BREAKYL 200 Microgram Buccal Film

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
FENTANYL CITRATE
Available from:
Meda Health Sales Ireland Limited
ATC code:
N02AB03
INN (International Name):
FENTANYL CITRATE
Dosage:
200 Microgram
Pharmaceutical form:
Buccal Film
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Phenylpiperidine derivatives
Authorization status:
Authorised
Authorization number:
PA1332/027/001
Authorization date:
2011-05-03

pl-breakyl_var008 –clean2 nd

PSUSA Feb2015tc

PACKAGELEAFLET:INFORMATIONFOR THEUSER

BREAKYL200microgrambuccalfilm

BREAKYL400microgrambuccalfilm

BREAKYL600microgrambuccalfilm

BREAKYL800microgrambuccalfilm

BREAKYL1200microgrambuccalfilm

BREAKYLStart200, 400, 600, 800microgrambuccalfilm

Active substance:Fentanyl

Read allofthis leafletcarefully before youstartusing this medicinebecauseitcontains important

informationforyou.

- Keep thisleaflet. You mayneedto readitagain.

- Ifyou have anyfurtherquestions,askyourdoctororpharmacist.

- This medicine hasbeen prescribedforyouonly. Do notpass itonto others. Itmay harmthem, even if

theirsigns ofillnessarethesame as yours.

- Ifyou getanyside effects,talktoyourdoctororpharmacist.Thisincludes anypossible sideeffects

notlistedinthis leaflet.See section 4.

Whatisin thisleaflet:

1. WhatBreakylis and whatitisused for

2. Whatyou needto knowbeforeyou useBreakyl

3. Howto useBreakyl

4. Possibleside effects

5. Howto storeBreakyl

6. Contents onthe packandotherinformation

1. WHATBREAKYLIS ANDWHATIT IS USEDFOR

Breakylbuccalfilmcontains theactivesubstancefentanyl, astrongpain-relievingmedicine known asan

opioid.Breakylis indicatedforthe managementofbreakthrough cancerpaininadultpatients.Breakthrough

painis additionalsudden pain.Thismayoccuralthoughyou havetakenyourregularopioid painrelieving

medicine.

Breakylmustonlybe used,ifyou are alreadytakingand are used toregularopioid therapylike morphine,

oxycodone, ortransdermalfentanylfora minimumofone weektotreatyourchronic cancerpain.

2. WHATYOUNEEDTOKNOWBEFOREYOUUSEBREAKYL

DonotuseBreakyl:

ifyouare allergic(hypersensitive)to fentanyl, oranyofthe otheringredientsofBreakyl(fora fulllistof

ingredients see“Furtherinformation”attheend ofthisleaflet).

ifyouare currentlytakingmonoamine-oxidase (MAO)inhibitors(used forseveredepression)orhave

done sointhe past2 weeks.

ifyousufferfromsevere breathingproblems orsevereobstructive lungconditions(likesevereasthma).

ifyou are notregularlyusinga prescribed opioid medicine(e.g. codeine,fentanyl,hydromorphone,

morphine, oxycodone,pethidine),everydayon a regularschedule,foratleasta week, to controlyour

persistentpain. Ifyouhavenotbeen usingthesemedicinesyoumustnotuseBreakyl, becauseitmay

increase the riskthatbreathingcouldbecome dangerouslyslowand/orshallow, oreven stop.

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

Ifyou sufferfromshort-termpain otherthan breakthrough pain.

Warnings andPrecautions

Talkto yourdoctorbeforestartingBreakyl,ifyou have anyofthe following,asyourdoctorwillneedtotake

accountofthis when prescribingyourdose:

Yourotheropioid pain medicine taken foryourchroniccancerpainis notstabilisedyet

You aresufferingfromany condition thathasan effecton yourbreathing.

You have ahead injuryorifyourdoctorhasdiagnosedanincreased cranialpressure.

You haveproblems with yourheart, especiallyslowheartrate,orotherheartproblems.

You have lowblood pressure, especiallydueto alowamountoffluidinthecirculation.

You have liverorkidneyproblems, asthese organshave an effectonthe wayin which yoursystem

breaks downthe medicine.

You aresufferingfromoralmucositis

You take antidepressants orantipsychotics, please referto the section„Othermedicinesand Breakyl‟

For more information see section 3.

Children andadolescents

Do notgive this medicine to children between the agesof0 and 18 years.

Breakylcontainsfentanylin an amountwhich can befataltoa child.Therefore, Breakylmustbe keptoutof

sightandreachofchildrenatalltimes.

Ifyou are anathlete,be awarethatthisproductmayproducea positive reactioninanti-dopingtests.

OthermedicinesandBreakyl

Please tellyourdoctororpharmacistifyou aretakingorhave recentlytaken anyothermedicines,including

medicinesobtained withouta prescription.

DonotuseBreakylifyou are currentlytakingmonoamine-oxidase(MAO)inhibitors(usedforsevere

depression)orhave donesoin the past2 weeks.

Ifyou are takinganyofthefollowingtalkto yourdoctororpharmacistbeforestartingBreakyl:

Anymedicine which mightnormallymake youtired orsleepy, e.g.:

sleepingpills,

medicinestotreatanxiety,nervousness, depression,

medicinestotreattenseorrigid muscle (muscle relaxants),

medicinestotreatallergies(antihistamines).

Medicinesthatmightinterfere withtheway,bywhich(theCYP3A4 isoenzyme in)yourbodybreaks down

Breakylasthesemayincreasethe bloodlevels offentanyl.Thismayresultin increased orprolonged effects

ofBreakyland maycausepotentiallyfatalbreathingproblems. Such medicinesare, e.g.:

medicinesforthe treatmentofbacterialinfections (such aserythromycin,clarithromycin, telithromycin)

medicinesforthe treatmentoffungalinfections(suchasketoconazole,itraconazole, fluconazole)

medicinestocontrolviralinfections,i.e. HIVinfections (such asritonavir,indinavir, nelfinavir,

saquinavir)

medicinesforthe treatmentofcardiovasculardiseases(suchasdiltiazem,verapamil)

medicinesagainstsevere nausea(such asaprepitant, dronabinol)

medicinesforthe treatmentofdepressions(such asfluoxetine)

medicineswhichinhibitgastricacid production(suchascimetidine)

Theriskofsideeffectsincreases ifyou aretakingmedicinessuchascertain antidepressants orpsychotics.

Breakylmayinteractwiththese medicines and you mayexperience mentalstatuschanges(e.g. agitation,

hallucinations, coma), andothereffectssuchasbodytemperature above 38°C, increasein heartrate,unstable

blood pressure, and exaggeration ofreflexes, muscularrigidity, lackofcoordination and/orgastrointestinal

symptoms (e.g. nausea, vomiting, diarrhoea). Yourdoctorwilltellyou whetherBreakylis suitable foryou.

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

Medicinesthatmayenhancetheway,bywhich(the CYP3A4 isoenzyme in)yourbodybreaks down

fentanyl, thusdecreasingtheefficacyofBreakylsuchas:

sleepingpills orsedatives(such asphenobarbital)

medicinestocontrolepileptic convolutions/seizures(such ascarbamazepine,phenytoin, oxcarbazepine)

medicinestocontrolviralproliferation (suchasefavirenz,nevirapine)

anti-inflammatoryorimmunosuppressive medicines(such asglucocorticoids)

medicinesforthe treatmentofdiabetes(such aspioglitazone)

antibioticsfortreatmentoftuberculosis(suchasrifabutin,rifampicin)

psycho-stimulatingmedicines(suchasmodafinil)

medicinesforthe treatmentofdepressions(such asSt.John's wort)

Ifyoustoptherapywith, ordecreasethedoseof,suchactive substanceswhile usingBreakyl,talktoyour

doctor. Yourdoctorwillcarefullymonitoryouforsigns ofopioidtoxicity, andmayadjustthe dose of

Breakylaccordingly.

Ifyousimultaneouslyusecertain typesofstrongpain-killers,called partialopioidagonists/antagonistse.g.

buprenorphine,nalbuphineand pentazocine,you could experienceopiate withdrawalsymptoms(nausea,

vomiting, diarrhoea,anxiety,chills,tremor,andsweating)while usingthesemedicines.

UsingBreakylwithfood,drinkandalcohol

Avoid drinkingalcohol, asalcoholmayadditionallysedateand depressyourrespiration.Donotdrink

grapefruitjuice, asthis mayslowdownthe wayyourbodybreaks downfentanyl,which mayresultin

increased orprolonged effectsofBreakyland maycausepotentiallyfatalbreathingproblems.

Pregnancy,breast-feedingandfertiliy

Ifyou are pregnantorbreast-feeding, thinkyoumaybepregnantorare planningtohave ababy, askyour

doctororpharmacistforadvicebeforetakingthismedicine.

Breakylshouldnotbe usedduringpregnancyunlessyou have discussed this withyourdoctor.Youshould

notuse Breakylduringchildbirth becausefentanylmaycauserespiratorydepression inthe new-born child.

Fentanylcan getinto breastmilkandmaycauseside effectsin the breast-fed infant. Do notuseBreakylif

you are breast-feeding. Youshould notstartbreast-feedinguntilatleast5 daysafterthe lastdoseofBreakyl.

Driving andusingmachines

Please askyourdoctorwhetheryou maysafelydrive acar, oroperate machineryafew hours aftertaking

Breakyl.

Opioidanalgesicslike fentanylmayimpairthe mentaland/orphysicalabilityrequiredforthe performance of

potentiallydangeroustasks.Donotdrive oroperate machineryifyou are feelingsleepyordizzy,have

blurredordouble vision,orhave difficultyin concentratingwhileusingBreakyl.

Breakylcontainspropylene glycol(E1520),sodiumbenzoate (E211),methyl-parahydroxybenzoate

(E218),andpropyl-parahydroxybenzoate (E216).

Sodiumbenzoateis mildlyirritanttotheskin, eyesandmucousmembranes.Methyl-parahydroxybenzoate

and propyl-parahydroxybenzoate maycauseallergic reactions(possiblydelayed).Propyleneglycolmay

causeskinirritation.

3. HOW TOUSEBREAKYL

Always use Breakylexactlyasyourdoctorhas told you. You should checkwithyourdoctororpharmacistif

you are notsure.

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

Dosage

When you startusingBreakylyourdoctorwillworkwith you tofindthe dose thatwillrelieve your

breakthrough pain(dosetitration).ThisisnecessarybecauseyourindividualsuccessfuldoseofBreakylcan

notbepredictedfromthe dailydose ofopioids you aretakingfortreatmentofyourchronic cancerpain, or

fromothermedicineswhich you mayhave taken fortreatmentofbreakthrough cancerpain.

For dose titration yourdoseis graduallyincreased. When you have reacheda dose, which providesyou with

adequatepain reliefwithin30 minutesand ifanypossiblyoccurringside effects are acceptable foryou, you

have identified the successfuldose.Itis importantthatyou followstrictlytheadviceofyourdoctor.

Usually, thefollowingprocedurewillbeusedfortheDoseTitration.

Dosetitration

You should startwiththeinitialdoseof200 microgramsofBreakyl.

Contactyourdoctor, ifyourbreakthroughpainis notrelievedwithin 30minutesafterapplication ofthe

Breakyldose. Ifyou havetolerated the dose,yourdoctorwilladviseyou totakethe nexthigherBreakyldose

forasubsequentbreakthrough pain episode. Yourdoctormaygraduallyincrease the dose from200 to 400

and 600 micrograms up to800 micrograms.

For thispurposeBreakylStartcontains one unitofeachstrength:200, 400, 600,and 800micrograms.

Byapplyinga combinationofBreakyl200microgrambuccalfilmssimultaneously, these higherdoses may

be achieved:

1buccalfilmBreakyl200 equalsa doseof200micrograms

2buccalfilms Breakyl200 equala doseof400micrograms

3buccalfilms Breakyl200 equala doseof600micrograms

4buccalfilms Breakyl200 equala doseof800micrograms

In casethe higheststrengthin BreakylStart(800micrograms)orthecombinationof4buccalfilms atone

time (800micrograms)is notsufficientforpainrelief,yourdoctormayprescribeBreakyl1200micrograms

foryou. Thisis the highestavailablestrength ofBreakyl.

When youhave identifiedthe successfuldose, yourdoctorwillprovide you with aprescriptionforthis dose

totreatsubsequentbreakthrough pain episodesbyusingthisidentified dose.

Breakylshouldonlybe used onceperbreakthrough pain episode andyou shouldwaitforatleast4 hours

before usingthenextBreakyldose.

Ifyoudo notachieveadequate painreliefwithin 30minutesafterapplicationofaBreakyldose,youmayuse

anotherrescuemedication forbreakthrough pain,ifyourdoctortold you so.

Frequencyofadministration

You should nottake more than fourBreakyldosesperday.

DoseReadjustment

You mustinformyourdoctorimmediatelyifyou areexperiencingmore thanfourbreakthrough pain

episodesperday.Yourdoctormaywish toincreasethedoseofyourmedicineforyourpersistentcancer

pain.Whenyourpersistentpainiscontrolledagain, yourdoctormayneed toadjustyourdose ofBreakyl.

Forbestresults, letyourdoctorknowaboutyourpainand howBreakylis workingforyou so thatthe dose

can beadjustedifneeded.

DonotchangethedosesofBreakylorofyourregularopioidtherapyon yourown. Changesin dosage must

be directedand monitoredbyyourdoctor.

Methodsofadministration

Breakylbuccalfilmis fororomucosaluse.When youattacha Breakylbuccalfilmtothe inside ofyour

cheek, fentanylis absorbeddirectlythrough theliningofyourmouth, intothe blood circulation.

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

OpentheBreakylsachetimmediatelypriorto use asindicatedbytheinstructionson thesachet;

Useyourtonguetowetthe insideofyourcheekorrinseyourmouth with waterto moistenthe areafor

placementofBreakyl;

With dryhands, take theBreakylbuccalfilmbetween yourforefingerand thumb withthepinkside facing

to the thumb (figure1)

PlacetheBreakylbuccalfilminside yourmouth, sothatthe pinksidemakessmooth contactwith the inner

liningofyourcheek(figure2);

Pressand holditin placeforaminimumof5 secondsuntilitsticksfirmly. Nowthe whiteside shouldbe

visible(figure3).

When applyingmore thanone Breakylbuccalfilmatthe same time, make sure each filmsticks directlyto

youroralmucosa.To avoidoverlap,itispossibleto applyfilms toboth,leftandrightsideofthe buccal

mucosa.

TheBreakylbuccalfilmshould stayin placeonits own afterthis period.You maydrinkliquidsafter5

minutes.

Thebuccalfilmwillusuallydissolvecompletelywithin 15 to30minutes afterapplication.In individual

cases complete dissolutionmaytakemore than30 minutes,butthis doesnotaffectfentanylabsorption.

Avoid manipulatingthebuccalfilmwithyourtongueorfingers.Youshould noteataslongasthebuccal

filmhasnotyetdissolved completely.

Do notchew orswallowBreakyl.Ifyou do so, you willlikelygetlessreliefofyourbreakthrough pain.

Ifyou usemoreBreakylthanyou should orthinksomeone has accidentally usedBreakyl

If, afterusingBreakyl,youbegin tofeelverysleepy, remove the Breakylbuccalfilmoreven partsofitfrom

yourmouthasquicklyaspossibleand callanotherperson tohelp you.

Youoryourcaregivershouldcontactyourdoctor, hospitaloremergencyroomforassessmentoftheriskand

foradvice,ifyou have taken more Breakylthan you should.

Symptoms ofoverdosemay be:

verysleepy

dizzy

feelingsickorvomiting

veryslowand/orshallowbreathing

orreduced bodytemperature, slowheartbeat, difficultiescoordinatingarms andlegs

IfsomeonehasaccidentallytakenBreakyl, theymayhave the same symptoms asdescribed above for

overdose.

Atthebeginningoftreatment,thesesymptomscan occur,ifyourdoseofBreakylis toohigh orifyou take

too much Breakyl.Youand yourcaregivershould discuss with yourdoctorhowto take immediate action if

this occurs.

Note to caregivers:

Ifyou see thatthe patienttakingBreakylorsomeonewho hasaccidentallytakenBreakylforwhomitis not

prescribed,hasslowand/orshallowbreathingorifyou have ahardtime wakingthe person up,take the

followingstepsimmediately:

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

In casethe Breakylbuccalfilmis stillstickingto theinnercheekofthe patient,remove thebuccalfilmor

even parts ofitfromtheindividual‟smouthas quicklyaspossible

Callforemergencyhelp

While waitingforemergencyhelp:

–Ifthe personis asleep, awaken the personbycallingher/hisname and shakingher/hisarmorshoulder

–Ifthe person seems to bebreathingslowly,prompther/himto breathe every5-10 seconds

–Ifthe person hasstoppedbreathing,givemouthtomouthresuscitation untilhelparrives

Ifyoustop usingBreakyl

You should discontinueBreakylwhenyouno longer-have anybreakthrough pain.Youmusthowever

continuetotake yourusualopioidpainrelievingmedicineto treatyourpersistentcancerpain asadvisedby

yourdoctor.

You mayexperiencewithdrawalsymptoms similartothe possible sideeffectsofBreakylwhen

discontinuingBreakyl.Ifyouexperiencewithdrawalsymptoms orifyou areconcernedaboutyourpain

relief, you should contactyourdoctor.Yourdoctorwillevaluateifyou needmedicinetoreduceoreliminate

the withdrawalsymptoms.

Ifyou have anyfurtherquestions onthe useofthismedicine, askyourdoctororpharmacist.

4. POSSIBLESIDEEFFECTS

Like allmedicines,Breakylcan causesideeffects, although noteverybodygets them.

Themostserious side effects areshallowbreathing, lowblood pressure andshock.Ifyoubecome very

sleepyorhave slowand/orshallowbreathing, you oryourcaregivershould contactyourdoctorimmediately

and callforemergencyhelp.Ifthebuccalfilmis stillinplace inyourcheek,itoreven parts ofitshould be

removedasquicklyaspossible.

Themostfrequentadversereactions observed werenausea,somnolence,and dizziness.

Because patientsusingBreakylarealso takingregularopioid therapysuch as morphine,oxycodoneor

transdermalfentanyl,fortheirpersistentpain,opioidsideeffectsmayarise fromeithermedication.Thus,it

is notpossibleto definitivelyseparatethe effects ofBreakylfromthoseofthe otheropioids.

Theadverse eventsconsideredto beatleastpossibly-relatedtotreatment, were asfollows:

Common(mayaffectup to1in10people):

-excessive tiredness/sleepiness, dizziness,headache, sedation

-sightproblems (e.g. blurred ordoublevision)

-nausea/feelingsick, constipation, vomiting, drymouth

-itchingofthe skin

-fatigue

-confusion

Uncommon(mayaffectupto1in100people):

-blood pressureincreased

-taste alteration, inactivity, memorydifficulties, disturbanceinthinking

-sloworshallowbreathing, sinus congestion

-diarrhoea, oralmucosalinflammation, gumbleeding, indigestion, mouth ulcers, oralpain, painful

swallowing

-unintentionallossofurine

-increasedsweating, tendencyto bruise

-muscle twitching, muscularweakness, paininjoints,muscularpain,pain inextremity, pain injaw

-decreasedappetite

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

-accidentalinjury(forexample, falls)

-flushing/feelinghot

-weakness, chills, fever, thirst

-feelinganxious ornervous,hallucinations,delusion,abnormaldreams, sleeplessness,restlessness

Very rare(mayaffectupto1 in 10,000people):

-musclejerks,convulsion(fits),abnormalsensations like tingling, numbness, increasedtouchinessalso

aroundthe mouth, difficultycoordinatingmovements

-severebreathingdifficulties

-abdominalpain, wind, abdominalbloating

-difficultypassingurine

-skin rash

-vasodilatation

-generalfeelingunwell

-swellingofarms orlegs

-abnormalthinking, feelingdetached, depression, mood swings, excessive feelingofwellbeing

Frequencynotknown (frequencycannotbeestimatedfromthe available data):

-withdrawalsyndrome (maymanifestbythe occurrence ofthefollowingsideeffects:nausea,vomiting,

diarrhoea, anxiety,chills, tremor, and sweating)

Thereisariskofabuseoraddiction withBreakyl.Theriskishigherifyou have everbeen addictedto or

abusedothermedicines, streetdrugs, oralcohol.However,addictionfollowingtherapeutic use ofopioids is

rare.

Ifanyofthe side effects gets serious, orifyou noticeanyside effects notlistedinthis leaflet, please tellyour

doctororpharmacist.

Reporting ofside effects

Ifyou getanyside effects, talkto yourdoctor, pharmacistornurse.This includesanypossible sideeffects

notlistedinthis leaflet. You can alsoreportside effects directlyvia HPRAPharmacovigilance, Earlsfort

Terrace, IRL-Dublin 2;Tel:+353 1 6764971; Fax:+353 1 6762517.Website:www.hpra.ie;E-mail:

medsafety@hpra.ie. Byreportingsideeffects you canhelp provide moreinformation onthesafetyofthis

medicine.

5. HOW TOSTOREBREAKYL

KeepBreakyloutofthesightandreachofchildrenatalltimes.Theamountoffentanylcontainedin Breakyl

can befataltoa child ora person, who does nottakeregularopioidtherapy.Breakylshouldbe keptin asafe

locked storage place.

Do notuse Breakylafterthe expirydate which is stated on the carton andeachsachetas{MM.YYYY}.The

expirydaterefers tothe lastdayofthatmonth.

Do notstore above30ºC.

Do notrefrigerate.

Storeintheoriginalpackage in orderto protectfrommoisture.

Do notuse ifthesachethasbeen damaged before opening.Ifa buccalfilmis damaged orcutduring

removal, itshouldnotbe used.

Do notthrowawayBreakylvia wastewaterorhousehold waste.Ifyou are no longerusingBreakyl, orifyou

haveleftoversachetsin yourhome,askyourpharmacisthowtodisposeofthesemedicinesno longer

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

required.Thesemeasureswillhelp to protecttheenvironmentand toavoid thatunused medication is taken

bychildren and/orpersons,forwhomitis notprescribed.

6. CONTENTS OF THEPACKANDOTHERINFORMATION

WhatBreakylcontains

Theactive substanceisfentanyl.

Breakyl200 microgrambuccalfilm

Onebuccalfilmcontains200 micrograms fentanyl(asfentanylcitrate),

Breakyl400 microgrambuccalfilm

One buccalfilmcontains400 micrograms fentanyl(asfentanylcitrate),

Breakyl600 microgrambuccalfilm

One buccalfilmcontains600 micrograms fentanyl(asfentanylcitrate),

Breakyl800 microgrambuccalfilm

One buccalfilmcontains800 micrograms fentanyl(asfentanylcitrate),or

Breakyl1200 microgrambuccalfilm

One buccalfilmcontains1200 micrograms fentanyl(as fentanylcitrate)

Theotheringredientsare

Active layer:

Propyleneglycol(E1520),

sodiumbenzoate(E211),

methyl-parahydroxybenzoate (E218),

propyl-parahydroxybenzoate (E216),

ferricoxide(red)(E172),

anhydrouscitricacid,

all-rac-alpha-tocopherylacetate,

monobasic sodiumphosphate(anhydrous),

sodiumhydroxide,

Tribasic sodiumphosphate(anhydrous),

polycarbophil,

hydroxypropylcellulose,

hydroxyethylcellulose,

Carmellosesodium.

Backinglayer:

sodiumbenzoate(E211),

methyl-parahydroxybenzoate (E218),

propyl-parahydroxybenzoate (E216),

anhydrous citric acid,

all-rac-alpha-tocopherylacetate,

hydroxypropylcellulose,

hydroxyethylcellulose,

titaniumdioxide(E171),

saccharin sodium,

peppermintoil.

WhatBreakyllooks like andcontents ofthe pack

pl-breakyl_PSUSA_&_QRD9_Apr2014_clean.doc

Breakylis asolublerectangular, flat, flexible buccalfilmwith a pinkside anda white side designedto

deliverfentanyldirectlyinto the blood circulation.Thepinkside containstheactive substancefentanyl.The

whiteside minimises fentanylrelease intothe saliva to avoid swallowingofthe active substance.

Thefollowingstencilshows thesizesofthe availableBreakylstrengths:

Microgram microgram microgram microgram microgram

Eachbuccalfilmisindividuallysealed in achild-resistantsachet.

Breakylis availablein the followingpresentations:

Breakyl200 microgram:cartons with4,10or28sachets with onebuccalfilmeach.

Breakyl400 microgram:cartons with4, 10or28sachets with onebuccalfilmeach.

Breakyl600 microgram:cartons with4, 10or28sachets with onebuccalfilmeach.

Breakyl800 microgram:cartons with4, 10or28sachets with onebuccalfilmeach.

Breakyl1200 microgram:cartons with4,10or28sachets withonebuccalfilmeach.

BreakylStart:4Sachetswith onebuccalfilmof200,400, 600and 800 microgrameach,in acarton.

Notallpacksizesmaybe marketed.

MarketingAuthorisationHolder

MedaHealth SalesIrelandLimited,

Unit 34/35, Block A,

DunboyneBusiness Park,

Dunboyne, Co.Meath,

Ireland

Manufacturer

MEDAPharma GmbH&Co. KG

Benzstr. 1

D-61352 Bad Homburg

Germany

Thismedicinalproductisauthorisedinthe MemberStatesoftheEEAunderthefollowing names:

Norway:Buquel/BuquelStart

Austria, Belgium, Bulgaria,Czech Republic, Denmark,Estonia, Finland, France,Germany, Greece,

Hungary,Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands,Poland, Portugal, Romania, Slovakia,

Spain, Sweden, UnitedKingdom:Breakyl/BreakylStart

Thisleafletwaslastrevisedin

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BREAKYL200microgrambuccalfilm

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onebuccalfilmcontains:

200microgramsfentanyl(asfentanylcitrate)

Excipientswithknowneffect:

Forthefulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Buccalfilm

Breakylisasolublerectangular,flat,flexiblebuccalfilmwithapinksideandawhitesidedesignedtodeliverfentanyl

directlyintothebloodcirculation.Thepinksidecontainstheactivesubstancefentanyl.Thewhitesideminimises

fentanylreleaseintothesalivatoavoidswallowingoftheactivesubstance.

ThefollowingstencilshowsthesizesoftheavailableBreakylstrengths:

____________________________________________________

microgammicrogrammicrogrammicrogrammicrogram

0.78cm 2 1.56cm 2 2.34cm 2 3.11cm 2 4.67cm 2

(Dimensionsprobablyincorrectifviewedelectronically.)

Breakyl,strength(microgram)

Excipient 200

propyleneglycol(E1520)(mg) 0.17

Sodiumbenzoate(E211)(mg) 0.11

methylparahydroxybenzoate(E218)(mg) 0.12

Health Products Regulatory Authority

______________________________________________________________________________________________________________________

Date Printed 12/05/2015 CRN 2160574 page number: 1

4CLINICALPARTICULARS

4.1TherapeuticIndications

Breakylisindicatedforthetreatmentofbreakthroughpain(BTP)inadultswithcancerwhoarealreadyreceiving

maintenanceopioidtherapyforchroniccancerpain.

BTPisatransitoryexacerbationofpainthatoccursonabackgroundofotherwisecontrolledpersistentpain.

Patientsreceivingmaintenanceopioidtherapyarethosewhoaretakingatleast60mgoforalmorphinedaily,atleast

25microgramsoftransdermalfentanylperhour,atleast30mgofoxycodonedaily,atleast8mgoforal

hydromorphonedailyoranequianalgesicdoseofanotheropioidforaweekorlonger.

4.2Posologyandmethodofadministration

Treatmenthastobeinitiatedbyandmaintainedundertheguidanceofaphysicianexperiencedinthemanagementof

opioidtherapyincancerpatients.Inordertominimisetherisksofopioid-relatedundesirableeffectsandtoidentifythe

“successful”dose,itisimperativethatpatientsbemonitoredcloselybyhealthprofessionalsduringthetitration

process.

AsthesuccessfuldoseofBreakylforbreakthroughcancerpaincannotbepredictedfromthedailymaintenancedose

ofopioidsorfromothermedicationforbreakthroughcancerpain,ithastobedeterminedbydosetitration.

DoseTitration

BeforepatientsstarttitrationwithBreakyl,itisexpectedthattheirbackgroundpersistentpainiscontrolledby

maintenanceuseofopioidtherapy.Incasepatientsexperiencemorethanfourbreakthroughpainepisodesperday,

increasingthemaintenanceopioiddosehastobeconsideredbeforestartingthetitrationprocesswithBreakyl.

Titrationinpatientsswitchingfromotherfentanylcontainingproducts

Duetodifferentabsorptionprofiles,switchingmustnotbedoneata1:1ratio.Ifswitchingfromanotheroralfentanyl

citrateproduct,independentdosetitrationwithBreakylisrequiredasbioavailabilitybetweenproductsdiffers

significantly(seegraphundersection5.2).

StartingDose:

TheinitialdoseofBreakylshouldbe200micrograms,titratingupwardsasnecessaryusingtherangeofavailable

dosagestrengths(200,400,600,800,1200micrograms).Titrationprocessshouldbecarefullymonitoreduntiladoseis

reachedthatprovidesadequateanalgesiawithacceptableundesirableeffectsafterasingledoseperepisodeof

breakthroughpain.Thisisdefinedasthesuccessfuldose.DosesofBreakylmustbeseparatedbyatleast4hours.

TwopresentationsofBreakylareavailablefordosetitration:

BreakylStart,containingonebuccalfilmof200,400,600,and800microgrameach

Breakyl200microgram,buccalfilm.

WithBreakyl200microgram,higherdosesmaybeachievedbyapplyingacombinationofBreakyl200microgram

buccalfilmssimultaneously:

1buccalfilmBreakyl200equalsadoseof200micrograms

2buccalfilmsBreakyl200equaladoseof400micrograms

3buccalfilmsBreakyl200equaladoseof600micrograms

4buccalfilmsBreakyl200equaladoseof800micrograms

IncasethehigheststrengthinBreakylStart(800micrograms)orthecombinationof4buccalfilmsBreakyl200atone

time(800micrograms)isnotsufficientforpainrelief,Breakyl1200maybeindicated.Thisisthehighestavailable

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Ifadequatepainreliefisachievedafterapplicationofaparticulardosestrength,subsequentbreakthroughpainepisodes

shouldbetreatedbyusingtheidentifiedBreakyldose.

Ifadequatepainreliefisnotachievedwithin30minutesafterapplicationofaparticularBreakyldose,andthepatient

hastoleratedthedose,thepatientshouldtreatthesubsequentbreakthroughpainepisodebyusingthenexthigher

Breakyldose.

Ifadequatepainreliefisnotachievedwithin30minutesafterapplicationofthe1200microgramBreakylbuccalfilm,

(thehighestavailabledosestrength),thepatientshoulddiscusstreatmentoptionswiththeirphysician.Thecombined

useoflowdosebuccalfilmstoreachthenexthigherdoseispossibleduringtitration.Thecombineduseoftotaldoses

exceeding1200microgramshasnotbeenevaluatedundercontrolledconditions.

Duringanyepisodeofbreakthroughpain,ifadequatepainreliefisnotachievedwithin30minutesafterapplicationofa

Breakylbuccalfilm,thepatientmayusearescuemedicinalproductforbreakthroughpain,ifdirectedbytheir

physician.However,opioidrescuemedicinalproductsshouldnotbeusedwhenunacceptableundesirableeffectsof

Breakylorsignsofopioidtoxicityhavebeennoted.

MaintenanceTherapy

Onceasuccessfuldoseisdetermined,usageofBreakylshouldbelimitedtofourorfewerepisodesofbreakthrough

painperday,whichmustbeseparatedbyatleast4hours.Breakylshouldonlybeusedonceperepisode.

DoseReadjustment

DosagereadjustmentofeitherBreakylorthemaintenance(around-the-clock)opioidanalgesicmayberequiredinsome

patientsinordertocontinuetoprovideadequatereliefofbreakthroughpain.Increasingthearound-the-clockopioid

doseusedforpersistentpainshouldbeconsideredinpatientsexperiencingmorethanfourbreakthroughpainepisodes

dailyoveraperiodofmorethanfourconsecutivedays.Ifthedoseofthelongactingopioidisincreased,thedoseof

Breakyltotreatbreakthroughpainmayneedtobereviewed.

DoseTitration–fordetailsseetextabove

BREAKYLisavailablein5dosagestrengths;

200,400,600,800and1200µg

Start Theinitialdoseis200µg

TitratethedoseincrementallyusingthenexthigherBREAKYLdoseuntilthe

patientreachesadosethatprovidesadequateanalgesiawithacceptableundesirable

effects.

Ifadequatepainreliefisachieved,

treatsubsequentbreakthroughpain

episodesusingtheidentifieddose. Ifadequatepainreliefisnotachieved

within30minutesafterapplicationand

thepatienthastoleratedthedose,use

thenexthigherBREAKYLdoseto

treatthenextepisodeofbreakthrough

pain.

DosesofBREAKYLmustbeseparatedbyatleast4hours.Duringanyepisodeof

breakthroughpain,ifadequatepainreliefisnotachievedwithin30minutes,the

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Discontinuationoftherapy

Breakylshouldbediscontinuedimmediatelyifpatientnolongerexperiencesbreakthroughpainepisodes.The

treatmentforthepersistentbackgroundpainshouldbekeptasprescribed.

Ifdiscontinuationofallopioidtherapyisrequired,thepatientmustbecloselyfollowedbythedoctor,inorderto

managetheriskofabruptwithdrawaleffects.

MethodofAdministration

Thepatientshould:

opentheBreakylsachetimmediatelypriortouseasindicatedbytheinstructionsprintedonthesachet

usetheirtonguetowettheinsideoftheircheekorrinsetheirmouthwithwatertomoistentheareaforplacementof

Breakyl

withdryhands,taketheBreakylbuccalfilmbetweenforefingerandthumbwiththepinksidefacingtothethumb

placetheBreakylbuccalfilminsidehis/hermouth,sothatthepinksidemakessmoothcontactwiththeinnerlining

ofhis/hercheek

pressandholditinplaceforaminimumof5secondsuntilitsticksfirmly;thenthewhitesideshouldbevisible.

(Comment:additionalbulletpointreferringtoBreakyl200microgram,buccalfilm,only:)

WhenapplyingmorethanoneBreakylbuccalfilmatthesametime,thepatienthastomakesurethateachfilm

sticksdirectlytohis/heroralmucosa.Toavoidoverlap,itispossibletoapplyfilmsonboth,leftandrightsideof

thebuccalmucosa.

TheBreakylbuccalfilmshouldstayinplaceonitsownafterthisperiod.Liquidsmaybeconsumedafter5minutes.

TheBreakylbuccalfilmwillusuallydissolvecompletelywithin15to30minutesafterapplication.Inindividualcases

completedissolutionoftheproductmaytakemorethanthirtyminutes,butthisdoesnotaffectfentanylabsorption.The

patientshouldbeinstructedtoavoidmanipulatingthebuccalfilmwiththeirtongueorfinger(s)andavoideatingfood

untilthebuccalfilmhasdissolved.

AbuccalfilmofBreakyl,ifchewedandswallowed,mightresultinlowerpeakconcentrationsandlowerbioavailability

thanwhenusedasdirected(seesection5.2).

PaediatricPopulation

ThesafetyandefficacyofBreakylinchildrenaged0to18yearshavenotbeenestablished.Nodataareavailable.

Useinolderpeople

Olderpeoplehavebeenshowntobemoresensitivetotheeffectsoffentanylwhenadministeredintravenously

comparedwiththeyoungerpopulation.Inolderpeople,eliminationoffentanylisslowerandtheterminalelimination

half-lifeislonger,whichmayresultinaccumulationoftheactivesubstanceandagreaterriskofundesirableeffects.

Thereforedosetitrationneedstobeapproachedwithparticularcare.However,inclinicalstudies,therewasno

differenceinthemediantitrateddoseofBreakylonpatientsaged65yearsandoldercomparedtothose<65years.

Useinspecialpatientpopulations

Specialcareshouldbetakenduringthetitrationprocessinpatientswithkidneyorliverdysfunction.

PatientswithGrade1mucositisshouldbemonitoredclosely,doseadjustmentmaybeconsidered.Theefficacyand

safetyofBreakylinpatientswithmucositismoreseverethanGrade1havenotbeenstudied.

Thebuccalfilmmustnotbeusedifthesachethasbeendamagedbeforeopening.

4.3Contraindications

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Simultaneoususeofmonoamine-oxidase(MAO)inhibitors,orwithin2weeksafterthecessationoftheuseofMAO

inhibitors(seealsosection4.5).

Severerespiratorydepressionorsevereobstructivelungconditions.

Patientswithoutmaintenanceopioidtherapy(seesection4.1)asthereisanincreasedriskofrespiratorydepression.

Treatmentofacutepainotherthanbreakthroughpain.

4.4Specialwarningsandprecautionsforuse

PatientsandtheircaregiversmustbeinstructedthatBreakylcontainsanactivesubstanceinanamountwhichcanbe

fataltoachild,andthereforetokeepBreakyloutofsightandreachofchildrenandnon-patientsatalltimes.

Inordertominimisetherisksofopioid-relatedundesirableeffectsandtoidentifytheeffectivedose,itisimperative

thatpatientsbemonitoredcloselybyaphysicianduringthetitrationprocess.

Itisimportantthatthelongactingopioidtreatmentusedtotreatthepatient'spersistentpainhasbeenstabilisedbefore

Breakyltherapybegins.

Respiratorydepression

Thereisariskofclinicallysignificantrespiratorydepressionassociatedwiththeuseoffentanyl.Particularcaution

shouldbeusedwhentitratingBreakylinpatientswithnon-severechronicobstructivepulmonarydiseaseorother

medicalconditionspredisposingthemtorespiratorydepression,asevennormallytherapeuticdosesofBreakylmay

furtherdecreaserespiratorydrivetothepointofrespiratoryfailure.

Increasedintracranialpressure

Breakylshouldonlybeadministeredwithextremecautioninpatientswhomaybeparticularlysusceptibletothe

intracranialeffectsofCO

retention,suchasthosewithevidenceofincreasedintracranialpressure,orimpaired

consciousness.Opioidsmayobscuretheclinicalcourseofapatientwithaheadinjuryandshouldbeusedonlyif

clinicallywarranted.

Cardiacdisease

Fentanylmayproducebradycardia.Fentanylshouldbeusedwithcautioninpatientswithpreviousorpre-existing

bradyarrhythmias.

Carefulconsiderationshouldbegiventopatientswithhypovolaemiaandhypotension.

Hepaticorrenalimpairment

Inaddition,Breakylshouldbeadministeredwithcautiontopatientswithliverorkidneydysfunction.Theinfluenceof

hepaticorrenalimpairmentonthepharmacokineticsofthemedicinalproducthasnotbeenevaluated.However,when

administeredintravenously,theclearanceoffentanylhasbeenshowntobealteredinhepaticandrenaldiseasedueto

alterationsinmetabolicclearanceandplasmaproteins.AfteradministrationofBreakyl,impairedliverorrenalfunction

maybothincreasethebioavailabilityoffentanylanddecreaseitssystemicclearance,whichcouldleadtoincreasedand

prolongedopioideffects.Therefore,specialcareshouldbetakenduringthetitrationprocessinpatientswithmoderate

orseverehepaticorrenaldisease.

SerotoninSyndrome

CautionisadvisedwhenBreakylisco-administeredwithdrugsthataffecttheserotoninergicneurotransmittersystems.

Thedevelopmentofapotentiallylife-threateningserotoninsyndromemayoccurwiththeconcomitantuseof

serotonergicdrugssuchasSelectiveSerotoninRe-uptakeInhibitors(SSRIs)andSerotoninNorepinephrineRe-uptake

Inhibitors(SNRIs),andwithdrugswhichimpairmetabolismofserotonin(includingMonoamineOxidaseInhibitors

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SerotonineSyndromemayincludemental-statuschanges(e.g.,agitation,hallucinations,coma),autonomicinstability

(e.g.,tachycardia,labilebloodpressure,hyperthermia),neuromuscularabnormalities(e.g.,hyperreflexia,

incoordination,rigidity),and/orgastrointestinalsymptoms(e.g.,nausea,vomiting,diarrhoea).

IfSerotoninsyndromeissuspected,treatmentwithBreakylshouldbediscontinued.

Tolerance,dependence

Toleranceandphysicaland/orpsychologicaldependencemaydevelopuponrepeatedadministrationofopioidssuchas

fentanyl.However,iatrogenicaddictionfollowingtherapeuticuseofopioidsisrare.

Athletesshouldbeinformedthattreatmentwithfentanylcouldleadtopositivedopingtests.

Breakylcontainssodiumbenzoate,methyl-parahydroxybenzoate,propyl-parahydroxybenzoate,andpropyleneglycol.

Sodiumbenzoateismildlyirritanttotheskin,eyesandmucousmembranes.Methyl-parahydroxybenzoateandpropyl-

parahydroxybenzoatemaycauseallergicreactions(possiblydelayed).Propyleneglycolmaycauseskinirritation.

PatientswithGrade1mucositisshouldbemonitoredclosely,doseadjustmentmaybeconsidered.Theefficacyand

safetyofBreakylinpatientswithmucositismoreseverethanGrade1havenotbeenstudied(seealsosections4.2and

5.2).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Breakylshouldnotbeusedinpatientswhoarereceivingorhavereceivedmonoamineoxidase(MAO)inhibitorswithin

thelast14daysbecausesevereandunpredictablepotentiationbyMAOinhibitorshasbeenreportedwithopioid

analgesics(seesection4.3).

SerotoninergicDrugs

Co-administrationoffentanylwithaserotoninergicagent,suchasaSelectiveSerotoninRe-uptakeInhibitor(SSRI)or

aSerotoninNorepinephrineRe-uptakeInhibitor(SNRI)oraMonoamineOxidaseInhibitor(MAOI)(pleaseseesection

4.3),mayincreasetheriskofserotoninsyndrome,apotentiallylife-threateningcondition.

FentanylismetabolizedbytheCYP3A4isoenzymeintheliverandintestinalmucosa(pleaseseealsosection5.2).

InhibitorsofCYP3A4suchas

macrolideantibiotics(e.g.erythromycin,clarithromycin,telithromycin)

azoleantifungals(e.g.ketoconazole,itraconazole,andfluconazole)

certainproteaseinhibitors(e.g.ritonavir,indinavir,nelfinavir,saquinavir)

calciumchannelblockers(e.g.diltiazemorverapamil)

anti-emetics(e.g.aprepitantordronabinol)

antidepressants(e.g.fluoxetin)

antacids(e.g.cimetidin)

mayincreasethebioavailabilityofswallowedfentanylandmayalsodecreaseitssystemicclearancewhichmayresult

inincreasedorprolongedopioideffectsandmaycausepotentiallyfatalrespiratorydepression.Similareffectscouldbe

seenafterconcurrentingestionofgrapefruitjuice,whichisknowntoinhibitCYP3A4.Hencecautionisadvisedif

fentanylisgivenconcomitantlywithCYP3A4inhibitors.PatientsreceivingBreakylwhobegintherapywith,or

increasethedoseof,CYP3A4inhibitorsshouldbecarefullymonitoredforsignsofopioidtoxicityoveranextended

periodoftime.

TheconcomitantuseofBreakylwithpotentCYP3A4inducerssuchas

barbituratesandothersedatives(e.g.phenobarbital)

anti-epileptics(e.g.carbamazepine,phenytoin,oxcarbazepine)

certainantivirals(e.g.efavirenz,nevirapine)

anti-inflammatoryorimmunosuppressiveagents(e.g.glucocorticoids)

anti-diabetics(e.g.pioglitazone)

antibioticsfortuberculosistreatment(e.g.rifabutin,rifampicin),

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antidepressants(e.g.St.John'swort)

mayresultinadecreaseinfentanylplasmaconcentrations,whichcoulddecreasetheefficacyofBreakyl.Patients

receivingBreakylwhostoptherapywith,ordecreasethedoseof,CYP3A4inducersshouldbemonitoredforsignsof

increasedBreakylactivity,ortoxicity,andthedoseofBreakylshouldbeadjustedaccordingly.

TheconcomitantuseofotherCNSdepressants,includingotheropioids,sedativesorhypnotics,generalanaesthetics,

phenothiazines,tranquillisers,skeletalmusclerelaxants,sedatingantihistaminesandalcoholmayproduceadditive

depressanteffects.

Theconcomitantuseofpartialopioidagonists/antagonists(e.g.pentazocine,butorphanol,buprenorphine,nalbuphine,

pentazocine)isnotrecommended.Theyhavehighaffinitytoopioidreceptorswithrelativelylowintrinsicactivityand

thereforepartiallyantagonisetheanalgesiceffectoffentanylandmayinducewithdrawalsymptomsinopioid

dependantpatients.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenoadequatedatafromtheuseoffentanylinpregnantwomen.Studiesinanimalshaveshownreproductive

toxicity(seesection5.3).Thepotentialriskforhumansisunknown.Fentanylshouldnotbeusedinpregnancyunless

clearlynecessary.

Followinglong-termtreatment,fentanylmaycausewithdrawalsymptomsinthenew-borninfant.

Itisadvisednottousefentanylduringlaboranddelivery(includingcaesareansection)becausefentanylpassesthrough

theplacentaandmaycauserespiratorydepressioninthefoetus.IfBreakylisadministered,anantidoteforthechild

shouldbereadilyavailable.

Breast-feeding

Fentanylpassesintobreastmilkandmaycausesedationandrespiratorydepressioninthebreast-fedchild.Fentanyl

shouldnotbeusedbybreastfeedingwomenandbreast-feedingshouldnotberestarteduntilatleast5daysafterthelast

administrationoffentanyl.

Fertility

Therearenohumandataonfertilityavailable.Inanimalstudies,maleandfemalefertilitywasimpairedatsedative

doses(seesection5.3).

4.7Effectsonabilitytodriveandusemachines

Nostudiesoftheeffectsontheabilitytodriveandusemachineshavebeenperformed.

However,opioidanalgesicsmayimpairthementaland/orphysicalabilityrequiredfortheperformanceofpotentially

dangeroustasks(e.g.,drivingacaroroperatingmachinery).Patientsshouldbeadvisednottodriveoroperate

machineryiftheyexperiencesomnolence,dizziness,blurredordoublevisionwhiletakingBreakyl.

4.8Undesirableeffects

Summaryofthesafetyprofile

TypicalopioidundesirableeffectsaretobeexpectedwithBreakyl.Frequently,thesewillceaseordecreaseinintensity

withcontinueduseoftheproduct,asthepatientistitratedtothemostappropriatedose.Themostseriousadverse

reactionsassociatedwithallopioidsincludingBreakylarerespiratorydepression(potentiallyleadingtorespiratory

arrest),circulatorydepression,hypotensionandshock,andallpatientsshouldbecloselymonitoredforthese.

BecausetheclinicalstudiesofBreakylweredesignedtoevaluatesafetyandefficacyintreatingpatientswith

breakthroughpainassociatedwithcancer,allpatientswerealsotakingconcomitantopioids,suchassustained-release

morphine,sustained-releaseoxycodoneortransdermalfentanyl,fortheirpersistentpain.Thus,itisnotpossibleto

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TheadversereactiondatapresentedherereflectontheonehandthecurrentexperiencewithBreakylforbreakthrough

painalongwithaconcomitantopioidforpersistentpain.Ontheotherhand,adverseeventslistedasveryrarehave

previouslybeenassociatedwiththesubstancefentanyl,buthavenotbeenobservedduringclinicalstudieswithBreakyl

uptonow.Therehasbeennoattempttocorrectforconcomitantuseofotheropioids,durationofBreakyltherapy,or

cancer-relatedsymptoms.

Themostfrequentadversereactionsobservedwerenausea,somnolence,anddizziness.

Tabulatedlistofadversereactions

Evaluationofundesirableeffectsisbasedonthefollowingfrequencies: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)ornotknown(cannotbe

estimatedfromtheavailabledata).

Theadverseeventsconsideredtobeatleastpossibly-relatedtotreatmentwereasfollows:

SystemOrganClass Common Uncommon Veryrare,or

frequencynotknown#

Metabolismand

nutritiondisorders Anorexia

Psychiatricdisorders confusionalstate anxiety,hallucination,

delusion,abnormal

dreams,nervousness,

insomnia,restlessness abnormalthinking,

depersonalisation,

depression,emotional

lability,euphoria

Nervoussystem

disorders somnolence,

dizziness,headache,

sedation dysgeusia,lethargy,

amnesia,cognitive

disorder myoclonus,paraesthesia

(including

hyperaesthesia/

circumoralparaesthesia),

abnormalgait/

incoordination

convulsion

Eyedisorders abnormalvision

(blurred,diplopia)

Vasculardisorders hotflush,flushing vasodilatation

Respiratory,thoracic

andmediastinal

disorders respiratory

depression,sinus

congestion dyspnoea

Gastrointestinal

disorders nausea,constipation,

vomiting,drymouth diarrhoea,stomatitis,

gingivalbleeding,

dyspepsia,mouth

ulceration,oralpain,

odynophagia abdominalpain,

flatulence,abdomen

enlarged

Skinand

subcutaneoustissue pruritus hyperhidrosis,

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Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

suspectedadversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971;

Fax:+35316762517.Website:www.hpra.ie;E-mail: medsafety@hpra.ie .

4.9Overdose

Symptoms

ThesymptomsofBreakyloverdoseorsignsoftoxicityareexpectedtobesimilarinnaturetothoseofintravenous

fentanylandotheropioids,andareanextensionofitspharmacologicalactions,withthemostserioussignificanteffect

beingrespiratorydepression.Othersymptomsmaybedeepsedation,coma,bradycardia,hypotonia,hypothermia,

decreasedmuscletonus,ataxia,convulsionsandmiosis.

Treatment

Formanagementofrespiratorydepressionimmediatecountermeasuresshouldbestarted.Theseincluderemovalofany

Breakylbuccalfilm,ifstillinthemouth,physicalandverbalstimulationofthepatient,assessmentofthelevelof

consciousness,andventilatoryandcirculatorystatus.Iftheclinicalsituationwarrants,apatentairwayshouldbe

ensured(possiblywithanoropharyngealairwayorendotrachealtube),oxygenadministeredandventilationassistedor

controlledifnecessary.

Intravenousaccessshouldbeobtained,andnaloxoneorotheropioidantagonistscanbeemployedasclinically

indicated.Thedurationofrespiratorydepressionfollowingoverdosemaybelongerthantheeffectsoftheopioid

antagonist'saction(e.g.,thehalf-lifeofnaloxonerangesfrom30to81minutes)andrepeatedadministrationor

continuousinfusionofnaloxoneorotheropioidantagonistsmaybenecessary.Reversalofthenarcoticeffectmay

disorders bruise

Musculoskeletaland

connectivetissue

disorders muscletwitching,

arthralgia,muscular

weakness,

musculoskeletalpain,

paininextremity,

paininjaw

Renalandurinary

disorders urinaryincontinence urinaryretention

Generaldisorders

andadministration

siteconditions fatigue asthenia,chills,

pyrexia,thirst malaise,peripheral

oedema,drugwithdrawal

syndrome*

Investigations bloodpressure

increased

Injury,poisoning

andprocedural

complications accidentalinjury(for

example,falls)

#frequencynotknown:onlydrugwithdrawalsyndrome*

*opiatewithdrawalsymptomssuchasnausea,vomiting,diarrhea,anxiety,chills,tremor,and

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anotheropioidantagonistisassociatedwiththeriskofprecipitatinganacutewithdrawalsyndrome.

Additionally,adequatebodytemperatureandfluidintakeshouldbemaintained.Ifsevereorpersistenthypotension

occurs,hypovolemiashouldbeconsideredandtheconditionshouldbemanagedwithappropriateparenteralfluid

therapy.Musclerigidity,incaseitoccurs,shouldbemanagedadditionally,asafinalalternative,byaneuromuscular

blockingagent.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:analgesics;opioids,phenylpiperidinederivatives

ATCcode:N02AB03

Fentanyl,apureopioidagonist,actsprimarilythroughinteractionwithµ-opioidreceptorslocatedinthebrain,spinal

cordandsmoothmuscle.Theprimarysiteoftherapeuticactionisthecentralnervoussystem(CNS).Theclinically

mostusefulpharmacologicaleffectoftheinteractionoffentanylwithµ-opioidreceptorsisanalgesia.

Inpatientswithchroniccancerpainonstabledosesofregularlyscheduledopioidstocontroltheirpersistentpain,

Breakylsignificantlyreducedpainintensity,assessedasthesumofpainintensitydifferences(SPID),comparedwith

placeboduring15,30,45,60minfollowingadministration.

Theanalgesiceffectsoffentanylarerelatedtothebloodleveloftheactivesubstance,ifproperallowanceismadefor

thedelayintoandoutoftheCNS(aprocesswitha3-5minutehalf-life).Inopioid-naïveindividuals,analgesiaoccurs

atbloodlevelsof1to2ng/ml,whilebloodlevelsof10-20ng/mlwouldproducesurgicalanaesthesiaandprofound

respiratorydepression.

Secondaryactionsincludemiosisandanincreaseinthetoneanddecreaseinthecontractionsofthegastrointestinal

smoothmuscle,whichresultsinprolongationofgastrointestinaltransittimeandmayberesponsibleforthe

constipatoryeffectofopioids.

Whileopioidsgenerallyincreasethetoneofurinarytractsmoothmuscle,theoveralleffecttendstovary,insomecases

producingurinaryurgency,inothersdifficultyinurination.

Allopioidµ-receptoragonists,includingfentanyl,producedosedependentrespiratorydepression.Theriskof

respiratorydepressionislessinpatientswithpainreceivingchronicopioidtherapywhodeveloptoleranceto

respiratorydepressionandotheropioideffects.

5.2Pharmacokineticproperties

Generalintroduction

Fentanylishighlylipophilicandcanbeabsorbedveryrapidlythroughtheoralmucosaandmoreslowlybythe

conventionalgastrointestinalroute.Itissubjecttofirst-passhepaticandintestinalmetabolismandthemetabolitesdo

notcontributetofentanyl'stherapeuticeffects.

Absorption

Inapharmacokineticstudy,followingbuccalapplication,Breakylwasrapidlyabsorbedandtheabsolutebioavailability

was71%.Thisabsolutebioavailabilitystudyalsodemonstratedsimilarpharmacokineticsinthesubsetsof6maleand6

femaleadultnormalvolunteers.

TheabsorptionpharmacokineticsoffentanylfromBreakylisacombinationofaninitialrapidabsorptionfromthe

buccalmucosaandamoreprolongedabsorptionofswallowedfentanylfromtheGItract.Basedontheabsolute

bioavailabilitystudy,approximately51%ofthetotaldoseofBreakylisrapidlyabsorbedfromthebuccalmucosaand

becomessystemicallyavailable.Theremaining49%ofthetotaldoseisswallowedwiththesalivaandthenslowly

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eliminationandbecomessystemicallyavailable.Thus,theobserved71%absolutebioavailabilityofBreakylisdivided

betweenrapidtransmucosalandslowerGIabsorption.

AunitdoseofBreakyl,ifchewedandswallowed,willlikelyresultinlowerpeakconcentrationsandlower

bioavailabilitythanwhenconsumedasdirected.

Doseproportionalityacrosstheavailablerangeofdosages(200to1200micrograms)ofBreakylhasbeen

demonstrated.AfterconsumptionofasinglebuccalfilmofBreakyl(200to1200micrograms),meanC

usually

rangesfrom0.38to2.19ng/ml(dependingondose)andT

rangesfrom45–240minutes(median60min).

ApplicationofBreakylonanactivesiteofmucositis(Grade1)inagroupofcancerpatientswasassociatedwith

decreasesintheC

andAUC

.ItisrecommendedthatpatientswithGrade1mucositisaremonitoredclosely,dose

adjustmentmaybeconsidered.TheefficacyandsafetyofBreakylwhenusedinpatientswithmucositismoresevere

thanGrade1havenotbeenstudied.

Meanfentanylplasmaconcentrationversustimeprofiles(24hoursand1sthouronly)followingsingledosesof

800µgBreakylor800µgcomparator(fentanyloromucosalapplicator)inhealthyadultsubjects

Distribution

Fentanylishighlylipophilic.Animaldatashowedthatfollowingabsorption,fentanylisrapidlydistributedtothebrain,

heart,lungs,kidneysandspleenfollowedbyaslowerredistributiontomusclesandfat.Theplasmaproteinbindingof

fentanylis80-85%.Themainbindingproteinisalpha -1-acidglycoprotein,butbothalbuminandlipoproteins

contributetosomeextent.Thefreefractionoffentanylincreaseswithacidosis.Themeanvolumeofdistributionat

steadystate(V

)is4l/kg.

Biotransformation

FentanylismetabolizedintheliverandintheintestinalmucosatonorfentanylbycytochromeP450,CYP3A4,isoform.

Norfentanylwasnotfoundtobepharmacologicallyactiveinanimalstudies.Fentanylisprimarily(morethan90%)

eliminatedbybiotransformationtoN-dealkylatedandhydroxylatedinactivemetabolites.

Elimination

Lessthan7%ofthedoseisexcretedunchangedintheurine,andonlyabout1%isexcretedunchangedinthefeces.The

metabolitesaremainlyexcretedintheurine,whilefecalexcretionislessimportant.Thetotalplasmaclearanceof

fentanylis0.5l/hr/kg(range0.3to0.7l/hr/kg).TheclinicallyrelevanthalflifeoffentanylafterBreakyladministration

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5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicity.

Embryo-foetaldevelopmentaltoxicitystudiesconductedinratsandrabbitsrevealednocompoundinduced

malformationsordevelopmentalvariationswhenadministeredduringtheperiodoforganogenesis.Inafertilityand

earlyembryonicdevelopmentstudyinrats,amale-mediatedeffectwasobservedathighdoses(300mcg/kg/day,s.c.)

andisconsistentwiththesedativeeffectsoffentanylinanimalstudies.Instudiesonpreandpostnataldevelopmentin

ratsthesurvivalrateofoffspringwassignificantlyreducedatdosescausingseverematernaltoxicity.Furtherfindings

atmaternallytoxicdosesinF1pupsweredelayedphysicaldevelopment,sensoryfunctions,reflexesandbehaviour.

Theseeffectscouldeitherbeindirecteffectsduetoalteredmaternalcareand/ordecreasedlactationrateoradirect

effectoffentanylonthepups.

Carcinogenicitystudies(26-weekdermalalternativebioassayinTg.ACtransgenicmice;two-yearsubcutaneous

carcinogenicitystudyinrats)didnotinduceanyfindingsindicativeofoncogenicpotential.Evaluationofbrainslides

fromthecarcinogenicitystudyinratsrevealedbrainlesionsinanimalsadministeredhighdosesoffentanylcitrate.The

relevanceofthesefindingstohumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Activelayer:

propyleneglycol(E1520),

sodiumbenzoate(E211),

methyl-parahydroxybenzoate(E218),

propyl-parahydroxybenzoate(E216),

ferricoxide(red)(E172),

anhydrouscitricacid,

all-rac-alpha-tocopherylacetate,

monobasicsodiumphosphate(anhydrous),

sodiumhydroxide,

tribasicsodiumphosphate(anhydrous),

polycarbophil,

hydroxypropylcellulose,

hydroxyethylcellulose,

carmellosesodium

Backinglayer:

sodiumbenzoate(E211),

methyl-parahydroxybenzoate(E218),

propyl-parahydroxybenzoate(E216),

anhydrouscitricacid,

all-rac-alpha-tocopherylacetate,

hydroxypropylcellulose,

hydroxyethylcellulose,

titaniumdioxide(E171),

saccharinsodium,

peppermintoil

6.2Incompatibilities

Health Products Regulatory Authority

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Date Printed 12/05/2015 CRN 2160574 page number: 12

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Donotstoreabove30ºC.

Donotrefrigerate.

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Eachbuccalfilmisindividuallywrappedinachild-resistantsachet,consistingofapolyacrylonitrile/aluminium/

polyethyleneterephthalate(PET)/paperlaminate.

Cartonsof4,10or28schaetswithonebuccalfilmeach.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Anyunusedmedicinalproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

MedaHealthSalesIrelandLtd.

Unit34/35

BlockA

DunboyneBusinessPark

Dunboyne

Co.Meath

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1332/27/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3rdMay2011

Dateoflastrenewal:31stDecember2012

10DATEOFREVISIONOFTHETEXT

Health Products Regulatory Authority

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Date Printed 12/05/2015 CRN 2160574 page number: 13

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