FLUANXOL

Main information

  • Trade name:
  • FLUANXOL Coated Tablets 0.5 Milligram
  • Dosage:
  • 0.5 Milligram
  • Pharmaceutical form:
  • Coated Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLUANXOL Coated Tablets 0.5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0115/002/001
  • Authorization date:
  • 01-04-1977
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fluanxol0.5mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains0.5mgflupentixolpresentasflupentixoldihydrochloride.

Excipients:Alsoincludeslactosemonohydrate27.7mgpertablet,andsucrosenotmorethan56mgpertablet.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

CoatedTablet(Tablet).

Round,biconvex,ochre-yellow,sugar-coatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Short-termmanagementofmildtomoderatedepressionwithorwithoutanxiety.

4.2Posologyandmethodofadministration

Adults

Initially1mgdailyasasinglemorningdoseor0.5mgtwicedaily.Afteroneweekthedosagemaybeincreasedto2

mgdailyifthereisaninadequateclinicalresponse.Dailydosageofmorethan2mgshouldbeindivideddosesuptoa

maximumof3mg.

Elderlypatients

Elderlypatientsshouldreceivehalftherecommendeddosages,i.e.0.5–1.5mgdaily.

Patientsoftenrespondtoflupentixolwithintwoorthreedays.Ifnoeffecthasbeenobservedwithinoneweekof

maximumdosagethedrugshouldbewithdrawn.

Children:

Fluanxolisnotrecommendedforuseinchildrenduetolackofclinicalexperience.

Reducedrenalfunction

Flupentixolcanbegiveninusualdosestopatientswithreducedrenalfunction.

Reducedhepaticfunction

Dosereduction(relativetothedegreeofhepaticimpairment)shouldbeconsidered.Ifpossible,whereassayfacilities

existdosageshouldbeadjustedaccordingtoserumlevels.

Methodofadministration

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4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients(seesection6.1)

Depressedlevelofconsciousnessduetoanycause(e.g.intoxicationwithalcohol,barbituratesoropiates)

Coma

Senileconfusionalstates

Severedepression

Patientswhohaveprovedintolerantofthioxanthenesorrelateddrugs.

4.4Specialwarningsandprecautionsforuse

AdministrationtopatientswithParkinsonismorextrapyramidaldisordermayinduceanexacerbationofthatdisorder.

Extrapyramidalreactionsintheformofacutedystonias(includingoculogyriccrisis),parkinsonianrigidity,tremor,

akinesiaandakathisiahavebeenreportedandmayoccurevenatlowerdosageinsusceptiblepatients.Sucheffects

wouldusuallybeencounteredearlyintreatment,butdelayedreactionsmayalsooccur.Antiparkinsonagentsshould

notbeprescribedroutinelybecauseofthepossibleriskofprecipitatingtoxic-confusionalstates,impairingefficacyor

causinganticholinergicside-effects.Theyshouldonlybegivenifrequiredandtheirrequirementreassessedatregular

intervals.

Tardivedyskinesiacanoccurwithneuroleptictreatment.Itismorecommonathighdosesforprolongedperiodsbut

hasbeenreportedatlowerdosageforshortperiods.Theriskseemstobegreaterintheelderly,especiallyfemales.It

hasbeenreportedthatfinevermicularmovementsofthetongueareanearlysign.Ithasbeenobservedoccasionallyin

patientsreceivingflupentixol.Theconcurrentuseofanticholinergicantiparkinsondrugsmayexacerbatethiseffect.

Thepotentialirreversibilityandseriousness,aswellastheunpredictabilityofthesyndrome,requiresespeciallycareful

assessmentoftheriskversusbenefit,andthelowestpossibledosageanddurationoftreatmentconsistentwith

therapeuticefficacy.Short-liveddyskinesiamayoccurafterabruptwithdrawalofthedrug.

Thehormonaleffectsofantipsychoticneurolepticdrugsincludehyperprolactinaemia,whichmaybeassociatedwith

galactorrhoea,gynaecomastia,oligomenorrhoeaoramenorrhoea.Sexualfunction,includingerectionandejaculation

maybeimpaired;butincreasedlibidohasalsobeenreported.

Thepossibilityofdevelopmentofneurolepticmalignantsyndrome(hyperthermia,musclerigidity,fluctuating

consciousness,instabilityoftheautonomousnervoussystem)existswithanyneuroleptic.Patientswithpre-existing

organicbrainsyndrome,mentalretardation,opiateoralcoholabuseareover-representedamongfatalcases.Rarecases

reportedasNMShavealsobeenreceivedinassociationwithflupentixol.ClinicalmanifestationsofNMSare

hyperpyrexia,musclerigidity,alteredmentalstatus,andevidenceofautonomicinstability(irregularpulseorblood

pressure,tachycardia,sweatingandcardiacarrhythmia).Additionalsignsmayincludeelevatedcreatinine,

phosphokinase,myoglubinuria(rhabdomylosis),andacuterenalfailure.Ifapatientdevelopssignsandsymptoms

indicativeofNMSorpresentswithunexplainedhighfeverwithoutadditionalclinicalmanifestationsofNMS,all

neurolepticmedication,includingflupentixolmustbediscontinued.

Treatment:Discontinuationoftheneuroleptic.Symptomatictreatmentanduseofgeneralsupportivemeasures.

Dantroleneandbromocriptinemaybehelpful.

Symptomsmaypersistformorethanaweekafteroralneurolepticsarediscontinuedandsomewhatlongerwhen

associatedwiththedepotformsofthedrug.

Flupentixolshouldbeusedwithgreatcautioninpatientswithsevereatherosclerosis,myocardialinsufficiencyor

severehepaticorrenalinsufficiency.

Flupentixolshouldalsobeusedwithcautioninpatientswithepilepsy(andconditionspredisposingtoepilepsye.g.

alcoholwithdrawalorbraindamage)andsevererespiratorydisease.

Aswithotherdrugsthatbelongtothetherapeuticclassofantipsychotics,flupentixolmaycauseQTprolongation.

PersistentlyprolongedQTintervalsmayincreasetheriskofmalignantarrthymias.Thereforeflupentixolshouldbe

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patientswithahistoryofcardiovasculardisorders,e.g.QTprolongation,significantbradycardia(<50beatsper

minute),arecentacutemyocardialinfarction,uncompensatedheartfailure,orcardiacarrhythmia.Concomitant

treatmentwithotherantipsychoticsshouldbeavoided(seesection4.5).

Suicide/suicidalthoughtsorclinicalworsening

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suicide-relatedevents).This

riskpersistsuntilsignificantremissionoccurs.

Asimprovementmaynotoccurduringthefirstfewweeksormoreoftreatment,patientsshouldbecloselymonitored

untilsuchimprovementoccurs.Itisgeneralclinicalexperiencethattheriskofsuicidemayincreaseintheearlystages

ofrecovery.

Patientswithahistoryofsuicide-relatedevents,orthoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatment,areknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,andshould

receivecarefulmonitoringduringtreatment.Ametaanalysisofplacebocontrolledclinicaltrialsofantidepressant

drugsinadultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwithantidepressants

comparedtoplaceboinpatientslessthan25yearsold.

Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patients(andcaregiversofpatients)shouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Inthelowerdoserangeflupentixolisnotrecommendedforexcitableoroveractivepatientssinceitsactivatingeffect

mayleadtoexaggerationofthesecharacteristics.

Patientsonlong-termtherapy,particularlyonhighdoses,shouldbemonitoredcarefullyandevaluatedperiodicallyto

decidewhetherthemaintenancedosecanbelowered.

Recurrenceofdepressionsymptomsonabruptwithdrawalisrare.However,gradualreductionofdosageisadvisable.

Dependencehasnotbeenreportedtodate.

Asdescribedforotherneurolepticsflupentixolmaymodifyinsulinandglucoseresponsescallingforadjustmentof

antidiabetictherapyinpatientswithdiabetes.

Flupentixolmayinitiallycausedrowsiness.Patientsshouldbewarnedofthispossibilityifdrivingoroperating

machinery.Alcoholmaypotentiatethiseffect(seesection4.7)

Likeotherneuroleptics,flupentixolshouldbeusedwithcautioninpatientswithorganicbrainsyndromeand

convulsion.

Casesofvenousthromboembolism(VTE)havebeenreportedwithantipsychoticdrugs.Sincepatientstreatedwith

antipsychoticsoftenpresentwithacquiredriskfactorsforVTE,allpossibleriskfactorsforVTEshouldbeidentified

beforeandduringtreatmentwithflupentixolandpreventivemeasuresundertaken.

Elderly

Careshouldalsobetakenintheelderly,particularlyinfrailoratriskofhypothermia,sedation,hypotensionor

confusion.

Cerebrovascular

Anapproximately3-foldincreasedriskofcerebrovascularadverseeventshavebeenseeninrandomisedplacebo

controlledclinicaltrialsinthedementiapopulationwithsomeatypicalantipsychotics.Themechanismforthis

increasedriskisnotknown.Anincreasedriskcannotbeexcludedforotherantipsychoticsorotherpatientpopulations.

Flupentixolshouldbeusedwithcautioninpatientswithriskfactorsforstroke.

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Datafromtwolargeobservationalstudiesshowedthatelderlypeoplewithdementiawhoaretreatedwith

antipsychoticsareatasmallincreasedriskofdeathcomparedwiththosewhoarenottreated.Thereareinsufficient

datatogiveafirmestimateoftheprecisemagnitudeoftheriskandthecauseoftheincreasedriskisnotknown.

Fluanxolisnotlicensedforthetreatmentofdementia-relatedbehaviouraldisturbances.

Excipients

Thetabletscontainlactosemonohydrate.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnotreceivethismedicine.Thetabletsalsocontain

sucrose.Patientswithrarehereditaryproblemsoffructoseintolerance,glucose-galactosemalabsorptionorsucrase-

isomaltaseinsufficiencyshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationsrequiringprecautionsforuse

Flupentixolmayinitiallycausedrowsinessandmayenhancethesedativeeffectofalcohol,barbiturates,othercentral

nervoussystemdepressants,andgeneralanaesthetics.Patientsshouldbewarnedofthispossibilityifdrivingor

operatingmachinery(seesection4.7)

Flupentixolmayreducetheeffectoflevodopaandtheeffectofadrenergicdrugs.

Concomitantuseofmetoclopramideandpiperazineincreasestheriskofextrapyramidaldisorder.

Neurolepticsmayincreaseorreducetheeffectofantihypertensivedrugs;theantihypertensiveeffectofguanethidine

andsimilaractingcompoundsisreduced.

Concomitantuseofneurolepticsandlithiumincreasestheriskofneurotoxicity.

Tricyclicantidepressantsandneurolepticsmutuallyinhibitthemetabolismofeachother.

Neurolepticsmayenhancethecardiacdepressanteffectsofquinidine;theabsorptionofcorticosteroidsanddigoxin;the

hypotensiveeffectofvasodilatorantihypertensiveagentssuchashydralazineandprolongtheactionofneuromuscular

blockingagents.

Asforotheratypicalantipsychotics,cautionisadvisedinpatientstakingflupentixolinconcomitantusewithoral

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

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

ticlopidineanddipyridamole).

IncreasesintheQTintervalrelatedtoantipsychotictreatmentmaybeexacerbatedbytheco-administrationofother

drugsknowntosignificantlyincreasetheQTinterval.Co-administrationofsuchdrugsshouldbeavoided.

Relevantclassesinclude:

Class1aandIIIantiarrhythmics(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.

Drugsknowntocauseelectrolytedisturbancessuchasthiazidediurectics(hypokalaemia)anddrugsknowntoincrease

theplasmaconcentrationofflupentixolshouldalsobeusedwithcautionastheymayincreasetheriskofQT

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4.6Fertility,pregnancyandlactation

Pregnancy

Patientsshouldbeadvisedtonotifytheirphysicianiftheybecomepregnantorintendtobecomepregnantduring

treatmentwithflupentixol.

Duetoinsufficientsafetyinformationinhumans,thismedicinalproductshouldnotbeusedinpregnancyunlessthe

expectedbenefitclearlyjustifiesthepotentialrisktothefoetus.

Thenewbornofmotherstreatedwithneurolepticsinlatepregnancy,orlabour,mayshowsignsofintoxicationsuchas

lethargy,tremorandhyperexcitability,andhavealowapgarscore.

Animalreproductionstudiesonflupentixolhavenotgivenevidenceofanincreasedincidenceoffoetaldamageorother

deleteriouseffectsonthereproductionprocess.

Lactation

Asflupentixolisfoundinbreastmilkinlowconcentrations,breast-feedingshouldnotbecontinuedduringflupentixol

therapyunlessintheopinionofthephysiciantheexpectedbenefittothepatientoutweighsthepotentialrisktothe

infant.

4.7Effectsonabilitytodriveandusemachines

Flupentixolmayinitiallycausedrowsiness.Patientsshouldbewarnedofthispossibilityifdrivingoroperating

machinery.Alcoholmaypotentiatethiseffect.(seesection4.4)

4.8Undesirableeffects

Undesirableeffectsareforthemajoritydosedependent.Thefrequencyandseverityaremostpronouncedintheearly

phaseoftreatmentanddeclineduringcontinuedtreatment.

Extrapyramidalreactionsmayoccur,especiallyintheearlyphaseoftreatment.Inmostcasesthesesideeffectscanbe

satisfactorilycontrolledbyreductionofdosageand/oruseofantiparkinsoniandrugs.Theroutineprophylacticuseof

antiparkinsoniandrugsisnotrecommended.Antiparkinsoniandrugsdonotalleviatetardivedyskinesiaandmay

aggravatethem.Reductionindosageor,ifpossible,discontinuationofflupentixoltherapyisrecommended.In

persistentakathisiaabenzodiazepineorpropranololmaybeuseful.

Frequenciesaretakenfromtheliteratureandspontaneousreporting.Frequenciesaredefinedas: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),or

notknown(cannotbeestimatedfromtheavailabledata).

Cardiacdisorders Common Tachycardia,palpitations.

Rare ElectrocardiogramQT

prolonged.

Bloodandlymphaticsystemdisorders Rare Thrombocytopenia,

neutropenia,leukopenia,

agranulocytosis.

Nervoussystemdisorders Verycommon Somnolence,akathisia,

hyperkinesia,hypokinesia.

Common Tremor,dystonia,dizziness,

headache.

UncommontoRare Tardivedyskinesia,dyskinesia,

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convulsion.

Veryrare Neurolepticmalignant

syndrome.

Eyedisorders Common Accommodationdisorder,

visionabnormal.

Uncommon Oculogyration.

Respiratory,thoracicandmediastinal

disorders Common Dyspnoea.

Gastrointestinaldisorders Verycommon Drymouth.

Common Salivaryhypersecretion,

constipation,vomiting,

dyspepsia,diarrhoea.

Uncommon Abdominalpain,nausea,

flatulence.

Renalandurinarydisorders Common Micturitiondisorder,urinary

retention.

Skinandsubcutaneoustissuedisorders Common Hyperhidrosis,pruritus.

Uncommon Rash,photosensitivityreaction,

dermatitis.

Musculoskeletalandconnectivetissue

disorder Common Myalgia.

Uncommon Musclerigidity.

Endocrinedisorders Rare Hyperprolactinaemia.

Metabolismandnutritiondisorders Common Increasedappetite,weight

increased.

Uncommon Decreasedappetite.

Rare Hyperglycaemia,glucose

toleranceabnormal.

Vasculardisorders Uncommon Hypotension,hotflush.

Veryrare Venousthromboembolism

Generaldisordersandadministration

siteconditions Common Asthenia,fatigue.

Immunesystemdisorders Rare Hypersensitivity,anaphylactic

reaction.

Hepatobiliarydisorders Uncommon Liverfunctiontestabnormal.

Veryrare Jaundice.

Reproductivesystemandbreast

disorders Uncommon Ejaculationfailure,erectile

dysfunction.

Rare Gynaecomastia,galactorrhoea,

amenorrhoea.

Psychiatricdisorders Common Insomnia,depression,

nervousness,agitation,libido

decreased.

Uncommon Confusionalstate.

Notknown suicidalideation,suicidal

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CasesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringFluanxoltherapyorearlyaftertreatment

discontinuation(seesection4.4)

Aswithotherdrugsbelongingtothetherapeuticclassofantipsychotics,rarecasesofQTprolongation,ventricular

arrythmias-ventricularfibrillation,ventriculartachycardia,TorsadedePointesandsuddenunexplaineddeathhave

beenreportedforflupentixol(seesection4.4).

Abruptdiscontinuationofflupentixolmaybeaccompaniedbywithdrawalsymptoms.Themostcommonsymptomsare

nausea,vomiting,anorexia,diarrhoea,rhinorrhoea,sweating,myalgias,paraesthesias,insomnia,restlessness,anxiety,

andagitation.Patientsmayalsoexperiencevertigo,alternatefeelingsofwarmthandcoldness,andtremor.Symptoms

generallybeginwithin1to4daysofwithdrawalandabatewithin7to14days.

4.9Overdose

Symptoms:

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

Thehighestorallyadministeredsingledoseinclinicaltrialswas80mg,andupto320mg/dayhasbeengiven.

ECGchanges,QTprolongation,TorsadedePointes,cardiacarrestandventriculararrhythmiashavebeenreported

whenadministeredinoverdosetogetherwithdrugsknowntoaffecttheheart.

Treatment:

Treatmentissymptomaticandsupportive.Gastriclavageshouldbecarriedoutassoonaspossibleafteroralingestion

andactivatedcharcoalmaybeadministered.Measurestosupporttherespiratoryandcardiovascularsystemsshouldbe

instituted.Adrenalineshouldnotbeusedasfurtherloweringofbloodpressuremayresult.Convulsionsmaybetreated

withdiazepamandextrapyramidalsymptomswithbiperiden.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup

Neuroleptics(antipsychotics)

ATC-code:N05AF01

Flupentixolisamixtureoftwogeometricisomers,theactivecis(Z)-flupentixolandtrans(E)-flupentixol,approximately

intheratioof1:1.

Theantipsychoticeffectofneurolepticsisrelatedtotheirdopaminereceptorblockingeffectbutpossiblyalso5-HT(5-

hydroxytryptamine)receptorblockadecontributes.

Cis(Z)-flupentixolhashighaffinityfor

-adrenoceptorsand5-HT

receptors,althoughlowerthanthatof

chlorprothixene,high-dosephenothiazinesandclozapine,butnoaffinityforcholinergicmuscarinereceptors.Ithas

onlyslightantihistaminergicpropertiesandno

-adrenoceptorblockingactivity.

Cis(Z)-flupentixolhasproventobeapotentneurolepticinallthebehaviouralstudiesforneuroleptic(dopamine

receptorblocking)activity.Correlationisfoundintheinvivotestmodels,theaffinityfordopamineD

bindingsitesin

vitroandtheaverage,dailyoralantipsychoticdoses.

Likemostotherneuroleptics,flupentixoldose–dependentlyincreasestheserumprolactinlevel.

Clinicalefficacy

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Flupentixolinlowdosages(1-2mg/day)hasantidepressant,anxiolyticandactivatingeffects.

Inmoderatedosages(3-25mg/day)flupentixolisintendedforthetreatmentofacuteandchronicpsychoses.Inthis

dosagerangeflupentixolhaspracticallynounspecificsedativeeffectandisnotsuitedforpatientswithsevere

psychomotoragitation.Besidescausingasignificantreductionorcompleteeliminationofthenuclearsymptomsof

schizophreniasuchashallucinations,delusionsandthoughtdisturbancesflupentixolalsohasdisinhibiting(antiautistic

andactivating)andmood-elevatingpropertiesmakingflupentixolparticularlyusefulinthetreatmentofapathetic,

withdrawn,depressedandpoorlymotivatedpatients.

Theantipsychoticeffectincreaseswithincreasingdosage;inadditionsomesedationshouldbeanticipated.Flupentixol

haswithinthewholedosagerangeapronouncedanxiolyticeffectandeveninhigh-dosetreatmentthemoodelevating

anddisinhibitingeffectsofflupentixolareretained.Highdosetreatmentdoesnotincreasethefrequencyof

extrapyramidalsymptoms.

5.2Pharmacokineticproperties

Thefollowingdataconcernstheactivecis(Z)-isomer.

Absorption

Oraladministrationresultsinmaximumserumlevelsinabout4-5hours.Oralbioavailabilityisabout40%.

Distribution

Theapparentvolumeofdistribution(V

)isabout14.1l/kg.Theplasmaproteinbindingisabout99%.

Biotransformation

Themetabolismofflupentixolproceedsalongthreemainroutes-sulphoxidation,sidechainN-dealkylationand

glucuronicacidconjugation.Themetabolitesaredevoidofpsychopharmacologicalactivity.Flupentixoldominates

overmetabolitesinbrainandothertissues.

Elimination

Theeliminationhalf-life(T

)isabout35hoursandthemeansystemicclearance(Cl

)isabout0.29l/min.

Flupentixolisexcretedmainlywithfaeces,butalsotosomedegreewiththeurine.Whentritiumlabelledflupentixol

wasadministeredtomantheexcretionpatternshowedtheexcretionviafaecestobeabout4timestheurinary

excretion.

Innursingmothersflupentixolisexcretedinsmallamountswiththebreastmilk.Theratiomilkconc./serumconc.in

womenisonanaverage1.3.

Linearity

Thekineticsislinear.Steadystateplasmalevelsareachievedinabout7days.Themeanminimumsteadystatelevel

correspondingto5mgflupentixolorallyonce-a-daywasabout1.7ng/ml(3.9nmol/l).

Elderlypatients

Pharmacokineticinvestigationshavenotbeendoneinelderlypatients.However,fortherelatedthioxanthenedrug,

zuclopenthixol,thepharmacokineticparametersarewidelyindependentoftheageofthepatients.

Reducedrenalfunction

Basedontheabovecharacteristicsforeliminationitisreasonabletoassumethatreducedkidneyfunctionislikelynot

tohavemuchinfluenceontheserumlevelsofparentdrug.

Reducedhepaticfunction

Nodataavailable.

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Aminimum(i.e.concentrationmeasuredjustbeforeadministrationofadose)serum(plasma)concentrationof1-

3ng/ml(2-8nmol/l)issuggestedasaguidelineformaintenancetreatmentofschizophrenicpatientswithalow-

moderatedegreeofillness.

5.3Preclinicalsafetydata

Acutetoxicity

Flupentixolhaslowacutetoxicity.

Chronictoxicity

Inchronictoxicitystudiestherewerenofindingsofconcernforthetherapeuticuseofflupentixol

Reproductiontoxicity

Basedondatafromreproductiontoxicitystudiesthereisnoreasontohavespecialconcernfortheuseofflupentixolin

womenofchild-bearingpotential.

Carcinogenicity

Flupentixolhasnocarcinogenicpotential.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate,

Potatostarch,

Gelatin,

Talc,

Magnesiumstearate.

Coating:

Gelatin,

Sucrose,

Sucrosepowder(sucrosewith2%potatostarch)

Colour:

Yellowironoxide(E172)

Waxpolish–amixtureofbeeswax,whitewaxandcarnaubawax

6.2Incompatibilities

Notapplicable

6.3ShelfLife

2years

6.4Specialprecautionsforstorage

Donotstoreabove25 °

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PVC/PVdCblistersinpacksof60tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

LundbeckLtd.

LundbeckHouse

CaldecotteLakeBusinessPark

Caldecotte

MiltonKeynesMK78LG

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA115/2/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1 st

April1977

Dateoflastrenewal:1 st

April2007

10DATEOFREVISIONOFTHETEXT

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