CLOPIXOL 25MG FILM-COATED TABLETS

Main information

  • Trade name:
  • CLOPIXOL 25MG FILM-COATED TABLETS
  • Dosage:
  • 25 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLOPIXOL 25MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0115/005/004
  • Authorization date:
  • 01-11-1982
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Clopixol25mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains25mgzuclopenthixol(as29.55mgzuclopenthixoldihydrochloride).

Excipients:Eachtabletcontains22mglactosemonohydrateand0.96mghydrogenatedcastoroil.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedTablet(tablet).

Round,biconvexred-brown,film-coatedtablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thetreatmentofpsychoses,especiallyschizophrenia,particularlyinpatientswhoareagitatedoraggressive.

4.2Posologyandmethodofadministration

Routeofadministration

Oral.

Adults

Theusualdoseis20-30mg/day,increasingasnecessarytoamaximumof150mg/day,individeddoses.Theusual

maintenancedoseinchronicschizophreniais20-50mg/dayindivideddoses.Lowerdosesmaybeappropriate

dependingonindividualpatientresponse.

Elderlypatients

Elderlypatientsshouldreceivedosagesinthelowerendofthedosagerange.

Children

Notrecommended.

Reducedrenalfunction

Clopixolcanbegiveninusualdosestopatientswithreducedrenalfunction.

Reducedhepaticfunction

Dosereduction(relativetothedegreeofhepaticimpairment)shouldbeconsidered.Ifpossible,whereassayfacilities

existdosageshouldbeadjustedaccordingtoserumlevels.

Methodofadministration

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4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients(seesection6.1)

Circulatorycollapse

Depressedlevelofconsiousnessduetoanycause(e.g.intoxicationwithalcohol,barbituratesoropiates)

Coma

Useinchildren

Useinsenileconfusionalstates

4.4Specialwarningsandprecautionsforuse

Extrapyramidalreactionsintheformofacutedystonias(includingoculogyriccrisis),parkinsonianrigidity,tremor,

akinesiaandakathisiahavebeenreportedandmayoccurevenatlowerdosageinsusceptiblepatients.Sucheffects

wouldusuallybeencounteredearlyintreatment,butdelayedreactionsmayalsooccur.Antiparkinsonagentsshould

notbeprescribedroutinelybecauseofthepossibleriskofprecipitatingtoxic-confusionalstates,impairingefficacyor

causinganticholinergicside-effects.Theyshouldonlybegivenifrequiredandtheirrequirementreassessedatregular

intervals.

Tardivedyskinesiacanoccurwithneuroleptictreatment.Itismorecommonathighdosesforprolongedperiodsbut

hasbeenreportedatlowerdosageforshortperiods.Theriskseemstobegreaterintheelderly,especiallyfemales.It

hasbeenreportedthatfinevermicularmovementsofthetongueareanearlysign.Ithasbeenobservedoccasionallyin

patientsreceivingzuclopenthixol.Theconcurrentuseofanticholinergicantiparkinsondrugsmayexacerbatethis

effect.Thepotentialirreversibilityandseriousness,aswellastheunpredictabilityofthesyndrome,requiresespecially

carefulassessmentoftheriskversusbenefit,andthelowestpossibledosageanddurationoftreatmentconsistentwith

therapeuticefficacy.Short-liveddyskinesiamayoccurafterabruptwithdrawalofthedrug.

Thehormonaleffectsofantipsychoticneurolepticdrugsincludehyperprolactinaemia,whichmaybeassociatedwith

galactorrhoea,gynaecomastia,oligomenorrhoeaoramenorrhoea.Sexualfunction,includingerectionandejaculation

maybeimpaired;butincreasedlibidohasalsobeenreported.

Thepossibilityofdevelopmentofneurolepticmalignantsyndromeexistswithanyneuroleptic.Theriskispossibly

greaterwiththemorepotentagents.Patientswithpre-existingorganicbrainsyndrome,mentalretardationandopiate

andalcoholabuseareover-representedamongfatalcases.RarecasesreportedasNMShavealsobeenreceivedin

associationwithzuclopenthixol.ClinicalmanifestationsofNMSarehyperpyrexia,musclerigidity,alteredmental

status,andevidenceofautonomicinstability(irregularpulseorbloodpressure,tachycardia,sweatingandcardiac

arrhythmia).Additionalsignsmayincludeelevatedcreatinine,phosphokinase,myoglubinuria( rhabdomyolysis ),and

acuterenalfailure.IfapatientdevelopssignsandsymptomsindicativeofNMSorpresentswithunexplainedhigh

feverwithoutadditionalclinicalmanifestationsofNMS,allneurolepticmedication,includingzuclopenthixolmustbe

discontinued.Symptomsmaypersistformorethanaweekafteroralneurolepticsarediscontinuedandsomewhat

longerwhenassociatedwiththedepotformsofthedrugs.

Likeotherantipsychotics,zuclopenthixolshouldbeusedwithcautioninpatientswithorganicbrainsyndrome,

convulsionandadvancedhepaticdisease.

Zuclopenthixolshouldalsobeusedwithcautioninpatientswhoareexcitableoroveractive,inpatientswithconvulsive

disorders,severeatherosclerosis,severerespiratorydiseaseandParkinson’sdisease.Careshouldalsobetakenin

patientswithpersonalorfamilyhistoryofnarrowangleglaucoma.

AdministrationtopatientswithParkinsonismorextrapyramidaldiseasemayinduceanexacerbationofthatdisorder.

Asdescribedforotherpsychotropicszuclopenthixolmaymodifyinsulinandglucoseresponsescallingforadjustment

oftheantidiabetictherapyindiabeticpatients.

Thegeneralcautionforuseofneurolepticsinhypothyroidism,thyrotoxicosis,myastheniagravisorprostatic

hypertrophyshouldbeobserved,butthereisnoevidencetosuggestthatzuclopenthixolgivesrisetoanyparticular

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Patientsonlong-termtherapy,particularlyonhighdoses,shouldbemonitoredcarefullyandevaluatedperiodicallyto

decidewhetherthemaintenancedosagecanbelowered.

Aswithotherdrugsbelongingtothetherapeuticclassofantipsychotics,zuclopenthixolmaycauseQTprolongation.

PersistentlyprolongedQTintervalsmayincreasetheriskofmalignantarrhythmias.Therefore,zuclopenthixolshould

beusedwithcautioninsusceptibleindividuals(withhypokalemia,hypomagnesiaorfamilyhistoryofQT

prolongation)andinpatientswithahistoryofcardiovasculardisorders,e.g.QTprolongation,significantbradycardia

< 50beatsperminute),arecentacutemyocardialinfarction,uncompensatedheartfailure,orcardiacarrhythmia.

Concomitanttreatmentwithotherantipsychoticsshouldbeavoided(seesection4.5).

Casesofvenousthromboembolism(VTE)havebeenreportedwithantipsychoticdrugs.Sincepatientstreatedwith

antipsychoticsoftenpresentwithacquiredriskfactorsforVTE,allpossibleriskfactorsforVTEshouldbeidentified

beforeandduringtreatmentwithClopixolandpreventivemeasuresundertaken.

Elderly

Careshouldalsobetakenintheelderly,particularlyiffrailoratriskofhypothermia,sedation,hypotensionor

confusion.

Cerebrovascular

Anapproximately3-foldincreasedriskofcerebrovascularadverseeventshavebeenseeninrandomisedplacebo

controlledclinicaltrialsinthedementiapopulationwithsomeatypicalantipsychotics.Themechanismforthis

increasedriskisnotknown.Anincreasedriskcannotbeexcludedforotherantipsychoticsorotherpatientpopulations.

Zuclopenthixolshouldbeusedwithcautioninpatientswithriskfactorsforstroke.

IncreasedMortalityinElderlypeoplewithDementia

Datafromtwolargeobservationalstudiesshowedthatelderlypeoplewithdementiawhoaretreatedwith

antipsychoticsareatasmallincreasedriskofdeathcomparedwiththosewhoarenottreated.Thereareinsufficient

datatogiveafirmestimateoftheprecisemagnitudeoftheriskandthecauseoftheincreasedriskisnotknown.

Clopixolisnotlicensedforthetreatmentofdementia-relatedbehaviouraldisturbances.

Excipients

Thetabletscontainlactosemonohydrate.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnotreceivethismedicine.

Thetabletsalsocontainhydrogenatedcastoroilwhichmaycausestomachupsetanddiarrhoea.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationsrequiringprecautionsforuse

Zuclopenthixolmayenhancethesedativeeffectofalcohol,andtheeffectsofbarbituratesandotherCNSdepressants

andmaypotentiatetheeffectsofgeneralanaesthetics.

Zuclopenthixoldihydrochloridemayreducetheeffectoflevodopaandtheeffectofadrenergicdrugs.

Concomitantuseofmetoclopramideandpiperazineincreasestheriskofextrapyramidaldisorder.

Neurolepticsmayincreaseorreducetheeffectofantihypertensivedrugs,theantihypertensiveeffectofguanethidine

andsimilaractingcompoundsisreduced.

Concomitantuseofneurolepticsandlithiumincreasestheriskofneurotoxicity.

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Neurolepticsmayenhancetheabsorptionofcorticosteroidsanddigoxin,thehypotensiveeffectsofvasodilator

antihypertensiveagentssuchashydralazineandprolongtheactionofneuromuscularblockingagents.

SincezuclopenthixolispartlymetabolisedbyCYP2D6,concomitantuseofdrugsknowntoinhibitthisenzymemay

leadtodecreasedclearanceofzuclopenthixol.

Asforotheratypicalantipsychotics,cautionisadvisedinpatientstakingzuclopenthixolinconcomitantusewithoral

anticoagulants(e.g.warfarin),andothermedicinalproductsknowntoaffectplateletfunction(e.g.phenothiazines,most

tricyclicantidepressants,acetylsalicyclicacid,andnon-steroidalanti-inflammatorymedicinalproducts(NSAIDs),

ticlopidineanddipyridamole).

IncreasesintheQTintervalrelatedtoantipsychotictreatmentmaybeexacerbatedbytheco -administrationofother

drugsknowntosignificantlyincreasetheQTinterval.Co-administrationofsuchdrugsshouldbeavoided.Relevant

classesinclude:

classIaandIIIantiarrhythmics(e.g.quinidine,amiodarone,sotalol,dofetilide)

someantipsychotics(e.g.thioridazine)

somemacrolides(e.g.erythromycin)

someantihistamines(e.g.terfenadine,astemizole)

somequinoloneantibiotics(e.g.gatifloxacin,moxifloxacin)

TheabovelistisnotexhaustiveandotherindividualdrugsknowntosignificantlyincreaseQTinterval(e.g.cisapride,

lithium)shouldbeavoided.

Drugsknowntocauseelectrolytedisturbancessuchasthiazidediuretics(hypokalemia)anddrugsknowntoincrease

theplasmaconcentrationofzuclopenthixolshouldalsobeusedwithcautionastheymayincreasetheriskofQT

prolongationandmalignantarrhythmias(seesection4.4).

4.6Fertility,pregnancyandlactation

Pregnancy

Patientsshouldbeadvisedtonotifytheirphysicianiftheybecomepregnantorintendtobecomepregnantduring

treatmentwithzuclopenthixol.

Duetoinsufficientsafetyinformationinhumansandconcernsraisedbyanimalreproductivestudies,thismedicinal

productshouldnotbeusedinpregnancyunlesstheexpectedbenefitclearlyjustifiesthepotentialrisktothefoetus.

Thenewbornsofmotherstreatedwithneurolepticsinlatepregnancy,orlabour,mayshowsignsofintoxicationsuchas

lethargy,tremorandhyperexcitabilityandhavealowapgarscore.

Animalembryo-foetaldevelopmentalreproductionstudiesonzuclopenthixolhavenotgivenevidenceofanincreased

incidenceoffoetalmalformationsoreffectsonembryoviability.Ananimalpreandpostnatalstudyshowedan

increaseinstillbirths,reducedpupsurvivalanddelayeddevelopmentofpupsatdoselevelscausingmaternaltoxicity.

Thepotentialriskforhumansinunknown.

Neonatesexposedtoantipsychotics(includingzuclopenthixol)duringthethirdtrimesterofpregnancyareatriskof

adversereactionsincludingextrapyramidaland/orwithdrawalsymptomsthatmayvaryinseverityandduration

followingdelivery.Therehavebeenreportsofagitation,hypertonia,hypotonia,tremor,somnolence,respiratory

distress,orfeedingdisorder.Consequently,newbornsshouldbemonitoredcarefully.

Lactation

Aszuclopenthixolisfoundinbreastmilkinlowconcentrations,breast-feedingshouldnotbecontinuedduringtherapy

unlessintheopinionofthephysiciantheexpectedbenefittothepatientoutweighsthepotentialrisktotheinfant.

4.7Effectsonabilitytodriveandusemachines

Clopixolisasedativedrug.Patientswhoareprescribedpsychotropicmedicationmaybeexpectedtohavesome

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machinery.

4.8Undesirableeffects

Undesirableeffectsareforthemajoritydosedependent.Thefrequencyandseverityaremostpronouncedintheearly

phaseoftreatmentanddeclineduringcontinuedtreatment.

Extrapyramidalreactionsmayoccur,especiallyintheearlyphaseoftreatment.Inmostcasesthesesideeffectscanbe

satisfactorilycontrolledbyreductionofdosageand/oruseofantiparkinsoniandrugs.Theroutineprophylacticuseof

antiparkinsoniandrugsisnotrecommended.Antiparkinsoniandrugsdonotalleviatetardivedyskinesiaandmay

aggravatethem.Reductionindosageor,ifpossible,discontinuationofzuclopenthixoltherapyisrecommended.In

persistentakathisiaabenzodiazepineorpropranololmaybeuseful.

Frequenciesaretakenfromtheliteratureandspontaneousreporting.Frequenciesaredefinedas:

verycommon(1/10),common(1/100to<1/10),uncommon(1/1000to<1/100),rare(1/10000to<1/1000),veryrare

(<1/10000),ornotknown(cannotbeestimatedfromtheavailabledata).

Cardiacdisorders Common Tachycardia,palpitations.

Rare ElectrocardiogramQTprolonged.

Bloodandlymphaticsystem

disorders Rare Thrombocytopenia,neutropenia,leukopenia,

agranulocytosis.

Nervoussystemdisorders Verycommon Somnolence,akathisia,hyperkinesia,

hypokinesia.

Common Tremor,dystonia,hypertonia,dizziness,

headache,paraesthesia,disturbanceinattention,

amnesia,gaitabnormal.

Uncommon Tardivedyskinesia,hyperreflexia,dyskinesia,

parkinsonism,syncope,ataxia,speechdisorder,

hypotonia,convulsion,migraine.

Veryrare Neurolepticmalignantsyndrome.

Eyedisorders Common Accommodationdisorder,visionabnormal.

Uncommon Oculogyration,mydriasis.

Earandlabyrinthdisorders Common Vertigo.

Uncommon Hyperacusis,tinnitus.

Respiratory,thoracicand

mediastinaldisorders Common Nasalcongestion,dyspnoea.

Gastrointestinaldisorders Verycommon Drymouth.

Common Salivaryhypersecretion,constipation,vomiting,

dyspepsia,diarrhoea.

Uncommon Abdominalpain,nausea,flatulence.

Renalandurinarydisorders Common Micturitiondisorder,urinaryretention,polyuria.

Pregnancy,puerperiumand

perinatalconditions Notknown Drugwithdrawalsyndromeneonatal(see4.6).

Skinandsubcutaneoustissue

disorders Common Hyperhidrosis,pruritus.

Uncommon Rash,photosensitivityreaction,pigmentation

disorder,seborrhoea,dermatitis,purpura.

Musculoskeletaland

connectivetissuedisorder Common Myalgia.

Uncommon Musclerigidity,trismus,torticollis.

Endocrinedisorders Rare Hyperprolactinaemia.

Metabolismandnutrition

disorders Common Increasedappetite,weightincreased.

Uncommon Decreasedappetite,weightdecreased.

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Aswithotherdrugsbelongingtothetherapeuticclassofantipsychotics,rarecasesofQTprolongation,ventricular

arrhythmias-ventricularfibrillation,ventriculartachycardia,TorsadedePointesandsuddenunexplaineddeathhave

beenreportedforzuclopenthixol(seesection4.4).

Abruptdiscontinuationofzuclopenthixolmaybeaccompaniedbywithdrawalsymptoms.Themostcommonsymptoms

arenausea,vomiting,anorexia,diarrhoea,rhinorrhoea,sweating,myalgias,paraesthesias,insomnia,restlessness,

anxiety,andagitation.Patientsmayalsoexperiencevertigo,alternatefeelingsofwarmthandcoldness,andtremor.

Symptomsgenerallybeginwithin1to4daysofwithdrawalandabatewithin7to14days.

4.9Overdose

Symptoms

Somnolence,coma,movementdisorders,convulsions,shock,hyperthermia/hypothermia.

ECGchanges,QTprolongation,TorsadedePointes,cardiacarrestandventriculararrhythmiashavebeenreported

whenzuclopenthixolhasbeentakeninoverdosetogetherwithdrugsknowntoaffecttheheart.

Thehighestorallyadministereddoseofzuclopenthixolinclinicaltrialswas450mgdaily.

Treatment

Treatmentissymptomaticandsupportive.Measurestosupporttherespiratoryandcardiovascularsystemsshouldbe

instituted.Epinephrine(adrenaline)shouldnotbeusedasfurtherloweringofbloodpressuremayresult.Convulsions

maybetreatedwithdiazepamandmovementdisorderssymptomswithbiperiden.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup

Antipsychotics-Thioxanthenederivative.

ATC-code:N05AF05

Mechanismofaction

Zuclopenthixolisaneurolepticofthethioxanthenegroup.

Theantipsychoticeffectofneurolepticsisrelatedtotheirdopaminereceptorblockingeffectbutpossiblyalso5 -HT(5-

hydroxytryptamine)receptorblockadecontributes.InvitrozuclopenthixolhashighaffinityforbothdopamineD

hyperlipidaemia.

Vasculardisorders Uncommon Hypotension,hotflush.

Veryrare Venousthromboembolism

Generaldisordersand

administrationsiteconditions Common Asthenia,fatigue,malaise,pain.

Uncommon Thirst,hypothermia,pyrexia.

Immunesystemdisorders Rare Hypersensitivity,anaphylacticreaction.

Hepato-biliarydisorders Uncommon Liverfunctiontestabnormal.

Veryrare Cholestatichepatitis,jaundice.

Reproductivesystemand

breastdisorders Uncommon Ejaculationfailure,erectiledysfunction,female

orgasmicdisorder,vulvovaginaldryness.

Rare Gynaecomastia,galactorrhoea,amenorrhoea,

priapism.

Psychiatricdisorders Common Insomnia,depression,anxiety,nervousness,

abnormaldreams,agitation,libidodecreased.

Uncommon Apathy,nightmare,libidoincreased,confusional

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receptors,for

-adrenoceptorsand5 -HT

receptorsbutnoaffinityforcholinergicmuscarinereceptors.Ithasweak

histamine(H

)receptoraffinityandno

-adrenoceptorblockingactivity.

InvivotheaffinityforD

bindingsitesdominatesovertheaffinityforD

receptors.Zuclopenthixolhasproventobea

potentneurolepticinallthebehaviouralstudiesforneuroleptic(dopaminereceptorblocking)activity.Correlationis

foundintheinvivotestmodels,theaffinityfordopamineD

bindingsitesinvitroandtheaverage,dailyoral

antipsychoticdoses.

Inhibitionoflocomotoractivityandprolongationofalcohol-andbarbiturate-inducedsleepingtimeindicateasedative

actionofzuclopenthixol.

Likemostotherneurolepticszuclopenthixolincreasestheserumprolactinlevel.

Clinicalefficacy

Inclinicalusezuclopenthixolisintendedforthetreatmentofacuteandchronicpsychoses.

Besidescausingasignificantreductionorcompleteeliminationofthenuclearsymptomsofschizophreniasuchas

hallucinations,delusionsandthoughtdisturbanceszuclopenthixolalsohasamarkedeffectonaccompanyingsymptoms

likehostility,suspiciousness,agitationandaggressiveness.

Zuclopenthixolinducesatransientdose-dependentsedation.However,suchaninitialsedationisusuallyadvantageous

intheacutephaseoftheillness.Tolerancetotheunspecificsedativeeffectdevelopsrapidly.

5.2Pharmacokineticproperties

Absorption

Oraladministrationresultsinmaximumserumlevelsinabout4hours.Zuclopenthixolcanbetakenwithoutregardto

foodintake.Oralbioavailabilityisabout44%.

Distribution

Theapparentvolumeofdistribution(V

)isabout20l/kg.

Theplasmaproteinbindingisabout98-99%.

Biotransformation

Themetabolismofzuclopenthixolproceedsalongthreemainroutes-sulphoxidation,sidechainN-dealkylationand

glucuronicacidconjugation.Themetabolitesaredevoidofpsychopharmacologicalactivity.Zuclopenthixoldominates

overmetabolitesinbrainandothertissues.

Elimination

Theeliminationhalf-life(T

)isabout20hoursandthemeansystemicclearance(Cl

)isabout0.86L/min.

Zuclopenthixolisexcretedmainlywithfaeces,butalsotosomedegree(about10%)withtheurine.Onlyabout0.1%

ofthedoseisexcretedunchangedwiththeurine,meaningthatthedrugloadonthekidneysisnegligible.

Innursingmotherszuclopenthixolisexcretedinsmallamountswiththebreastmilk.Insteadystatethepre-dosemean

ratiomilkconc./serumconc.inwomentreatedorallyorwiththedecanoatewasabout0.29.

Linearity

Thekineticsislinear.Steadystateplasmalevelsareachievedinabout3-5days.Themeanminimumsteadystatelevel

correspondingto20mgzuclopenthixolorallyonceadaywasabout25nmol/l.

Elderlypatients

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Reducedrenalfunction

Basedontheabovecharacteristicsforeliminationitisreasonabletoassumethatreducedkidneyfunctionislikelynot

tohavemuchinfluenceontheserumlevelsofparentdrug.

Reducedhepaticfunction

Nodataavailable.

Polymorphism

Aninvivoinvestigationhasshownthatsomepartofthemetabolicpathwaysissubjecttogeneticpolymorphismofthe

sparteine/debrisoquineoxidation(CYP2D6).

Pharmacokinetic/Pharmacodynamicrelationship

Aminimum(i.e.concentrationmeasuredjustbeforeadministrationofadose)serumconcentrationof2.8-12ng/ml(7-

30nmol/l)issuggestedasguidelineformaintenancetreatmentofschizophrenicpatientswithlow-moderatedegreeof

illness.

5.3Preclinicalsafetydata

Acutetoxicity

Zuclopenthixolhaslowacutetoxicity.

Chronictoxicity

Inchronictoxicitystudiestherewerenofindingsofconcernforthetherapeuticuseofzuclopenthixol.

Reproductiontoxicity

Zuclopenthixolwastestedfordevelopmentaltoxicityinratsandrabbitsafteroraladministration.Undertheconditionsof

thestudies,zuclopenthixoldidnotinducemalformationsoraffectembryo-foetalviability.

However,inaperi/postnatalstudyinrats,dosagesof5and15mg/kg/dayresultedinanincreaseofstillbirths,reduced

pupsurvivalanddelayeddevelopmentofpups.Theclinicalsignificanceofthesefindingsisunclearanditispossible

thattheeffectonpupswasduetoneglectfromthedamsthatwereexposedtodosesofzuclopenthixolproducing

maternaltoxicity.

Mutagenicityandcarcinogenicity

Zuclopenthixolhasnomutagenicorcarcinogenicpotential.

Inaratoncogenecitystudy30mg/kg/dayfortwoyears(topdosage)resultedinslightnon-statisticalincreasesinthe

incidenceofmammaryadenocarcinomas,pancreaticisletcelladenomas,carcinomasinfemales,andthyroid

parafollicularcarcinomas.TheslightincreaseintheincidenceofthesetumorsisacommonfindingforD

antagonists,

whichincreaseprolactinsecretionwhenadministeredtorats.Thephysiologicaldifferencesbetweenratsandhumans

withregardtoprolactinmaketheclinicalsignificanceofthesefindingsunclear,butitisacceptedasnotpredictingan

oncogenicriskinpatients.

Localtoxicity

Localmuscledamageisseenafterinjectionofaqueoussolutionsofneuroleptics,includingzuclopenthixol.Themuscle

damageshowsamuchhigherdegreeaftertheaqueoussolutionsofneurolepticsthanaftertheoilysolutionsof

zuclopenthixolacetateandzuclopenthixoldecanoate.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore:

Potatostarch

Lactosemonohydrate

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Copovidone

Glycerol

Talc

Hydrogenatedcastoroil

MagnesiumStearate

Coating:

Hypromellose

Macrogol6000

Colours:

TitaniumDioxide(E171)

RedIronOxide(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Storebelow25 o

C.Storeintheoriginalpackage.Keepthecontainertightlyclosed.

6.5Natureandcontentsofcontainer

PolypropyleneorHighDensityPolyethylene(HDPE)containers.

Contents:100tablets

ThescrewcapoftheHDPEcontainerscontainsadessicant.

ThescrewcapoftheHDPEcontainersischildresistant.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

LundbeckLtd.

LundbeckHouse

CaldecotteLakeBusinessPark

Caldecotte

MiltonKeynesMK78LG

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorization:01November1982

Dateoflastrenewal: 01November2007

10DATEOFREVISIONOFTHETEXT

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