AERRANE (ISOFLURANE), INHALATION VAPOUR, LIQUID

Main information

  • Trade name:
  • AERRANE (ISOFLURANE), INHALATION VAPOUR, LIQUID
  • Dosage:
  • 100 %v/ v
  • Pharmaceutical form:
  • Inhalation Vapour Liquid
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AERRANE (ISOFLURANE), INHALATION VAPOUR, LIQUID
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0167/106/001
  • Authorization date:
  • 02-12-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0167/106/001

CaseNo:2084267

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

BaxterHealthcareLimited

CaxtonWay,Thetford,NorfolkIP243SE,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AErrane(isoflurane),100%v/vinhalationvapour,liquid

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom16/08/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/08/2010 CRN 2084267 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AErrane(isoflurane),100%v/vinhalationvapour,liquid

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Isoflurane100%v/v.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Inhalationvapour,liquid

Clear,colourlessliquid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inductionandmaintenanceofgeneralanaesthesiainadultsandchildren.Useofisofluraneindentalanaesthesiashould

berestrictedtohospitalsordaycareunitsonly(seeContraindications,Section4.3).

4.2Posologyandmethodofadministration

Inordertobeabletoaccuratelycontrolthepreciseconcentrationofisoflurane,vaporisersthathavebeenspecially

calibratedforisofluraneshouldbeused.

Induction

Toavoidexcitementandbecauseoftheirritanteffectsontherespiratorytract,anintravenousinductionagentshould

beadministered,followedbyinhalationofisoflurane.

Inductionshouldbeinitiatedat0.5%.Concentrationsof1.5-3.0%inO

orO

Ousuallyproducesurgical

anaesthesiain7-10minutes.

Maintenance

Theusualconcentrationis1-2.5%inO

Oor1.5–3.5%withO

alone.

ForCaesareansection,0.5-0.75%inamixtureofO

Oissuitable.

Recovery

TheconcentrationofAErranemustbereducedto0.5%attheendoftheoperation,orto0%duringclosureofthe

woundtoallowpromptrecovery.

Ifalladministrationofanaestheticagentshasbeenstopped,theairpassagesofthepatientshouldbeventilatedseveral

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Ifthevectorgasisamixtureof50%O

and50%N

O,thevalueoftheminimumalveolarconcentrationofisoflurane

isapproximately0.65%.

4.3Contraindications

Hypersensitivitytohalogenatedanaesthetics.

Knownorsuspectedgeneticdispositiontowardmalignanthyperthermia.

Patientswithahistoryofmalignanthyperthermia,orinwhomliverdysfunction,jaundiceorunexplainedfever,

leucocytosis,oreosinophiliahasoccurredafteraprevioushalogenatedanaestheticadministration.

Allpatients(adultsandchildren)undergoingdentalproceduresoutsideahospitalordaycareunit(seeSection

4.4).

4.4Specialwarningsandprecautionsforuse

AErranemustonlybeusedbyalicensedanaesthetist.Sincethedepthofanaesthesiacanchangeeasilyandrapidly

withAErrane,onlyvaporisersthathavebeenspeciallycalibratedforthisproductmaybeused.Theextentofblood

pressurereductionandrespiratorydepressioncanbeanindicationoftheextentofanaesthesia.Spontaneousrespiration

mustbecarefullymonitoredandmustbeassistedifnecessary.Allpatientsanaesthetisedwithisofluraneshouldbe

constantlymonitored,includingECG,BP,oxygensaturationandend-tidalCO

,inasettingwherefullresuscitative

equipmentisavailableandwithstafffullytrainedinresuscitativetechniques.Thepresenceofadditionalriskfactors

shouldbetakenintoconsideration(seealsoSection4.8).

Withtheuseofhalogenatedanaesthetics,disruptionoftheliverfunction,icterus,andfatallivernecrosishavebeen

reported.Suchreactionsappeartoindicatehypersensitivityreactionstoanaesthetics.Cirrhosis,viralhepatitis,orother

pre-existingliverdiseasecanbeareasontoselectananaestheticotherthanahalogenatedanaesthetic.

Isofluraneisaprofoundrespiratorydepressantwhoseeffectisaccentuatedbynarcoticpremedicationorconcurrentuse

ofotherrespiratorydepressants.Respirationshouldbecloselymonitored,andassistedorcontrolledventilation

employedwhennecessary.

Thereisinsufficientexperienceofuseinrepeatedanaesthesiatomakeadefiniterecommendationinthisregard.As

withallhalogenatedanaestheticsrepeatanaesthesiawithinashortperiodoftimeshouldbeapproachedwithcaution.

Patientswithmyastheniagravisareextremelysensitivetodrugsthatproducerespiratorydepression.Theseeffectsare

potentiatedwithsomegeneralanaesthetics.Isofluraneshouldbeusedwithcautioninthesepatients.

Itisrecommendedthatventilationbecontrolledinneurosurgerypatients:cerebralbloodflowremainsunchangedinthe

courseoflightanaesthesia,buttendstoriseinthecourseofdeeperanaesthesia.Anincreaseinintracranialpressure

maybeavertedorabolishedbyhyperventilationofthesubjectbeforeorduringanaesthesia.

AErraneshouldnotbeadministeredtopatientswhocandevelopbronchoconstrictionsincebronchospasmscan

occur.Inthecaseofneurosurgicaloperations,respirationshouldbeadequatelychecked.Aswithotherhalogenated

anaesthetics,AErraneincreasestheflowofbloodthroughthebrainandisaccompaniedbyatransientincreasein

cerebrospinalfluidpressure.Inmostcases,thispressureincreasecanbepreventedbyhyperventilation.

Isofluranecanproduceacoronaryvasodilationatthearteriolarlevelinselectedanimalmodels;thedrugisprobably

alsoacoronarydilatorinhumans.Isoflurane,likesomeothercoronaryarteriolardilators,hasbeenshowntodivert

bloodfromcollateraldependentmyocardiumtonormallyperfusedareasinananimalmodel("coronarysteal").Clinical

studiestodateevaluatingmyocardialischaemia,infarctionanddeathasoutcomeparametershavenotestablishedthat

thecoronaryarteriolardilationpropertyofisofluraneisassociatedwithcoronarystealormyocardialischaemiain

patientswithcoronaryarterydisease.

InlightofthefactthatAErraneactsinanirritatingmanneronthemucousmembranes,theproductisdifficulttouseif

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tracheobronchialsecretioncanincreaseandcanbethecauseoflaryngospasms.

Atransientincreaseinbromsulphthaleinretention,bloodglucose,andserumcreatininewithadecreaseintheserum

urealevel,serumcholesterollevel,andalkalinephosphataselevel,hasbeenobservedfollowingadministrationof

isoflurane.

Inthecaseofsensitiveindividuals,isofluraneanaesthesiacaninduceahypermetabolicstateintheskeletalmuscles,

whichleadstoahighoxygenconsumptionandaclinicalsyndromethatisknownasmalignanthyperthermia.

Aswithotherhalogenatedanaesthetics,isofluranehasbeenreportedtointeractwithdrycarbondioxideadsorbents

duringclosedcircuitanaesthesia,toformcarbonmonoxide.Inhalationofcarbonmonoxidemayleadtoformationof

significantlevelsofcarboxyhaemoglobininexposedpatients.Intheeventthatapatientonclosedcircuitanaesthesia

usingisofluranedevelopsoxygendesaturation,whichdoesnotrespondtotheusualtherapeuticcorrectivemeasures,

directmeasurementofcarboxyhaemoglobinshouldbecarriedout.Notethatpulseoximetryisnotareliablemethod

fordetectingcarboxyhaemoglobin.Allnecessaryprecautionsshouldbetakentoinsurethatcarbondioxideadsorbents

arenotallowedtodryout.

Useofisofluraneinhypovolaemic,hypotensiveanddebilitatedpatientshasnotbeenextensivelyinvestigated.Aswith

otherpotentinhaledanaesthetics,alowerconcentrationisrecommendedforuseinthesepatients.

Useofisofluraneinhypovolaemic,hypotensiveanddebilitatedpatientshasnotbeenextensivelyinvestigated.Aswith

otherpotentinhaledanaesthetics,alowerconcentrationisrecommendedforuseinthesepatients.

Isofluranemustalwaysbeusedwithcautioninpatientswithuntreateddecompensationofcardiocirculatoryfunction,

andonlyaftercarefulconsiderationoftherisksandbenefitsbasedonthepatient'sclinicalsituation.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Thesimultaneousadministrationofisofluraneandthefollowingproductsrequiresstrictsupervisionoftheconditionof

thepatient;

Contraindicatedcombination:

NonselectiveMAOI:Riskofcrisisduringtheoperation.Treatmentshouldbestopped15dayspriortosurgery.

Combinationsadvisedagainst:

Beta-sympathomimetics(isoprenaline)andalpha-andbeta-sympathomimetics(epinephrineoradrenaline;

norepinephrineornoradrenaline):riskofseriousventriculararrhythmiaasaresultofanincreaseinheartrate.

Combinationsrequiringprecautionsinusing:

Beta-blockers:Riskofblockageofthecardiovascularcompensationmechanism,asaresultofwhichnegative

inotropiceffectsareintensified.Theactionofbeta-blockerscanbesuppressedduringtheoperationwiththeuseof

beta-sympathicomimeticagents.Ingeneral,anymedicationwithabeta-blockerneednotbestoppedandanabrupt

reductionofthedosageshouldbeavoided.

Isoniazid:riskofpotentiatingthehepatotoxiceffect,withincreasedformationoftoxicmetabolitesofisoniazid.

Treatmentwithisoniazidshouldbesuspendedoneweekbeforetheoperationandshouldnotberesumeduntil15days

afterwards.

Epinephrine(adrenaline)utilisedforitslocalhaemostaticaction,bysub-cutaneousorgingivalinjections:Risk

ofseriousventriculararrhythmiaasaconsequenceofincreasedheartrate,althoughthemyocardialsensitivitywith

respecttoepinephrineislowerwiththeuseofisofluranethaninthecaseofotherhalogenatedanaesthetics.Thus,the

dosageshouldbelimitedto,forexample,0.1mgepinephrinewithin10minutesor0.3mgwithinonehourinadults.

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ephedrineanditsderivatives):riskofintraoperativehypersensitivityepisode.Inthecaseofaplannedoperation,itis

preferabletointerruptthetreatmentafewdaysbeforetheoperation.

Inthemajorityofcaseswhereadrugtreatmentisindispensable,thereisnoreasontosuspenditbeforegeneral

anaesthesia.Itsufficestoinformtheanaesthetistaboutit.

Musclerelaxingagents:Riskofintensificationoftheactionofdepolarisingrelaxantsand,inparticular,non-

depolarisingrelaxants.Thusitisrecommendedthatapproximatelyonethirdtoonehalfoftheusualdoseofthese

substancesbeadministered.Thedisappearanceofthemyoneuraleffecttakeslongerwithisofluranethanwithother

conventionalanaesthetics.

Neostigminehasaneffectonthenon-depolarisingrelaxants,buthasnoeffectontherelaxingactionofisofluraneitself.

Opioids,benzodiazepinesorothersedatives:lowerdosesofisofluranearerequiredinpatientsreceiving

opioids,benzodiazepinesorothersedatives.Inaddition,concomitantnitrousoxidereducesisofluraneMACvalues.As

opioidsmaycauserespiratorydepression,precautionsshouldbetakenwhenusedtogetherwithisoflurane.

Calciumantagonists:isofluranemayleadtomarkedhypotensioninpatientstreatedwithcalciumantagonists,

particularlydihydropyrridinederivatives.

4.6Pregnancyandlactation

InsufficientinformationisavailabletorecommenduseinpregnancyorobstetricsotherthanforCaesareansection.

Breastfeedingshouldnotbegivenforupto12hoursaftertheterminationofanaesthesia.

Increasedbloodlosshasbeenobservedinpatientsundergoinggynaecologicalsurgicalproceduresinvolvinguterine

curettage.

4.7Effectsonabilitytodriveandusemachines

FollowinganaesthesiawithAErrane,thepatientmustnotdriveoroperatemachineryfor24hours.Thepatientshould

onlybesenthomewithanescort,andshouldnotconsumeanyalcohol.

4.8Undesirableeffects

Common(>1/100)

Blood:Leukocytosis

Circulation:Arrhythmias,hypotension.

Metabolic:Increasedserumglucoseandserumcreatinine.Decreasedserumcholesteroland

alkalinephosphatase.Increasedbromosulfophtaleinretention.

Respiratory:Respiratorydepression,cough.

Other:Chills.

Lesscommon(<1/100->1/1000)

Gastrointestinal:Vomiting,nausea.

Rare(<1/1000->1/10,000)

Gastrointestinal:Postoperativeileus.

Liver:Impairedliverfunction,icterus,hepatitis.

Metabolic:Malignanthyperthermia.

Respiratory:Laryngospasm,bronchospasm.

VeryRare(<1/10,000)

Liver:Hepaticnecrosis.

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4.9Overdose

Incaseofoverdosage,stopadministrationoftheanaestheticagent,checkwhetherairpassagesareopen,anddepending

onthecircumstances,continuewithassistedorcontrolledrespirationusingpureoxygen.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Isofluraneisaninhalation-typeanaesthetic,belongingtothegroupofhalogenatedanaesthetics.Inductionandrecovery

fromanaesthesiatakeplacerapidlywithisoflurane.

Isofluranehastheslightlyirritatingodourofether,whichcanlimitthespeedofinduction.

Pharyngealandlaryngealreflexesarerapidlydiminishedasaresultofwhichtrachealintubationisrenderedeasy.

Minimumalveolarconcentrations(MACs)ofisofluraneinhumans:

5.2Pharmacokineticproperties

AErraneismetabolisedminimallyincomparisontootherhalogenatedanaesthetics.Onaverage95%oftheAErraneis

recoveredintheexpiredair;0.2%oftheAErranethatistakenupwithinthebodyismetabolised.Theprincipal

metaboliteistrifluoroaceticacid.TheaverageserumlevelofinorganicfluorideinpatientsadministeredAErrane

anaesthesiaisbetween3and4micromol/litre.

Inpatientsanaesthetisedwithisoflurane,themeanserumconcentrationofinorganicfluoridesisusuallylessthan5

micromol/litreandoccursaboutfourhoursafteranaesthesia,returningtonormallevelswithin24hours.Thisshould

notalterrenalfunctioninanormalsubject.

Althoughpeakinorganicfluorideconcentrationswhichresultfromthebreakdownofisofluranearegenerallymuch

lowerthanthoseconsideredtobenephrotoxic,noinformationisavailableonlevelsinpatientswithcompromisedrenal

function.Thedrugshouldthereforebeusedwithextremecautioninthesepatients,orinthosereceivingnephrotoxic

drugsconcomitantly.

5.3Preclinicalsafetydata

Age(years) O

2 -100% O

2 +N

2 O(60%)

Neonates 1.60 -

1-6months 1.87 -

7-11months 1.80 -

1-2years 1.60 -

3-5years 1.62 -

6-10years 1.40 0.58

10-15years 1.16 0.53

Age(years) O

2 -100% O

2 +N

2 O(70%)

26±4 1.28 0.56

44±7 1.15 0.50

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

None.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

AErraneissuppliedin100mland250mlroundamber-coloured,TypeIIIglassbottleswithphenolicorpolypropylene

resinscrewcaps.TheclosurecontainsaLDPEliner.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Seeundersection4.2,PosologyandMethodofAdministration.

Anydiscardedanaestheticshouldbecollectedinaglassorplasticcontainer,whichcanbesealedanddisposedof

throughthehospital’swastedisposalservice.

7MARKETINGAUTHORISATIONHOLDER

8MARKETINGAUTHORISATIONNUMBER

PA167/106/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:08August1985

Dateoflastrenewal:31March2007

10DATEOFREVISIONOFTHETEXT

BaxterHealthcareLtd.

CaxtonWay

Thetford

Norfolk

IP243SE

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