FENTADUR 25 MICROGRAMS/ HOUR TRANSDERMAL PATCH

Main information

  • Trade name:
  • FENTADUR 25 MICROGRAMS/ HOUR TRANSDERMAL PATCH
  • Dosage:
  • 25 Microgram per hour
  • Pharmaceutical form:
  • Transdermal Patch
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FENTADUR 25 MICROGRAMS/HOUR TRANSDERMAL PATCH
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/070/001
  • Authorization date:
  • 06-01-2012
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fentadur25micrograms/hourTransdermalPatch

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachFentadur25micrograms/hourTransdermalPatchcontains2.75mgoffentanylinapatchsizeof10cm 2

,releasing

25microgramsoffentanylperhour.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

TransdermalPatch

Fentadurtransdermalpatchisarectangular,tancolouredpatchplacedbetweentwooversized,transparentprotective

layerswhichmustberemovedpriortothepatchapplication.

Thepatcheswillbeimprinted:

“Fentadur25µg/h”inredink

4CLINICALPARTICULARS

4.1TherapeuticIndications

Severechronicpainwhichcanbeadequatelymanagedonlywithopioidanalgesics.

4.2Posologyandmethodofadministration

Thedosingisindividualandbasedonthepatient’sopioidhistoryandtakesintoaccount:

possibledevelopmentoftolerance

thecurrentgeneralcondition,themedicalstatusofthepatient,and

thedegreeofseverityofthedisorder

Therequiredfentanyldosageisadjustedindividuallyandshouldbeassessedregularlyaftereachadministration.

Patientsreceivingopioidtreatmentforthefirsttime

Patcheswithareleaserateof12.5micrograms/hourareavailableandshouldbeusedforinitialdosing.Inveryelderly

orweakpatients,itisnotrecommendedtoinitiateanopioidtreatmentwithFentanyl,duetotheirknownsusceptibility

toopioidtreatments.Inthesecases,itwouldbepreferabletoinitiateatreatmentwithlowdosesofimmediaterelease

morphineandtoprescribeFentanylafterdeterminationoftheoptimaldosage.

Switchingfromotheropioids

Whenchangingoverfromoralorparenteralopioidstofentanyltreatment,theinitialdosageshouldbecalculatedas

follows:

1.Thequantityofanalgesicsrequiredoverthelast24hoursshouldbedetermined.

2.TheobtainedsumshouldbeconvertedtocorrespondtotheoralmorphinedosageusingTable1.

3.Thecorrespondingfentanyldosageshouldbedeterminedasfollows:

a)usingTable2forpatientswhohaveaneedforopioidrotation(conversionratiooforalmorphineto

transdermalfentanylequalto150:1)

b)usingTable3forpatientsstableandwelltoleratedopioidtherapy(conversionratiooforalmorphineto

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Table1:Equianalgesicpotencyconversion

Alldosagesgiveninthetableareequivalentinanalgesiceffectto10mgparenteralmorphine.

Table2:Recommendedinitialdoseoftransdermalfentanylbasedondailyoralmorphinedose(forpatientswho

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Table3:Recommendedinitialdoseoftransdermalfentanylbasedondailyoralmorphinedose(forpatientson

stableandwelltoleratedopioidtherapy)

Bycombiningseveraltransdermalpatches,afentanylreleaserateofover100micrograms/hcanbeachieved.

TheinitialevaluationofthemaximumanalgesiceffectofFentanylshouldnotbemadebeforethepatchhasbeenworn

for24hours.Thisisduetothegradualincreaseinserumfentanylconcentrationsduringthefirst24hoursafter

applicationofthepatch.

Inthefirst12hoursafterchangingtoFentanylthepatientcontinuestoreceivethepreviousanalgesicattheprevious

dose;overthenext12hoursthisanalgesicisadministeredaccordingtoneed.

Dosetitrationandmaintenancetherapy

Thepatchshouldbereplacedevery72hours.Thedoseshouldbetitratedindividuallyuntilanalgesicefficacyis

attained.Inpatientswhoexperienceamarkeddecreaseintheperiod48-72hoursafterapplication,replacementof

Fentanylafter48hoursmaybenecessary.

Patcheswithareleaserateof12.5micrograms/hourareavailableandareappropriatefordosetitrationinthelower

dosagearea.Ifanalgesiaisinsufficientattheendoftheinitialapplicationperiod,thedosemaybeincreasedafter3

days,untilthedesiredeffectisobtainedforeachpatient.Additionaldoseadjustmentshouldnormallybeperformedin

12.5micrograms/houror25micrograms/hourincrements,althoughthesupplementaryanalgesicrequirementsandpain

statusofthepatientshouldbetakenintoaccount.

Patientsmayrequireperiodicsupplementaldosesofashort-actinganalgesicforbreakthroughpain.Additionalor

alternativemethodsofanalgesiaoralternativeadministrationofopioidsshouldbeconsideredwhentheFentanyldose

exceeds300micrograms/hour.

Withdrawalsymptomshavebeenreportedwhenchangingfromlong-termtreatmentwithmorphinetotransdermal

fentanyldespiteadequateanalgesicefficacy.Incaseofwithdrawalsymptomsitisrecommendedtotreatthosewith

short-actingmorphineinlowdoses.

Changingorendingtherapy

Ifdiscontinuationofthepatchisnecessary,anyreplacementwithotheropioidsshouldbegradual,startingatalow

doseandincreasingslowly.Thisisbecausefentanyllevelsfallgraduallyafterthepatchisremoved;ittakesatleast17

hoursforthefentanylserumconcentrationtodecreaseby50%.Asageneralrule,thediscontinuationofopioid

analgesiashouldbegradual,inordertopreventwithdrawalsymptoms(nausea,vomiting,diarrhoea,anxietyand

musculartremor).Tables2and3shouldnotbeusedtoswitchfromtransdermalfentanyltoamorphinetreatment.

Durationofadministration

Thepatchshouldbechangedafter72hours.Ifanearlierchangebecomesnecessaryinindividualcases,nochange

shouldbemadebefore48hourshaveelapsed,otherwiseariseinmeanfentanylconcentrationsmayoccur.Anewskin

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tothesameareaofskin.Theanalgesiceffectmaypersistforsometimeafterremovalofthetransdermalpatch.

Iftracesofthetransdermalpatchremainontheskinafteritsremoval,thesecanbecleanedoffusingcopiousamounts

ofsoapandwater.

Noalcoholorothersolventsmustbeusedforcleaning,asthesemaypenetratetheskinduetotheeffectofthepatch.

Dosetitrationandmaintenance

IftheanalgesiceffectofFentadurisinsufficient,supplementarymorphineoranothershort-durationopioidshouldbe

administered.Dependingontheadditionalanalgesicneedsandthepainstatusofthechild,itmaybedecidedtouse

morepatches.Doseadjustmentsshouldbedonein12mcg/hoursteps.

Useinelderlypatients

Datafromintravenousstudieswithfentanylsuggestthatelderlypatientsmayhavereducedclearance,aprolongedhalf-

lifeandtheymaybemoresensitivetothedrugthanyoungerpatients.Studiesoffentanylinelderlypatients

demonstratedfentanylpharmacokineticswhichdidnotdiffersignificantlyfromyoungpatientsalthoughserum

concentrationstendedtobehigher.

Elderly,cachectic,ordebilitatedpatientsshouldbeobservedcarefullyforsignsoffentanyltoxicityandthedose

reducedifnecessary(seesections4.4and5.2).

Hepaticandrenalimpairment

Patientswithimpairedhepaticorrenalfunctionshouldbeobservedcarefullyandthedosereducedifnecessary(see

section4.4).

Paediatricpopulation

Theexperienceinchildrenunder12yearsofageislimited.Fentanylshouldnotbeusedinthispopulation.

GenerallyFentanylshouldbeadministeredonlytoopioid-tolerantpediatricpatients(ages2to16)whoarealready

receivingatleast30mgoralmorphineequivalentsperday.Toconvertpediatricpatientsfromoralorparenteralopioids

toFentanyl,refertoEquianalgesicpotencyconversion(Table1),andRecommendedFentanyldosebasedupondaily

oralmorphinedose(Table4).

Table4:RecommendedFentanyldosebasedupondailyoralmorphinedose

Forchildrenwhoreceivedmorethan90mgoralmorphineaday,onlylimitedinformationiscurrentlyavailablefrom

clinicaltrials.Inthepaediatricstudies,therequiredFentadurdosewascalculatedconservatively:30mgto45mgoral

morphineperdayoritsequivalentopioiddosewasreplacedbyoneFentanyl12µg/hrpatch.Itshouldbenotedthat

thisconversionscheduleforchildrenonlyappliestotheswitchfromoralmorphine(oritsequivalent)toFentadur.The

conversionschedulecouldnotbeusedtoconvertfromFentadurintootheropioids,asoverdosecouldthenoccur.

TheanalgesiceffectofthefirstdoseofFentadurwillnotbeoptimalwithinthefirst24hours.Therefore,duringthe

first12hoursafterswitchingtofentanyltransdermalpatches,thepatientshouldbegiventhepreviousregulardoseof

analgesics.Inthenext12hours,theseanalgesicsshouldbeprovidedbasedonclinicalneed.

Methodofadministration

Directlyafterremovalfromthepackandthereleaseliner,thepatchisappliedtoanon-hairyareaofskinontheupper

body(chest,back,upperarm).Toremovehair,scissorsshouldbeusedinsteadofrazors.

Priortoapplication,theskinshouldbecarefullywashedwithcleanwater(nocleaningagents)andthoroughlydried.

Thetransdermalpatchisthenappliedusingslightpressurewiththepalmofthehandforapproximately30seconds.

Theskinareatowhichthepatchisappliedshouldbefreeofmicrolesions(e.g.duetoirradiationorshaving)andskin

irritation.

Oral24-hourMorphine

(mg/day) FentanylDose(µg/h)

ForPediatrics

30-45

45-90 ForPediatrics

12

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Occasionally,additionaladhesionofthepatchmayberequired.

Ifprogressivedoseincreasesaremade,theactivesurfacearearequiredmayreachapointwherenofurtherincreaseis

possible.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients

Acuteorpostoperativepain,sincedosetitrationisnotpossibleduringshort-termuse.

Severeimpairmentofthecentralnervoussystem

4.4Specialwarningsandprecautionsforuse

Theproductshouldbeusedonlyaspartofanintegratedtreatmentofpainincaseswherethepatientisadequately

assessedmedically,sociallyandpsychologically.

Itisnotpossibletoensuretheinterchangeabilityofdifferentfentanylcontainingtransdermalpatchproductin

individualpatients.Therefore,itshouldbeemphasisedthatpatientsshouldnotbechangedfromonefentanyl

containingproducttoanotherwithoutspecificcounsellingonthechangefromtheirhealthcareprofessionals.

TreatmentwithFentadurshouldonlybeinitiatedbyanexperiencedphysicianfamiliarwiththepharmacokineticsof

fentanyltransdermalpatchesandtheriskforseverehypoventilation.Thepotentialforseriousorlife-threatening

hypoventilationexistsevenifthelowestdoseofFentadurisusedininitiatingtherapyinopioid-naïvepatients.Itis

recommendedthatFentadurbeusedinpatientswhohavedemonstratedopioidtolerance(SeeSection4.2).

Afterexhibitingaseriousadversereactionapatientshouldbemonitoredfor24hoursfollowingremovalofa

transdermalpatchduetothehalf-lifeoffentanyl(seesection5.2)

Inchronicnon-cancerpain,itmightbepreferabletoinitiatethetreatmentwithimmediate-releasestrongopioids(e.g.

morphine)andtoprescribefentanyltransdermalpatchafterdeterminationoftheefficacyandtheoptimaldosageofthe

strongopioid.

Thetransdermalpatchshouldnotbecut,sincenoinformationisavailableonthequality,efficacyandsafetyofsuch

dividedpatches.

Ifhigherdosagesthan500mgmorphine-equivalentareneeded,areassessmentofopioid-therapyisrecommended.

Breakthroughpain

Studieshaveshownthatalmostallpatients,despitetreatmentwithafentanylpatch,requiresupplementaltreatment

withpotentrapid-releasemedicinalproductstoarrestbreakthroughpain.

Respiratorydepression

AswithallpotentopioidssomepatientsmayexperiencerespiratorydepressionwiththeFentadurandpatientsmustbe

observedforthiseffect.Respiratorydepressionmaypersistbeyondtheremovalofthepatch.Theincidenceof

respiratorydepressionincreasesasthefentanyldoseisincreased.CNSactivesubstancesmayworsentherespiratory

depression(seesection4.5).

Inpatientswithexistingrespiratorydepression,fentanylshouldonlybeusedwithcautionandatlowerdose.

Chronicpulmonarydisease

Inpatientswithchronicobstructiveorotherpulmonarydiseasesfentanylmayhavemoresevereadversereactions;in

suchpatientsopioidsmaydecreaserespiratorydriveandincreaseairwayresistance.

Drugdependence

Toleranceandphysicalandpsychologicaldependencemaydevelopuponrepeatedadministrationofopioids,butisrare

intreatmentofcancerrelatedpain.

Increasedintracranialpressure

Fentadurshouldbeusedwithcautioninpatientswhomaybeparticularlysusceptibletotheintracranialeffectsof

carbondioxideretentionsuchasthosewithevidenceofincreasedintracranialpressure,impairedconsciousnessor

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Fentanylshouldbeusedwithcautioninpatientsinwhomacerebraltumourhasbeendetected.

Cardiacdisease

Opioidsmaycausehypotension,especiallyinpatientswithhypovolemia.Cautionshouldthereforebetakenin

treatmentofpatientswithhypotensionand/orpatientswithhypovolemia.Fentadurmayproducebradycardia.Fentadur

transdermalpatchshouldthereforebeadministeredwithcautiontopatientswithbradyarrhythmias.

Impairedliverfunction

Fentadurismetabolisedintoinactivemetabolitesintheliver,sopatientswithhepaticdiseasemighthaveadelayed

elimination.Patientswithhepaticimpairmentshouldbeobservedcarefullyandthedosereducedifnecessary.

Renalimpairment

Lessthan10%offentanylisexcretedunchangedbythekidneys,andunlikemorphine,therearenoknownactive

metaboliteseliminatedbythekidneys.Dataobtainedwithintravenousfentanylinpatientswithrenalfailuresuggest

thatthevolumeofdistributionoffentanylmaybechangedbydialysis.Thismayaffectserumconcentrations.If

patientswithrenalimpairmentreceivetransdermalfentanyltheyshouldbeobservedcarefullyforsignsoffentanyl

toxicityandthedosereducedifnecessary.

Patientswithfever/externalheat

Significantincreasesinbodytemperaturecanpotentiallyincreasefentanylabsorptionrate.Therefore,patientswho

developfevershouldbemonitoredforopioidadversereactions.

PatientsshouldbeadvisedtoavoidexposingtheFentadurapplicationsitetodirectexternalheatsourcessuchas

heatingpads,hotwaterbottles,electricblankets,heatedwaterbeds,heatortanninglamps,intensivesunbathing,

prolongedhotbaths,saunasorhotwhirlpoolspabathswhilewearingthepatch,sincethereispotentialfortemperature

dependentincreasesinreleaseoffentanylfromthepatch.

ElderlyPatients

Datafromintravenousstudieswithfentanylsuggestthattheelderlypatientsmayhavereducedclearanceanda

prolongedhalf-life.Moreoverelderlypatientsmaybemoresensitivetotheactivesubstancethanyoungerpatients.

However,studiesoffentanyltransdermalpatchinelderlypatientsdemonstratedfentanylpharmacokineticswhichdid

notdiffersignificantlyfromyoungpatientsalthoughserumconcentrationstendedtobehigher.Elderlyorcachectic

patientsshouldbeobservedcarefullyforsignsoffentanyltoxicityandthedosereducedifnecessary.

Paediatricpatients

Fentadurshouldnotbeadministeredtoopioidnaïvepaediatricpatients(seesection4.2).Thepotentialforseriousor

life-threateninghypoventilationexistsregardlessofthedoseoftransdermalfentanyladministered(seeTable1and4in

section4.2).

Theuseoffentanylpatchesmayleadtoapositivedopingtest.Theuseoffentanylpatchesasadopingagentmaybe

hazardoustothehealth.

Patientswithmyastheniagravis

Non-epileptic(myo)clonicreactionscanoccur.

Cautionshouldbeexercisedwhentreatingpatientswithmyastheniagravis.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theconcomitantuseofbarbituricacidderivativesshouldbeavoided,sincetherespiratorydepressingeffectoffentanyl

maybeincreased.

Theconcomitantuseofbuprenorphine,nalbuphineorpentazocineisnotrecommended.Theyhavehighaffinityto

opioidreceptorswithrelativelylowintrinsicactivityandthereforepartiallyantagonisetheanalgesiceffectoffentanyl

andmayinducewithdrawalsymptomsinopioiddependantpatients(seesection4.4)

TheconcomitantuseofotherCNSdepressantsmayproduceaddictivedepressanteffectsandhypoventilation,

hypotensionaswellasprofoundsedationorcomamayoccur.TheCNSdepressantsmentionedaboveinclude:

Opioids

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hypnotics

generalanaesthetics

skeletalmusclerelaxants

sedatingantihistamines

alcoholicbeverages

Therefore,theuseofanyoftheabove-mentionedconcomitantmedicinalproductsandactivesubstancesrequires

observationofthepatient.

MAO-inhibitorshavebeenreportedtoincreasetheeffectofnarcoticanalgesics,especiallyinpatientswithcardiac

failure.Therefore,fentanylshouldnotbeusedwithin14daysafterdiscontinuationoftreatmentwithMAO-inhibitors.

Fentanyl,ahighclearanceactivesubstance,israpidlyandextensivelymetabolisedmainlybyCYP3A4.

Itraconazole(apotentCYP3A4inhibitor)at200mg/daygivenorallyforfourdayshadnotsignificanteffectonthe

pharmacokineticsofintravenousfentanyl.Increasedplasmaconcentrationswere,however,observedinindividual

subjects.Oraladministrationofritonavir(oneofthemostpotentCYP3A4inhibitors)reducedtheclearanceof

intravenousfentanylbytwothirdsanddoubledthehalf-life.ConcomitantuseofpotentCYP3A4-inhibitors(e.g.

ritonavir,ketoconazole,itraconazole,macrolideantibiotics)withtransdermallyadministeredfentanylmayresultin

increasedplasmaconcentrationsoffentanyl.Thismayincreaseorprolongboththetherapeuticeffectsandtheadverse

reactionsand,whichmaycausesevererespiratorydepression.Insuchcasesincreasedcareandobservationofthe

patientshouldbeundertaken.CombineduseofritonavirorotherpotentCYP3A4-inhibitorswithtransdermalfentanyl

isnotrecommended,unlessthepatientiscarefullyobserved.

4.6Fertility,pregnancyandlactation

Thesafetyoffentanylinpregnancyhasnotbeenestablished.Studiesinanimalshaveshownreproductivetoxicity(see

section5.3).Thepotentialriskforhumansisunknown.Fentadurshouldnotbeusedinpregnancyunlessclearly

necessary.

Long-termtreatmentduringpregnancymaycausewithdrawalsymptomsintheinfant.

Itisadvisednottousefentanylduringlabouranddelivery(includingcaesareansection)sincefentanylpassesthe

placentaandmaycauserespiratorydepressioninthenewborninfant.

Fentanylisexcretedintobreastmilkandmaycausesedationandrespiratorydepressioninthebreast-fedinfant.

Lactationshouldthereforebediscontinuedduringtreatmentandforatleast72hoursaftertheremovalofFentadur(see

alsosection4.4).

4.7Effectsonabilitytodriveandusemachines

Fentanylhasamajorinfluenceontheabilitytodriveandusemachines.Thishastobeexpectedespeciallyatthe

beginningoftreatment,atanychangeofdosageaswellasinconnectionwithalcoholorantipsychotics.Patients

stabilisedonaspecificdosagewillnotnecessarilyberestricted.Therefore,patientsshouldconsulttheirphysicianasto

whetherdrivingoruseofmachinesisreasonable.

4.8Undesirableeffects

Thefollowingfrequenciesareusedforthedescriptionoftheoccurrenceofadversereactions:

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)

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Metabolismandnutritiondisorder

NotKnown:Anorexia

Nervoussystemdisorders

Verycommon:Dizziness,headache

Uncommon:Tremor,paraesthesia,speechdisorder

Veryrare:Ataxia,seizures(includingclonicandgrandmalseizures)

NotKnown:Convulsions(includingclonicconvulsionsandgrandmalconvulsion),amnesia

Eyedisorders

Common:conjunctivitis

Rare:Amblyopia

Cardiacdisorders

Common:palpitations

Uncommon:Tachycardia,bradycardia

Rare:Arrhythmia

Respiratory,thoracicandmediastinaldisorders

Common:Yawning,rhinitis

Uncommon:Dyspnoea,hypoventilation

Veryrare:Respiratorydepression,apnoea

Renalandurinarydisorders

Common:Urinarytractinfection

Uncommon:Urinaryretention

Veryrare:Oliguria,cystalgia

Gastrointestinaldisorders

Verycommon:Nausea,vomiting,constipation

Common:Xerostomia,dyspepsia

Uncommon:Diarrhoea

Rare:Hiccups

Veryrare:Painfulflatulence,ileus

Skinandsubcutaneoustissuedisorders

Verycommon:Sweating,pruritus

Uncommon:Exanthema,erythema

Rash,erythemaandprurituswillusuallydisappearwithinonedayafterthepatchhasbeen

removed.

Vasculardisorders

Uncommon:Hypertension,hypotension

Rare:Vasodilatation

Generaldisordersandadministrationsiteconditions

Rare:Oedema,coldfeeling

Common:skinreactionsontheapplicationsite,fatigue,malaise,influenzalikeillness,asthenia

Immunesystemdisorders

Veryrare:Anaphylaxis

Psychiatricdisorders

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Themostcommonadversereactionsfollowingadministrationatusualdosesaredrowsiness,confusion,nausea,

vomitingandconstipation.Thefirstofthesearetransientandtheircauseshouldbeinvestigatedifsymptomspersist.

Constipation,ontheotherhand,doesnotstopiftreatmentcontinues.Alloftheseeffectscanbeexpectedandshould,

therefore,beanticipatedinordertooptimisetreatment,especiallyconstipation.Correctivetreatmentmayoftenbe

required.

4.9Overdose

Symptoms

Thesymptomsoffentanyloverdoseareanextensionofitspharmacologicalactions,e.g.lethargy,coma,respiratory

depressionwithCheyne-Stokesrespirationand/orcyanosis.Othersymptomsmaybehypothermia,decreasedmuscle

tonus,bradycardia,hypotension.Signsoftoxicityaredeepsedation,ataxia,miosis,convulsionsandrespiratory

depression,whichisthemainsymptom.

Treatment

Formanagementofrespiratorydepressionimmediatecountermeasuresshouldbestarted,includingremovingthepatch

andphysicallyorverballystimulatingthepatient.Theseactionscanbefollowedbyadministrationofaspecificopioid

antagonistsuchasnaloxone.

Astartingdoseof0.4-2mgnaloxonehydrochlorideintravenouslyisrecommendedforadults.Ifneeded,asimilardose

canbegivenevery2or3minutes,orbeadministeredascontinuedinfusionas2mgin500mlsodiumchloride9

mg/mlsolution(0.9%)solutionforinjectionorglucose50mg/ml(5%)solution.Theinfusionrateshouldbeadjusted

accordingtopreviousbolusinjectionsandtheindividualresponseofthepatient.Ifintravenousadministrationis

impossible,naloxonehydrochloridecanalsobegivenintramuscularlyorsubcutaneously.Followingintramuscularor

subcutaneousadministrationtheonsetofactionwillbeslowercomparedwithintravenousadministration.

Intramuscularadministrationwillgiveamoreprolongedeffectthanintravenousadministration.Respiratorydepression

duetooverdosecanpersistlongerthantheeffectoftheopioidantagonist.Reversingthenarcoticeffectcangiveriseto

acutepainandreleaseofcatecholamines.Intensivecareunittreatmentisimportant,ifrequiredbythepatient’sclinical

condition.Ifsevereorpersistenthypotensionoccurs,hypovolemiashouldbeconsidered,andtheconditionshouldbe

managedwithappropriateparenteralfluidtherapy.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:opioids;phenylpiperidinederivatives,ATCCode:N02AB03

Fentanylisanopioidanalgesicwhichinteractspredominantlywiththeµ-receptor.

Itsprincipaltherapeuticeffectsareanalgesiaandsedation.

Theserumconcentrationsoffentanylthatcauseaminimalanalgesiceffectinopioid-naïvepatientsfluctuatebetween

Common:Sedation,nervousness,lossofappetite,depression

Uncommon:Euphoria,amnesia,insomnia,hallucinations,agitation

Veryrare:Delusionalideas,statesofexcitement,asthenia,depression,anxiety,confusion,

sexualdysfunction,withdrawalsymptoms

Otherundesirableeffects

Notknown(cannotbeestimatedfromtheavailabledata):Long-termuseoffentanylcanleadto

developmentoftoleranceandphysicalandpsychologicaldependence.Afterswitchingfrom

previouslyprescribedopioidanalgesicstoFentadurorafterabruptdiscontinuationoftherapy

patientsmayshowopioidwithdrawalsymptoms(forinstance:nausea,vomiting,diarrhoea,

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Boththelowesteffectivefentanylconcentrationandtheconcentrationcausingadversereactionswillincreasewiththe

developmentofincreasingtolerance.Thetendencytodeveloptolerancevariesconsiderablybetweenindividuals.

5.2Pharmacokineticproperties

FollowingadministrationofFentadur,fentanyliscontinuouslyabsorbedthroughtheskinoveraperiodof72hours.

Duetothepolymermatrixandthediffusionoffentanylthroughtheskinlayers,thereleaserateremainsrelatively

constant.

Absorption

AfterthefirstapplicationofFentadur,serumfentanylconcentrationsincreasesgradually,generallylevellingoff

between12and24hours,andremainingrelativelyconstantfortheremainderofthe72-hourapplicationperiod.The

serumfentanylconcentrationsattainedaredependantonthefentanyltransdermalpatchsize.Forallpracticalpurposes

bythesecond72-hourapplication,asteadystateserumconcentrationisreachedandismaintainedduringsubsequent

applicationsofapatchofthesamesize.

Distribution

Theplasmaproteinbindingforfentanylis84%.

Biotransformation

FentanylismetabolisedprimarilyintheliverviaCYP3A4.Themajormetabolite,norfentanyl,isinactive.

Elimination

WhentreatmentwithFentadur,iswithdrawn,serumfentanylconcentrationsdeclinegradually,fallingapproximately

50%in13-22hoursinadultsor22-25hoursinchildren,respectively.Continuedabsorptionoffentanylfromtheskin

accountsforaslowerreductioninserumconcentrationthanisseenafteranintravenousinfusion.

Around75%offentanylisexcretedintotheurine,mostlyasmetabolites,withlessthan10%asunchangedactive

substance.About9%ofthedoseisrecoveredinthefaeces,primarilyasmetabolites.

Pharmacokineticsinspecialgroups

Elderlyanddebilitatedpatientsmayhavereducedclearanceoffentanylleadingtoprolongedterminalhalflife.In

patientswithrenalorhepaticimpairment,clearanceoffentanylmaybealteredbecauseofchangesofplasmaproteins

andmetabolicclearanceresultinginincreasedserumconcentrations.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicityandgenotoxicity.

Animalstudieshaveshownreducedfertilityandincreasedmortalityinratfoetuses.Teratogeniceffectshave,however,

notbeendemonstrated.

Long-termcarcinogenicitystudieshavenotbeenperformed.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Overlayliner

Polyethyleneterephthalatefilmwithfluorocarbonreleasecoating.

BackingLayer

Polyethyleneterephthalate/ethylenevinylacetatecopolymerfilm

DrugadhesiveLayer

Siliconeadhesive(polydimethylsiloxane,silicateresin)

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Ratecontrollingmembrane

Ethylenevinylacetatecopolymerfilm

SkinadhesiveLayer

Siliconeadhesive(polydimethylsiloxane,silicateresin)

Polydimethylsiloxane

Releaseliner

Polyethyleneterephthalatefilmwithfluorocarbonreleasecoating

Printingink

Redink

6.2Incompatibilities

Notapplicable

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Theproductispackagedbetweentwosheetsofamulti-laminatepouchingmaterial,containingaluminumfoilasthe

primarybarriercomponentandalayerofionomerresinattachedtothealuminiumlayer,andindirectcontactwiththe

product.Thetwosheetsofthemultilaminatefilmaresealedtogetherattheedgessoastoenclosetheproductinachild

resistantsachet.

Packsizes:

Packagewith3transdermalpatches,

Packagewith5transdermalpatches,

Packagewith10transdermalpatches,

Packagewith16transdermalpatches

Packagewith20transdermalpatches

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Highquantitiesoffentanylremaininthetransdermalpatchesevenafteruse.Usedtransdermalpatchesshouldbefolded

withtheadhesivesurfacesinwardsanddiscardedorwheneverpossiblereturnedtothepharmacy.Anyunused

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/01/2012 CRN 2110897 page number: 11

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk,

NationalDigitalPark,

CitywestBusinessCampus,

Dublin24,

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/70/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:6thJanuary2012

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 30/01/2012 CRN 2110897 page number: 12