FENTANYL 50 MICROGRAMS/HOUR TRANSDERMAL PATCH

Main information

  • Trade name:
  • FENTANYL 50 MICROGRAMS/HOUR TRANSDERMAL PATCH
  • Dosage:
  • 50 Microgram
  • Pharmaceutical form:
  • Transdermal Patch
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FENTANYL 50 MICROGRAMS/HOUR TRANSDERMAL PATCH
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/070/002
  • Authorization date:
  • 20-05-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0711/070/002

CaseNo:2043337

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

RowexLtd

Bantry,Co.Cork,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Fentanyl50micrograms/hourTransdermalPatch

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom21/02/2008until19/05/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 06/03/2008 CRN 2043337 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fentanyl50micrograms/hourTransdermalPatch

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtransdermalpatch(activesurfacearea20cm²)contains5mgfentanyl(correspondingto50microgram/hour

fentanylreleaserate).

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Transdermalpatch

Transparentandoblongtransdermalpatchwhichconsistsofaprotectivelayer(toberemovedpriortoapplicationof

thepatch)andfourfunctionallayers:anocclusivebacking,adrugreservoir,areleasemembraneandanadhesive

surface.

Surfaceareaofthetransdermalpatch:

Fentanyl50micrograms/hourTransdermalPatch:20cm²

4CLINICALPARTICULARS

4.1TherapeuticIndications

Chronicseverepainrequiringtreatmentwithopioidanalgesics,e.g.cancerpain.

4.2Posologyandmethodofadministration

Fentanyltransdermalpatchesreleasetheactivesubstanceover72hours.Thefentanylreleaserateis25,50,75and100

microgram/hourandthecorrespondingactivesurfaceareais10,20,30and40cm 2

Therequiredfentanyldosageisadjustedindividuallyandshouldbeassessedregularlyaftereachadministration.

Choiceofinitialdosage:Thedosageleveloffentanylisbasedupontheprevioususeofopioidsandtakesintoaccount

thepossibledevelopmentoftolerance,concomitantmedicinaltreatment,thepatient'sgeneralstateofhealthandthe

degreeofseverityofthedisorder.

Inopioid-naivepatients,whohavenotpreviouslybeentreatedwithopioids,theinitialdosageshouldnotexceed

25microgram/hour.

Changingfromotheropioidtreatment

Whenchangingoverfromoralorparenteralopioidstofentanyltreatment,theinitialdosageshouldbecalculatedas

follows:

1.Thequantityofanalgesicsrequiredoverthelast24hoursshouldbedetermined.

2.TheobtainedsumshouldbeconvertedtocorrespondtheoralmorphinedosageusingTable1.

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Table1:Equianalgesicefficacyofmedicinalproducts

Alli.m.andoraldosagesgiveninthetableareequivalentinanalgesiceffectto10mgmorphineadministered

intramuscularly.

[Ref.:FoleyKM:TheTreatmentofCancerPain.NEJM1985;313(2):84-95.]

*Basedonstudiesconductedwithsingledoses,inwhichthei.m.dosageofeachabove-mentionedagentwascompared

withmorphineinordertoachieveanequivalentefficacy.Oraldosagesaretherecommendeddosageswhenchanging

fromparenteraltooraladministration.

**Theefficacyratioof3:1formorphinei.m./oraldosageisbaseduponastudyconductedinpatientssufferingfrom

chronicpain.

Table2:RecommendeddosageofFentanyltransdermalpatchesbasedupontheoraldailymorphinedosage*

*Theseoralmorphinedosageswereusedasabasisinclinicaltrialswhenchangingmedicationtofentanyltransdermal

patches.Otherconversionschemeswhichhaveprovedtheirusefulnessinclinicalpracticeareexistingandmaybe

applied.

Bothinopioid-naivepatientsandinthosewhohavepreviouslyusedopioids,themaximumanalgesicefficacyof

Fentanyltransdermalpatchescannotbeevaluateduntilthetransdermalpatchhasbeeninsitufor24hours,sincethe

serumconcentrationoffentanylrisesgraduallyoveraperiodof24hours.Previousanalgesictreatmentshouldtherefore

notbediscontinuedbefore12hoursaftertheapplicationofthefirsttransdermalpatch,thenadministeredasneeded.

Nameofmedicinal

product Equianalgesicdosage(mg)

i.m.* Oral

Morphine 10 30(assumingrepeatedadministration)**

60(assumingasingledoseoroccasionaldoses)

Hydromorphine 1.5 7.5

Methadone 10 20

Oxycodone 10-15 20-30

Levorphanol 2 4

Oxymorphine 1 10(rectal)

Diamorphine 5 60

Pethidine 75 -

Codeine 130 200

Buprenorphine 0.4 0.8(sublingual)

Ketobemidone 10 30

Oralmorphine DosageofFentanyltransdermalpatches

(mg/24h) (micrograms/h)

<135 25

135-224 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

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of72hours.Inpatientswhoexperienceamarkeddecreaseinanalgesiaintheperiodof48-72hoursafterapplication,

replacementoftheFentanyltransdermalpatchafter48hoursmaybenecessary.Thedosageistitratedindividually,

untiltheanalgesiceffectisattained.Ifanalgesiaisinadequateattheendoftheinitialapplicationperiod,thedosage

maybeincreasedatintervalsof3days,untilthedesiredeffectisobtainedforeachpatient.Thedosageisnormally

raisedinincrementsof25microgram/hour,buttheneedforadditionalmedicationandthepainexperiencedbythe

patientshouldbetakenintoaccount.Whentherequireddosageexceeds100microgram/hour,severaltransdermal

patchesmaybeusedatthesametime.

Patientsmayrequireashort-actinganalgesicforso-called"breakthrough"pain.Additionaloralternativemethodsof

analgesiashouldbeconsideredwhentheFentanyltransdermalpatchdoseexceeds300microgram/hour.

Conversionordiscontinuationoftreatment

Toconvertpatientstoanotheropioid,Fentanyltransdermalpatchisremovedandthedoseofthenewanalgesictitrated

baseduponthepatient`sreportofpainuntiladequateanalgesiahasbeenattained.Opioidwithdrawalsymptoms(such

asnausea,vomiting,diarrhoea,anxietyandmusculartremor)arepossibleinsomepatientsafterconversionordose

reduction.ForpatientsrequiringdiscontinuationofFentanyltransdermalpatches,agradualdownwardtitrationis

recommendedsinceitisnotknownatwhatdoseleveltheopioidmaybediscontinuedwithoutproducingthesignsand

symptomsofabruptwithdrawal.FentanyllevelsfallgraduallyafterFentanyltransdermalpatchisremoved(seesection

5.2).

Useinchildren

Inchildren,thestartingdoseandtitrationschedulerequiresafentanylreleaserateoflessthan25microgram/hour.Due

tothedosagestrengthsofthisproduct,useinchildrenisnotrecommended.

Useinelderlypatients

Elderlypatientsshouldcarefullybeobservedforsymptomsofanoverdosageandthedosepossiblybereduced(see

section4.4).

Useinpatientswithhepaticorrenalimpairment

Patientswithimpairedhepaticorrenalfunctionshouldcarefullybeobservedforsymptomsofanoverdosageandthe

dosepossiblybereduced(seesection4.4).

Useinfebrilepatients

Doseadjustmentmaybenecessaryinpatientsduringepisodesoffever(seesection4.4).

Methodofadministration

Fortransdermaluse.

Fentanyltransdermalpatchshouldbeappliedtonon-irritatedandnon-irradiatedskinonaflatsurfaceofthetorsoor

upperarm.Hairattheapplicationsite(hairlessareaispreferred)shouldbeclipped(notshaved)priortosystem

application.Ifthesiterequirestobecleansedpriortoapplicationofthepatch,thisshouldbedonewithwater.Soaps,

oils,lotions,alcoholoranyotheragentthatmightirritatetheskinoralteritscharacteristicsshouldnotbeused.The

skinshouldbecompletelydrybeforeapplicationofthepatch.

Sincethetransdermalpatchisprotectedoutwardlybyawaterproofcoveringfoil,itmayalsobewornwhentakinga

shower.

Fentanyltransdermalpatchistobeattachedassoonasthepackhasbeenopened.Followingremovaloftheprotective

layer,thetransdermalpatchshouldbepressedfirmlyinplacewiththepalmofthehandforapproximately30seconds,

makingsurethecontactiscomplete,especiallyaroundtheedges.Anadditionalfixingofthetransdermalpatchmaybe

necessary.Fentanyltransdermalpatchshouldbeworncontinuouslyfor72hoursafterwhichthetransdermalpatchis

replaced.Anewtransdermalpatchshouldalwaysbeappliedtoadifferentsitefromthepreviousone.Thesame

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4.3Contraindications

4.4Specialwarningsandprecautionsforuse

Afterexhibitingaseriousadversereactionapatientshouldbemonitoredfor24hoursfollowingremovalofa

transdermalpatchduetothehalflifeoffentanyl(seesection5.2).

BothunusedandusedFentanyltransdermalpatchesshouldbekeptoutofreachandsightofchildren.

Fentanyltransdermalpatchesshouldnotbedivided,cutordamagedinanyotherway,sincethiswouldresultinthe

uncontrolledreleaseoffentanyl.

TreatmentwithFentanyltransdermalpatchesshouldonlybeinitiatedbyanexperiencedphysicianfamiliarwiththe

pharmacokineticsofFentanyltransdermalpatchesandtheriskforseverehypoventilation.

Respiratorydepression

Fentanylmaycausesignificantrespiratorydepression.Patientsmustbeobservedforthiseffect,thelikelihoodofwhich

increaseswithincreasingdosage(seealsosection4.9)butisalsodependentonthedevelopedtoleranceforthisside

effect.Respiratorydepressionmaypersistafterremovalofthetransdermalpatch,sincetheserumconcentrationof

fentanylfallsslowly.

ThecombineduseofmedicinalproductsthatactupontheCNStogetherwithfentanylmayincreasetheriskof

respiratorydepression(seesection4.5).Fentanylshouldbeusedonlywithcautionandatlowerdoseinpatientswith

existingrespiratorydepression.

Ifapatientistoundergomeasuresthatfullyremovethesensationofpain(anaesthetisationofsympatheticnerves),itis

advisabletoprepareforthepossibilityofrespiratorydepression.Beforesuchmeasuresarecarriedout,thefentanyl

dosageshouldbereducedorachangeovershouldbemadetorapid-orshort-actingopioidmedication.

Chroniclungdisease

Inpatientssufferingfromchronicobstructivepulmonarydiseaseorsomeotherdiseasesoftherespiratoryorgans,

fentanyltreatmentmaycausemoreseriousundesirableeffectssuchasafallinrespirationrateandanincreasein

airwayresistance.

Drugdependence

Asaresultofrepeatedadministration,toleranceandpsychologicaland/orphysicaldependenceontheagentmay

develop.Therapy-induceddependenceishoweverrare.

Increasedintracranialpressure

Cautionshouldbeexercisedwhenusingfentanylforpatientswhoareparticularlysusceptibletotheeffectsof

intracranialcarbondioxideretention,suchaspatientsinwhomanincreaseincerebralpressure,animpairedlevelof

consciousnessorcomahasbeenobserved.Fentanylshouldbeusedwithcautioninpatientsinwhomacerebraltumour

hasbeendetected.

Cardiacdiseases

Fentanylmaycausebradycardiaandforthisreasoncautionshouldbeexercisedwhentreatingpatientswith

bradyarrhythmia.

Opioidscancausehypotension,especiallyinpatientswhoarehypovolemic.Forthisreasoncautionshouldbe

-Knownhypersensitivitytofentanyl,anyoftheexcipientsortothetransdermalpatchadhesive.

-Acuteorpost-operativepain,sincedosagetitrationisnotpossibleduringshort-termuse.

-Severelyimpairedcentralnervoussystemfunction.

-Concomitantuseofmonoamineoxidase(MAO)-inhibitorsorwithin14daysafterdiscontinuationoftreatment

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Hepaticdiseases

Fentanylismetabolisedtopharmacologicallyinactivemetabolitesintheliver.Inpatientswithimpairedliverfunction

theeliminationoffentanylmaybedelayed.Therefore,patientswithanimpairedliverfunctionmayneedalowerdose

andshouldbecloselymonitoredforundesirableeffects.

Renaldiseases

Lessthan10%offentanylisexcretedunchangedviathekidneys.Unlikemorphine,fentanyldoesnothaveknown

activemetabolitesthatareeliminatedthroughthekidneys.Dataobtainedwithintravenousfentanylinpatientswith

renalfailuresuggestthatthevolumeofdistributionoffentanylmaybechangedbydialysis.Thismayaffectserum

concentrations.IfpatientswithrenalimpairmentreceiveFentanyltransdermalpatches,theyshouldbeobserved

carefullyforsignsofpossibleundesirableeffectsandthedosereducedifnecessary.

Fever/externalheatsources

Onthebasisofapharmacokineticmodel,serumfentanyllevelsmayrisebyapproximatelyonethirdiftheskin

temperaturerisesto40°C.Consequently,patientswithfevershouldbemonitoredverycloselyforopioidsideeffects

andifnecessarythefentanyldosageshouldbeadjusted(seesection4.2).Patientsshouldalsobeadvisedtoavoid

exposingtheFentanyltransdermalpatchapplicationsitetodirectexternalheatsourcessuchasheatingpads,hotwater

bottles,electricblankets,heatlampsorhotwhirlpoolspabathswhilewearingthepatch,sincethereispotentialfor

temperaturedependentincreasesinreleaseoffentanylfromthepatch.

Thetransdermalpatchmustalwaysberemovedbeforetakingasauna.Saunabathingispossibleonlywhenreplacinga

transdermalpatch(atintervalsof72hours).Anewtransdermalpatchistobeappliedtocool,verydryskin.

ElderlyPatients

Datafromintravenousstudieswithfentanylsuggestthatelderlypatientsmayhavereducedclearance,aprolongedhalf-

lifeandtheymaybemoresensitivetothedrugthanyoungerpatients.Studiesoffentanyltransdermalpatchesinelderly

patientsdemonstratedfentanylpharmacokineticswhichdidnotdiffersignificantlyfromyoungpatientsalthoughserum

concentrationstendedtobehigher.Elderly,cachectic,ordebilitatedpatientsshouldbeobservedcarefullyforsignsof

fentanyltoxicityandthedosereducedifnecessary.

Others

Non-epileptic(myo)clonicreactionscanoccur.

Cautionshouldbeexercisedwhentreatingpatientswithmyastheniagravis.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Centralnervoussystem

FentanylexhibitsanadditiveeffectwithotherCNSdepressants(e.g.opioids,sedatives,hypnotics,general

anaesthetics,phenothiazines,anxiolytics,musclerelaxants,sedativeantihistaminesandalcoholicbeverages).

Combinedusemayresultinhypoventilation,hypotension,intensesedationorcoma.Patientsusingtheseagentsshould

beobservedverycloselyduringfentanyltreatment.

AgentsaffectingCytochromeP4503A4

Fentanylisahigh-clearancedrugandismainlymetabolisedbytheenzymeCYP3A4.PotentinhibitorsofCYP3A4

suchasritonavir,ketoconazole,itraconazoleandsomeofthemacrolideantibioticsmaygiverisetoincreasedplasma

concentrationsoffentanyl.

Orallyadministereditraconazole(apotentinhibitorofCYP3A4enzyme),200mgdailyfor4days,didnotsignificantly

affectthepharmacokineticsofintravenouslyadministeredfentanyl.

Orallyadministeredritonavir(oneofthemostpotentCYP3A4enzymeinhibitors)reducedtheclearanceof

intravenouslyadministeredfentanylbytwothirds.

TheinteractionoftransdermallyadministeredfentanylandpotentCYP3A4enzymeinhibitorscouldresultinprolonged

therapeuticeffectandadversereactionsincludingrespiratorydepression.ConcomitanttreatmentwithpotentCYP3A4

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adversereactions.

Aspethidineandmonoamineoxidaseinhibitors(e.g.tranylcypromine)reciprocallypotentiatetheirtoxiceffects,a

similarinteractioncanbeexpectedwithfentanyl.

Althoughpentazocineorbuprenorphinehaveananalgesiceffect,theypartiallyantagonisesomeeffectsoffentanyl

(e.g.analgesia)andmayinducewithdrawalsymptomsinopioiddependants.

4.6Pregnancyandlactation

Thesafetyoftheuseoffentanyltransdermalpatchesduringpregnancyisnotestablished.Experimentalstudiesin

animalshaveshownreproductivetoxicity(seesection5.3).Thepotentialriskforhumanisunknown.Consequently

Fentanyltransdermalpatchesshouldnotbeusedduringpregnancyunlessclearlynecessary.

Long-termtreatmentduringpregnancymaycausewithdrawalsymptomsintheneonate.

Itisadvisednottousefentanylduringlaboranddelivery(includingcaesareansection)becausefentanylpassesthe

placentaandmaycauserespiratorydepressioninthefetus/newbornchild.

Fentanylpassesintobreast-milkandmaycausesedationandrespiratorydepressioninthesucklingchild.Therefore,

breastfeedingshouldbestoppedforatleast72hoursafterthelastadministrationofFentanyltransdermalpatch.

4.7Effectsonabilitytodriveandusemachines

Fentanyltransdermalpatcheshavemajorinfluenceontheabilitytodriveandusemachines.Thishastobeexpected

especiallyatthebeginningoftreatment,atanychangeofdosageaswellasinconnectionwithalcoholortranquilizers.

Patientsstabilizedonaspecificdosagewillnotnecessarilyberestricted.Therefore,patientsshouldconsulttheir

physicianastowhetherdrivingoruseofmachinesispermitted.

4.8Undesirableeffects

Thefollowingfrequencydataisthebasisforthedescriptionofadversereactions:

Verycommon(>1/10),common(>1/100,<1/10),uncommon(>1/1000,<1/100),rare(>1/10000,<1/1000),veryrare

(<1/10000).

Themostseriousundesirableeffectoffentanylisrespiratorydepression.

Psychiatricdisorders

Verycommon:Somnolence.

Common:Sedation,confusion,depression,anxiety,nervousness,hallucinations,diminishedappetite.

Uncommon:Euphoria,amnesia,insomnia,agitation.

Veryrare:Delusionalidea,asthenia,disorderofsexualfunction.

Nervoussystemdisorders

Verycommon:Drowsiness,headache.

Uncommon:Tremor,paraesthesia,speechdisorder.

Veryrare:Ataxia.

Non-epilepticmyoclonicreactions.

Eyedisorders

Rare:Amblyopia.

Cardiacdisorders

Uncommon:Bradycardia,tachycardia,hypotension,hypertension.

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Respiratory,thoracicandmediastinaldisorders

Uncommon:Dyspnea,hypoventilation.

Veryrare:Respiratorydepression,apnea.

Haemoptysis,pulmonarycongestionandpharyngitis.

Gastrointestinaldisorders

Verycommon:Nausea,vomiting,constipation.

Common:Xerostomia,dyspespsia.

Uncommon:Diarrhoea.

Rare:Hiccup.

Veryrare:Ileus,painfulflatulence.

Hypersensitivitydisorders

Anaphylacticreactions,laryngospasm.

Skinandsubcutaneoustissuedisorders

Verycommon:Sweating,pruritus.

Common:Skinreactiononapplicationsite.

Uncommon:Rash,erythema.

Rash,erythemaandpruritusgenerallydisappearwithin24hoursofremovalofthetransdermalpatch.

Renalandurinarydisorders

Uncommon:Urinaryretention.

Veryrare:Oliguria,bladderpain.

Bodyasawhole:

Rare:Oedema,sensationofcold.

Otherundesirableeffects

Tolerance,physicalandpsychologicaldepencencemaydevelopduringadministrationoffentanyloveralongerperiod

oftime.

Opioidwithdrawalsymptoms(suchasnausea,vomiting,diarrhoea,anxietyandmusculartremor)mayoccurinsome

patientsaftertheychangeoverfromapreviouslyprescribedopioidanalgesictoFentanyltransdermalpatches.

4.9Overdose

Symptomsofanoverdose

Thesymptomsareexaggerationsofthepharmacologicaleffectsoffentanyl,suchasstupor,coma,respiratory

depressionwithcheyne-stokesbreathingand/orcyanosis.Otherpossiblesymptomsarehypothermia,lossofmuscle

tension,bradycardiaandhypotension.Signsoftoxicationaredeepsedation,ataxia,miosis,seizuresandrespiratory

depression,whichisthemainsymptom.

Therapyforanoverdose

Formanagementofrespiratorydepression,immediatecountermeasuresincluderemovingFentanyltransdermalpatch

andphysicallyorverballystimulatingthepatient.Theseactionscanbefollowedbyadministrationofaspecificopioid

antagonistsuchasnaloxone.

Aninitialdoseof0.4-2mgofnaloxonehydrochloridei.v.inadultsisrecommended.Ifnecessary,theinitialdoseisto

berepeatedevery2or3minutes,orgivenasacontinuousinfusionof2mgin500mlofisotonicsodiumchloride

solution(0.9%)or5%dextrosesolution(0.004mg/ml).Theinfusionrateshouldbeadjustedtothepreviousbolus

injectionsandthepatient`sindividualresponse.Iftheintravenousrouteisunavailable,naloxonehydrochloridemaybe

administeredalsoi.m.ors.c.Afteri.m.ands.c.application,theonsetofactionisonlyslightlylessrapidthanafteri.v.

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Thei.m.routeproducesamoreprolongedeffectthani.v.administration.Respiratorydepressionresultingfrom

overdosagemaylastlongerthantheeffectoftheopioidantagonist.Reversalofthenarcoticeffectmayresultinacute

onsetofpainandthereleaseofcatecholamines.

Ifrequiredbythepatient'sclinicalcondition,intensivecareunittreatmentisessential.

Ifsevereorpersistenthypotensionoccurs,thepossibilityofhypovolaemiashouldbeconsideredandthesituation

remediedwithsuchparenteralfluidtreatmentasisconsideredappropriate.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:opioidanalgesic.

ATCCode:N02AB03.

Fentanylisanopioidanalgesicwithanaffinityfortheµ(mu)-receptors.Itsprincipaltherapeuticeffectsareanalgesia

andsedation.Inpatientswhohavenotbeenpreviouslytreatedwithopioids,analgesicefficacyisachievedwithserum

fentanylconcentrationsof0.3-1.5ng/ml.Theincidenceofadverseeffectsincreaseswhenserumconcentrationsexceed

2ng/ml.Duringlong-termtherapypotentialadverseeffectsmayemergewithhigherserumconcentrations.Thespeed

oftolerancedevelopmentshowsconsiderableinter-individualvariety.

5.2Pharmacokineticproperties

Areleasemembranecontrolsthetransdermaldeliveryoffentanyl.Transdermaldiffusionoccursatarelativelyeven

speedfor72hoursfollowingtheapplicationofthetransdermalpatch.

Absorption:

AfterthefirstapplicationofFentanyltransdermalpatches,serumfentanylconcentrationsincreasegradually,generally

levellingoffbetween12and24hours,andremainingrelativelyconstantfortheremainderofthe72-hourapplication

period.TheserumfentanylconcentrationsattainedaredependantontheFentanyltransdermalpatchsize.Forall

practicalpurposesbythesecond72-hourapplication,asteadystateserumconcentrationisreachedandismaintained

duringsubsequentapplicationsofapatchofthesamesize.

Distribution:

Theplasmaproteinbindingforfentanylis84%.

Biotransformation:

FentanylismetabolizedprimarilyintheliverviaCYP3A4.Themajormetabolite,norfentanyl,isinactive.

Elimination:

WhentreatmentwithFentanyltransdermalpatchesiswithdrawn,serumfentanylconcentrationsdeclinegradually,

fallingapproximately50%in13-22hoursinadultsor22-25hoursinchildren,respectively.Continuedabsorptionof

fentanylfromtheskinaccountsforaslowerreductioninserumconcentrationthanisseenafteranintravenousinfusion.

Around75%offentanylisexcretedintotheurine,mostlyasmetabolites,withlessthan10%asunchangeddrug.About

9%ofthedoseisrecoveredinthefaeces,primarilyasmetabolites.

Pharmacokineticsinspecialgroups

Elderlyanddebilitatedpatientsmayhavereducedclearanceoffentanylleadingtoprolongedterminalhalflife.In

patientswithrenalorhepaticimpairment,clearanceoffentanylmaybealteredbecauseofchangesofplasmaproteins

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5.3Preclinicalsafetydata

Similareffectsaspreviouslydescribedforotheropioidswereobservedinrepeateddosetoxicitystudiesupto4weeks.

Inaratstudyfentanyldidnotinfluencemalefertility.Studieswithfemaleratsrevealedreducedfertilityandenhanced

embryonalmortality.Morerecentstudiesshowedthateffectsontheembryowereduetomaternaltoxicityandnotto

directeffectsofthesubstanceonthedevelopingembryo.Therewerenoindicationsforteratogeniceffectsinstudiesin

twospecies.

Inastudyonpre-andpostnataldevelopmentthesurvivalrateofoffspringwassignificantlyreducedatdoseswhich

slightlyreducedmaternalweight.Thiseffectcouldeitherbeduetoalteredmaternalcareoradirecteffectoffentanyl

onthepups.Effectsonsomaticdevelopmentandbehaviouroftheoffspringwerenotobserved.

Mutagenicitytestinginbacteriaandinrodentsyieldednegativeresults.Aswellasotheropioidsfentanylshowed

mutageniceffectsinvitroinmammaliancells.Amutagenicriskintherapeuticconditionseemsunlikelysinceeffects

wereinducedonlyinveryhighconcentrations.

Longtermcarcinogenicitystudieshavenotbeenperformed.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Occlusivebacking:

Polyethylene-terephthalate/ethylenvinylacetate-copolymer

Drugreservoir:

Ethanol96%

Hydroxyethylcellulose

Purifiedwater

Releasemembrane:

Thylenvinylacetate-copolymer

Adhesivesurface:

Siliconemedicaladhesive

Protectivelayer(removebeforepatchapplication):

Polyethylene-terephthalate,releasecoated

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

36months

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.Donotrefrigerateorfreeze.

6.5Natureandcontentsofcontainer

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Packagescontaining3,5,7,10,14and20transdermalpatches

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Usedtransdermalpatchesaretobefoldedwiththeadhesivesurfacesfacingeachotheranddisposedofinan

appropriatemanner.Unusedpacksaretobereturnedtothepharmacist.

7MARKETINGAUTHORISATIONHOLDER

ROWEXLTD

Bantry

CoCork

8MARKETINGAUTHORISATIONNUMBER

PA711/70/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:20May2005

10DATEOFREVISIONOFTHETEXT

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