CENTRADOL

Main information

  • Trade name:
  • CENTRADOL Transdermal Patch
  • Pharmaceutical form:
  • Transdermal Patch
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CENTRADOL Transdermal Patch
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1032/002/003
  • Authorization date:
  • 03-05-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1032/002/003

CaseNo:2065739

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

GrunenthalGmbH

Zieglerstr.6,D-52078Aachen,Germany

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Centradol70micrograms/hTransdermalPatch

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom21/05/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Centradol70micrograms/hTransdermalPatch

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetransdermalpatchcontains40mgbuprenorphine.

Areacontainingtheactivesubstance:50cm²

Nominalreleaserate:70microgramsofbuprenorphineperhour(overaperiodof96hours).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Transdermalpatch

Skincolouredtransdermalpatchwithroundedcornersmarked:

Centradol70µg/h,buprenorphinum40mg

4CLINICALPARTICULARS

4.1TherapeuticIndications

Moderatetoseverecancerpainandseverepainwhichdoesnotrespondtonon-opioidanalgesics.

Centradolisnotsuitableforthetreatmentofacutepain.

4.2Posologyandmethodofadministration

Posology

Patientsover18yearsofage

TheCentradoldosageshouldbeadaptedtotheconditionoftheindividualpatient(painintensity,suffering,individual

reaction).Thelowestpossibledosageprovidingadequatepainreliefshouldbegiven.Threetransdermalpatchstrengths

areavailabletoprovidesuchadaptivetreatment:Centradol35micrograms/h,Centradol52.5micrograms/hand

Centradol70micrograms/h.

Initialdoseselection:patientswhohavepreviouslynotreceivedanyanalgesicsshouldstartwiththelowest

transdermalpatchstrength(Centradol35micrograms/h).PatientspreviouslygivenaWHOstep-Ianalgesic(non-

opioid)orastep-IIanalgesic(weakopioid)shouldalsobeginwithCentradol35micrograms/h.AccordingtotheWHO

recommendations,theadministrationofanon-opioidanalgesiccanbecontinued,dependingonthepatient'soverall

medicalcondition.

Whenswitchingfromastep-IIIanalgesic(strongopioid)toCentradolandchoosingtheinitialtransdermalpatch

strength,thenatureofthepreviousmedication,administrationandthemeandailydoseshouldbetakenintoaccountin

ordertoavoidtherecurrenceofpain.Ingeneralitisadvisabletotitratethedoseindividually,startingwiththelowest

transdermalpatchstrength(Centradol35micrograms/h).

Clinicalexperiencehasshownthatpatientswhowerepreviouslytreatedwithhigherdailydosagesofastrongopioid

(inthedimensionofapproximately120mgoralmorphine)maystartthetherapywiththenexthighertransdermalpatch

strength(seealsosection5.1).

Toallowforindividualdoseadaptationinanadequatetimeperiodsufficientsupplementaryimmediaterelease

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ThenecessarystrengthofCentradolmustbeadaptedtotherequirementsoftheindividualpatientandcheckedat

regularintervals.

AfterapplicationofthefirstCentradoltransdermalpatchthebuprenorphineserumconcentrationsriseslowlybothin

patientswhohavebeentreatedpreviouslywithanalgesicsandinthosewhohavenot.Thereforeinitially,thereis

unlikelytobearapidonsetofeffect.Consequently,afirstevaluationoftheanalgesiceffectshouldonlybemadeafter

24hours.

Thepreviousanalgesicmedication(withtheexceptionoftransdermalopioids)shouldbegiveninthesamedoseduring

thefirst12hoursafterswitchingtoCentradolandappropriaterescuemedicationondemandinthefollowing12hours.

Dosetitrationandmaintenancetherapy

Centradolshouldbereplacedafter96hours(4days)atthelatest.Forconvenienceofuse,thetransdermalpatchcanbe

changedtwiceaweekatregularintervals,e.g.alwaysonMondaymorningandThursdayevening.Thedoseshouldbe

titratedindividuallyuntilanalgesicefficacyisattained.Ifanalgesiaisinsufficientattheendoftheinitialapplication

period,thedosemaybeincreased,eitherbyapplyingmorethanonetransdermalpatchofthesamestrengthorby

switchingtothenexttransdermalpatchstrength.Atthesametimenomorethantwotransdermalpatchesregardlessof

thestrengthshouldbeapplied.

BeforeapplicationofthenextCentradolstrengththeamountoftotalopioidsadministeredinadditiontotheprevious

transdermalpatchshouldbetakenintoconsideration,i.e.thetotalamountofopioidsrequired,andthedosageadjusted

accordingly.Patientsrequiringasupplementaryanalgesic(e.g.forbreakthroughpain)duringmaintenancetherapymay

takeforexampleonetotwo0.2mgbuprenorphinesublingualtabletsevery24hoursinadditiontothetransdermal

patch.Iftheregularadditionof0.4–0.6mgsublingualbuprenorphineisnecessary,thenextstrengthshouldbeused.

Patientsunder18yearsofage

AsCentradolhasnotbeenstudiedinpatientsunder18yearsofage,theuseofthemedicinalproductinpatientsbelow

thisageisnotrecommended.

Elderlypatients

NodosageadjustmentofCentradolisrequiredforelderlypatients.

Patientswithrenalinsufficiency

Sincethepharmacokineticsofbuprenorphineisnotalteredduringthecourseofrenalfailure,itsuseinpatientswith

renalinsufficiency,includingdialysispatients,ispossible.

BuprePatientswithhepaticinsufficiency

Buprenorphineismetabolisedintheliver.Theintensityanddurationofitsactionmaybeaffectedinpatientswith

impairedliverfunction.Thereforepatientswithliverinsufficiencyshouldbecarefullymonitoredduringtreatmentwith

Centradol.

Methodofapplication

Centradolshouldbeappliedtonon-irritated,cleanskinonanon-hairyflatsurface,butnottoanypartsoftheskinwith

largescars.Preferablesitesontheupperbodyare:upperbackorbelowthecollar-boneonthechest.Anyremaining

hairsshouldbecutoffwithapairofscissors(notshaved).Ifthesiteofapplicationrequirescleansing,thisshouldbe

donewithwater.Soaporanyothercleansingagentsshouldnotbeused.Skinpreparationsthatmightaffectadhesionof

thetransdermalpatchtotheareaselectedforapplicationofCentradolshouldbeavoided.

TheskinmustbecompletelydrybeforeapplicationCentradolistobeappliedimmediatelyafterremovalfromthe

sachet.Followingremovalofthereleaseliner,thetransdermalpatchshouldbepressedfirmlyinplacewiththepalmof

thehandforapproximately30seconds.Thetransdermalpatchwillnotbeaffectedwhenbathing,showeringor

swimming.However,itshouldnotbeexposedtoexcessiveheat(e.g.sauna,infrared-radiation).

Centradolshouldbeworncontinuouslyforupto4days.Afterremovaloftheprevioustransdermalpatchanew

Centradoltransdermalpatchshouldbeappliedtoadifferentskinsite.Atleastoneweekshouldelapsebeforeanew

transdermalpatchisappliedtothesameareaofskin.

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Centradolshouldundernocircumstancesbeadministeredforlongerthanabsolutelynecessary.Iflong-termpain

treatmentwithCentradolisnecessaryinviewofthenatureandseverityoftheillness,thencarefulandregular

monitoringshouldbecarriedout(ifnecessarywithbreaksintreatment)toestablishwhetherandtowhatextentfurther

treatmentisnecessary.

DiscontinuationofCentradol

AfterremovalofCentradolbuprenorphineserumconcentrationsdecreasegraduallyandthustheanalgesiceffectis

maintainedforacertainamountoftime.ThisshouldbeconsideredwhentherapywithCentradolistobefollowedby

otheropioids.Asageneralrule,asubsequentopioidshouldnotbeadministeredwithin24hoursafterremovalof

Centradol.Forthetimebeingonlylimitedinformationisavailableonthestartingdoseofotheropioidsadministered

afterdiscontinuationofCentradol.

4.3Contraindications

Centradoliscontraindicatedin:

-hypersensitivitytotheactivesubstancebuprenorphineortoanyoftheexcipients(fortheexcipients,seesection6.1)

-inopioid-dependentpatientsandfornarcoticwithdrawaltreatment

-conditionsinwhichtherespiratorycentreandfunctionareseverelyimpairedormaybecomeso

-patientswhoarereceivingMAOinhibitorsorhavetakenthemwithinthelasttwoweeks(seesection4.5)

-patientssufferingfrommyastheniagravis

-patientssufferingfromdeliriumtremens.

-pregnancy(seesection4.6)

4.4Specialwarningsandprecautionsforuse

Centradolmustonlybeusedwithparticularcautioninacutealcoholintoxication,convulsivedisorders,inpatientswith

headinjury,shock,areducedlevelofconsciousnessofuncertainorigin,increasedintracranialpressurewithoutthe

possibilityofventilation.

Buprenorphineoccasionallycausesrespiratorydepression.Thereforecareshouldbetakenwhentreatingpatientswith

impairedrespiratoryfunctionorpatientsreceivingmedicinalproductswhichcancauserespiratorydepression.

Buprenorphinehasasubstantiallylowerdependenceliabilitythanpureopioidagonists.Inhealthyvolunteerand

patientstudieswithCentradol,withdrawalreactionshavenotbeenobserved.However,afterlong-termuseof

Centradolwithdrawalsymptoms,similartothoseoccurringduringopiatewithdrawal,cannotbeentirelyexcluded(see

section4.8).Thesesymptomsare:agitation,anxiety,nervousness,insomnia,hyperkinesia,tremorandgastrointestinal

disorders.

Inpatientsabusingopioids,substitutionwithbuprenorphinemaypreventwithdrawalsymptoms.Thishasresultedin

someabuseofbuprenorphineandcautionshouldbeexercisedwhenprescribingittopatientssuspectedofhavingdrug

abuseproblems.

Buprenorphineismetabolisedintheliver.Theintensityanddurationofeffectmaybealteredinpatientswithliver

functiondisorders.ThereforesuchpatientsshouldbecarefullymonitoredduringCentradoltreatment.

AsCentradolhasnotbeenstudiedinpatientsunder18yearsofage,theuseofthemedicinalproductinpatientsbelow

thisageisnotrecommended.

Patientswithfever/externalheat

Feverandthepresenceofheatmayincreasethepermeabilityoftheskin.Theoreticallyinsuchsituations

buprenorphineserumconcentrationsmayberaisedduringtreatment.ThereforeontreatmentwithCentradol,attention

shouldbepaidtotheincreasedpossibilityofopioidreactionsinfebrilepatientsorthosewithincreasedskin

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

OnadministrationofMAOinhibitorsinthelast14dayspriortotheadministrationoftheopioidpethidinelife-

threateninginteractionshavebeenobservedaffectingthecentralnervoussystemandrespiratoryandcardiovascular

function.ThesameinteractionsbetweenMAOinhibitorsandCentradolcannotberuledout(seesection4.3).

WhenCentradolisappliedtogetherwithotheropioids,anaesthetics,hypnotics,sedatives,antidepressants,neuroleptics,

andingeneral,medicinalproductsthatdepressrespirationandthecentralnervoussystem,theCNSeffectsmaybe

intensified.Thisappliesalsotoalcohol.

AdministeredtogetherwithinhibitorsorinducersofCYP3A4theefficacyofCentradolmaybeintensified(inhibitors)

orweakened(inducers).

4.6Pregnancyandlactation

Pregnancy

TherearenoadequatedatafromtheuseofCentradolinpregnantwomen.Studiesinanimalshaveshownreproductive

toxicity(seesection5.3).Thepotentialriskforhumansisunknown.

Towardstheendofpregnancyhighdosesofbuprenorphinemayinducerespiratorydepressionintheneonateevenafter

ashortperiodofadministration.Long-termadministrationofbuprenorphineduringthelastthreemonthsofpregnancy

maycauseawithdrawalsyndromeintheneonate.

ThereforeCentradoliscontraindicatedduringpregnancy.

Lactation

Buprenorphineisexcretedinhumanmilk.Inrats,buprenorphinehasbeenfoundtoinhibitlactation.

Centradolshouldnotbeusedduringlactation.

4.7Effectsonabilitytodriveandusemachines

Centradolhasmajorinfluenceontheabilitytodriveandusemachines.

Evenwhenusedaccordingtoinstructions,Centradolmayaffectthepatient’sreactionstosuchanextentthatroad

safetyandtheabilitytooperatemachinerymaybeimpaired.

Thisappliesparticularlyatthebeginningoftreatment,atanychangeofdosageandwhenCentradolisusedin

conjunctionwithothercentrallyactingsubstancesincludingalcohol,tranquillisers,sedativesandhypnotics.

Patientswhoareaffected(e.g.feelingdizzyordrowsyorexperienceblurredordoublevision)shouldnotdriveoruse

machineswhileusingCentradolandforatleast24hoursafterthepatchhasbeenremoved.

Patientsstabilizedonaspecificdosagewillnotnecessarilyberestrictediftheabovementionedsymptomsarenot

present.

4.8Undesirableeffects

ThefollowingadversereactionswerereportedafteradministrationofCentradolinclinicalstudiesandfrom

postmarketingsurveillance.

Thefrequenciesaregivenasfollows:

Verycommon(1/10)

Common(1/100,<1/10)

Uncommon(1/1,000,<1/100)

Rare ( 1/10,000,<1/1,000)

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Notknown(cannotbeestimatedfromtheavailabledata)

Themostcommonlyreportedsystemicadversereactionswerenauseaandvomiting.

Themostcommonlyreportedlocaladversereactionswereerythemaandpruritus.

Immunesystemdisorders

Veryrare:seriousallergicreactions*

Metabolismandnutritiondisorders

Rare:appetitelost

Psychiatricdisorders

Uncommon: confusion,sleepdisorder,restlessness

Rare: psychotomimeticeffects(e.g.hallucinations,anxiety,nightmares),decreasedlibido

Veryrare: dependence,moodswings

Nervoussystemdisorders

Common: dizziness,headache

Uncommon: sedation,somnolence

Rare: concentrationimpaired,speechdisorder,numbness,dysequilibrium,paraesthesia(e.g.

prickingorburningskin

sensation)

Veryrare: musclefasciculation,parageusia

Eyedisorders

Rare: visualdisturbance,blurringofvision,eyelidoedema

Veryrare: miosis

Earandlabyrinthdisorders

Veryrare: earpain

Cardiac/Vasculardisorders

Uncommon: circulatorydisorders(suchashypotensionor,rarely,evencirculatorycollapse)

Rare: hotflushes

Respiratory,thoracicandmediastinaldisorders

Common: dyspnoea

Rare: respiratorydepression

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Gastrointestinaldisorders

Verycommon: nausea

Common: vomiting,constipation

Uncommon: drymouth

Rare: pyrosis

Veryrare: retching

Skinandsubcutaneoustissuedisorders

Verycommon: erythema,pruritus

Common: exanthema,diaphoresis

Uncommon: rash

Rare: urticaria

Veryrare: pustules,vesicles

Renalandurinarydisorders

Uncommon: urinaryretention,micturitiondisorders

Reproductivesystemandbreastdisorders

Rare: decreasederection

Generaldisordersandadministrationsiteconditions

Common: oedema,tiredness

Uncommon: weariness

Rare: withdrawalsymptoms*,administrationsitereactions

Veryrare: thoracicpain

*seesectionc)

Insomecasesdelayedallergicreactionsoccurredwithmarkedsignsofinflammation.Insuchcasestreatment

withCentradolshouldbeterminated.

Buprenorphinehasalowriskofdependence.AfterdiscontinuationofCentradol,withdrawalsymptomsare

unlikely.Thisisduetotheveryslowdissociationofbuprenorphinefromtheopiatereceptorsandtothegradual

decreaseofbuprenorphineserumconcentrations(usuallyoveraperiodof30hoursafterremovalofthelast

transdermalpatch).However,afterlong-termuseofCentradolwithdrawalsymptoms,similartothoseoccurring

duringopiatewithdrawal,cannotbeentirelyexcluded.Thesesymptomsinclude:agitation,anxiety,

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4.9Overdose

Buprenorphinehasawidesafetymargin.Duetotherate-controlleddeliveryofsmallamountsofbuprenorphineinto

thebloodcirculationhighortoxicbuprenorphineconcentrationsinthebloodareunlikely.Themaximumserum

concentrationofbuprenorphineaftertheapplicationoftheCentradol70micrograms/htransdermalpatchisaboutsix

timeslessthanaftertheintravenousadministrationofthetherapeuticdoseof0.3mgbuprenorphine.

Symptoms

Inprincipal,onoverdosewithbuprenorphine,symptomssimilartothoseofothercentrallyactinganalgesics(opioids)

aretobeexpected.Theseare:respiratorydepression,sedation,somnolence,nausea,vomiting,cardiovascularcollapse,

andmarkedmiosis.

Treatment

Generalemergencymeasuresapply.Keeptheairwayopen(aspiration!),maintainrespirationandcirculationdepending

onthesymptoms.Naloxonehasalimitedimpactontherespiratorydepressanteffectofbuprenorphine.Highdosesare

neededgiveneitherasrepeatedbolusesorinfusion(forexamplestartingwithabolusadministrationof1-2mg

intravenously.Havingattainedanadequateantagonisticeffect,administrationbyinfusionisrecommendedtomaintain

constantnaloxoneplasmalevels).Therefore,adequateventilationshouldbeestablished.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Opioids,Oripavinederivatives.ATCcode:N02AE01.

Buprenorphineisastrongopioidwithagonisticactivityatthemu-opioidreceptorandantagonisticactivityatthe

kappa-opioidreceptor.Buprenorphineappearstohavethegeneralcharacteristicsofmorphine,buthasitsownspecific

pharmacologyandclinicalattributes.

Inaddition,numerousfactors,e.g.indicationandclinicalsetting,routeofadministrationandtheinterindividual

variability,haveanimpactonanalgesiaandthereforehavetobeconsideredwhencomparinganalgesics.

Indailyclinicalpracticedifferentopioidsarerankedbyarelativepotency,althoughthisistobeconsidereda

simplification.

Therelativepotencyofbuprenorphineindifferentapplicationformsandindifferentclinicalsettingshasbeen

describedinliteratureasfollows:

Morphinep.o.:BUPi.m.as1:67-150(singledose;acutepainmodel)

Morphinep.o.:BUPs.l.as1:60-100(singledose,acutepainmodel;multipledose,chronicpain,cancerpain)

Morphinep.o.:BUPTTSas1:75-115(multipledose,chronicpain)

Abbreviations:

p.o=oral;i.m.=intramuscular;s.l.=sublingual;TTS=transdermal;BUP=buprenorphine

Adversereactionsaresimilartothoseofotherstrongopioidanalgesics.Buprenorphineappearstohavealower

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5.2Pharmacokineticproperties

a)Generalcharacteristicsoftheactivesubstance

Buprenorphinehasaplasmaproteinbindingofabout96%.

BuprenorphineismetabolisedinthelivertoN-dealkylbuprenorphine(norbuprenorphine)andtoglucuronide

conjugatedmetabolites. 2

oftheactivesubstanceiseliminatedunchangedinthefaecesand 1

eliminatedas

conjugatesofunchangedordealkylatedbuprenorphineviatheurinarysystem.Thereisevidenceofenterohepatic

recirculation.

Studiesinnon-pregnantandpregnantratshaveshownthatbuprenorphinepassestheblood-brainandplacentalbarriers.

Concentrationsinthebrain(whichcontainedonlyunchangedbuprenorphine)afterparenteraladministrationwere2-3

timeshigherthanafteroraladministration.Afterintramuscularororaladministrationbuprenorphineapparently

accumulatesinthefoetalgastrointestinallumen–presumablyduetobiliaryexcretion,asenterohepaticcirculationhas

notfullydeveloped.

b)CharacteristicsofCentradolinhealthyvolunteers

AftertheapplicationofCentradolbuprenorphineisabsorbedthroughtheskin.Thecontinuousdeliveryof

buprenorphineintothesystemiccirculationisbycontrolledreleasefromtheadhesivepolymer-basedmatrixsystem.

AftertheinitialapplicationofCentradoltheplasmaconcentrationsofbuprenorphinegraduallyincrease,andafter12-

24htheplasmaconcentrationsreachtheminimumeffectiveconcentrationof100pg/ml.Fromthestudiesperformed

withtheCentradol35micrograms/hinhealthyvolunteers,anaverageC

of200to300pg/mlandanaveraget

60-80hweredetermined.Inonevolunteerstudy,Centradol35micrograms/handCentradol70micrograms/hwere

appliedinacross-overdesign.Fromthisstudy,doseproportionalityforthedifferentstrengthswasdemonstrated.

AfterremovalofCentradoltheplasmaconcentrationsofbuprenorphinesteadilydecreaseandareeliminatedwitha

half-lifeofapprox.30hours(range22-36).Duetothecontinuousabsorptionofbuprenorphinefromthedepotinthe

skineliminationisslowerthanafterintravenousadministration.

5.3Preclinicalsafetydata

Standardtoxicologicalstudieshavenotshownevidenceofanyparticularpotentialrisksforhumans.Intestswith

repeateddosesofbuprenorphineinratstheincreaseinbodyweightwasreduced.

Studiesonfertilityandgeneralreproductivecapacityofratsshowednodetrimentaleffects.Studiesinratsandrabbits

revealedsignsoffetotoxicityandincreasedpostimplantationloss.

Studiesinratsshoweddiminishedintra-uterinegrowth,delaysinthedevelopmentofcertainneurologicalfunctionsand

highperi/postnatalmortalityintheneonatesaftertreatmentofthedamsduringgestationorlactation.Thereisevidence

thatcomplicateddeliveryandreducedlactationcontributedtotheseeffects.Therewasnoevidenceofembryotoxicity

includingteratogenicityinratsorrabbits.

Invitroandinvivoexaminationsonthemutagenicpotentialofbuprenorphinedidnotindicateanyclinicallyrelevant

effects.

Inlong-termstudiesinratsandmicetherewasnoevidenceofanycarcinogenicpotentialrelevantforhumans.

Toxicologicaldataavailabledidnotindicateasensitisingpotentialoftheadditivesofthetransdermalpatches.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Adhesivematrix(containingbuprenorphine):[(Z)-octadec-9-en-1-yl]oleate,povidoneK90,4-oxopentanicacid,poly

[acrylicacid-co-butylacrylate-co-(2-ethylhexyl)acrylate-co-vinylacetate](5:15:75:5),cross-linked

Adhesivematrix(withoutbuprenorphine):poly[acrylicacid-co-butylacrylate-co-(2-ethylhexyl)acrylate-co-

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Separatingfoilbetweentheadhesivematriceswithandwithoutbuprenorphine:poly(ethyleneterephthalate)–foil

Backinglayer:poly(ethyleneterephthalate)–tissue

Releaseliner(onthefrontcoveringtheadhesivematrixcontainingbuprenorphine):poly(ethyleneterephthalate)–foil,

siliconised,coatedononesidewithaluminium

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Typeofcontainer:

Sealedsachet,composedofidenticaltopandbottomlayersofheat-sealablelaminate,comprising(fromoutsideto

inside)paper,lowdensitypolyethylene,aluminiumandpoly(acrylicacid-co-ethylene)(=surlyn).

Packsizes:

Packscontaining3,5,10or30individuallysealedtransdermalpatches.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

GrünenthalGmbH,

Zieglerstrasse6,

D-52078Aachen,

Germany

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:03May2002

Dateoflastrenewal:24July2006

10DATEOFREVISIONOFTHETEXT

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