FORANE

Main information

  • Trade name:
  • FORANE Inhalation Gas 99.9 w/w
  • Dosage:
  • 99.9 w/w
  • Pharmaceutical form:
  • Inhalation Gas
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FORANE Inhalation Gas 99.9 w/w
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0038/030/001
  • Authorization date:
  • 23-06-1983
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Forane,99.9%w/w,InhalationVapour,Liquid.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Isoflurane(notlessthan99.9%w/w).

3PHARMACEUTICALFORM

InhalationVapour,Liquid.

Clearcolourlessliquidwithslightlymustyodourforvaporisationandadministrationasaninhalationgas.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inductionandmaintenanceofgeneralanaesthesiainadultsandchildren.Useofisofluraneindentalanaesthesiashould

berestrictedtohospitalsordaycareunitsonly(seesection4.3).

4.2Posologyandmethodofadministration

VaporisersspeciallycalibratedforForaneshouldbeusedsothattheconcentrationofanaestheticdeliveredcanbe

accuratelycontrolled.

Overall,MACvaluesforForanediminishwithage.ThetablebelowindicatesaverageMACvaluesfordifferentage

groups.

MAC(minimumalveolarconcentrationsinpaediatricpatients):

MAC(minimumalveolarconcentrationsinadultpatients):

Premedication

Drugsusedforpremedicationshouldbeselectedfortheindividualpatient,bearinginmindtherespiratorydepressant

effectofForane.Theuseofanticholinergicdrugsisamatterofchoice,butmaybeadvisableforinhalationinductionin

paediatrics.

Induction

Age AverageMACValueinOxygen

0-1month(neonate) 1.60%

1-6months 1.87%

6-12months 1.80%

1-5years 1.60%

Age AverageMACValuein

100%Oxygen 70%N

2 O

26±4years 1.28% 0.56%

44±7years 1.15% 0.50%

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withoxygenorwithanoxygen/nitrousoxidemixturemaybeused.

ItisrecommendedthatinductionwithForanebeinitiatedataconcentrationof0.5%.Concentrationsof1.5to3.0%

usuallyproducesurgicalanaesthesiain7to10minutes.

Maintenance

Surgicallevelsofanaesthesiamaybemaintainedwith1.0-2.5%Foraneinoxygen/nitrousoxidemixtures.An

additional0.5-1.0%Foranemayberequiredwhengivenwithoxygenalone.Forcaesareansection,0.5-0.75%Forane

inamixtureofoxygen/nitrousoxideissuitable.

ArterialpressurelevelsduringmaintenancetendtobeinverselyrelatedtoalveolarForaneconcentrationsinthe

absenceofothercomplicatingfactors.Excessivefallsinbloodpressure(unlessduetohypovolaemia)mayberelatedto

depthofanaesthesiaand,inthesecircumstances,shouldbecorrectedbyreducingtheinspiredForaneconcentration.

Elderly

Aswithotheragents,lesserconcentrationsofForanearenormallyrequiredtomaintainsurgicalanaesthesiainelderly

patients.SeeaboveforMACvalues.

4.3Contraindications

Useinpatientsinwhomliverdysfunction,jaundiceorunexplainedfever,leucocytosisoreosinophiliahasoccurred

afteraprevioushalogenatedanaestheticadministration.

Foraneiscontra-indicatedinpatientswithknownsensitivitytoForaneorotherhalogenatedanaesthetics.Itisalso

contraindicatedinpatientswithknownorsuspectedgeneticsusceptibilitytomalignanthyperthermia.

Foraneiscontraindicatedinallpatients(adultsandchildren)undergoingdentalproceduresoutsideahospitalorday

careunit(seesection4.4).

4.4Specialwarningsandprecautionsforuse

SincelevelsofanaesthesiamaybealteredquicklyandeasilywithForane,onlyvaporiserswhichdeliverapredictable

outputwithreasonableaccuracy,ortechniquesduringwhichinspiredorexpiredconcentrationscanbemonitored,

shouldbeused.Thedegreeofhypotensionandrespiratorydepressionmayprovidesomeindicationofanaesthetic

depth.

AllpatientsanaesthetisedwithForaneshouldbeconstantlymonitored,includingECG,BP,oxygensaturationandend

tidalCO

inasettingwherefullresuscitativeequipmentisavailableandwithstafffullytrainedinresuscitative

techniques.Thepresenceofadditionalriskfactorsshouldbetakenintoconsideration(seesection4.8).

Foraneisaprofoundrespiratorydepressant,whicheffectisaccentuatedbynarcoticpremedicationorconcurrentuseof

otherrespiratorydepressants.Respirationshouldbecloselymonitoredandassistedorcontrolledventilationemployed

wherenecessary.Measurementoftidalvolumemayprovideanindicationofdepthofanaesthesiainthespontaneously

breathingpatient.

Hypotensionandmyocardialdepressionarerelatedtothedepthofanaesthesia.Theconcomitantuseofnitrousoxide

andsurgicalstimulationmaylimittheextentofthehypotension.Excessivefallinbloodpressure,unlessdueto

hypovolaemia,shouldbecorrectedbylighteningthedepthofanaesthesia.

Regardlessoftheanaestheticemployed,maintenanceofnormalhemodynamicsisimportantfortheavoidanceof

myocardialischemiainpatientswithcoronaryarterydisease.

Aswithotherhalogenatedagents,Foranemustbeusedwithcautioninpatientswithincreasedintracranialpressure.

Foranemaycauseariseincerebrospinalfluidpressureandcerebralbloodflow,whichmaybereversibleby

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Reportsdemonstratethatisofluranecanproducehepaticinjuryrangingfrommildtransientincreasesinliverenzymes

tofatalhepaticnecrosisinrareinstances.Repeatedexposuretohalogenatedhrdorcarbonanaestheticsmayincreasethe

riskofhepaticinjury,especiallyiftheintervalislessthan3months..

CautionshouldbeexercisedwhenadministeringForanetopatientswithpre-existingliverdisease.

Malignanthyperthermia

Insusceptibleindividuals,Forane(isoflurane)anaesthesiamaytriggeraskeletalmusclehypermetabolicstateleadingto

highoxygendemandandtheclinicalsyndromeknownasmalignanthyperthermia.Thesyndromeincludesnon-

specificfeaturessuchasmusclerigidity,tachycardia,tachypnea,cyanosis,arrhythmias,andunstablebloodpressures.

(Itshouldalsobenotedthatmanyofthesenon-specificsignsmayappearwithlightanaesthesia,acutehypoxia,etc.)

Anincreaseinoverallmetabolismmaybereflectedinanelevatedtemperature(whichmayriserapidlyearlyorlatein

thecase,butusuallyisnotthefirstsignofaugmentedmetabolism)andanincreasedusageoftheCO

absorption

system(hotcanister).PaO

andpHmaydecreaseandhyperkalemiaandabasedeficitmayappear.

Treatmentincludesdiscontinuanceoftriggeringagents(e.g.Forane).Intravenousadministrationofdantrolenesodium,

andapplicationofsupportivetherapy.Suchtherapyincludesvigorouseffortstorestorebodytemperaturetonormal,

respiratoryandcirculatorysupportasindicated,andmanagementofelectrolyte-fluid-acid-basederangements.

(Consultprescribinginformationfordantrolenesodiumintravenousforadditionalinformationonpatient

management).Renalfailuremayappearlaterandurineflowshouldbesustainedifpossible.

Useofinhaledanaestheticagentshasbeenassociatedwithrareincreasesinserumpotassiumlevelsthathaveresulted

incardiacarrhythmiasanddeathinpaediatricpatientsduringthepostoperativeperiod.Patientswithlatentaswellas

overtneuromusculardisease,particularlyDuchennemusculardystrophy,appeartobemostvulnerable.Concomitant

useofsuccinylcholinehasbeenassociatedwithmost,butnotallofthesecases.Thesepatientsalsoexperienced

significantelevationsinserumcreatinekinaselevelsandinsomecaseschangesinurineconsistantwithmyoglobinuria.

Despitethesimilarityinpresentationtomalignanthyperthermia,noneofthesepatientsexhibitedsignsorsymptomsof

musclerigidityofhypermetabolicstate.Earlyandaggressiveinterventiontotreatthehyperkalaemiaandresistant

arrhythmiasisrecommended,asissubsequentevaluationforlatentneuromusculardisease.

Althoughpeakinorganicfluorideconcentrationswhichresultfromthebreakdownofisofluranearegenerallymuch

lowerthanthoseconsiderednephrotoxic,noinformationisavailableonlevelsinpatientswithcompromisedrenal

function.Thedrugshouldthereforebeusedwithextremecautioninthesepatients,orinthosereceivingnephrotoxic

drugsconcomitantly.

Thisagentshouldbeadministeredcautiouslytothoseonantihypertensivesoranydrugwhichmayinfluencethe

responseofthesympatheticnervoussystem.

SomehalogenatedinhalationagentswithaCH-F

moiety,i.e.desflurane,isofluraneandenfluranehavebeenreported

tointeractwithdryCO

absorbentstoformcarbonmonoxide.Inordertominimisetheriskofformationofcarbon

monoxideinclosedandre-breathingcircuits,andthepossibilityofincreasedcarboxyhaemoglobinlevelsinexposed

patients,CO

absorbentsshouldnotbeallowedtodryout.

Standardanaesthesiamonitorssuchaspulseoximetersarenotareliablemethodfordetectingcarboxyhaemoglobin.

Directmeasurementofcarboxyhaemoglobinshouldbecarriedoutintheeventthatapatientonclosedcircuit

anaesthesiawithanimplicatedagentdevelopsoxygendesaturationwhichdoesnotrespondtotheusualtherapeutic

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Rarecasesofextremeheat,smokeand/orspontaneousfireintheanesthesiamachinehavebeenreportedduringthe

administrationofgeneralanesthesiawithdrugsinthisclasswhenusedinconjunctionwithdesiccatedCO

absorbents,

specificallythosecontainingpotassiumhydroxide(e.g.Baralyme).WhenacliniciansuspectsthattheCO

absorbent

maybedesiccated,itshouldbereplacedbeforeadministrationofIsoflurane.ThecolourindicatorofmostCO

absorbentsdoesnotnecessarilychangeasaresultofdesiccation.Therefore,thelackofsignificantcolourchange

shouldnotbetakenasanassuranceofadequatehydration.CO

absorbentsshouldbereplacedroutinelyregardlessof

thestateofthecolourindicator.

Theactionofnon-depolarisingrelaxantsismarkedlypotentiatedwithisoflurane.Isoflurane,aswellasothergeneral

anaesthetics,maycauseaslightdecreaseinintellectualfunctionfortwoorthreedaysfollowinganaesthesia.Aswith

otheranaesthetics,smallchangesinmoodsandsymptomsmaypersistforupto6daysafteradministration.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Isofluranemarkedlypotentiatestheeffectsofallcommonlyusedmusclerelaxants,especiallythenon-depolarising

agents,andtheseagentsshouldbeusedinreduceddosage.Careshouldalsobeexercisedwhenusingantibioticsofthe

aminoglycosidegroupe.g.neomycin,concurrentlywithisoflurane.Neostigminedoesnotantagonisethedirectmuscle

relaxanteffectofisoflurane.

Isofluranedoesnotsensitisethemyocardiumtotheeffectsofcatecholaminesindogs.Limiteddatasuggeststhat

subcutaneousinfiltrationof0.25mg(50mlof1:200,000solution)adrenalineof3.4mcg/kgina70kgadult,doesnot

produceanincreaseinventriculararrhythmias,providedthereisnoconcomitantmyocardialhypoxia.Theutmostcare

mustbeusedtopreventoverdosageorundulyrapidadrenalineabsorption.

Isofluraneshouldbeadministeredwithcautiontopatientsonbetaadrenergicblockers.Limitedanimaldatasuggests

thatisofluranemaybeusedsafelyinthepresenceoftherapeuticlevelsofpropranolol.

TheMACofisofluranceisdecreasedbytheuseofnitrousoxide(seesection4.2)

4.6Fertility,pregnancyandlactation

Reproductionstudieshavebeencarriedoutonanimalsafterrepeatedexposurestoanaestheticconcentrationsof

Forane.Studieswiththeratdemonstratednoeffectonthefertility,pregnancyordeliveryorontheviabilityofthe

offspring.Noevidenceofteratogenicitywasrevealed.Comparableexperimentsinrabbitsproducedsimilarnegative

results.Therelevanceofthesestudiestothehumanisnotknown.Safetyinpregnancyhasnotbeenestablished.

AdequatedatahavenotbeendevelopedtoestablishtheuseofForaneinpregnancyorobstetricsotherthanfor

caesareansection.

Itisnotknownwetherisofluranceisexcretedinhumanmilkthereforecautionshouldbeexercisedwhenisofluraneis

administeredtoanursingwoman.

Gynaecologicaluse

Bloodlossescomparablewiththosefoundfollowinganaesthesiawithotherinhalationagentshavebeenobservedwith

Foraneinpatientsundergoinguterinecurettage.

4.7Effectsonabilitytodriveandusemachines

Theactionofnon-depolarizingrelaxantsismarkedlypotentiatedwithisoflurane.Isoflurane,aswellasothergeneral

saleanaesthetics,maycauseaslightdecreaseinintellectualfunctionfortwoorthreedaysfollowinganesthesia.As

withotheranesthetics,smallchangesinmoodsandsymptomsmaypersistforupto6daysafteradministration.This

mustbetakenintoaccountwhenpatientsresumenormaldailyactivities,includingdrivingoroperatingheavy

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4.8Undesirableeffects

Aswithotherhalogenatedanaesthetics,hypotensionandrespiratorydepressionhavebeenobserved.Closemonitoring

ofbloodpressureandrespirationisrecommended.

Thisagentcausesariseinbloodsugarlevelsduringanaesthesia.Thisshouldbeborneinmindduringadministration

todiabeticsubjects.

*Maybeassociatedwithhypersensitivityreactions,particularlyinassociationwithlong-termoccupationalexposuretoinhaled

anestheticagents.

4.9Overdose

Supportivemeasuresmaybenecessarytocorrecthypotensionandrespiratorydepressionresultingfromexcessively

deeplevelsofanaesthesia.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:N01AB06Halogenatedhydrocarbon.

Inductionandparticularlyrecoveryarerapid.Althoughslightpungencymaylimittherateofinduction,excessive

salivationandtracheobronchialsecretionsarenotstimulated.Pharyngealandlaryngealreflexesarediminished

quickly.LevelsofanaesthesiachangerapidlywithForane.Heartrhythmremainsstable.

SummaryofMostFrequentAdverseDrugReactions

SOC Frequency AdverseReactions

Immunesystemdisorders NotKnown Anaphylacticreaction*

Hypersensitivity*

Nervoussystemdisorders NotKnown Convulsions

Cardiacdisorders NotKnown Arrhythmia

Vasculardisorders NotKnown Hypotension

Respiratory,thoracicand

mediastinaldisorders NotKnown Dyspnoea*

Wheezing*

Respiratorydepression

Gastrointestinaldisorders NotKnown Vomiting

Nausea

Hepatobiliarydisorders NotKnown Hepaticnecrosis

Hepaticinjury

Skinandsubcutaneoustissue

disorders NotKnown Swellingface*

Dermatitiscontact*

Rash*

Generaldisordersand

administrationsiteconditions NotKnown Hyperthermiamalignant

Chestdiscomfort*

Chills

Investigations NotKnown Electroencephalographabnormal

Whitebloodcellcountincreased

Hepaticenzymeincreased

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Foraneappearstosensitisethemyocardiumtoadrenalinetoanevenlesserextentthanenflurane.Limiteddatasuggest

thatsubcutaneousinfiltrationofupto50mlof1:200,000solutionadrenalinedoesnotinduceventriculararrhythmias

inpatientsanaesthetisedwithForane(SeealsoSection4.5).

Muscularrelaxationmaybeadequateforsomeintra-abdominaloperationsatnormallevelsofanaesthesia,butshould

greaterrelaxationberequiredsmalldosesofintravenousmusclerelaxantsmaybeused.Allcommonlyusedmuscle

relaxantsaremarkedlypotentiatedbyForane,theeffectbeingmostprofoundwithnon-depolarisingagents.

Neostigminereversestheeffectsofnon-depolarisingmusclerelaxantsbuthasnoeffectontherelaxantpropertiesof

Foraneitself.AllcommonlyusedmusclerelaxantsarecompatiblewithForane(seealsosection4.5).

5.2Pharmacokineticproperties

Foraneundergoesminimalbiotransformationinman.Inthepost-operativeperiodonly0.17%oftheForanetakenup

canberecoveredasurinarymetabolites.Peakseruminorganicfluoridevaluesusuallyaveragelessthan5µmol/litre

andoccuraboutfourhoursafteranaesthesia,returningtonormallevelswithin24hours.Nosignsofrenalinjuryhave

beenreportedafterForaneadministration.

5.3Preclinicalsafetydata

Nonestated.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

None.

6.2Incompatibilities

SomehalogenatedinhalationagentswithaCH-F

moiety,i.e.desflurane,isofluraneandenfluranehavebeenreported

tointeractwithdryCO

absorbentstoformcarbonmonoxide.Inordertominimisetheriskofformationofcarbon

monoxideinclosedandre-breathingcircuits,andthepossibilityofincreasedcarboxyhaemoglobinlevelsinexposed

patients,CO

absorbentsshouldnotbeallowedtodryout(seealsosection4.4).

6.3ShelfLife

5years.

In-usestability:Usewithin3monthsfromopeningwhenstoredintheoriginalpackageandbelow25 º

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalpackageinordertoprotectfromlight.Keepthebottletightlyclosed.

6.5Natureandcontentsofcontainer

100mland250mlTypeIIIPh.Eur.amberglassbottles,closedwithanaluminiumcapwithLDPEliner.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

VaporisersspeciallycalibratedforForaneshouldbeusedsothattheconcentrationofanaestheticdeliveredcanbe

accuratelycontrolled.

Itisrecommendedthatvapourfromthisandotherinhalationagentsbeefficientlyextractedfromtheareaofuse.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratoriesIrelandLimited,

4051KingswoodDrive

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA0038/030/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:23 rd

June1983

Dateoflastrenewal:23 rd

June2008

10DATEOFREVISIONOFTHETEXT

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