.8/h

12.5-18.8/h -

Continuousinfusion,labourpain

relief 4) 1.25 5-10/h 6.25-12.5/h - -

ThoracicEpiduralAdministration

Continuousinfusion 1.25

5-10/h

4-7.5/h 6.3-12.5/h

10-18.8/h -

Intra-ArticularBlock 5)

(eg,

followingkneearthroscopy) 2.5 ≤40 ≤100 5-10 2-4hafter

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Notes:

Ingeneral,surgicalanaesthesia(e.g.epiduraladministration)requirestheuseofhigherconcentrationsanddoses.When

alessintenseblockisrequired,theuseofalowerconcentrationisindicated.Thevolumeofmedicinalproductused

willaffecttheextentofspreadofanaesthesia.

Inordertoavoidintravascularinjection,aspirationshouldberepeatedpriortoandduringadministrationofthemain

dose,whichshouldbeinjectedslowlyorinincrementaldoses,atarateof25-50mg/min,whilecloselyobservingthe

patient'svitalfunctionsandmaintainingverbalcontact.Whenanepiduraldoseistobeinjected,aprecedingtestdose

of3-5mlbupivacainecontainingadrenaline(epinephrine)isrecommended.

Aninadvertentintravascularinjectionmayberecognisedbyatemporaryincreaseinheartrateandanaccidental

intrathecalinjectionbysignsofaspinalblock.Iftoxicsymptomsoccur,theinjectionshouldbestoppedimmediately.

Paediatricpatients1to12yearsofage

Thedosesinthetableshouldberegardedasguidelinesforuseinpaediatrics.Individualvariationsoccur.Inchildren

withahighbodyweightagradualreductionofthedosageisoftennecessaryandshouldbebasedontheidealbody

weight.Standardtextbooksshouldbeconsultedforfactorsaffectingspecificblocktechniquesandforindividual

patientrequirements.

Dosagerecommendationsforchildren

Inchildrenthedosageshouldbecalculatedonaweightbasisupto2mg/kg.

Fordosesnotrealisable/practicablewiththisstrengthotherstrengthsofthismedicinalproductareavailable.

Instructionforuse

Forsingleuseonly.Thesolution/dilutionshouldbeinspectedvisuallypriortouse.

FieldBlock(eg,minornerveblocks

andinfiltration) 2.5 ≤60 ≤150 1-3 3-4

1)Doseincludestestdose.

2)Thedoseforamajornerveblockmustbeadjustedaccordingtositeofadministrationandpatientstatus.

Interscaleneandbrachialplexusblocksmaybeassociatedwithahigherfrequencyofseriousadversereactions,

regardlessofthelocalanaestheticused,seealsosection4.4.

3)Intotal<500mg/24h.

4)Thissolutionisoftenusedforepiduraladministrationincombinationwithasuitableopioidforpainmanagement.

Intotal<500mg/24h.

5)Ifadditionalbupivacaineisusedbyanyothertechniquesinthesamepatient,anoveralldoselimitof150mg

shouldnotbeexceeded.

Conc.

mg/ml Volume

ml/kg Dosemg/kg Onset

min Duration

hours

AcutePainManagement(pre-andPostoperative)

CaudalEpidural

Administration 2.5 0.6-0.8 1.5-2 20-30 2-6

LumbarEpidural

Administration 2.5 0.6-0.8 1.5-2 20-30 2-6

ThoracicEpidural

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4.3Contraindications

Bupivacaine-Pfizeriscontra-indicatedinpatientswithhypersensitivitytobupivacainehydrochloridemonohydrate,

localanaestheticagentsoftheamidetypeortoanyoftheotherexcipients.

Solutionsofbupivacainehydrochloridemonohydratearecontra-indicatedforintravenousregionalanaesthesia(Bier's-

block)andobstetricalparacervicalblock.

Thefollowinggeneralcontraindicationsshouldbetakenintoconsiderationincaseofintrathecaland/orepidural

anaesthesia.

activeacutediseasesoftheCentralNervousSystemsuchasmeningitis,tumours,poliomyelitisandintracranic

hemorrhage.

Spinalstenosisandactivediseaseofthespinalcolumn(forexample:spondylitis,tuberculosis,tumours)orrecent

traumaticevents(forexamplefractures)

Septicaemia.

perniciousanemiaassociatedwithsub-acutedegenerationofthebonemarrow

pyogenicinfectionoftheskininthesiteofinjectionorinthesurroundingarea

cardiogenicorhypovolemicshock

coagulationdisordersorcurrentanticoagulanttreatments.

Epiduralanaesthesia,regardlessofthelocalanaestheticused,hasitsowncontra-indicationswhichinclude:

Activediseaseofthecentralnervoussystemsuchasmeningitis,poliomyelitis,intracranialhaemorrhage,sub-acute

combineddegenerationofthecordduetoperniciousanaemiaandcerebralandspinaltumours;tuberculosisofthe

spine;pyrogenicinfectionoftheskinatoradjacenttothesiteoflumbarpuncture;cardiogenicorhypovolaemicshock;

coagulationdisordersorongoinganticoagulationtreatment.

4.4Specialwarningsandprecautionsforuse

Generalprecautionsandriskofbupivacianeuse:

Therehavebeenreportsofcardiacarrestduringtheuseofbupivacaineforepiduralanaesthesiaorperipheralnerve

blockadewhereresuscitativeeffortshavebeendifficult,andwererequiredtobeprolongedbeforethepatient

responded.However,insomeinstancesresuscitationhasprovenimpossibledespiteapparentlyadequatepreparation

andappropriatemanagement.

Likealllocalanaestheticmedicinalproducts,bupivacainemaycauseacutetoxicityeffectsonthecentralnervousand

cardiovascularsystemsifutilisedforlocalanaestheticproceduresresultinginhighbloodconcentrationsofthe

medicinalproduct.Thisisespeciallythecaseafterunintentionalintravascularadministration.Ventriculararrhythmia,

ventricularfibrillation,suddencardiovascularcollapseanddeathhavebeenreportedinconnectionwithhighsystemic

concentrationsofbupivacaine.

Majorperipheralnerveblocksmayrequiretheadministrationofalargevolumeoflocalanaestheticinareasofhigh

vascularity,oftenclosetolargevesselswherethereisanincreasedriskofintravascularinjectionand/orsystemic

absorption.Thismayleadtohighplasmaconcentrations.

Beforeanynerveblockisattempted,intravenousaccessforresuscitationpurposesshouldbeestablished.Clinicians

shouldhavereceivedadequateandappropriatetrainingintheproceduretobeperformedandshouldbefamiliarwith

thediagnosisandtreatmentofsideeffects,systemictoxicityorothercomplications(seesection4.9).

Adequateresuscitationequipmentshouldbeavailablewheneverlocalorgeneralanaesthesiaisadministered.The

clinicianresponsibleshouldtakethenecessaryprecautionstoavoidintravascularinjection(seesection4.2).

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Injectionofrepeateddosesofbupivacainehydrochloridemaycausesignificantincreasesinbloodlevelswitheach

repeateddoseduetoslowaccumulationofthemedicinalproduct.Tolerancevarieswiththestatusofthepatient.

Debilitated,elderlyoracutelyillpatientsshouldbegivenreduceddosescommensuratewiththeirphysicalstatus.

Patientsatrisk,andRiskassociatedwithcertainanaesthesiatechniques:

Patientstreatedwithanti-arrhythmicmedicinalproductsclassIII(e.g.amiodarone)shouldbeunderclosesurveillance

andECGmonitoring,sincecardiaceffectsmaybeadditive.

Onlyinrarecaseshaveamidelocalanaestheticsbeenassociatedwithallergicreactions(inmostsevereinstances

anaphylacticshock).

Patientsallergictoester-typelocalanaestheticmedicinalproducts(procaine,tetracaine,benzocaine,etc.)havenot

showncross-sensitivitytoagentsoftheamidetypesuchasbupivacaine.

Localanaestheticsshouldbeusedwithcautionforepiduralanaesthesiainpatientswithimpairedcardiovascular

functionsincetheymaybelessabletocompensateforfunctionalchangesassociatedwiththeprolongationofA-V

conductionproducedbythesemedicinalproducts.

Sincebupivacaineismetabolisedintheliver,itshouldbeusedcautiouslyinpatientswithliverdiseaseorwithreduced

liverbloodflow.

Thephysiologicaleffectsgeneratedbyacentralneuralblockadearemorepronouncedinthepresenceofhypotension.

Patientswithhypovolaemiaduetoanycausecandevelopsuddenandseverehypotensionduringepiduralanaesthesia.

Epiduralanaesthesiashouldthereforebeavoidedorusedwithcautioninpatientswithuntreatedhypovolaemiaor

significantlyimpairedvenousreturn.

Epiduralanaesthesiawithanylocalanaestheticcancausehypotensionandbradycardiawhichshouldbeanticipatedand

appropriateprecautionstaken.Thesemayincludepre-loadingthecirculationwithcrystalloidorcolloidsolution.If

hypotensiondevelopsitshouldbetreatedwithavasopressorsuchasephedrine10-15mgintravenously.Severe

hypotensionmayresultfromhypovolaemiaduetohaemorrhageordehydration,oraorto-cavalocclusioninpatients

withmassiveascites,largeabdominaltumoursorlatepregnancy.Markedhypotensionshouldbeavoidedinpatients

withcardiacdecompensation.

Patientswithhypovolaemiaduetoanycausecandevelopsuddenandseverehypotensionduringepiduralanaesthesia.

Epiduralanaesthesiacancauseintercostalparalysisandpatientswithpleuraleffusionsmaysufferrespiratory

embarrassment.Septicaemiacanincreasetheriskofintraspinalabscessformationinthepostoperativeperiod.

Smalldosesoflocalanaestheticsinjectedintotheheadandneck,includingretrobulbar,dentalandstellateganglion

blocks,mayproducesystemictoxicityduetoinadvertentintra-arterialinjection.

Retrobulbarinjectionsmayveryrarelyreachthecranialsubarachnoidspacecausingserious/severereactions,including

temporaryblindness,cardiovascularcollapse,apnoea,convulsions.

Retro-andperibulbarinjectionsoflocalanaestheticscarryalowriskofpersistentocularmuscledysfunction.The

primarycausesincludetraumaand/orlocaltoxiceffectsonmusclesand/ornerves.Theseverityofsuchtissuereactions

isrelatedtothedegreeoftrauma,theconcentrationofthelocalanaestheticandthedurationofexposureofthetissueto

thelocalanaesthetic.Forthisreason,aswithalllocalanaesthetics,thelowesteffectiveconcentrationanddoseoflocal

anaestheticshouldbeused.

Particularcautionistobetakenincaseofinjectinglocalanaestheticsintoinflamedorinfectedareas.

Thismedicinalproductcontains0.14mmol(3.15mg)sodiumperml.Tobetakenintoconsiderationbypatientsona

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Bupivacaineshouldbeusedwithcautioninpatientsreceivingotherlocalanaestheticsoragentsstructurallyrelatedto

amide-typelocalanaesthetics,e.g.certainanti-arrhythmics,suchaslidocaineandmexiletine,sincethesystemictoxic

effectsareadditive.

Specificinteractionstudieswithbupivacaineandanti-arrhythmicmedicinalproductclassIII(e.g.amiodarone)have

notbeenperformed,butcautionshouldbeadvised,(seealsoSection4.4).

Casesofseverehypotensionarereportedwhenclonidinewasmixedwithlocalanaestheticslikebupivacaïneinblocks.

Combinationswithketaminemaycauseneurotoxicity.

4.6Fertility,pregnancyandlactation

Therearelimitedamountofdatafromtheuseofbupivacaineinhumanpregnancy.Animalstudieshaveshown

decreasedpupsurvivalandembryotoxiceffects(seesection5.3).Thepotentialriskforhumanisunknown.

Bupivacaineinjectionshouldthereforenotbegiveninpregnancyunlessthebenefitsareconsideredtooutweighthe

risks.

Bupivacainesolutionsarecontraindicatedforuseinparacervicalblockinobstetrics,becausefoetalbradycardiamay

occurfollowingparacervicalblock(seesection4.3).

Bupivacaineentersthemother'smilk,butinsuchsmallquantitiesthatthereisnoriskofaffectingthechildat

therapeuticdoselevels.

4.7Effectsonabilitytodriveandusemachines

Besidesthedirectanaestheticeffect,localanaestheticsmayhaveaverymildeffectonmentalfunctionandco-

ordinationevenintheabsenceofovertCNStoxicity,andmaytemporarilyimpairlocomotionandalertness.

4.8Undesirableeffects

Serioussystemicadversereactionsarerare,butmayoccurinconnectionwithoverdosage(seesection4.9)or

unintentionalintravascularinjection.

Bupivacainecausessystemictoxicitysimilartothatobservedwithotherlocalanaestheticagents.Itiscausedbyhigh

plasmaconcentrationsasaresultofexcessivedosage,rapidabsorptionor,mostcommonly,inadvertentintravascular

injection.Pronouncedacidosisorhypoxiamayincreasetheriskandseverityoftoxicreactions.Suchreactionsinvolve

thecentralnervoussystem(CNS)andthecardiovascularsystem.CNSreactionsarecharacterisedbynumbnessofthe

tongue,light-headedness,dizziness,blurredvisionandmuscletwitch,followedbydrowsiness,convulsions,

unconsciousnessandpossiblyrespiratoryarrest.

Cardiovascularreactionsarerelatedtodepressionoftheconductionsystemoftheheartandmyocardiumleadingto

decreasedcardiacoutput,heartblock,hypotension,bradycardiaandsometimesventriculararrhythmias,including

ventriculartachycardia,ventricularfibrillationandcardiacarrest.Usuallythesewillbeprecededoraccompaniedby

majorCNStoxicity,i.e.convulsions,butinrarecasescardiacarresthasoccurredwithoutprodromalCNSeffects.

Epiduralanaesthesiaitselfcancauseadversereactionsregardlessofthelocalanaestheticagentused.Theseinclude

hypotensionandbradycardiaduetosympatheticblockadeand/orvasovagalfainting.

Inseverecasescardiacarrestmayoccur.

Accidentalsub-arachnoidinjectioncanleadtoveryhighspinalanaesthesiapossiblywithapnoeaandsevere

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Neurologicaldamageisararebutwellrecognisedconsequenceofregionalandparticularlyepiduralandspinal

anaesthesia.Itmaybeduetoseveralcauses,e.g.directinjurytothespinalcordorspinalnerves,anteriorspinalartery

syndrome,injectionofanirritantsubstance,oraninjectionofanon-sterilesolution.Thesemayresultinlocalisedareas

ofparaesthesiaoranaesthesia,motorweakness,lossofsphinctercontrolandparaplegia.Occasionallytheseare

permanent.

Hepaticdysfunction,withreversibleincreasesofSGOT,SGPT,alkalinephosphatesandbilirubin,hasbeenobserved

followingrepeatedinjectionsorlong-terminfusionsofbupivacaine.Ifsignsofhepaticdysfunctionareobservedduring

treatmentwithbupivacaine,themedicinalproductshouldbediscontinued.

AdversereactionsarepresentedaccordingtotheMedDRAsystemorganclassesandMedDRAfrequencyconvention:

Verycommon( ≥1/10)

Common( ≥1/100to<1/10)

Uncommon( ≥1/1,000to<1/100)

Rare( ≥1/10,000to<1/1,000)

Veryrare(<1/10,000)

Notknown(cannotbeestimatedfromtheavailabledata)

4.9Overdose

Accidentalintravascularinjectionsoflocalanaestheticsmaycauseimmediate(withinsecondstoafewminutes)

systemictoxicreactions.Intheeventofoverdose,systemictoxicityappearslater(15-60minutesafterinjection)dueto

Verycommon Vasculardisorders Hypotension

Gastrointestinaldisorders Nausea

Common Nervoussystemdisorders Paraesthesia,dizziness

Cardiacdisorders Bradycardia

Vasculardisorders Hypertension

Gastrointestinaldisorders Vomiting

Renalandurinary

disorders Urinaryretention

Uncommon Nervoussystemdisorders SignsandsymptomsofCNStoxicity

(convulsions,circumoralparesthesia,

numbnessofthetongue,

hyperacusis,blurredvision,

unconsciousness,tremor,light

headedness,tinnitus,dysarthria).

Rare Immunesystemdisorders Allergicreactions,anaphylactic

reactions/shock

Nervoussystemdisorders Neuropathy,peripherynerveinjury,

arachnoiditis

Eyedisorders Diplopia

Cardiacdisorders Cardiacarrest,cardiacarrhythmia

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Acutesystemictoxicity

Systemictoxicreactionsprimarilyinvolvethecentralnervoussystem(CNS)andthecardiovascularsystem.Such

reactionsarecausedbyhighbloodconcentrationsofalocalanaesthetic,whichmayappeardueto(accidental)

intravascularinjection,overdoseorexceptionallyrapidabsorptionfromhighlyvascularisedareas(seesection4.4).

CNSreactionsaresimilarforallamidelocalanaesthetics,whilecardiacreactionsaremoredependentonthemedicinal

product,bothquantitativelyandqualitatively.Signsoftoxicityinthecentralnervoussystemgenerallyprecede

cardiovasculartoxiceffects,unlessthepatientisreceivingageneralanaestheticorisheavilysedatedwithmedicinal

productssuchasbenzodiazepineorbarbiturate.

Centralnervoussystemtoxicityisagradedresponsewithsymptomsandsignsofescalatingseverity.Thefirst

symptomsareusually,circumoralparaesthesia,numbnessofthetongue,light-headedness,hyperacusis,tinnitusand

visualdisturbances.Dysarthria,musculartwitchingortremorsaremoreseriousandprecedetheonsetofgeneralised

convulsions.Thesesignsmustnotbemistakenforneuroticbehaviour.Unconsciousnessandgrandmalconvulsions

mayfollow,whichmaylastfromafewsecondstoseveralminutes.Hypoxiaandhypercarbiaoccurrapidlyfollowing

convulsionsduetotheincreasedmuscularactivity,togetherwiththeinterferencewithrespirationandpossiblelossof

functionalairways.Inseverecasesapnoeamayoccur.Acidosis,hyperkalaemia,hypocalcaemiaandhypoxiaincrease

andextendthetoxiceffectsoflocalanaesthetics.

Recoveryisduetoredistributionofthelocalanaestheticmedicinalproductfromthecentralnervoussystemand

subsequentmetabolismandexcretion.Recoverymayberapidunlesslargeamountsofthemedicinalproducthavebeen

injected.

Cardiovascularsystemtoxicitymaybeseeninseverecasesandisgenerallyprecededbysignsoftoxicityinthe

centralnervoussystem.Inpatientsunderheavysedationorreceivingageneralanaesthetic,prodromalCNSsymptoms

maybeabsent.Hypotension,bradycardia,arrhythmiaandevencardiacarrestmayoccurasaresultofhighsystemic

concentrationsoflocalanaesthetics,butinrarecasescardiacarresthasoccurredwithoutprodromalCNSeffects.

Inchildren,earlysignsoflocalanaesthetictoxicitymaybedifficulttodetectincaseswheretheblockisgivenduring

generalanaesthesia.

Treatmentofacutetoxicity

Ifsignsofacutesystemictoxicityappear,injectionofthelocalanaestheticshouldbeimmediatelystopped.

Treatmentofapatientwithsystemictoxicityconsistsofarrestingconvulsionsandensuringadequateventilationwith

oxygen,ifnecessarybyassistedorcontrolledventilation(respiration).Ifconvulsionsoccurtheymustbetreated

promptlybyintravenousinjectionofthiopental100-200mgordiazepam5-10mg.

Prolongedconvulsionsmayjeopardisethepatient'sventilationandoxygenation.Ifso,injectionofamusclerelaxant

(e.g.succinylcholine1mg/kgbw)willfacilitateventilation,andoxygenationcanbecontrolled.Earlyendotracheal

intubationmustbeconsideredinsuchsituations.

Onceconvulsionshavebeencontrolledandadequateventilationofthelungsensured,noothertreatmentisgenerally

required.Ifhypotensionispresent,however,avasopressor,preferablyonewithinotropicactivity,e.g.ephedrine15-30

mg,shouldbegivenintravenously.

Ifcirculatoryarrestshouldoccur,immediatecardiopulmonaryresuscitationshouldbeinstituted.Optimaloxygenation

andventilationandcirculatorysupportaswellastreatmentofacidosisareofvitalimportance.

Ifcardiovasculardepressionoccurs(hypotension,bradycardia),appropriatetreatmentwithintravenousfluids,

vasopressor,and/orinotropicagentsshouldbeconsidered.Childrenshouldbegivendosescommensuratewithage

andweight.

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Anesthetics,local;Amides

ATCcode:NOlBBOl.

Bupivacaineisapotentamidelocalanaestheticwithaprolongeddurationofaction.Itaffectssensorynervesmorethan

motornervesandisidealforproducinganalgesiawithoutmotorblockade.

5.2Pharmacokineticproperties

Inadults,theterminalhalf-lifeofbupivacaineis3.5hours.Themaximumbloodconcentrationvarieswiththesiteof

injectionandishighestafterintercostalnerveblockade.

Totaldose,ratherthanconcentration,isanimportantdeterminantofpeakbloodlevels.

Bupivacaineisbiodegradedintheliverandonly6%isexcretedunchangedintheurine.

5.3Preclinicalsafetydata

Basedonconventionalstudiesofsafetypharmacology,acuteandsubchronictoxicity,non-clinicaldatarevealno

specialhazardotherthanthosealreadyreportedelsewhereinthisdocument.

Themutagenicandcarcinogenicpotentialofbupivacainehasnotbeendetermined.

Bupivacainecrossestheplacenta.Inreproductiontoxicitystudies,decreasedsurvivaloftheoffspringofratsand

embryolethalitywasnotedinrabbitsatbupivacainedoses,whichwerefive-ornine-foldthemaximumrecommended

dailydoseinhumans.Astudyinrhesusmonkeyssuggestedalteredpostnatalbehaviourfollowingexpositionto

bupivacaineatbirth.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

0.4%sodiumhydroxide(forpHadjustment)

0.85%hydrochloricacid(forpHadjustment)

Waterforinjections

6.2Incompatibilities

Bupivacainemayprecipitateifdilutedwithalkalinesolutionsandshouldnotbedilutedorco-administeredwith

sodiumbicarbonateinjections.Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthose

mentionedinsection6.6.

6.3ShelfLife

3years

Afterfirstopening:tobeusedimmediatelyandunusedsolutiontodiscard.

Afterdilution:Chemicalandphysicalinusestabilityhasbeendemonstratedfor36hoursat25ºC.

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6.4Specialprecautionsforstorage

Storebelow30°C.Donotrefrigerateorfreeze.

6.5Natureandcontentsofcontainer

10mltypeIclearglassvialwithbromobutylrubberclosure

20mltypeIclearglassvialwithbromobutylrubberclosure

Packsizes:

5X10mlSolutionforInjection

1X20mlSolutionforInjection

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Anyunusedsolutionshouldbediscarded.Bupivacaineiscompatiblewhenmixedwithsodiumchloride9mg/ml

(0.9%)solutionforinjection,RingerLactateSolutionandSufentanilCitrate50µg/ml.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk,NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/31/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1stApril2011

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