FETANEX

Main information

  • Trade name:
  • FETANEX Transdermal Patch 75 Microgram
  • Dosage:
  • 75 Microgram
  • Pharmaceutical form:
  • Transdermal Patch
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FETANEX Transdermal Patch 75 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/137/005
  • Authorization date:
  • 14-11-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0711/137/005

CaseNo:2066768

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

RowexLtd

Bantry,Co.Cork,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Fetanex75microgram/hourtransdermalpatch

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom25/06/2009until13/11/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fetanex75microgram/hourtransdermalpatch

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachpatchreleases75microgramsfentanylperhour.Eachpatchof31.5cm²contains12.6mgfentanyl.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Transdermalpatch

Transparentroundedoblongtransdermalpatchwithimprintonthebackingfilm:“fentanyl75µg/h”

Thepatchconsistsofareleaseliner(toberemovedpriortoapplicationofthepatch)andtwofunctionallayers:oneself-adhesive

matrixlayercontainingfentanylandabackingfilmimpermeabletowater.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Severechronicpainwhichcanbeadequatelymanagedonlywithopioidanalgesics.

4.2Posologyandmethodofadministration

Fetanextransdermalpatchesreleasefentanylover72hours.

Thedosingisindividualandbasedonthepatient`sopioidhistoryandtakesintoaccount:

thepossibledevelopmentoftolerance,

thecurrentgeneralcondition,themedicalstatusofthepatient,and

thedegreeofseverityofthedisorder.

Therequiredfentanyldosageisadjustedindividuallyandshouldbeassessedregularlyaftereachadministration.

Patientsreceivingopioidtreatmentforthefirsttime

Inpatientswhohavenotpreviouslyreceivedstrongopioids,theinitialdosageshouldnotexceed12.5-25microgram/hour.

Inveryelderlyorweakpatients,itisnotrecommendedtoinitiateanopioidtreatmentwithFetanextransdermalpatches,dueto

theirknownsusceptibilitytoopioidtreatments.Inthesecases,itwouldbepreferabletoinitiateatreatmentwithlowdosesof

immediatereleasemorphineandtoprescribeFetanextransdermalpatchesafterdeterminationoftheoptimaldosage.

Switchingfromotheropioids

Whenchangingoverfromoralorparenteralopioidstofentanyltreatment,theinitialdosageshouldbecalculatedasfollows:

1.Thequantityofanalgesicsrequiredoverthelast24hoursshouldbedetermined.

2.TheobtainedsumshouldbeconvertedtocorrespondtotheoralmorphinedosageusingTable1.

3.Thecorrespondingfentanyldosageshouldbedeterminedasfollows:

a)usingTable2forpatientswhohaveaneedforopioidrotation(conversionratiooforalmorphinetotransdermalfentanylequal

to150:1)

b)usingTable3forpatientsonstableandwelltoleratedopioidtherapy(conversionratiooforalmorphinetotransdermalfentanyl

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Table1:Equianalgesicpotencyconversion

Alldosagesgiveninthetableareequivalentinanalgesiceffectto10mgparenteralmorphine.

Activesubstance Equianalgesicdoses(mg)

i.m. Oral

Morphine 10 30-40

Hydromorphone 1.5 7.5

Oxycodone 10-15 20-30

Methadone 10 20

Levorphanol 2 4

Oxymorphine 1 10(rectal)

Diamorphine 5 60

Pethidine 75 -

Codeine - 200

Buprenorphine 0.4 0.8(sublingual)

Ketobemidone 10 20-30

Table2:RecommendedinitialdoseoftransdermalFentanylbasedondailyoralmorphinedose

(forpatientswhohaveaneedforopioidrotation)

Oral

morphinedose Transdermalfentanylrelease

(mg/24h) (micrograms/h)

Forpaediatricpatients *

30-44 12.5

45-134 25

Foradults

<44 12.5

45-134 25

135-179 37.5

180-224 50

225-314 75

315-404 100

405-494 125

495-584 150

585-674 175

675-764 200

765-854 225

855-944 250

945-1034 275

1035-1124 300

*ConversiontoFentanyltransdermalpatchdosesgreaterthan25microgram/houristhesameforadultandpaediatricpatients.

Table3:Recommendedinitialdoseoftransdermalfentanylbasedondailyoralmorphinedose

(forpatientsonstableandwelltoleratedopioidtherapy)

Oral Transdermal

morphinedose fentanylrelease

(mg/24h) (micrograms/h)

<60 12.5

60-89 25

90-119 37.5

120-149 50

150-209 75

210-269 100

270-329 125

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390-449 175

450-509 200

510-569 225

570-629 250

630-689 275

690-749 300

Bycombiningseveraltransdermalpatches,afentanylreleaserateofover100micrograms/hcanbeachieved.

TheinitialevaluationofthemaximumanalgesiceffectofFetanextransdermalpatchshouldnotbemadebeforethepatchhasbeen

wornfor24hours.Thisisduetothegradualincreaseinserumfentanylconcentrationsduringthefirst24hoursafterapplication

ofthepatch.

Inthefirst12hoursafterchangingtoFetanextransdermalpatchthepatientcontinuestoreceivethepreviousanalgesicatthe

previousdose;overthenext12hoursthisanalgesicisadministeredaccordingtoneed.

Dosetitrationandmaintenancetherapy

Thepatchshouldbereplacedevery72hours.Thedoseshouldbetitratedindividuallyuntilanalgesicefficacyisattained.In

patientswhoexperienceamarkeddecreaseintheperiod48-72hoursafterapplication,replacementofFetanextransdermalpatch

after48hoursmaybenecessary.Thedose12.5microgram/hourisappropriatefordosetitrationinthelowerdosagearea.If

analgesiaisinsufficientattheendoftheinitialapplicationperiod,thedosemaybeincreasedafter3days,untilthedesiredeffect

isobtainedforeachpatient.Additionaldoseadjustmentshouldnormallybeperformedin12.5microgram/houror25

microgram/hourincrements,althoughthesupplementaryanalgesicrequirementsandpainstatusofthepatientshouldbetakeninto

account.Patientsmayrequireperiodicsupplementaldosesofashort-actinganalgesicforbreakthroughpain(e.g.morphine).

Additionaloralternativemethodsofanalgesiaoralternativeadministrationofopioidsshouldbeconsideredwhenthetransdermal

fentanyldoseexceeds300microgram/hour.

Withdrawalsymptomshavebeenreportedwhenchangingfromlong-termtreatmentwithmorphinetotransdermalfentanyl

despiteadequateanalgesicefficacy.Incaseofwithdrawalsymptomsitisrecommendedtotreatthosewithshort-actingmorphine

inlowdoses.

Changingorendingtherapy

Ifdiscontinuationofthepatchisnecessary,anyreplacementwithotheropioidsshouldbegradual,startingatalowdoseand

increasingslowly.Thisisbecausefentanyllevelsfallgraduallyafterthepatchisremoved;ittakesatleast17hoursforthe

fentanylserumconcentrationtodecreaseby50%(seesection5.2).Asageneralrule,thediscontinuationofopioidanalgesia

shouldbegradual,inordertopreventwithdrawalsymptoms(suchasnausea,vomiting,diarrhea,anxietyandmusculartremor).

Tables2and3shouldnotbeusedtoswitchfromtransdermalfentanyltoamorphinetreatment.

Paediatricpopulation

Fetanextransdermalpatchshouldnotbeusedinchildrenunder2yearsofage.

Fetanextransdermalpatchshouldbeadministeredonlytoopioid-tolerantpaediatricpatients(ages2to16years)whoarealready

receivingatleast30mgoralmorphineequivalentsperday.Toconvertpaediatricpatientsfromoralorparenteralopioidsto

Fetanextransdermalpatch,refertoTable1andTable2.

Forchildrenwhoreceivemorethan90mgoralmorphineaday,onlylimitedinformationiscurrentlyavailablefromclinicaltrials.

Inthepaediatricstudies,therequiredfentanyltransdermalpatchdosewascalculatedconservatively:30mgto45mgoral

morphineperdayoritsequivalentopioiddosewasreplacedbyoneFentanyltransdermalpatch12.5microgram/hour.Itshouldbe

notedthatthisconversionscheduleforchildrenonlyappliestotheswitchfromoralmorphine(oritsequivalent)toFentanyl

transdermalpatches.TheconversionschedulecouldnotbeusedtoconvertfromFetanextransdermalpatchesintootheropioids,

asoverdosecouldthenoccur.

TheanalgesiceffectofthefirstdoseofFetanextransdermalpatchwillnotbeoptimalwithinthefirst24hours.Therefore,during

thefirst12hoursafterswitchingtoFetanextransdermalpatch,thepatientshouldbegiventhepreviousregulardoseofanalgesics.

Inthenext12hours,theseanalgesicsshouldbeprovidedbasedonclinicalneed.

Sincepeakfentanyllevelsoccurafter12to24hoursoftreatment,monitoringofthepaediatricpatientforadverseevents,which

mayincludehypoventilation,isrecommendedforatleast48hoursafterinitiationofFetanextransdermalpatchtherapyorup-

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Dosetitrationandmaintenancetherapy

IftheanalgesiceffectofFetanextransdermalpatchisinsufficient,supplementarymorphineoranothershort-durationopioid

shouldbeadministered.Dependingontheadditionalanalgesicneedsandthepainstatusofthechild,itmaybedecidedtouse

morepatches.Doseadjustmentsshouldbedonein12.5microgram/hoursteps.

Useinelderlypatients

Elderlyshouldbeobservedcarefullyandthedosereducedifnecessary(seesection4.4).

Hepaticandrenalimpairment

Patientswithhepaticorrenalimpairmentshouldbeobservedcarefullyandthedosereducedifnecessary(seesection4.4).

Methodofadministration

Fortransdermaluse.

Directlyafterremovalfromthepackandthereleaseliner,thepatchisappliedtoanon-hairyareaofskinontheupperbody

(chest,back,upperarm).

Foruseinchildren:Therearenosafetyandpharmacokineticdataavailableforotherapplicationsites.

Inyoungchildren,theupperbackisthepreferredlocationtoapplythepatch,tominimizethepotentialofthechildremovingthe

patch.

Toremovehair,scissorsshouldbeusedinsteadofrazors.

Priortoapplication,theskinshouldbecarefullywashedwithcleanwater(nocleaningagents)andthoroughlydried.The

transdermalpatchisthenappliedusingslightpressurewiththepalmofthehandforapproximately30seconds.Theskinareato

whichthepatchisappliedshouldbefreeofmicrolesions(e.g.duetoirradiationorshaving)andskinirritation.

Asthetransdermalpatchisprotectedbyanouterwaterproofbackingfilm,itcanalsobewornwhileshowering.

Ifprogressivedoseincreasesaremade,theactivesurfacearearequiredmayreachapointwherenofurtherincreaseispossible.

Durationofadministration

Thepatchshouldbechangedafter72hours.Ifanearlierchangebecomesnecessaryinindividualcases,nochangeshouldbe

madebefore48hourshaveelapsed,otherwiseariseinmeanfentanylconcentrationsmayoccur.Anewskinareamustbeselected

foreachapplication.Aperiodof7daysshouldbeallowedtoelapsebeforeapplyinganewpatchtothesameareaofskin.The

analgesiceffectmaypersistforsometimeafterremovalofthetransdermalpatch.

Iftracesofthetransdermalpatchremainontheskinafterremovalofthepatch,thesecanbecleanedoffusingcopiousamountsof

soapandwater.Noalcoholorothersolventsmustbeusedforcleaningasthesemaypenetratetheskinduetotheeffectofthe

patch.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients

Acuteorpostoperativepain,sincedosagetitrationisnotpossibleduringshorttermuse

Severeimpairmentofthecentralnervoussystem

4.4Specialwarningsandprecautionsforuse

Theproductshouldbeusedonlyaspartofanintegratedtreatmentofpainincaseswherethepatientisadequatelyassessed

medically,sociallyandpsychologically.

TreatmentwithFetanextransdermalpatchshouldonlybeinitiatedbyanexperiencedphysicianfamiliarwiththe

pharmacokineticsoffentanyltransdermalpatchesandtheriskforseverehypoventilation.

Afterexhibitingaseriousadversereactionapatientshouldbemonitoredfor24hoursfollowingremovalofatransdermalpatch

duetothehalflifeoffentanyl(seesection5.2).

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

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Thetransdermalpatchshouldnotbecut,sincenoinformationisavailableonthequality,efficacyandsafetyofsuchdivided

patches.

Ifhigherdosagesthan500mgmorphine-equivalentareneeded,areassessmentofopioid-therapyisrecommended.

Themostcommonadversereactionsfollowingadministrationatusualdosesaredrowsiness,confusion,nausea,vomitingand

constipation.Thefirstofthesearetransientandtheircauseshouldbeinvestigatedifsymptomspersist.Constipation,ontheother

hand,doesnotstopiftreatmentcontinues.Alloftheseeffectscanbeexpectedandshould,therefore,beanticipatedinorderto

optimisetreatment,especiallyconstipation.Correctivetreatmentmayoftenberequired(seesection4.8).

Breakthroughpain

Studieshaveshownthatalmostallpatients,despitetreatmentwithafentanylpatch,requiresupplementaltreatmentwithpotent

rapid-releasemedicinalproductstoarrestbreakthrough-pain.

Respiratorydepression

AswithallpotentopioidssomepatientsmayexperiencerespiratorydepressionwiththeFentanyltransdermalpatch,andpatients

mustbeobservedforthiseffect.Respiratorydepressionmaypersistbeyondtheremovalofthepatch.Theincidenceofrespiratory

depressionincreasesasthefentanyldoseisincreased.CNSactivesubstancesmayworsentherespiratorydepression(seesection

4.5).Inpatientswithexistingrespiratorydepressionfentanylshouldonlybeusedwithcautionandatlowerdose.

Chronicpulmonarydisease

Inpatientswithchronicobstructiveorotherpulmonarydiseasesfentanylmayhavemoresevereadversereactions;insuchpatients

opioidsmaydecreaserespiratorydriveandincreaseairwayresistance.

Drugdependence

Toleranceandphysicalandpsychologicaldependencemaydevelopuponrepeatedadministrationofopioids,butisrarein

treatmentofcancerrelatedpain.

Increasedintracranialpressure

Fetanexshouldbeusedwithcautioninpatientswhomaybeparticularlysusceptibletotheintracranialeffectsofcarbondioxide

retentionsuchasthosewithevidenceofincreasedintracranialpressure,impairedconsciousnessorcoma.

Cardiacdisease

Opioidsmaycausehypotension,especiallyinpatientswithhypovolemia.Cautionshouldthereforebetakenintreatmentof

patientswithhypotensionand/orpatientswithhypovolemia.

Fentanylmayproducebradycardia.Fetanextransdermalpatchshouldthereforebeadministeredwithcautiontopatientswith

bradyarrhythmias.

Impairedliverfunction

Fentanylismetabolisedtoinactivemetabolitesintheliver,sopatientswithhepaticdiseasemighthaveadelayedelimination.

Patientswithhepaticimpairmentshouldbeobservedcarefullyandthedosereducedifnecessary.

Renalimpairment

Lessthan10%offentanylisexcretedunchangedbythekidneys,andunlikemorphine,therearenoknownactivemetabolites

eliminatedbythekidneys.Dataobtainedwithintravenousfentanylinpatientswithrenalfailuresuggestthatthevolumeof

distributionoffentanylmaybechangedbydialysis.Thismayaffectserumconcentrations.Ifpatientswithrenalimpairment

receivetransdermalfentanyltheyshouldbeobservedcarefullyforsignsoffentanyltoxicityandthedosereducedifnecessary.

Patientswithfever/externalheat

Significantincreasesinbodytemperaturecanpotentiallyincreasefentanylabsorptionrate.Thereforepatientswhodevelopfever

shouldbemonitoredforopioidadversereactions.Thepatchapplicationsiteshouldnotbeexposedtoheatfromexternalheat

sources,e.g.sauna.

ElderlyPatients

Datafromintravenousstudieswithfentanylsuggestthatelderlypatientsmayhavereducedclearanceandaprolongedhalf-life.

Moreoverelderlypatientsmaybemoresensitivetotheactivesubstancethanyoungerpatients.However,studiesoffentanyl

transdermalpatchinelderlypatientsdemonstratedfentanylpharmacokineticswhichdidnotdiffersignificantlyfromyoung

patientsalthoughserumconcentrationstendedtobehigher.Elderlyorcachecticpatientsshouldbeobservedcarefullyandthe

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Paediatricpopulation

Fetanextransdermalpatchshouldnotbeadministeredtoopioidnaïvepaediatricpatients(seesection4.2).Thepotentialfor

seriousorlife-threateninghypoventilationexistsregardlessofthedoseoftransdermalfentanyladministered(seeTables1and2in

section4.2).

Transdermalfentanylwasnotstudiedinchildrenunder2yearsofage.Fentanyltransdermalpatchshouldbeadministeredonlyto

opioid-tolerantchildrenage2yearsorolder(seesection4.2).Fentanyltransdermalpatchshouldnotbeusedinchildrenunder2

yearsofage.

Toguardagainstaccidentalingestionbychildren,cautionshouldbeusedwhenchoosingtheapplicationsiteforFetanex

transdermalpatch(seesection4.2)andtheadhesionofthepatchshouldbemonitoredclosely.

Patientswithmyastheniagravis

Non-epileptic(myo)clonicreactionscanoccur.Cautionshouldbeexercisedwhentreatingpatientswithmyastheniagravis.

Fetanextransdermalpatchmustbeusedonlyontheskinofthepersonforwhomithasbeenmedicallyprescribed.Inisolated

cases,thepatchhasbecomeattachedtotheskinofanotherpersonafterclosebodycontact.Thepatchshouldberemoved

immediatelyinsuchcases.

Fordisposalinstructionsseesection6.6.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theconcomitantuseofbarbituricacidderivativesshouldbeavoided,sincetherespiratorydepressingeffectoffentanylmaybe

increased.

Theconcomitantuseofbuprenorphine,nalbuphineorpentazocineisnotrecommended.Theyhavehighaffinitytoopioid

receptorswithrelativelylowintrinsicactivityandthereforepartiallyantagonisetheanalgesiceffectoffentanylandmayinduce

withdrawalsymptomsinopioiddependentpatients(seealsosection4.4).

TheconcomitantuseofotherCNSdepressantsmayproduceadditivedepressanteffectsandhypoventilation,hypotensionaswell

asprofoundsedationorcomamayoccur.TheCNSdepressantsmentionedaboveinclude:

-opioids

-anxiolyticsandtranquillizers

.hypnotics

-generalanaesthetics

-phenothiazines

-skeletalmusclerelaxants

-sedatingantihistamines

-alcoholicbeverages

Therefore,theuseofanyoftheabovementionedconcomitantmedicinalproductsandactivesubstancesrequiresobservationof

thepatient.

MAO-inhibitorshavebeenreportedtoincreasetheeffectofnarcoticanalgesics,especiallyinpatientswithcardiacfailure.

Therefore,fentanylshouldnotbeusedwithin14daysafterdiscontinuationoftreatmentwithMAO-inhibitors.

Fentanyl,ahighclearanceactivesubstance,israpidlyandextensivelymetabolisedmainlybyCYP3A4.

Itraconazole(apotentCYP3A4inhibitor)at200mg/daygivenorallyforfourdayshadnosignificanteffectonthe

pharmacokineticsofintravenousfentanyl.Increasedplasmaconcentrationswere,however,observedinindividualsubjects.Oral

administrationofritonavir(oneofthemostpotentCYP3A4inhibitors)reducedtheclearanceofintravenousfentanylbytwo

thirdsanddoubledthehalf-life.ConcomitantuseofpotentCYP3A4-inhibitors(e.g.ritonavir,ketoconazole,itraconazole,some

macrolideantibiotics)withtransdermallyadministeredfentanylmayresultinincreasedplasmaconcentrationsoffentanyl.This

mayincreaseorprolongboththetherapeuticeffectsandtheadversereactions,whichmaycausesevererespiratorydepression.In

suchcasesincreasedcareandobservationofthepatientshouldbeundertaken.Combineduseofritonavirorotherpotent

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4.6Pregnancyandlactation

Thesafetyoffentanylinpregnancyhasnotbeenestablished.Studiesinanimalshaveshownreproductivetoxicity(seesection

5.3).Thepotentialriskforhumansisunknown.Fentanylshouldonlybeusedduringpregnancywhenclearlynecessary.

Long-termtreatmentduringpregnancymaycausewithdrawalsymptomsintheinfant.

Itisadvisednottousefetanexduringlabouranddelivery(includingcaesareansection)sincefentanylpassestheplacentaandmay

causerespiratorydepressioninthefoetusorinthenew-borninfant.

Fentanylisexcretedintobreastmilkandmaycausesedationandrespiratorydepressioninthebreast-fedinfant.Lactationshould

thereforebediscontinuedduringtreatmentandforatleast72hoursaftertheremovalofFetanextransdermalpatch.

4.7Effectsonabilitytodriveandusemachines

Fetanexhasmajorinfluenceontheabilitytodriveandusemachines.Thishastobeexpectedespeciallyatthebeginningof

treatment,atanychangeofdosageaswellasinconnectionwithalcoholortranquilizers.Patientsstabilizedonaspecificdosage

willnotnecessarilyberestricted.Therefore,patientsshouldconsulttheirphysicianastowhetherdrivingoruseofmachinesis

permitted.

4.8Undesirableeffects

Theadverseeventprofileinchildrenandadolescentstreatedwithtransdermalfentanylwassimilartothatobservedinadults.No

riskwasidentifiedinthepaediatricpopulationbeyondthatexpectedwiththeuseofopioidsforthereliefofpainassociatedwith

seriousillnessandtheredoesnotappeartobeanypaediatric-specificriskassociatedwithtransdermalfentanyluseinchildrenas

youngas2yearsoldwhenusedasdirected.Verycommonadverseeventsreportedinpaediatricclinicaltrialswerefever,

vomiting,andnausea.

Thefollowingfrequenciesareusedforthedescriptionoftheoccurrenceofadversereactions:

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

Notknown(cannotbeestimatedfromtheavailabledata)

Themostseriousundesirableeffectoffentanylisrespiratorydepression.

Cardiacdisorders

Uncommon:Tachycardia,bradycardia

Rare:Arrhythmia

Nervoussystemdisorders

Verycommon:Headache,dizziness

Uncommon:Tremor,paraesthesia,speechdisorder

Veryrare:Ataxia,seizures(includingclonicandgrandmalseizures)

Eyedisorders

Veryrare:Amblyopia

Respiratory,thoracicandmediastinaldisorders

Uncommon:Dyspnea,hypoventilation

Veryrare:Respiratorydepression,apnea

Gastrointestinaldisorders

Verycommon:Nausea,vomiting,constipation

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Uncommon:Diarrhoea

Rare:Hiccups

Veryrare:Painfulflatulence,ileus

Renalandurinarydisorders

Uncommon:Urinaryretention

Veryrare:Cystalgia,oliguria

Skinandsubcutaneoustissuedisorders

Verycommon:Sweating,pruritus

Common:Skinreactionsontheapplicationsite

Uncommon:Exanthema,erythema

Rash,erythemaandprurituswillusuallydisappearwithinonedayafterthepatchhasbeenremoved.

Vasculardisorders

Uncommon:Hypertension,hypotension

Rare:Vasodilatation

Generaldisordersandadministrationsiteconditions

Rare:Oedema,coldfeeling

Immunesystemdisorders

Veryrare:Anaphylaxis

Psychiatricdisorders

Verycommon:Somnolence.

Common:Sedation,nervousness,lossofappetite

Uncommon:Euphoria,amnesia,insomnia,hallucinations,agitation

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

symptoms

Otherundesirableeffects

Notknown:Long-termuseoffentanylcanleadtodevelopmentoftoleranceandphysicalandpsychologicaldependence.After

switchingfrompreviouslyprescribedopioidanalgesicstofetanextransdermalpatchorafterabruptdiscontinuationoftherapy

patientsmayshowopioidwithdrawalsymptoms(forinstancenausea,vomiting,diarrhea,anxietyandshivering).

4.9Overdose

Symptoms

Thesymptomsoffentanyloverdoseareanextensionofitspharmacologicalactions,e.g.lethargy,coma,respiratorydepression

withCheyne-Stokesrespirationand/orcyanosis.Othersymptomsmaybehypothermia,decreasedmuscletonus,bradycardia,

hypotension.Signsoftoxicityaredeepsedation,ataxia,miosis,convulsionsandrespiratorydepression,whichisthemain

symptom.

Treatment

Formanagementofrespiratorydepressionimmediatecountermeasuresshouldbestarted,includingremovingthepatchand

physicallyorverballystimulatingthepatient.Theseactionscanbefollowedbyadministrationofaspecificopioidantagonistsuch

asnaloxone.

Astartingdoseof0.4-2mgnaloxonehydrochloridei.v.isrecommendedforadults.Ifneeded,asimilardosecanbegivenevery2

or3minutes,orbeadministeredascontinuedinfusionas2mgin500mlsodiumchloride9mg/mlsolution(0.9%)orglucose50

mg/mlsolution(5%).Theinfusionrateshouldbeadjustedaccordingtopreviousbolusinjectionsandtheindividualresponseof

thepatient.Ifintravenousadministrationisimpossible,naloxonehydrochloridecanalsobegivenintramuscularlyor

subcutaneously.Followingintramuscularorsubcutaneousadministrationtheonsetofactionwillbeslowercomparedwith

intravenousadministration.Intramuscularadministrationwillgiveamoreprolongedeffectthanintravenousadministration.

Respiratorydepressionduetooverdosecanpersistlongerthantheeffectoftheopioidantagonist.Reversingthenarcoticeffect

cangiverisetoacutepainandreleaseofcatecholamines.Intensivecareunittreatmentisimportant,ifrequiredbythepatient’s

clinicalcondition.Ifsevereorpersistenthypotensionoccurs,hypovolemiashouldbeconsidered,andtheconditionshouldbe

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:analgesics;opioids;phenylpiperidinederivatives

ATCCode:N02AB03

Fentanylisanopioidanalgesicwhichinteractspredominantlywiththeµ-receptor.Itsprincipaltherapeuticeffectsareanalgesia

andsedation.Theserumconcentrationsoffentanylthatcauseaminimalanalgesiceffectinopioid-naivepatientsfluctuate

between0.3–1.5ng/ml;anincreasedincidenceofadversereactionsisobservedifserumlevelsexceed2ng/ml.

Boththelowesteffectivefentanylconcentrationandtheconcentrationcausingadversereactionswillincreasewiththe

developmentofincreasingtolerance.Thetendencytodeveloptolerancevariesconsiderablybetweenindividuals.

Paediatricpopulation

Thesafetyoftransdermalfentanylwasevaluatedinthreeopen-labeltrialsin293paediatricpatientswithchronicpain,2yearsof

agethroughto18yearsofage,ofwhich66childrenwereagedto2to6years.Inthesestudies,30mgto45mgoralmorphineper

daywasreplacedbyonefentanyl12microgram/hourtransdermalpatch.Startingdoseof25microgram/hourandhigherwereused

by181patientswhohadbeenonpriordailyopioiddosesofatleast45mgperdoseoforalmorphine.

5.2Pharmacokineticproperties

FollowingadministrationofFentanyltransdermalpatch,fentanyliscontinuouslyabsorbedthroughtheskinoveraperiodof72

hours.Duetothepolymermatrixandthediffusionoffentanylthroughtheskinlayers,thereleaserateremainsrelativelyconstant.

Absorption

AfterthefirstapplicationofFetanextransdermalpatch,serumfentanylconcentrationsincreasegradually,generallylevellingoff

between12and24hours,andremainingrelativelyconstantfortheremainderofthe72-hourapplicationperiod.Theserum

fentanylconcentrationsattainedaredependentontheFetanextransdermalpatchsize.Forallpracticalpurposesbythesecond72-

hourapplication,asteadystateserumconcentrationisreachedandismaintainedduringsubsequentapplicationsofapatchofthe

samesize.

Distribution

Theplasmaproteinbindingforfentanylis84%.

Biotransformation

FentanylismetabolizedprimarilyintheliverviaCYP3A4.Themajormetabolite,norfentanyl,isinactive.

Elimination

WhentreatmentwithFentanyltransdermalpatchesiswithdrawn,serumfentanylconcentrationsdeclinegradually,falling

approximately50%in13-22hoursinadultsor22-25hoursinchildren,respectively.Continuedabsorptionoffentanylfromthe

skinaccountsforaslowerreductioninserumconcentrationthanisseenafteranintravenousinfusion.

Around75%offentanylisexcretedintotheurine,mostlyasmetabolites,withlessthan10%asunchangedactivesubstance.

About9%ofthedoseisrecoveredinthefaeces,primarilyasmetabolites.

Pharmacokineticsinspecialgroups

Adjustingforbodyweight,clearance(l/hour/kg)inpaediatricpatientsappearstobe82%higherinchildren2to5yearsoldand

25%higherinchildren6to10yearsoldwhencomparedtochildren11to16yearsold,whoarelikelytohavethesameclearance

asadults.Thesefindingshavebeentakenintoconsiderationindeterminingthedosingrecommendationsforpaediatricpatients.

Elderlyanddebilitatedpatientsmayhavereducedclearanceoffentanylleadingtoprolongedterminalhalflife.Inpatientswith

renalorhepaticimpairment,clearanceoffentanylmaybealteredbecauseofchangesofplasmaproteinsandmetabolicclearance

resultinginincreasedserumconcentrations

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeateddose

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Animalstudieshaveshownreducedfertilityandincreasedmortalityinratfoetuses.Teratogeniceffectshave,however,notbeen

demonstrated.

Long-termcarcinogenicitystudieshavenotbeenperformed.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Releaseliner:

Poly(ethyleneterephthalate)foil,siliconised

Self-adhesivematrixlayer:

Acrylic-vinylacetatecopolymer

Backingfilm:

Poly(ethyleneterephthalate)foil

Printingink

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Eachtransdermalpatchispackedinaseparatechild-resistantsachetmadeofPETP/Al/PE.

Packswith1,2,3,4,5,7,8,10,14,16and20transdermalpatches.

Hospitalpackswith5transdermalpatches.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Significantquantitiesoffentanylremaininthetransdermalpatchesevenafteruse.Usedtransdermalpatchesshouldbefolded

withtheadhesivesurfacesinwardsandduetosafetyandenvironmentalreasons,discardedsafelyorwheneverpossiblereturnedto

thepharmacy.Anyunusedmedicinalproductshouldbediscardedsafelyorreturnedtothepharmacy.

7MARKETINGAUTHORISATIONHOLDER

RowexLtd

Bantry

Co.Cork

Ireland

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14thNovember2008

10DATEOFREVISIONOFTHETEXT

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