ARICEPT 10 Milligram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
DONEPEZIL HYDROCHLORIDE
Available from:
PCO Manufacturing
INN (International Name):
DONEPEZIL HYDROCHLORIDE
Dosage:
10 Milligram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may not be renewed (A)
Authorization status:
Authorised
Authorization number:
PPA0465/108/002
Authorization date:
0000-00-00

Pil465-108-1-2-3362

PATIENTINFORMATIONLEAFLET

Aricept

5mgFilm-coatedTablets

Aricept

10mgFilm-coatedTablets

DonepezilHydrochloride

Youandyourcaregivershouldreadallofthisleafletcarefully

beforeyoustarttakingthismedicine.

– Keepthisleaflet.Youmayneedtoreaditagain.

– Ifyouhaveanyfurtherquestions,askyourdoctororpharmacist.

– Thismedicinehasbeenprescribedforyou.Donotpassitonto

others.Itmayharmthem,eveniftheir symptomsarethesameas

yours.

– Ifanyofthesideeffectsgetserious,orifyounoticeanyside

effectsnotlistedinthisleaflet,pleasetellyourdoctoror

pharmacist.

INTHISLEAFLET:

1. WhatARICEPTisandwhatitisusedfor

2. BeforeyoutakeARICEPT

3. HowtotakeARICEPT

4. Possiblesideeffects

5. HowtostoreARICEPT

6. Furtherinformation

1. WHATARICEPTISANDWHATITISUSEDFOR

ARICEPT(donepezilhydrochloride)belongstoagroupofmedicines

calledacetylcholinesteraseinhibitors.

Donepezilincreasesthelevelsofasubstance(acetylcholine)inthe

braininvolvedinmemoryfunctionbyslowingdownthebreakdownof

acetylcholine.

Itisusedtotreatthesymptomsofdementiainpeoplediagnosedas

havingmildtomoderatelysevereAlzheimer'sdisease.Thesymptoms

includeincreasingmemoryloss,confusionandbehaviouralchanges.As

aresult,sufferersofAlzheimer'sdiseasefinditmoreandmoredifficult

tocarryouttheirnormaldailyactivities.

ARICEPTisforuseinadultpatientsonly.

2. BEFOREYOUTAKEARICEPT

DoNOTtakeARICEPT

Ifyouareallergic(hypersensitive)todonepezilhydrochloride,orto

piperidinederivatives,ortoanyoftheotheringredientsof

ARICEPTlistedinsection6

TakespecialcarewithARICEPT

TellyourdoctororpharmacistbeforestartingtotakeARICEPTifyou

haveorhavehad:

stomachorduodenalulcers

seizures(fits)orconvulsions

aheartcondition(irregularorveryslowheartbeat)

asthmaorotherlongtermlungdisease

liverproblemsorhepatitis

difficultypassingurineormildkidneydisease

Alsotellyourdoctorifyouarepregnantorthinkyoumightbepregnant

Takingothermedicines

Pleasetellyourdoctororpharmacistifyouaretaking,orhaverecently

taken,anyothermedicine.Thisincludesmedicinesthatyourdoctorhas

notprescribedforyoubutwhichyouhaveboughtyourselffroma

chemist/pharmacist.Italsoappliestomedicinesyoumaytakesometime

inthefutureifyoucontinuetotakeARICEPT.Thisisbecausethese

medicinesmayweakenorstrengthentheeffectsofARICEPT.

Especiallytellyourdoctorifyouaretakinganyofthefollowingtypesof

medicines:

otherAlzheimer'sdiseasemedicines,e.g.galantamine

painkillersortreatmentforarthritise.g.aspirin,non-steroidalanti-

inflammatory(NSAID)drugssuchasibuprofen,ordiclofenac

sodium

anticholinergicsmedicines,e.g.tolterodine

antibioticse.g.erythromycin,rifampicin

anti-fungalmedicinee.g.ketoconazole

anti-depressantse.g.fluoxetine

anticonvulsantse.g.phenytoin,carbamazepine

medicationforaheartconditione.g.quinidine,beta-blockers

(propanololandatenolol)

musclerelaxantse.g.diazepam,succinylcholine

generalanaesthetic

medicinesobtainedwithoutaprescriptione.g.herbalremedies

Ifyouaregoingtohaveanoperationthatrequiresyoutohaveageneral

anaesthetic,youshouldtellyourdoctorandtheanaesthetistthatyou

aretakingARICEPT.Thisisbecauseyourmedicinemayaffectthe

amountofanaestheticneeded.

ARICEPTcanbeusedinpatientswithkidneydiseaseormildto

moderateliverdisease.Tellyourdoctorfirstifyouhavekidneyorliver

disease.PatientswithsevereliverdiseaseshouldnottakeARICEPT.

Tellyourdoctororpharmacistthenameofyourcaregiver.Your

caregiverwillhelpyoutotakeyourmedicineasitisprescribed.

TakingARICEPTwithfoodanddrink

FoodwillnotinfluencetheeffectofARICEPT.

ARICEPTshouldnotbetakenwithalcoholbecausealcoholmaychange

itseffect.

Pregnancyandbreast-feeding

ARICEPTmustnotbeusedwhilebreastfeeding.

Ifyouarepregnant,orthinkyoumightbepregnant,askyourdoctorfor

advicebeforetakinganymedicine.

Drivingandusingmachines

Alzheimer'sdiseasemayimpair yourabilitytodriveoroperate

machineryandyoumustnotperformtheseactivitiesunlessyourdoctor

tellsyouthatitissafetodoso.

Also,yourmedicinecancausetiredness,dizzinessandmusclecramp.If

youexperienceanyoftheseeffectsyoumustnotdriveoroperate

machinery.

ImportantinformationaboutsomeoftheingredientsofARICEPT

Thismedicinecontainslactose.Ifyouhavebeentoldbyyourdoctorthat

youhaveanintolerancetosomesugars,youshouldcontactyourdoctor

beforetakingARICEPT.

3. HOWTOTAKEARICEPT

HowmuchARICEPTshouldyoutake?

Usually,youwillstartbytaking5mg(onewhitetablet)everynight.After

onemonth,yourdoctormaytellyoutotake10mg(oneyellowtablet)

everynight.

SwallowyourARICEPTtabletwithadrinkofwaterbeforeyougotobed

atnight.

Thetabletstrengthyouwilltakemaychangedependingonthelengthof

timeyouhavebeentakingthemedicineandonwhatyourdoctor

recommends.Themaximumrecommendeddoseis10mgeachnight.

Alwaysfollowyourdoctor's,orpharmacist'sadviceabouthowandwhen

totakeyourmedicine.

Donotalterthedoseyourselfwithoutyourdoctor'sadvice.

Moreinformationcanbe foundonthebackofthe leaflet

ForhowlongshouldyoutakeARICEPT?

Yourdoctororpharmacistwilladviseyouonhowlongyoushould

continuetotakeyourtablets.Youwillneedtoseeyourdoctorfromtime

totimetoreviewyourtreatmentandassessyoursymptoms.

IfyoustoptakingARICEPT

Donotstoptakingthetabletsunlesstoldtodosobyyourdoctor.Ifyou

stoptakingARICEPT,thebenefitsofyourtreatmentwillgraduallyfade

away.

IfyoutakemoreARICEPTthanyoushould

DONOTtakemorethanonetableteachday.Callyourdoctor

immediatelyifyoutakemorethanyoushould.Ifyoucannotcontactyour

doctor,contactthelocalhospitalAccidentandEmergencydepartmentat

once.Alwaystakethetabletsandthecartonwithyoutothehospitalso

thatthedoctorknowswhathasbeentaken.Symptomsofoverdosing

includefeelingandbeingsick,drooling,sweating,slowheartrate,low

bloodpressure(light-headednessordizzinesswhenstanding),

breathingproblems,losingconsciousnessandseizures(fits)or

convulsions.

IfyouforgettotakeARICEPT

Ifyouforgettotakeatablet,justtakeonetabletthefollowingdayatthe

usualtime.Donottakeadoubledosetomakeupforaforgottentablet.

Ifyouforgettotakeyourmedicineformorethanoneweek,callyour

doctorbeforetakinganymoremedicine.

4. POSSIBLESIDEEFFECTS

Likeallmedicines,ARICEPTcancausesideeffects,althoughnot

everybodygetsthem.

Thefollowingsideeffectshavebeenreportedbypeopletaking

ARICEPT.

Tellyourdoctorifyouhaveanyoftheseeffectswhileyouare

takingARICEPT.

Pil465-108-1-2-3362

Serious side effects:

Youmusttellyourdoctorimmediatelyifyounoticetheseseriousside

effectsmentioned.Youmayneedurgentmedicaltreatment.

Liverdamagee.g.hepatitis.Thesymptomsofhepatitisarefeeling

orbeingsick,lossofappetite,feelinggenerallyunwell,fever,

itching,yellowingoftheskinandeyes,anddarkcolouredurine

(probablyaffectingfewerthan1in10,000)

Stomachorduodenalulcers.Thesymptomsofulcersarestomach

painanddiscomfort(indigestion)feltbetweenthenavelandthe

breastbone(affects1to10usersin1,000)

Bleedinginthestomachorintestines.Thismaycauseyoutopass

blacktarlikestoolsorvisiblebloodfromtherectum(affects1to10

usersin1,000)

Seizures(fits)orconvulsions(affects1to10usersin1,000)

Tellyourdoctorimmediatelyifyounoticefeverwithmuscle

stiffness,sweatingoraloweredlevelofconsciousness(adisorder

called“NeurolepticMalignantSyndrome”,asurgentmedical

treatmentmaybeneeded.

Verycommonsideeffects

(affects1userin10):

diarrhoea

feelingorbeingsick

headaches

Commonsideeffects

(affects1to10usersin100):

musclecramp

tiredness

difficultyinsleeping(insomnia)

thecommoncold

lossofappetite

hallucinations(seeingorhearingthingsthatarenotreallythere)

unusualdreamsincludingnightmares

agitation

aggressivebehaviour

fainting

dizziness

stomachfeelinguncomfortable

rash

itching

passingurineuncontrollably

pain

accidents(patientsmaybemorepronetofallsandaccidental

injury)

Uncommonsideeffects

(affects1to10usersin1,000):

slowheartbeat

Rareside effects(affects1to10users in10,000):

stiffness,shakingoruncontrollablemovementespeciallyoftheface

andtonguebutalsoofthelimbs

Ifanyofthe side effectsgetsserious,orifyounoticeanyside

effectsnotlistedinthisleaflet,pleasetellyourdoctoror

pharmacist.

5. HOWTOSTOREARICEPT

DONOTuseARICEPTtabletsaftertheexpirydatethatisprintedonthe

label.Theexpirydatereferstothelastdayofthatmonth.

Donotstorethismedicineabove30°C.Keepoutofthereachandsight

ofchildren.

Ifyourdoctortellsyoutostoptakingyourmedicine,youshouldreturn

anyyouhavenotusedtoyourpharmacist.

Medicinesshouldbedisposedofviawastewaterorhouseholdwaste.

Askyourpharmacisthowtodisposeofmedicinesnolongerrequired.

Thesemeasureswillhelptoprotecttheenvironment.

6. FURTHERINFORMATION

WHATdoARICEPTTabletscontain?

Theactivesubstanceisdonepezilhydrochloride.The5mgtablet

contains5mgofdonepezilhydrochlorideandthe10mgtabletcontains

10mgofdonepezilhydrochloride.

Theotheringredientsare:

Lactosemonohydrate

Maizestarch

Microcrystallinecellulose

Hyprolose

MagnesiumStearate

FilmCoating:

Talc

Macrogol

Hypromellose

Titaniumdioxide(E171),

Yellowironoxide(E172)(10mgtabletsonly).

WhatdoARICEPTtabletslooklike?

Aricept5mgTabletsarewhite,round,biconvextabletswith'ARICEPT'

ononesideand'5'ontheothersideorwhiteround,biconvextablets.

Aricept10mgTabletsareyellow,round,biconvextabletswith

'ARICEPT'ononesideand'10'ontheothersideoryellow,round,

biconvextablets.

Packsize:AriceptTabletsareavailableinblisterpacksof28tablets.

ProductprocuredfromwithintheEUandrepackagedbythe

ParallelProductAuthorisationHolder:PCOManufacturing,Unit10,

Ashbourne,BusinessPark,Rath,Ashbourne,Co.Meath.

MANUFACTURER

Aricept5mgand10mgTabletsaremanufacturedbyPFIZERPGM,

ZoneIndustrielle29,routedesindustries,37530PocésurCisse,France

orEisaiManufacturingLimited,EuropeanKnowledgeCentre,Mosquito

Way,Hatfield,Herts,AL109SN,UnitedKingdomorPfizerLimited,

Sandwich,Kent,UK.

PARALLELPRODUCTAUTHORISATIONNUMBERS:

PPA465/108/1-2

Ariceptisaregisteredtrademarkof EisaiR&DManagementCo.,Ltd.

AsthedaysoftheweekarenotlistedontheblisterfoilinEnglish,

pleaseusethefollowingtableshouldyourequireatranslation:

English Spanish French Greek

Mon(Monday) Lu(Lunes) Lun

(Lundi) Δ(Δευτέρα)

Tue(Tuesday) Ma

(Martes) Mar

(Mardi) Τρ(Τρίτη)

Wed

(Wednesday) Mie

(Miércoles) Mer

(Mercredi) Τε(Τετάρτη)

Thu

(Thursday) Ju

(Jueves) Jeu(Jeudi) Πέ(Πέμπτη)

Fri(Friday) Vie

(Viernes) Ven

(Vendredi) Πα

(Παρασκευή)

Sat(Saturday) Sa

(Sábado) Sam

(Samedi) Σ(Σάββατο)

Sun(Sunday) Do

(Domingo) Dim

(Dimanche) Κ(ΗΚυριακή)

DateofLeafletPreparationbyPCOManufacturing:03/2013

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ARICEPT10mgfilmcoatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgdonepezilhydrochloride.

Excipientwithknowneffect:lactosemonohydrate

Forthefulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromFranceandUK:

Yellowround,biconvextabletsembossed‘ARICEPT’ononesideand‘10’ontheotherside.

ProductimportedfromItaly:

Yellowround,biconvextabletsembossed‘ARICEPT’ononesideand‘10’ontheothersideORyellow,round

biconvextabletswithnomarkings.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ARICEPTtabletsareindicatedforthesymptomatictreatmentofmildtomoderatelysevereAlzheimer’sdementia.

4.2Posologyandmethodofadministration

Adults/Elderly:

Treatmentisinitiatedat5mg/day(once-a-daydosing).ARICEPTshouldbetakenorally,intheevening,justpriorto

retiring.The5mg/daydoseshouldbemaintainedforatleastonemonthinordertoallowtheearliestclinicalresponses

totreatmenttobeassessedandtoallowsteady-stateconcentrationsofdonepezilhydrochloridetobeachieved.

Followingaone-monthclinicalassessmentoftreatmentat5mg/day,thedoseofARICEPTcanbeincreasedto10

mg/day(once-a-daydosing).

Themaximumrecommendeddailydoseis10mg.Dosesgreaterthan10mg/dayhavenotbeenstudiedinclinicaltrials.

TreatmentshouldbeinitiatedandsupervisedbyaphysicianexperiencedinthediagnosisandtreatmentofAlzheimer’s

dementia.Diagnosisshouldbemadeaccordingtoacceptedguidelines(e.g.DSMIV,ICD10).Therapywithdonepezil

shouldonlybestartedifacaregiverisavailablewhowillregularlymonitordrugintakeforthepatient.Maintenance

treatmentcanbecontinuedforaslongasatherapeuticbenefitforthepatientexists.

Therefore,theclinicalbenefitofdonepezilshouldbereassessedonaregularbasis.Discontinuationshouldbe

consideredwhenevidenceofatherapeuticeffectisnolongerpresent.Individualresponsetodonepezilcannotbe

predicted.

Upondiscontinuationoftreatment,agradualabatementofthebeneficialeffectsofARICEPTisseen.

Renalandhepaticimpairment:

Asimilardoseschedulecanbefollowedforpatientswithrenalimpairment,asclearanceofdonepezilhydrochlorideis

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 1

Duetopossibleincreasedexposureinmildtomoderatehepaticimpairment(seesection5.2),doseescalationshouldbe

performedaccordingtoindividualtolerability.Therearenodataforpatientswithseverehepaticimpairment.

Children:

ARICEPTisnotrecommendedforuseinchildren.

4.3Contraindications

ARICEPTiscontraindicatedinpatientswithaknownhypersensitivitytodonepezilhydrochloride,piperidine

derivatives,ortoanyexcipientsusedintheformulation.

4.4Specialwarningsandprecautionsforuse

TheuseofARICEPTinpatientswithsevereAlzheimer’sdementia,othertypesofdementiaorothertypesofmemory

impairment(e.g.,age-relatedcognitivedecline),hasnotbeeninvestigated.

Anaesthesia:ARICEPT,asacholinesteraseinhibitor,islikelytoexaggeratesuccinylcholine-typemusclerelaxation

duringanaesthesia.

CardiovascularConditions:Becauseoftheirpharmacologicalaction,cholinesteraseinhibitorsmayhavevagotonic

effectsonheartrate(e.g.,bradycardia).Thepotentialforthisactionmaybeparticularlyimportanttopatientswith"sick

sinussyndrome"orothersupraventricularcardiacconductionconditions,suchassinoatrialoratrioventricularblock.

Therehavebeenreportsofsyncopeandseizures.Ininvestigatingsuchpatientsthepossibilityofheartblockorlong

sinusalpausesshouldbeconsidered.

GastrointestinalConditions:Patientsatincreasedriskfordevelopingulcers,e.g.,thosewithahistoryofulcerdisease

orthosereceivingconcurrentnonsteroidalanti-inflammatorydrugs(NSAIDs),shouldbemonitoredforsymptoms.

However,theclinicalstudieswithARICEPTshowednoincrease,relativetoplacebo,intheincidenceofeitherpeptic

ulcerdiseaseorgastrointestinalbleeding.

Genitourinary:AlthoughnotobservedinclinicaltrialsofARICEPT,cholinomimeticsmaycausebladderoutflow

obstruction.

NeurologicalConditions:Seizures:Cholinomimeticsarebelievedtohavesomepotentialtocausegeneralised

convulsions.However,seizureactivitymayalsobeamanifestationofAlzheimer'sDisease.

Cholinomimeticsmayhavethepotentialtoexacerbateorinduceextrapyramidalsymptoms.

NeurolepticMalignantSyndrome(NMS):NMS,apotentiallylife-threateningconditioncharacterisedbyhyperthermia,

musclerigidity,autonomicinstability,alteredconsciousnessandelevatedserumcreatinephosphokinaselevels,has

beenreportedtooccurveryrarelyinassociationwithdonepezil,particularlyinpatientsalsoreceivingconcomitant

antipsychotics.Additionalsignsmayincludemyoglobinuria(rhabdomyolysis)andacuterenalfailure.Ifapatient

developssignsandsymptomsindicativeofNMS,orpresentswithunexplainedhighfeverwithoutadditionalclinical

manifestationsofNMS,treatmentshouldbediscontinued.

PulmonaryConditions:Becauseoftheircholinomimeticactions,cholinesteraseinhibitorsshouldbeprescribedwith

caretopatientswithahistoryofasthmaorobstructivepulmonarydisease.

TheadministrationofARICEPTconcomitantlywithotherinhibitorsofacetylcholinesterase,agonistsorantagonistsof

thecholinergicsystemshouldbeavoided.

SevereHepaticImpairment:Therearenodataforpatientswithseverehepaticimpairment.

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 2

Threeclinicaltrialsof6monthsdurationwereconductedstudyingindividualsmeetingtheNINDS-AIRENcriteriafor

probableorpossiblevasculardementia(VaD).TheNINDS-AIRENcriteriaaredesignedtoidentifypatientswhose

dementiaappearstobeduesolelytovascularcausesandtoexcludepatientswithAlzheimer’sdisease.

Inthefirststudy,themortalityrateswere2/198(1.0%)ondonepezilhydrochloride5mg,5/206(2.4%)ondonepezil

hydrochloride10mgand7/199(3.5%)onplacebo.Inthesecondstudy,themortalityrateswere4/208(1.9%)on

donepezilhydrochloride5mg,3/215(1.4%)ondonepezilhydrochloride10mgand1/193(0.5%)onplacebo.Inthe

thirdstudy,themortalityrateswere11/648(1.7%)ondonepezilhydrochloride5mgand0/326(0%)onplacebo.The

mortalityrateforthethreeVaDstudiescombinedinthedonepezilhydrochloridegroup(1.7%)wasnumericallyhigher

thanintheplacebogroup(1.1%),however,thisdifferencewasnotstatisticallysignificant.Themajorityofdeathsin

patientstakingeitherdonepezilhydrochlorideorplaceboappeartoresultfromvariousvascularrelatedcauses,which

couldbeexpectedinthiselderlypopulationwithunderlyingvasculardisease.Ananalysisofallseriousnonfataland

fatalvasculareventsshowednodifferenceintherateofoccurrenceinthedonepezilhydrochloridegrouprelativeto

placebo.

InpooledAlzheimer’sdiseasestudies(n=4146),andwhentheseAlzheimer’sdiseasestudieswerepooledwithother

dementiastudiesincludingthevasculardementiastudies(totaln=6888),themortalityrateintheplacebogroups

numericallyexceededthatinthedonepezilhydrochloridegroups.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Donepezilhydrochlorideand/oranyofitsmetabolitesdonotinhibitthemetabolismoftheophylline,warfarin,

cimetidineordigoxininhumans.Themetabolismofdonepezilhydrochlorideisnotaffectedbyconcurrent

administrationofdigoxinorcimetidine.InvitrostudieshaveshownthatthecytochromeP450isoenzymes3A4andto

aminorextent2D6areinvolvedinthemetabolismofdonepezil.Druginteractionstudiesperformedinvitroshowthat

ketoconazoleandquinidine,inhibitorsofCYP3A4and2D6respectively,inhibitdonepezilmetabolism.Thereforethese

andotherCYP3A4inhibitors,suchasitraconazoleanderythromycin,andCYP2D6inhibitors,suchasfluoxetinecould

inhibitthemetabolismofdonepezil.Inastudyinhealthyvolunteers,ketoconazoleincreasedmeandonepezil

concentrationsbyabout30%.

Enzymeinducers,suchasrifampicin,phenytoin,carbamazepineandalcoholmayreducethelevelsofdonepezil.

Sincethemagnitudeofaninhibitingorinducingeffectisunknown,suchdrugcombinationsshouldbeusedwithcare.

Donepezilhydrochloridehasthepotentialtointerferewithmedicationshavinganticholinergicactivity.Thereisalso

thepotentialforsynergisticactivitywithconcomitanttreatmentinvolvingmedicationssuchassuccinylcholine,other

neuro-muscularblockingagentsorcholinergicagonistsorbetablockingagentswhichhaveeffectsoncardiac

conduction.

4.6Fertility,pregnancyandlactation

Pregnancy:

Therearenoadequatedatafromtheuseofdonepezilinpregnantwomen.

Studiesinanimalshavenotshownteratogeniceffectbuthaveshownperiandpostnataltoxicity(seesection5.3

preclinicalsafetydata).Thepotentialriskforhumansisunknown.

Ariceptshouldnotbeusedduringpregnancyunlessclearlynecessary.

Lactation:

Donepezilisexcretedinthemilkofrats.Itisnotknownwhetherdonepezilhydrochlorideisexcretedinhumanbreast

milkandtherearenostudiesinlactatingwomen.Therefore,womenondonepezilshouldnotbreastfeed.

4.7Effectsonabilitytodriveandusemachines

Donepezilhasminorormoderateinfluenceontheabilitytodriveandusemachines.

Dementiamaycauseimpairmentofdrivingperformanceorcompromisetheabilitytousemachinery.

Furthermore,donepezilcaninducefatigue,dizzinessandmusclecramps,mainlywheninitiatingorincreasingthedose.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 3

complexmachines.

4.8Undesirableeffects

Themostcommonadverseeventsarediarrhoea,musclecramps,fatigue,nausea,vomitingandinsomnia.Adverse

reactionsreportedasmorethananisolatedcasearelistedbelow,bysystemorganclassandbyfrequency.Frequencies

aredefinedas:verycommon(1/10)common(1/100,<1/10),uncommon(1/1,000,<1/100),andrare(1/10,000,

<1/1,000);veryrare(<1/10000)andnotknown(cannotbeestimatedfromavailabledata).

SystemOrgan

Class Very

Common Common Uncommon Rare Very

Rare

Infectionsand

infestations Commoncold

Metabolismand

nutritiondisorders Anorexia

Psychiatric

disorders Hallucinations**

Agitation**

Aggressive

behaviour**

Abnormal

dreamsand

nightmares**

Nervoussystem

disorders Syncope*

Dizziness

Insomnia Seizure* Extrapyrimidal

symptoms Neuroleptic

malignant

syndrome

Cardiacdisorders Bradycardia Sino-atrialblock

Atrioventricular

block

Gastrointestinal

disorders Diarrhoea

Nausea Vomiting

Abdominal

disturbance Gastrointestinal

haemorrhage

Gastricand

duodenalulcers

Hepato-biliary

disorders Liverdysfunction

including

hepatitis***

Skinand

subcutaneous

tissuedisorders Rash

Pruritis

Musculoskeletal,

connectivetissue

andbonedisorders Muscle

cramps

Renalandurinary

disorders Urinary

incontinence

Generaldisorders

andadministration

site Headache Fatigue

Pain

Investigations Minorincreasein

serum

concentrationof

musclecreatine

kinase

Injuryand

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 4

*Ininvestigatingpatientsforsyncopeorseizurethepossibilityofheartblockorlongsinusalpausesshouldbe

considered(seesection4.4)

**Reportsofhallucinations,abnormaldreams,nightmares,agitationandaggressivebehaviourhaveresolvedondose

reductionordiscontinuationoftreatment.

***Incasesofunexplainedliverdysfunction,withdrawalofARICEPTshouldbeconsidered.

4.9Overdose

Theestimatedmedianlethaldoseofdonepezilhydrochloridefollowingadministrationofasingleoraldoseinmiceand

ratsis45and32mg/kg,respectively,orapproximately225and160timesthemaximumrecommendedhumandoseof

10mgperday.Dose-relatedsignsofcholinergicstimulationwereobservedinanimalsandincludedreduced

spontaneousmovement,proneposition,staggeringgait,lacrimation,clonicconvulsions,depressedrespiration,

salivation,miosis,fasciculationandlowerbodysurfacetemperature.Overdosagewithcholinesteraseinhibitorscan

resultincholinergiccrisischaracterizedbyseverenausea,vomiting,salivation,sweating,bradycardia,hypotension,

respiratorydepression,collapseandconvulsions.Increasingmuscleweaknessisapossibilityandmayresultindeathif

respiratorymusclesareinvolved.Asinanycaseofoverdose,generalsupportivemeasuresshouldbeutilised.Tertiary

anticholinergicssuchasatropinemaybeusedasanantidoteforARICEPToverdosage.Intravenousatropinesulphate

titratedtoeffectisrecommended:aninitialdoseof1.0to2.0mgIVwithsubsequentdosesbaseduponclinical

response.Atypicalresponsesinbloodpressureandheartratehavebeenreportedwithothercholinomimeticswhenco-

administeredwithquaternaryanticholinergicssuchasglycopyrrolate.Itisnotknownwhetherdonepezilhydrochloride

and/oritsmetabolitescanberemovedbydialysis(hemodialysis,peritonealdialysis,orhemofiltration).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Thepharmacotherapeuticgroup:anti-dementiadrugs;anticholinesterase;ATC-codeN06DA02.

Donepezilhydrochlorideisaspecificandreversibleinhibitorofacetylcholinesterase,thepredominantcholinesterasein

thebrain.Donepezilhydrochlorideisinvitroover1000timesmorepotentaninhibitorofthisenzymethanof

butyrylcholinesterase,anenzymethatispresentmainlyoutsidethecentralnervoussystem.

Alzheimer’sDementia

InpatientswithAlzheimer'sDementiaparticipatinginclinicaltrials,administrationofsingledailydosesof5mgor10

mgofARICEPTproducedsteady-stateinhibitionofacetylcholinesteraseactivity(measuredinerythrocytemembranes)

of63.6%and77.3%,respectivelywhenmeasuredpostdose.Theinhibitionofacetylcholinesterase(AChE)inred

bloodcellsbydonepezilhydrochloridehasbeenshowntocorrelatetochangesinADAS-cog,asensitivescalewhich

examinesselectedaspectsofcognition.Thepotentialfordonepezilhydrochloridetoalterthecourseoftheunderlying

neuropathologyhasnotbeenstudied.ThusAriceptcannotbeconsideredtohaveanyeffectontheprogressofthe

disease.

EfficacyoftreatmentwithAricepthasbeeninvestigatedinfourplacebo-controlledtrials,2trialsof6monthduration

and2trialsof1-yearduration.

Inthe6monthsclinicaltrial,ananalysiswasdoneattheconclusionofdonepeziltreatmentusingacombinationof

threeefficacycriteria:theADAS-Cog(ameasureofcognitiveperformance),theClinicianInterviewBasedImpression

ofChangewithCaregiverInput(ameasureofglobalfunction)andtheActivitiesofDailyLivingSubscaleofthe

ClinicalDementiaRatingScale(ameasureofcapabilitiesincommunityaffairs,homeandhobbiesandpersonalcare).

Patientswhofulfilledthecriterialistedbelowwereconsideredtreatmentresponders.

Response=ImprovementofADAS-Cogofatleast4points

NodeteriorationofCIBIC+

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 5

*p<0.05

**p<0.01

Ariceptproducedadose-dependentstatisticallysignificantincreaseinthepercentageofpatientswhowerejudged

treatmentresponders.

5.2Pharmacokineticproperties

Absorption:Maximumplasmalevelsarereachedapproximately3to4hoursafteroraladministration.Plasma

concentrationsandareaunderthecurveriseinproportiontothedose.Theterminaldispositionhalf-lifeis

approximately70hours,thus,administrationofmultiplesingle-dailydosesresultsingradualapproachtosteady-state.

Approximatesteady-stateisachievedwithin3weeksafterinitiationoftherapy.Onceatsteady-state,plasmadonepezil

hydrochlorideconcentrationsandtherelatedpharmacodynamicactivityshowlittlevariabilityoverthecourseofthe

day.Fooddidnotaffecttheabsorptionofdonepezilhydrochloride.

Distribution:Donepezilhydrochlorideisapproximately95%boundtohumanplasmaproteins.Theplasmaprotein

bindingoftheactivemetabolite6-O-desmethyldonepezilinisnotknown.Thedistributionofdonepezilhydrochloride

invariousbodytissueshasnotbeendefinitivelystudied.However,inamassbalancestudyconductedinhealthymale

volunteers,240hoursaftertheadministrationofasingle5mgdoseof C-labeleddonepezilhydrochloride,

approximately28%ofthelabelremainedunrecovered.Thissuggeststhatdonepezilhydrochlorideand/orits

metabolitesmaypersistinthebodyformorethan10days.

Metabolism/Excretion:Donepezilhydrochlorideisbothexcretedintheurineintactandmetabolisedbythecytochrome

P450systemtomultiplemetabolites,notallofwhichhavebeenidentified.Followingadministrationofasingle5mg

doseof C-labeleddonepezilhydrochloride,plasmaradioactivity,expressedasapercentoftheadministereddose,

waspresentprimarilyasintactdonepezilhydrochloride(30%),6-O-desmethyldonepezil(11%-onlymetabolitethat

exhibitsactivitysimilartodonepezilhydrochloride),donepezil-cis-N-oxide(9%),5-O-desmethyldonepezil(7%)and

theglucuronideconjugateof5-O-desmethyldonepezil(3%).Approximately57%ofthetotaladministered

radioactivitywasrecoveredfromtheurine(17%asunchangeddonepezil),and14.5%wasrecoveredfromthefaeces,

suggestingbiotransformationandurinaryexcretionastheprimaryroutesofelimination.

Thereisnoevidencetosuggestenterohepaticrecirculationofdonepezilhydrochlorideand/oranyofitsmetabolites.

Plasmadonepezilconcentrationsdeclinewithahalf-lifeofapproximately70hours.

Sex,raceandsmokinghistoryhavenoclinicallysignificantinfluenceonplasmaconcentrationsofdonepezil

hydrochloride.Thepharmacokineticsofdonepezilhasnotbeenformallystudiedinhealthyelderlysubjectsorin

Alzheimer’sorvasculardementiapatients.Howevermeanplasmalevelsinpatientscloselyagreedwiththoseofyoung

healthyvolunteers.

Patientswithmildtomoderatehepaticimpairmenthadincreaseddonepezilsteadystateconcentrations;meanAUCby

%Response

IntenttoTreat Evaluable

Population Population

n=365 n=352

PlaceboGroup 10% 10%

Aricept 5-mg

Group 18%* 18%*

Aricept 10-mg 21%* 22%**

Group

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 6

5.3Preclinicalsafetydata

Extensivetestinginexperimentalanimalshasdemonstratedthatthiscompoundcausesfeweffectsotherthanthe

intendedpharmacologicaleffectsconsistentwithitsactionasacholinergicstimulator(seesection4.9).Donepezilis

notmutagenicinbacterialandmammaliancellmutationassays.Someclastogeniceffectswereobservedinvitroat

concentrationsovertlytoxictothecellsandmorethan3000timesthesteady-stateplasmaconcentrations.No

clastogenicorothergenotoxiceffectswereobservedinthemousemicronucleusmodelinvivo.Therewasnoevidence

ofoncogenicpotentialinlongtermcarcinogenicitystudiesineitherratsormice.

Donepezilhydrochloridehadnoeffectonfertilityinrats,andwasnotteratogenicinratsorrabbits,buthadaslight

effectonstillbirthsandearlypupsurvivalwhenadministeredtopregnantratsat50timesthehumandose(seesection

4.6).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maizestarch

Microcrystallinecellulose

Hyprolose

MagnesiumStearate

Filmcoating

Talc

Macrogol

Hypromellose

Titaniumdioxide(E171)

Yellowironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelflifeexpirydateforthisproductshallbethedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

Blisterpackcontaining28tabletsinanover-labelledoutercarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfromsuch

medicinalproductandotherhandlingoftheproduct

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 7

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/108/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorizations:19September2003

Dateoflastrenewal:19September2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/05/2014 CRN 2144007 page number: 8

Similar products

Search alerts related to this product

View documents history

Share this information