AERRANE (ISOFLURANE), INHALATION VAPOUR, LIQUID 100 %v/v Inhalation Vapour Liquid

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
ISOFLURANE
Available from:
Baxter Healthcare Limited
INN (International Name):
ISOFLURANE
Dosage:
100 %v/v
Pharmaceutical form:
Inhalation Vapour Liquid
Prescription type:
Product subject to prescription which may not be renewed (A)
Authorization status:
Authorised
Authorization number:
PA0167/106/001
Authorization date:
0000-00-00

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Read all of this leaflet carefully before you are given

this medicine.It contains important information for

you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor,

nurse or pharmacist.

If you get any side effects, talk to your doctor, nurse

or pharmacist. This includes any possible side effects

not listed in this leaflet

In this leaflet:

1. What AErrane is and what it is used for

2. What you need to know before you are given

AErrane

3. How you will be given AErrane

4. Possible side effects

5. How to store AErrane

6. Contents of the pack and other information

1.What AErrane is and what it is

used for

AErrane contains isoflurane. AErrane is a general

anaesthetic used in surgery. It is an inhalation

anaesthetic (it is given to you as a vapour for you to

breathe in). Breathing in isoflurane vapour causes you to

fall into a deep, painless sleep.

It also maintains a deep, painless sleep (general

2.What you need to know before you are

given AErrane

Your doctor will not give you AErrane if:

you are allergic (hypersensitive) to isoflurane or

other inhalation anaesthetics such as desflurane,

sevoflurane, halothane and enflurane

you, or any relative suffer from a condition called

malignant hyperthermia. Malignant hyperthermia is

when you suddenly develop a dangerously high body

temperature during or shortly after surgery.

following anaesthesia with AErrane or other

inhalation anaesthetics (e.g. desflurane, sevoflurane,

halothane) in the past, you have had:

– liver problems

– jaundice (yellowing of the skin and white of the

eyeballs)

– unexplained fever

– increased levels of white blood cells called

leucocytes (leucocytosis)

– increased levels of a certain type of white blood

cells called eosinophils (eosinophilia)

You must not be given AErrane for operations during

pregnancy, childbirth or the period just after childbirth.

AErrane may, however, be used for a Caesarean section.

AErrane will not be used for dental procedures outside of

hospital or daycare units.

If any of the above applies to you, please inform your

doctor, surgeon or anaesthetist before you are treated

Package leaflet:Information for the patient

AErrane (isoflurane),100% v/v inhalation vapour,liquid

Active substance: isoflurane

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Warnings and Precautions

Talk to your doctor, nurse or pharmacist before being

given AErrane.

Your doctor will take special care with this medicine if:

You have a disorder of the cells (a condition called

mitochondrial disorder)

you suffer from liver problems such as:

– hepatitis (inflamed liver)

– cirrhosis of the liver (replacement of healthy liver

tissue with scar tissue). This can happen if you

drink too much alcohol

– any other liver disease

you have recently had an operation for which you

received general anaesthesia with an inhalation

anaesthetic

You are suffering from the symptoms of any illness

other than those connected with your operation, such

as severe headaches, nausea, vomiting, severe chest

pain or a condition that affects muscles

(a neuromuscular disease e.g. Duchenne muscular

dystrophy or myasthenia gravis).

You suffer with bronchoconstriction (a tightening of

the lungs and airways leading to coughing, wheezing

or shortness of breath).

The patient is a child under two years of age.

Your doctor may give you less AErrane if:

you have a low blood volume (hypovolaemia)

you have low blood pressure (hypotension)

you are weakened (debilitated)

AErrane can cause irritation of the lining of the mouth

and the airways, which may result in an increased saliva

flow and increased secretions from the windpipe and

upper airways. In children this may make it harder for

them to breathe in or can cause a muscle spasm of the

vocal chords (voicebox) called a laryngospasm.

If you are given AErrane, you may have brief:

changes in liver function

increases in blood sugar (glucose) levels

decreases in blood levels of a fat called cholesterol

changes in blood enzyme levels

AErrane can cause malignant hyperthermia (when you

suddenly develop a dangerously high body temperature

during or shortly after surgery). Fatal outcome of

malignant hyperthermia has been reported with AErrane.

Your doctor will monitor your breathing

during treatment,especially if you are given

any other medicines which can affect your

breathing,like:

sedatives (e.g. diazepam, nitrazepam)

strong pain killers (e.g. opioids such as fentanyl,

If any of the above apply to you or your child, check with

your doctor, nurse or pharmacist. You may need to be

checked carefully and your treatment may be changed.

Other medicines and AErrane:

Tell your doctor, nurse or pharmacist if you are taking,

have recently taken or might take any other medicines.

This includes medicines that you have obtained yourself,

without a prescription, including herbal medicines and

natural products.

You must take special care if you are also taking any of

the following medicines:

non selective MAOIs (monoamine oxidase inhibitor

such as phenelzine, isocarboxazid): Your doctor will

instruct you to stop taking such medicines 15 days

before you have your operation.

heart medicines called beta-sympathomimetics (e.g.

isoprenaline) and alpha- and beta-sympathomimetics

(e.g. adrenaline, noradrenaline): These may increase

your heart rate and cause a serious irregular

heartbeat.

beta-blockers (e.g. atenolol, metoprolol): These are

heart medicines often given to treat a high blood

pressure.

isoniazid: A medicine used to treat tuberculosis (TB).

Your doctor will instruct you to stop using isoniazid

one week before your operation. Do not start taking

isoniazid again until 15 days after your operation.

indirect sympathomimetic drugs e.g.:

– amphetamines, amphetamine derivatives (used

to treat attention-deficit hyperactivity disorder

(ADHD))

– drugs which reduce your appetite

– ephedrine and ephedrine derivatives (commonly

found in cough and cold medicines)

These medicines may cause an increased risk of high

blood pressure when given together with AErrane.

Your doctor will instruct you if and when to stop

these medicines.

muscle relaxants (e.g. suxamethonium, pancuronium,

atracurium, vecuronium). These medicines are used

during general anaesthesia to relax your muscles.

Your anaesthetist may need to reduce the dose of

these medicines.

opioids (e.g. morphine, fentanyl, remifentanil): These

medicines are strong pain killers and are often used

during general anaesthesia.

calcium antagonists: Used for treating high blood

pressure (e.g. felodipine, nicardipine)

If you are not sure if any of the above applies to you, talk

to your doctor, nurse or pharmacist before having AErrane.

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Using AErrane with food and drink

AErrane is a medicine to make and keep you asleep so

you can undergo surgery. You should ask your doctor,

surgeon or anaesthetist when and what you can eat or

drink after you wake up. You should not drink alcohol.

Your doctor will tell you when you can resume drinking

alcohol.

Pregnancy and breast-feeding

You will only be given AErrane whilst you are pregnant

if the benefit outweighs the risk, as there is limited data

of use in pregnant women. However, lower doses of

AErrane can be used during Caesarian section.

As it is not known if AErrane is excreted in human milk,

you should avoid breast feeding after an operation if you

were given AErrane as the general anaesthetic.

Consult your doctor, surgeon or anaesthetist if you are

pregnant, might be pregnant, or if you are breast-feeding.

Driving and using machines

Do not drive or operate tools or machines for at least

24 hours after your operation if you were given AErrane.

Receiving an anaesthetic may influence your alertness

and behaviour which may affect your ability to carry out

normal tasks for up to 6 days. Make sure that someone

takes you home after your operation.

3.How you will be given AErrane

The recommended dose

AErrane will be given to you by an anaesthetist. The

anaesthetist will decide on how much you need and

when it is to be given. The dose will vary according to

your age, weight and the type of surgery you need.

AErrane is produced from liquid isoflurane in a vaporiser.

You may receive AErrane in one of two ways:

you may be given an injection of another anaesthetic

to make you sleep before being given AErrane

through a mask. This is the most common way that

you may receive AErrane.

you may be asked to breathe the isoflurane vapour

through a mask to make you sleep. You will fall

asleep quickly and very easily. This is a less common

way to receive AErrane.

After your surgery, your anaesthetist will stop giving you

If you have too much AErrane

If you are given too much AErrane the medicine will

be stopped. You will be given pure oxygen. Your blood

pressure and heart function will be carefully checked

while you recover.

If you have any further questions on the use of this

product,ask your doctor,nurse or pharmacist.

4.Possible Side Effects

Like all medicines, this medicine can cause side effects.

Most side effects are mild to moderate in their severity

and are brief but there may be some serious side effects.

Tell your doctor,nurse or pharmacist

straight away if you notice any of the

following side effects,which can be serious.

Common (may affect up to 1 in 10 people)

Irregular heart beat or palpitations

Low blood pressure

Slow shallow breathing

Cough

Shivering, chills

Increases in blood sugar levels

Abnormal levels of certain cells or products found in

your blood

Uncommon (may affect up to 1 in 100 people)

Nausea and vomiting

Rare (may affect up to 1 in 1,000 people)

Raised body temperature due to malignant

hyperthermia

A tightening of your lungs and airways causing a

difficulty in breathing

Inability of the liver to function properly, including

liver injury, hepatitis, jaundice, liver cell death

Muscles of your intestine may stop working

temporarily, causing discomfort, bloating and

vomiting

Very rare (may affect up to 1 in 10,000 people)

Presence of carboxyhaemoglobin in the blood

Not known (the number of people affected is unknown)

Allergic reaction, hypersensitivity

Haemorrhage (uncontrolled bleeding)

Agitation, alterations in mood, sometimes extreme

Convulsions, confusion, mental impairment

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Shortness of breath, wheezing, chest discomfort

Skin rash, swelling of the face

Increases in blood potassium levels

Increases in blood fluoride levels (due to your body

breaking down isoflurane) Abnormal results from a

EEG (electroencephalogram) test

Abnormal electrocardiogram (ECG), change in heart

rate or rhythm (e.g slow heart beat or fast heart beat)

Cardiac arrest

Presence of myoglobin (material from the muscles) in

the urine

Muscle destruction

Increased blood levels of an enzyme called Creatinine

Phosphokinase

If you get any side effects, talk to your doctor, nurse or

pharmacist. This includes any possible side effects not

listed in this leaflet.

5.How to store AErrane

Keep this medicine out of the sight and reach of children

This medicine requires no special storage conditions.

Do not use AErrane after the expiry date that is printed

on the label. The expiry date refers to the last day of that

month.

Do not throw any medicines via wastewater or household

waste. Ask your pharmacist how to throw away

medicines you no longer use. These measures will help

protect the environment.

6.Contents of the pack and other

information

What AErrane contains

The active substance is isoflurane.

There are no other ingredients.

What AErrane looks like and contents of the

pack

AErrane is a liquid.

It is supplied in 100 ml and 250 ml bottles with screw

cap closures.

The Marketing Authorisation holder is

Baxter Healthcare Limited

Caxton Way, Thetford

Norfolk IP24 3SE, UK

AErrane is manufactured by

Baxter S.A.

Lessines, Belgium

For any information about this medicinal product,

please contact the local representative of the Marketing

Authorisation Holder.

This leaflet was last revised in November 2013

For information about AErrane or to request

this leaflet in formats such as audio or

large print please contact the Marketing

Authorisation Holder:

Tel: +44 1635 206 345

Baxter and AErrane are trademarks of Baxter

International Inc.

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

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

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Isoflurane100%v/v.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Inhalationvapour,liquid

Clear,colourlessliquid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inductionandmaintenanceofgeneralanaesthesiainadultsandchildren.Useofisofluraneindentalanaesthesiashouldbe

restrictedtohospitalsordaycareunitsonly(seeContraindications,Section4.3).

4.2Posologyandmethodofadministration

Inordertobeabletoaccuratelycontrolthepreciseconcentrationofisoflurane,vaporisersthathavebeenspecially

calibratedforisofluraneshouldbeused.

Induction

Toavoidexcitementandbecauseoftheirritanteffectsontherespiratorytract,anintravenousinductionagentshouldbe

administered,followedbyinhalationofisoflurane.

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

orO

Ousuallyproducesurgicalanaesthesia

in7-10minutes.

Maintenance

Theusualconcentrationis1-2.5%inO

Oor1.5–3.5%withO

alone.

ForCaesareansection,0.5-0.75%inamixtureofO

Oissuitable.

Recovery

TheconcentrationofAErranemustbereducedto0.5%attheendoftheoperation,orto0%duringclosureofthewoundto

allowpromptrecovery.

Ifalladministrationofanaestheticagentshasbeenstopped,theairpassagesofthepatientshouldbeventilatedseveral

timeswith100%oxygenuntilcompleteawakeningoccurs.

Ifthevectorgasisamixtureof50%O

and50%N

O,thevalueoftheminimumalveolarconcentrationofisofluraneis

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4.3Contraindications

Isofluraneiscontraindicatedinpatientswithknownsensitivitytoisofluraneorotherhalogenatedanaesthetics.

Itisalsocontraindicatedinpatientswithknownorsuspectedgeneticsusceptibilitytomalignanthyperthermia.

Patientsinwhomliverdysfunction,jaundiceorunexplainedfever,leucocytosis,oreosinophiliahasoccurred

afteraprevioushalogenatedanaestheticadministration.

Allpatients(adultsandchildren)undergoingdentalproceduresoutsideahospitalordaycareunit(seeSection

4.4).

4.4Specialwarningsandprecautionsforuse

Aswithanypotentgeneralanaesthetic,isofluraneshouldonlybeadministeredinanadequatelyequipped

anaesthetisingenvironmentbythosewhoarefamiliarwiththepharmacologyofthedrugandqualifiedbytrainingand

experiencetomanagetheanaesthetisedpatient.

Vaporizersspeciallycalibratedforisofluraneshouldbeusedsothattheconcentrationofanestheticdeliveredcanbe

accuratelycontrolled.Hypotensionandrespiratorydepressionincreaseasanaesthesiaisdeepened.Theextentofblood

pressurereductionandrespiratorydepressioncanbeanindicationoftheextentofanaesthesia.Spontaneousrespiration

mustbecarefullymonitoredandmustbeassistedifnecessary.Allpatientsanaesthetisedwithisofluraneshouldbe

constantlymonitored,includingECG,BP,oxygensaturationandend-tidalCO

,inasettingwherefullresuscitative

equipmentisavailableandwithstafffullytrainedinresuscitativetechniques.Thepresenceofadditionalriskfactors

shouldbetakenintoconsideration(seealsoSection4.8).

Sincelevelsofanaesthesiamaybealteredquicklyandeasilywithisoflurane,onlyvaporiserswhichdelivera

predictableoutputwithreasonableaccuracy,ortechniquesduringwhichinspiredorexpiredconcentrationscanbe

monitored,shouldbeused.Thedegreeofhypotensionandrespiratorydepressionmayprovidesomeindicationof

anaestheticdepth.

ReportsofQTprolongation,associatedwithtorsadedepointes(inexceptionalcases,fatal)havebeenreceived.

CautionshouldbeexercisedwhenadministeringisofluranetopatientsatriskforQTprolongation.

Cautionshouldbeexercisedinadministeringgeneralanesthesia,includingisoflurane,topatientswithmitochondrial

disorders.

Increasedbloodlossescomparablewiththosefoundfollowinganaesthesiawithotherinhalationagentshavebeen

recordedwithIsofluraneinpatientsundergoinggynaecologicalsurgicalproceduresinvolvinguterinecurettage.

Withtheuseofhalogenatedanaesthetics,disruptionoftheliverfunction,icterus,andfatallivernecrosishavebeen

reported.Suchreactionsappeartoindicatehypersensitivityreactionstoanaesthetics.Isofluranecanproducehepatic

injuryrangingfrommildtransientincreasesofliverenzymestofatalhepaticnecrosisinveryrareinstances

Ithasbeenreportedthatpreviousexposuretohalogenatedhydrocarbonanaesthetics,especiallyiftheintervalisless

than3months,mayincreasethepotentialforhepaticinjury.Cirrhosis,viralhepatitisorotherpreexistingliverdisease

canbeareasontoselectananaestheticotherthanahalogenatedanaesthetic.

Isofluraneisaprofoundrespiratorydepressantwhoseeffectisaccentuatedbynarcoticpremedicationorconcurrentuseof

otherrespiratorydepressants.Respirationshouldbecloselymonitored,andassistedorcontrolledventilationemployed

whennecessary(Seesection4.8).

Thereisinsufficientexperienceofuseinrepeatedanaesthesiatomakeadefiniterecommendationinthisregard.Aswith

allhalogenatedanaestheticsrepeatanaesthesiawithinashortperiodoftimeshouldbeapproachedwithcaution.

Apotentiationofneuromuscularfatiguecanbeseeninpatientswithneuromusculardiseases,suchasmyasthenia

gravis.Isofluraneshouldbeusedwithcautioninthesepatients.

Itisrecommendedthatventilationbecontrolledinneurosurgerypatients:cerebralbloodflowremainsunchangedinthe

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beatransientriseincerebralspinalfluidpressure. Inmostcases,thispressureincreasecanbepreventedby

hyperventilation.

Isofluranemustbeusedwithcautioninpatientswithincreasedintracranialpressure.Insuchcaseshyperventilation

maybenecessary

Isofluraneshouldbeadministeredwithcautiontopatientswhocandevelopbronchoconstrictionsincebronchospasm

canoccur(seesection4.8).

Regardlessoftheanaestheticsemployed,maintenanceofnormalhemodynamicsisimportanttotheavoidanceof

myocardialischemiainpatientswithcoronaryarterydisease.Isofluranecanproduceacoronaryvasodilationatthe

arteriolarlevelinselectedanimalmodels;thedrugisprobablyalsoacoronarydilatorinhumans.Isoflurane,likesome

othercoronaryarteriolardilators,hasbeenshowntodivertbloodfromcollateraldependentmyocardiumtonormally

perfusedareasinananimalmodel("coronarysteal").Clinicalstudiestodateevaluatingmyocardialischaemia,infarction

anddeathasoutcomeparametershavenotestablishedthatthecoronaryarteriolardilationpropertyofisofluraneis

associatedwithcoronarystealormyocardialischaemiainpatientswithcoronaryarterydisease.

InlightofthefactthatAErraneactsinanirritatingmanneronthemucousmembranes,theproductisdifficulttouseif

inhalationanaesthesiaisappliedviamask.

Duringtheinductionofanaesthesia,salivaflowandthracheobronchialsecretioncanincreaseandcanbethecauseof

laryngospasm,particularlyinchildren(seesection4.8).

Atransientincreaseinbromsulphthaleinretention,bloodglucose,andserumcreatininewithadecreaseintheserumurea

level,serumcholesterollevel,andalkalinephosphataselevel,hasbeenobservedfollowingadministrationofisoflurane.

MalignantHyperthermia

Insusceptibleindividuals,isofluraneanaesthesiamaytriggeraskeletalmusclehypermetabolicstateleadingtohigh

oxygendemandandtheclinicalsyndromeknownasmalignanthyperthermia.Thesyndromeincludesnonspecific

featuressuchasmusclerigidity,tachycardia,tachypnea,cyanosis,arrhythmias,andunstablebloodpressures.(Itshould

alsobenotedthatmanyofthesenonspecificsignsmayappearwithlightanaesthesia,acutehypoxia,etc.)Anincrease

inoverallmetabolismmaybereflectedinanelevatedtemperature(whichmayriserapidlyearlyorlateinthecase,but

usuallyisnotthefirstsignofaugmentedmetabolism)andanincreasedusageoftheCO

absorptionsystem(hot

canister).PaO

andpHmaydecrease,andhyperkalemiaandabasedeficitmayappear.Fataloutcomeofmalignant

hyperthermiahasbeenreportedwithisoflurane.Treatmentincludesdiscontinuanceoftriggeringagents(e.g.

isoflurane),intravenousadministrationofdantrolenesodium,andapplicationofsupportivetherapy.Suchtherapy

includesvigorouseffortstorestorebodytemperaturetonormal,respiratoryandcirculatorysupportasindicated,and

managementofelectrolyte-fluid-acid-basederangements.(Consultprescribinginformationfordantrolenesodium

intravenousforadditionalinformationonpatientmanagement.)Renalfailuremayappearlater.

Isolatedcasesofincreasedcarboxyhemoglobinhavebeenreportedwiththeuseofhalogenatedinhalationagentswitha

Hmoiety(i.e.,desflurane,enfluraneandisoflurane).Noclinicallysignificantconcentrationsofcarbonmonoxide

areproducedinthepresenceofnormallyhydratedabsorbents.Careshouldbetakentofollowmanufacturers'

instructionsforCO

absorbents.

Aswithotherhalogenatedanaesthetics,isofluranehasbeenreportedtointeractwithdrycarbondioxideadsorbentsduring

closedcircuitanaesthesia,toformcarbonmonoxide.Inhalationofcarbonmonoxidemayleadtoformationofsignificant

levelsofcarboxyhaemoglobininexposedpatients.Intheeventthatapatientonclosedcircuitanaesthesiausingisoflurane

developsoxygendesaturation,whichdoesnotrespondtotheusualtherapeuticcorrectivemeasures,directmeasurementof

carboxyhaemoglobinshouldbecarriedout.Notethatpulseoximetryisnotareliablemethodfordetecting

carboxyhaemoglobin.Allnecessaryprecautionsshouldbetakentoinsurethatcarbondioxideadsorbentsarenotallowed

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Useofisofluraneinhypovolaemic,hypotensiveanddebilitatedpatientshasnotbeenextensivelyinvestigated.Aswith

otherpotentinhaledanaesthetics,alowerconcentrationisrecommendedforuseinthesepatients.

Isofluranemustalwaysbeusedwithcautioninpatientswithuntreateddecompensationof

cardiocirculatoryfunction,andonlyaftercarefulconsiderationoftherisksandbenefitsbasedonthepatient'sclinical

situation.

Useofinhaledanaestheticagentshasbeenassociatedwithrareincreasesinserumpotassiumlevelsthathaveresulted

incardiacarrhythmiasanddeathinpediatricpatientsduringthepostoperativeperiod.Patientswithlatentaswellas

overtneuromusculardisease,particularlyDuchennemusculardystrophy,appeartobemostvulnerable.Concomitant

useofsuccinylcholinehasbeenassociatedwithmost,butnotall,ofthesecases.Thesepatientsalsoexperienced

significantelevationsinserumcreatinekinaselevelsand,insomecases,changesinurineconsistentwith

myoglobinuria.Despitethesimilarityinpresentationtomalignanthyperthermia,noneofthesepatientsexhibitedsigns

orsymptomsofmusclerigidityorhypermetabolicstate.Earlyandaggressiveinterventiontotreatthehyperkalemia

andresistantarrhythmiasisrecommended,asissubsequentevaluationforlatentneuromusculardisease.

Rarecasesofextremeheat,smokeand/orspontaneousfireintheanaesthesiamachine

havebeenreportedduringadministrationofgeneralanaesthesiawithdrugsinthisclasswhenusedinconjunctionwith

desiccatedCO2absorbents,specificallythosecontainingpotassiumhydroxide(e.g.Baralyme).Whenaclinician

suspectsthattheCO2absorbentmaybedesiccated,itshouldbereplacedbeforeadministrationofisoflurane.Thecolor

indicatorofmostCO2absorbentsdoesnotnecessarilychangeasaresultofdesiccation.Therefore,thelackof

significantcolorchangeshouldnotbetakenasanassuranceofadequatehydration.CO2absorbentsshouldbereplaced

routinelyregardlessofthestateofthecolourindicator.

Isofluranemaycauseaslightdecreaseinintellectualfunctionfor2-4daysfollowinganaesthesia.Smallchangesin

moodsandsymptomsmaypersistforupto6daysafteradministration.Thismustbetakenintoaccountwhenpatients

resumenormaldailyactivities,includingdrivingoroperatingheavymachinery(pleaserefertosection4.7).

Isofluranerelaxestheuterusmuscle,andthelowestpossibleconcentrationofisofluraneshouldbeusedinobstetrical

operations(Pleaserefertosection4.6).

AllcommonlyusedmusclerelaxantsaremarkedlypotentiatedbyIsoflurane,theeffectbeingmostprofoundwithnon-

depolarizingagents.(seesection4.5)

ChildrenUnderTwoYearsofAge-Cautionshouldbeexercisedwhenisofluraneisusedinsmallchildrendueto

limitedexperiencewiththispatient-group.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Thesimultaneousadministrationofisofluraneandthefollowingproductsrequiresstrictsupervisionoftheconditionof

thepatient;

Combinationsadvisedagainst:

Beta-sympathomimeticagentslikeisoprenalineandalpha-andbeta-sympathomimeticagentslikeadrenalineand

noradrenalineshouldbeusedwithcautionduringisofluranenarcosis,duetoapotentialriskofventricular

arrhythmia.Non-selectiveMAO-inhibitors:Riskofcrisisandhemodynamicinstabilityduringsurgeryormedical

procedures.Treatmentshouldbestopped15dayspriortosurgery.

Combinationsrequiringprecautionsinusing:

Beta-blockers:Concomitantuseofbetablockersmayexaggeratethecardiovasculareffectsofinhalational

anesthetics,includinghypotensionandnegativeinotropiceffects.Cardiovascularcompensationreactionsmaybe

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UseofIsofluraneandisoniazidecanincreasetheriskofpotentiationofthehepatotoxiceffects.

Adrenaline,bysubcutaneousorgingivalinjections:riskofseriousventriculararrhythmiaasaconsequenceof

increasedheartrate,althoughthemyocardialsensitivitywithrespecttoadrenalineislowerwiththeuseof

isofluranethaninthecaseofhalothane.Dosesofadrenalinegreaterthan5mcg/kg,whenadministered

submucosally,mayproducemultipleventriculararrhythmias.

Indirect-actingsympathomimetics(amphetaminesandtheirderivatives,psychostimulants,appetitesuppressants,

ephedrineanditsderivatives):Riskofperioperativehypertension.Inpatientsundergoingelectivesurgery,

treatmentshouldideallybediscontinuedseveraldaysbeforesurgery.

Inthemajorityofcaseswhereadrugtreatmentisindispensable,thereisnoreasontosuspenditbeforegeneral

anaesthesia.Itsufficestoinformtheanaesthetistaboutit.

Allcommonlyusedmusclerelaxantsaremarkedlypotentiatedbyisoflurane,theeffectbeingmostprofoundwith

non-depolarizingagents.Neostigminehasaneffectonthenondepolarisingrelaxants,buthasnoeffectonthe

relaxingactionofisofluraneitself.Thusitisrecommendedthatapproximatelyonethirdtoonehalfoftheusualdose

ofthesesubstancesbeadministered.Thedisappearanceofthemyoneuraleffecttakeslongerwithisofluranethanwith

otherconventionalanaesthetics.

Opioids,benzodiazepinesandothersedativeagentsareassociatedwithrespiratorydepression,andcautionshould

beexercisedwhenconcomitantlyadministeredwithisoflurane.

Calciumantagonists,inparticulardihydropyridinederivates:isofluranemayleadto markedhypotensionin

patientstreatedwithcalciumantagonists.

Cautionshouldbeexercisedwhencalciumantagonistsareusedconcomitantlywithinhalationanaestheticsdueto

theriskofadditivenegativeinotropiceffect.

MAC(minimumalveolarconcentration)isreducedbyconcomitantadministrationofN20inadults(seesection

4.2).

4.6Fertility,pregnancyandlactation

UseinPregnancy

Therearenoorlimitedamountofdatafromtheuseofisofluraneinpregnantwomen.Studiesinanimalshaveshown

reproductivetoxicity.Isofluraneshouldonlybeusedduringpregnancyifthebenefitoutweighsthepotentialrisk.

UseinCaesareanSection

Isoflurane,inconcentrationsupto0.75%,hasbeenshowntobesafeforthemaintenanceofanaesthesiaforcaesarean

section(pleaserefertosection4.4).

Isofluranerelaxestheuterusmuscle,andthelowestpossibleconcentrationofisofluraneshouldbeusedinobstetrical

operations.

NursingMothers

Itisnotknownwhetherisoflurane/metabolitesareexcretedinhumanmilk.Becausemanydrugsareexcretedinhuman

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4.7Effectsonabilitytodriveandusemachines

Themedicinalproductcanhaveinfluenceondrivingandusingmachines.Thepatientshouldnotdriveorusemachines

foratleast24hoursafteranaesthesiawithisoflurane.Changesinbehaviourandintellectualfunctionmaypersistforup

to6daysafteradministration.Thismustbetakenintoaccountwhenpatientsresumenormaldailyactivities,including

drivingoroperatingheavymachinery.

4.8Undesirableeffects

a.Summaryofthesafetyprofile

Adversereactionsencounteredintheadministrationofisofluraneareingeneraldosedependentextensionsof

pharmacophysiologiceffectsandincluderespiratorydepression,hypotensionandarrhythmias.Potentialserious

undesirableeffectsincludemalignanthyperthermia,anaphylacticreactionsandliveradversereactions(pleasereferto

section4.4and4.8).Shivering,nausea,vomitingandileushavebeenobservedinthepostoperativeperiod.

b.Tabulatedsummaryofadversereactions

Thefollowingtabledisplaysadversereactionsreportedinclinicaltrialsandfrompost-marketingexperience.Where

frequencycannotbeestimatedfromtheavailabledata,itisshownas“notknown”.

SummaryofMostFrequentAdverseDrugReactions

SOC Frequency AdverseReactions

Bloodandlymphaticsystem

disorders VeryRare

Carboxyhaemoglobinaemia 2

Common

Leucocytosis 1

Immunesystemdisorders Notknown Anaphylacticreaction 1

Notknown Hypersensitivity 1

Metabolsimandnutrition

disorders Notknown Hyperkalaemia 2

Common Bloodglucoseincreased

Common IncreasedBromsulphthalein

retention

Psychiatricdisorders Notknown Delirium

Notknown Agitation

Notknown Moodaltered 5

Nervoussystemdisorders Notknown Convulsion

Notknown Mentalimpairment 4

Cardiacdisorders Common Arrhythmia

Vasculardisorders Common

Hypotension 2

Notknown Haemorrhage 3

Respiratory,thoracicand

mediastinaldisorders Rare

Bronchospasm 2

Notknown

Dyspnoea 1

Notknown

Wheezing 1

Common

Respiratorydepression 2

Rare

Laryngospasm 2

Common Cough

Gastrointestinaldisorders Rare PostoperativeIleus

Uncommon Vomiting

Uncommon Nausea

Hepatobiliarydisorders Veryrare Hepaticnecrosis 2

NotKnown Hepatocellularinjury 2

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See4.8(c)

See4.4

Inpatientsundergoinggynaecologicalsurgicalproceduresinvolvinguterinecurettage.See4.4.

Maycauseaslightdecreaseinintellectualfunctionfor2-4daysafteranaesthesia.See4.4.

Smallchangesinmoodsandsymptomsmaypersistforupto6days.See4.4.

ADRfrequencyisbaseduponthefollowingscale:VeryCommon(1/10);Common(1/100-<1/10),

Uncommon(1/1,000-<1/100),Rare(1/10,000-<1/1,000),VeryRare(<1/10,000)

c.Descriptionofselectedadversereactions

Transientelevationsinwhitebloodcounthavebeenobservedevenintheabsenceofsurgicalstress.

Rarereportsofhypersensitivity(includingdermatitiscontact,rash,dyspnoea,wheezing,chestdiscomfort,swelling

face,oranaphylacticreaction)havebeenreceived,especiallyinassociationwithlong-termoccupationalexposureto

inhaledanaestheticagents,includingisoflurane.Thesereactionshavebeenconfirmedbyclinicaltesting(e.g.,

methacholinechallenge).Theetiologyofanaphylacticreactionsexperiencedduringinhalationalanaestheticexposure

is,however,unclearbecauseoftheexposuretomultipleconcomitantdrugs,manyofwhichareknowntocausesuch

reactions.

Minimallyraisedlevelsofseruminorganicfluorideoccurduringandafterisofluraneanaesthesia,dueto

biodegradationoftheagent.Itisunlikelythatthelowlevelsofseruminorganicfluorideobserved(mean4.4µmol/lin

onestudy)couldcauserenaltoxicity,asthesearewellbelowtheproposedthresholdlevelsforkidneytoxicity.

d.Paediatricpopulation

Useofinhaledanaestheticagentshasbeenassociatedwithrareincreasesinserumpotassiumlevelsthathaveresulted

incardiacarrhythmiasanddeathinpaediatricpatientsduringthepostoperativeperiod.(See4.4.)

Duringtheinductionofanaesthesia,salivaflowandtracheobronchialsecretioncanincreaseandcanbethecauseof

laryngospasm.(See4.4.)

e.Otherspecialpopulations

Rare ImpairedLiverFunction

Rare Icterus

Rare Hepatitis

Skinandsubcutaneoustissue

disorders Notknown

Swellingface 1

Notknown Dermatitiscontact 1

Notknown Rash 1

Renalandurinarydisorders Common Bloodcreatinineincreased

Notknown Bloodureadecreased

Generaldisordersand

administrationsiteconditions Common Chills

Rare

Hyperthermiamalignant 2

Notknown ChestDiscomfort

Investigations Notknown

Hepaticenzymeincreased 2

Notknown

Fluorideincreased 1

Notknown Electroencephalogram

abnormal

Common Bloodcholesteroldecreased

Common Bloodalkalinephosphatase

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Useofinhaledanaestheticagentshasbeenassociatedwithrareincreasesinserumpotassiumlevelsthathaveresulted

incardiacarrhythmiasanddeathinpaediatricpatientsduringthepostoperativeperiod.Patientswithlatentaswellas

overtneuromusculardisease,particularlyDuchennemusculardystrophy,appeartobemostvulnerable.(See4.4.)

Elderly:

Lesserconcentrationsofisofluranearenormallyrequiredtomaintainsurgicalanaesthesiainelderlypatients.(See4.2.)

4.9Overdose

Incaseofoverdosage,stopadministrationoftheanaestheticagent,checkwhetherairpassagesareopen,anddepending

onthecircumstances,continuewithassistedorcontrolledrespirationusingpureoxygen.

Hypotensionandrespiratorydepressionhavebeenobserved.

Closemonitoringofbloodpressureandrespirationisrecommended.Supportivemeasuresmaybenecessarytocorrect

hypotensionandrespiratorydepressionresultingfromexcessivelydeeplevelsofanaesthesia.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Isofluraneisaninhalation-typeanaesthetic,belongingtothegroupofhalogenatedanaesthetics.Inductionandrecovery

fromanaesthesiatakeplacerapidlywithisoflurane.

Isofluranehastheslightlyirritatingodourofether,whichcanlimitthespeedofinduction.

Pharyngealandlaryngealreflexesarerapidlydiminishedasaresultofwhichtrachealintubationisrenderedeasy.

Minimumalveolarconcentrations(MACs)ofisofluraneinhumans:

5.2Pharmacokineticproperties

AErraneismetabolisedminimallyincomparisontootherhalogenatedanaesthetics.Onaverage95%oftheAErraneis

recoveredintheexpiredair;0.2%oftheAErranethatistakenupwithinthebodyismetabolised.Theprincipalmetabolite

istrifluoroaceticacid.TheaverageserumlevelofinorganicfluorideinpatientsadministeredAErraneanaesthesiais

between3and4micromol/litre.

Inpatientsanaesthetisedwithisoflurane,themeanserumconcentrationofinorganicfluoridesisusuallylessthan5

micromol/litreandoccursaboutfourhoursafteranaesthesia,returningtonormallevelswithin24hours.Thisshouldnot

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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Althoughpeakinorganicfluorideconcentrationswhichresultfromthebreakdownofisofluranearegenerallymuchlower

thanthoseconsideredtobenephrotoxic,noinformationisavailableonlevelsinpatientswithcompromisedrenalfunction.

Thedrugshouldthereforebeusedwithextremecautioninthesepatients,orinthosereceivingnephrotoxicdrugs

concomitantly.

5.3Preclinicalsafetydata

Nospecialdata.

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

BaxterHealthcareLtd.

CaxtonWay

Thetford

Norfolk

IP243SE

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:08August1985

Dateoflastrenewal:31March2007

10DATEOFREVISIONOFTHETEXT

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