CITALOPRAM

Main information

  • Trade name:
  • CITALOPRAM Film Coated Tablet 20 Milligram
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CITALOPRAM Film Coated Tablet 20 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/072/001
  • Authorization date:
  • 13-10-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0577/072/001

CaseNo:2024541

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDermottLaboratoriesLtdt/aGerardLaboratories

35/36BaldoyleIndustrialEstate,GrangeRoad,Dublin13,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Citalopram20mgFilm-CoatedTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/01/2007.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 22/09/2007 CRN 2024541 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Citalopram20mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainscitalopramhydrobromideequivalentto20mgofcitalopram.

Excipient(s):

53.28mgLactoseMonohydrate

Forafulllistofexcipientsseesection6.1

3PHARMACEUTICALFORM

Filmcoatedtablet

Awhite,ovalfilmcoatedtabletmarkedwith“CMscoreline20”ononesideand“G”ontheother.Thetabletcanbe

dividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Citalopramisindicatedforthetreatmentofdepressiveillnessesintheinitialstageandasmaintenanceagainstrelapse

orrecurrence.Citalopramisalsoindicatedinthetreatmentofpanicdisorderwithorwithoutagoraphobia.

4.2Posologyandmethodofadministration

Fortreatmentofdepression

Adults:

Theusualdoseis20mgcitalopramoncedaily,withamaximumrecommendeddoseof60mgperday;the

maximumdosewillbedependentontheresponseoftheindividualpatient.Thedosemaybetakeninthemorning

orevening,withorwithoutfood.Atreatmentperiodofatleast6monthsisrecommendedtogiveadequate

protectionagainstthepossibilityofarelapse.

Fortreatmentofpanicdisorder:

Asingledoseof10mgperdayforthefirstweekisrecommended;afterthisthedosemaybeincreasedto20mgper

day.Thedosemaycontinuetobeincreasedto60mgperdaydependingonindividualpatientresponse.Maximum

effectivenessisreachedafter3months.Itmaybenecessarytocontinuetreatmentforseveralmonths.

Elderly:

Therecommendeddailydoseis20mg.Thismaybeincreasedtoamaximumof40mg.

Childrenandadolescentsundertheageof18:

Citalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years(Seesection

4.4SpecialWarningsandSpecialPrecautionsforUse).

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Dosageadjustmentisnotnecessaryforpatientswithmildtomoderaterenaldysfunction.Noinformationis

availableforcaseoffinalstageimpairmentofrenalfunction(creatinineclearance<20mL/minute).

PoorCYP2C19metabolisers:

ForknownpoorCYP2C19metabolisersaninitialdoseof10mgdailythefirsttwoweeksoftreatmentis

recommended.Dependingontheoutcomeofthetreatmentthedosecanthereafterbeincreasedto20mg(see

section5.2).

Withdrawalsymptomsseenondiscontinuation:

Abruptdiscontinuationshouldbeavoided.Whenstoppingtreatmentwithcitalopramthedoseshouldbegradually

reducedoveraperiodofatleastonetotwoweeksinordertoreducetheriskofwithdrawalreactions(seesection

4.4SpecialWarningsandSpecialPrecautionsforUseandsection4.8UndesirableEffects).Ifintolerablesymptoms

occurfollowingadecreaseinthedoseorupondiscontinuationoftreatment,thenresumingthepreviously

prescribeddosemaybeconsidered.Subsequently,thephysicianmaycontinuedecreasingthedose,butatamore

gradualrate.

4.3Contraindications

Hypersensitivitytocitalopram

MonoamineOxidaseInhibitors:

CasesofseriousandsometimesfatalreactionshavebeenreportedinpatientsreceivinganSSRIincombinationwith

monoamineoxidaseinhibitor(MAOI),includingtheselectiveMAOIselegilineandthereversibleMAOI(RIMA),

moclobemideandinpatientswhohaverecentlydiscontinuedanSSRIandhavebeenstartedonaMAOI.

Somecasespresentedwithfeaturesresemblingserotoninsyndrome.SymptomsofadruginteractionwithaMAOI

include:hyperthermia,rigidity,myoclonus,autonomicinstabilitywithpossiblerapidfluctuationsofvitalsigns,mental

statuschangesthatincludeconfusion,irritabilityandextremeagitationprogressingtodeliriumandcoma.

CitalopramshouldnotbeusedincombinationwithaMAOI.Citaloprammaybestarted14daysafterdiscontinuing

treatmentwithanirreversibleMAOIandatleastonedayafterdiscontinuingtreatmentwiththereversibleMAOI

(RIMA),moclobemide.Atleast7daysshouldelapseafterdiscontinuingcitalopramtreatmentbeforestartingaMAOI

orRIMA.

4.4Specialwarningsandprecautionsforuse

Useinchildren&adolescentsunder18yearsofage-

Citalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years.Suicide-related

behaviours(suicideattemptsandsuicidalthoughts)andhostility(predominantlyaggression,oppositionalbehaviour

andanger)weremorefrequentlyobservedinclinicaltrialsamongchildrenandadolescentstreatedwithantidepressants

comparedtothosetreatedwithplacebo.If,basedonclinicalneed,adecisiontotreatisneverthelesstaken,thepatient

shouldbecarefullymonitoredfortheappearanceofsuicidalsymptoms.Inaddition,long-termsafetydatainchildren

andadolescentsconcerninggrowth,maturationandcognitiveandbehaviouraldevelopmentarelacking.

Diabetes–Inpatientswithdiabetes,treatmentwithanSSRImayalterglycaemiccontrol,possiblyduetoimprovement

ofdepressivesymptoms.Insulinandororalhypoglycaemicdosagemayneedtobeadjusted.

Seizures:-Seizuresareapotentialriskwithantidepressantdrugs.Thedrugshouldbediscontinuedinanypatientwho

developsseizures.Citalopramshouldbeavoidedinpatientswithunstableepilepsyandpatientswith

controlledepilepsyshouldbecarefullymonitored.Citalopramshouldbediscontinuedifthereisanincreaseinseizure

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ECT–ThereislittleclinicalexperienceofconcurrentadministrationofcitalopramandECT,thereforecautionis

advisable.

Mania–Citalopramshouldbeusedwithcautioninpatientswithahistoryofmania/hypomania.Citalopramshouldbe

discontinuedinanypatiententeringamanicphase.

Suicide/suicidalthoughts–Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide

(suicide-relatedevents).Thisriskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthe

firstfewweeksormoreoftreatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneral

clinicalexperiencethattheriskofsuicidemayincreaseintheearlystagesofrecovery.

Otherpsychiatricconditionsforwhichcitalopramisprescribedcanalsobeassociatedwithanincreasedriskofsuicide-

relatedevents.Inaddition,theseconditionsmaybeco-morbidwithmajordepressivedisorder.Thesameprecautions

observedwhentreatingpatientswithmajordepressivedisordershouldthereforebeobservedwhentreatingpatients

withotherpsychiatricdisorders.

Patientswithahistoryofsuicide-relatedevents,thoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatmentareatagreaterriskofsuicidalthoughtsorsuicideattempts,andshouldreceivecareful

monitoringduringtreatment.Inaddition,thereisapossibilityofanincreasedriskofsuicidalbehaviourinyoung

adults.

Patients,(andcaregiversofpatients)shouldbealertedabouttheneedtomonitorfortheemergenceofsucheventsand

toseekmedicaladviceimmediatelyifthesesymptomspresent.

Haemorrhage–Therehavebeenreportsofcutaneousbleedingabnormalitiessuchasecchymosesandpurpurawith

SSRIs.CautionisadvisedinpatientstakingSSRIs,particularlyinconcomitantusewithdrugsknowntoaffectplatelet

function(e.g.atypicalantipsychoticsandphenothiazines,mosttricyclicantidepressants,aspirinandnon-steroidalanti-

inflammatorydrugs(NSAIDs))aswellasinpatientswithahistoryofbleedingdisorders.

Experiencewithcitalopramhasnotrevealedanyclinicallyrelevantinteractionswithneuroleptics.However,aswith

otherSSRIs,thepossibilityofapharmacodynamicinteractioncannotbeexcluded.

Akathisia/psychomotorrestlessness-TheuseofSSRIs/SNRIshasbeenassociatedwiththedevelopmentofakathisia,

characterisedbyasubjectivelyunpleasantordistressingrestlessnessandneedtomoveoftenaccompaniedbyan

inabilitytositorstandstill.Thisismostlikelytooccurwithinthefirstfewweeksoftreatment.Inpatientswho

developthesesymptoms,increasingthedosemaybedetrimental.

Withdrawalsymptomsseenondiscontinuation-Withdrawalsymptomswhentreatmentisdiscontinuedarecommon,

particularlyifdiscontinuationisabrupt(seesection4.8Undesirableeffects).

Theriskofwithdrawalsymptomsmaybedependentonseveralfactorsincludingthedurationanddoseoftherapyand

therateofdosereduction.Dizziness,sensorydisturbances(includingparaesthesiaandelectricshocksensations),sleep

disturbances(includinginsomniaandintensedreams),agitationoranxiety,nauseaand/orvomiting,tremor,confusion,

sweating,headache,diarrhoea,palpitations,emotionalinstability,irritability,andvisualdisturbanceshavebeen

reportedfollowingdiscontinuationofSSRIs/SNRIs.Generallythesesymptomsaremildtomoderate,however,insome

patientstheymaybesevereinintensity.Theyusuallyoccurwithinthefirstfewdaysofdiscontinuingtreatment,but

therehavebeenveryrarereportsofsuchsymptomsinpatientswhohaveinadvertentlymissedadose.Generallythese

symptomsareself-limitingandusuallyresolvewithin2weeks,thoughinsomeindividualstheymaybeprolonged(2-3

monthsormore).Itisthereforeadvisedthatcitalopramshouldbegraduallytaperedwhendiscontinuingtreatmentover

aperiodofseveralweeksormonths,accordingtothepatient’sneeds(see"WithdrawalSymptomsSeenon

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Considerationshouldbegiventofactorswhichmayaffectthedispositionofaminormetaboliteofcitalopram

(didemethylcitalopram)sinceincreasedlevelsofthismetabolitecouldtheoreticallyprolongtheQTcintervalin

susceptibleindividuals.However,inECGmonitoringof2500patientsinclinicaltrials,including277patientswithpre-

existingcardiacconditions,noclinicallysignificantchangeswerenoted.

Aswithmostantidepressants,citalopramshouldbediscontinuedifthepatiententersamanicphase.Thereislittle

clinicalexperienceofconcurrentuseofcitalopramandECT.

Somepatientswithpanicdisorderexperienceaninitialanxiogeniceffectwhenstartingpharmacotherapy.Alow

startingdose(seePosology)reducesthelikelihoodofthiseffect.

Thetabletscontainlactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiency

orglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

MonoamineOxidaseInhibitors(MAOIs)shouldnotbeusedincombinationwithSSRIs.

ThemetabolismofcitalopramisonlypartlydependentonthehepaticcytochromeP450isozymeCYP2D6and,unlike

someotherSSRIs,citalopramisonlyaweakinhibitorofthisimportantenzymesystemwhichisinvolvedinthe

metabolismofmanydrugs(includingantiarrhythmics,neuroleptics,beta-blockers,TCAsandsomeSSRIs).Protein

bindingisrelativelylow(<80%).Thesepropertiesgivecitalopramalowpotentialforclinicallysignificantdrug

interactions.

Alcohol–Thecombinationofcitalopramandalcoholisnotadvisable.Howeverclinicalstudieshaverevealedno

adversepharmacodynamicinteractionsbetweencitalopramandalcohol.

Serotonergicdrugs–Co-administrationwithserotonergicdrugs(e.g.tramadol,sumatriptan)mayleadtoenhancement

of5-HTassociatedeffects.UntilfurtherevidenceisavailableitisadvisednottouseCitalopramsimultaneouslywith

5-HTagonists.

Lithium&tryptophan-Thereisnopharmacokineticinteractionbetweenlithiumandcitalopram.Howevertherehave

beenreportsofenhancedeffectswhenSSRIshavebeengivenwithlithiumortryptophanandthereforetheconcomitant

useofcitalopramwiththesedrugsshouldbeundertakenwithcaution.Theroutinemonitoringoflithiumlevelsneed

notbeadjusted.

Inapharmacokineticstudynoeffectwasdemonstratedoneithercitalopramorimipraminelevels,althoughthelevelof

desipramine,theprimarymetaboliteofimipramine,wasincreased.Inanimalstudiescimetidinehadlittleorno

influenceoncitalopramkinetics.

DynamicinteractionsbetweencitalopramandherbalremedyStJohn’swort(Hypericumperforatum)canoccur,

resultinginanincreaseinundesirableeffects.

Nopharmacodynamicinteractionshavebeennotedinclinicalstudiesinwhichcitalopramhasbeengiven

concomitantlywithbenzodiazepines,neuroleptics,analgesics,lithium,alcohol,antihistamines,anti-hypertensivedrugs,

beta-blockersandothercardiovasculardrugs.

QTprolongation-CautioniswarrantedforconcomitantuseofotherQTintervalprolongingmedicinesor

hypokalaemia/hypomagnesaemiainducingdrugsasthey,likeCitalopram,alsoprolongtheQTinterval.

Seizures-SSRIscanlowertheseizurethreshold.Cautionisadvisedwhenconcomitantlyusingothermedicinal

productscapableofloweringtheseizurethreshold(e.g.antidepressants(tricyclics,SSRIs),neuroleptics

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Escitalopram-ThemetabolismofescitalopramismainlymediatedbyCYP2C19.CYP3A4andCYP2D6mayalso

contributetothemetabolismalthoughtoasmallerextent.ThemetabolismofthemajormetaboliteS-DCT

(demethylatedescitalopram)seemstobepartlycatalysedbyCYP2D6.

Co-administrationofescitalopramwithomeprazole30mgoncedaily(aCYP2C19inhibitor)resultedinmoderate

(approximately50%)increaseintheplasmaconcentrationsofescitalopram.

Thus,cautionshouldbeexercisedwhenusedconcomitantlywithCYP2C19inhibitors(e.g.omeprazole,esomeprazole,

fluvoxamine,lansoprazole,ticlopidine)orcimetidine.Areductioninthedoseofcitaloprammaybenecessarybasedon

monitoringofundesirableeffectsduringconcomitanttreatment.

4.6Pregnancyandlactation

Pregnancy–Therearelimiteddatafromtheuseofcitalopraminpregnantwomen.Studiesinratshaveshown

teratogeniceffectsathighdoseswhichcausedmaternaltoxicity(seesection5.3).Thepotentialriskforhumansis

unknown.Citalopramshouldonlybeusedinpregnancyifconsideredclearlynecessary.

Newborninfantsshouldbeobservedifmaternaluseofcitalopramcontinuesintothelaterstagesofpregnancy,

particularlythethirdtrimester.Abruptdiscontinuationshouldbeavoidedduringpregnancy.

Thefollowingsymptomsmayoccurinthenew-borninfantaftermaternalSSRI/SNRIuseinlaterstagesofpregnancy:

respiratorydistress,cyanosis,apnoea,seizures,temperatureinstability,feedingdifficulty,vomiting,hypoglycaemia,

hypertonia,hypotonia,hyperreflexia,tremor,jitteriness,irritability,lethargy,constantcrying,somnolenceand

difficultysleeping.Thesesymptomscouldbeduetoeitherserotonergiceffectsorwithdrawalsymptoms.Inamajority

ofinstancesthecomplicationsbeginimmediatelyorsoon(<24hours)afterdelivery.

Lactation–Citalopramisexcretedinmilkinsmallquantities.Theadvantagesofbreastfeedingshouldoutweighthe

potentialundesirableeffectsforthechild.

4.7Effectsonabilitytodriveandusemachines

Patientsprescribedpsychotropicmedicationmayhavesomeimpairmentofconcentrationduetotheillness,the

medication,orboth.Patientsshouldbecautionedabouttheirabilitytodriveacarandoperatemachinery.Citalopram

itselfdoesnotcauseanyimpairmenttointellectualfunctionorpsychomotorperformance.

4.8Undesirableeffects

Adverseeffectsobservedwithcitalopramareingeneralmildandtransient.Theyaremostprominentduringthefirst

oneortwoweeksoftreatmentandusuallyattenuateasthedepressivestateimproves.

Themostcommonlyobservedadverseeventsassociatedwiththeuseofcitalopramandnotseenatanequalincidence

amongplacebo-treatedpatientswere:nausea,somnolence,drymouth,increasedsweatingandtremor.Theincidenceof

eachinexcessoverplaceboislow(<10%).

Withdrawalsymptomsseenondiscontinuation:

DiscontinuationofSSRIs/SNRIs(particularlywhenabrupt)commonlyleadstowithdrawalsymptoms.Dizziness,

sensorydisturbances(includingparaesthesiaandelectricshocksensations),sleepdisturbances(includinginsomniaand

intensedreams),agitationoranxiety,nauseaand/orvomiting,tremor,confusion,sweating,headache,diarrhoea,

palpitations,emotionalinstability,irritability,andvisualdisturbanceshavebeenreported.Generallytheseeventsare

mildtomoderateandareself-limiting,however,insomepatientstheymaybesevereand/orprolonged.Itistherefore

advisedthatwhencitalopramtreatmentisnolongerrequired,gradualdiscontinuationbydosetaperingshouldbe

carriedout(seesection4.2PosologyandMethodofAdministrationandsection4.4SpecialWarningsandSpecial

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Verycommon

(1/10) Common

(1/100to<1/10) Uncommon(

1/1,000to

1/100 Rare

(1/10,000to

1/1000) NotKnown

Metabolismand

nutrition

disorders Weightdecrease,

weightincrease

Psychiatric

disorders Somnolence,

insomnia,agitation,

nervousness Sleep,disorders,

impaired

concentration,

abnormal

dreaming,

amnesia,anxiety,

decreasedlibido,

increased

appetite,

anorexia,apathy,

Euphoria,increased

libido Suicidalthoughts/

behaviour(see

section4.4)

Nervoussystem

disorders Headache,tremor,

dizziness Migraine,

paraesthesia Convulsions Akathisia(see

section4.4).

Serotonin

syndrome. Choreoathetosis

Eyedisorders Abnormal

accommodation Abnormalitiesof

vision

Earandlabyrinth

disorders Tinnitus

Cardiacdisorders Palpitations Tachycardia CasesofQT

prolongationhave

beenreportedpost-

marketing.

Vascular

disorders Postural

hypotension

Respiratory,

thoracicand

mediastinal

disorders Rhinitis Coughing

Gastrointestinal

disorders Nausea,drymouth,

constipation,

diarrhoea Dyspepsia,

vomiting,

abdominalpain,

flatulence,

increased

salivation

Hepato-biliary

disorders Cholestasis

Skinand

subcutaneous

tissuedisorders Increasedsweating Rash,pruritus

Musculoskeletal,

connectivetissue

andbone

disorders Myalgia Movement

disorders

Renalandurinary

disorders Micturition

disorder,polyuria

Reproductive

systemandbreast

disorders Ejaculation

failure,female

anorgasmi,

impotence Galactorrhoea

General

Disorders Asthenia Fatigue,taste

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4.9Overdose

Citalopramisgiventopatientsatpotentialriskofsuicideandsomereportsofattemptedsuicidehavebeenreceived.

Detailisoftenlackingregardingprecisedoseorcombinationwithotherdrugsand/oralcohol.

Symptoms:

Somnolence,coma,stupor,seizures,ECGchanges(e.g.prolongedQTinterval),atrialandventriculararrhythmia,

nausea,vomiting,transpiration,cyanosis,hyperventilation.Featuresofserotoninsyndromemayoccur,particularly

whenothersubstancesareco-ingested.

Treatment:

Thereisnoknownspecificantidotetocitalopram.Treatmentshouldbesymptomaticandsupportive.Activated

charcoal,osmoticallyworkinglaxative(suchassodiumsulphate)andstomachevacuationshouldbeconsidered.If

consciousnessisimpairedthepatientshouldbeintubated.ECGandvitalsignsshouldbemonitored.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:selectiveserotoninreuptakeinhibitors

ATCcode:N06AB04.

Citalopramhasbeendemonstratedtobeapotentinhibitorofserotonin(5-HT)-uptake.Long-termtreatmentwith

citalopramdoesnotinducetolerancetotheinhibitionof5-HT–uptake.

CitalopramisthemostSelectiveSerotoninReuptakeInhibitor(SSRI)yetdescribed,withminimaleffecton

noradrenaline(NA),dopamine(DA)andgammaaminobutyricacid(GABA)uptake.Citalopramhasnoorverylow

affinityforaseriesofreceptorsincluding5-HT1A,5-HT2,dopamineD1andD2receptors,alpha1-,alpha2-andbeta-

adrenoceptors,histamineH1,muscarinecholinergic,benzodiazepine,andopioidreceptors.Thisisincontrasttomany

tricyclicantidepressantsandsomeofthenewerSSRI’s.Lackofreceptoraffinityhasbeenconfirmedusingaseriesof

functionalinvitrotestsinisolatedorgansaswellasfunctionalinvitrotests.Thisabsenceofeffectsonreceptorscould

explainwhycitalopramproducesfewerofthetraditionalsideeffectssuchasdrymouth,bladderandgutdisturbance,

blurredvision,sedation,cardiotoxicityandorthostatichypotension.

Liketricyclicantidepressants,otherSSRI’sandMAOinhibitors,citalopramsuppressesREM–sleepandincreases

deepslow-wavesleep.Suppressionofrapideyemovement(REM)sleepisconsideredapredictorofantidepressant

activity.Althoughcitalopramdoesnotbindtoopioidreceptorsitpotentiatestheanti-nociceptiveeffectofcommonly

usedopioidanalgesics.Therewaspotentiationofd-amphetamine-inducedhyperactivityfollowingadministrationof

citalopram.

ThemainmetabolitesofcitalopramareallSSRIsalthoughtheirpotencyandselectivityratiosarelowerthanthoseof

citalopram.However,theselectivityratiosofthemetabolitesforCitalopramarehigherthanmanyofthenewerSSRIs.

Themetabolitesdonotcontributetotheoverallantidepressanteffect.

Citalopramdoesnotimpaircognitive(intellectualfunction)andpsychomotorperformanceinhumansandhasnoor

minimalsedativeproperties,eitheraloneorincombinationwithalcohol.

Asingledosestudyinhumanvolunteersshowedthatcitalopramdidnotreducesalivaflowandinnoneofthestudies

inhealthyvolunteersdidcitalopramhavesignificantinfluenceoncardiovascularparameters.Citalopramhasnoeffect

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5.2Pharmacokineticproperties

Absorption:Absorptionisalmostcompleteandindependentoffoodintake(T

average/mean3.8hours).Oral

bioavailabilityisabout80%.

Distribution:Theapparentvolumeofdistribution(V

isabout12.3L/kg.Theplasmaproteinbindingisbelow80%

forcitalopramanditsmainmetabolites.

Biotransformation:Citalopramismetabolisedtotheactivedemethylcitalopram,didemethylcitalopram,citalopram-N-

oxideandaninactivemetabolitesarealsoSSRIs,althoughweakerthantheparentcompound.Unchangedcitalopramis

thepredominantcompoundinplasma.ThemainmetabolisingenzymeisCYP2C19.SomecontributionfromCYP3A4

andCYP2D6ispossible.

Elimination:Theeliminationhalf-life(T

1/2ß )isabout1.5daysandthesystemiccitalopramplasmaclearance(CI

)is

about0.33L/min,andoralplasmaclearance(CI

oral )isabout0.41L/min.

Citalopramisexcretedmainlyviatheliver(85%)andtheremainder(15%)viathekidneys.About12%ofthedaily

doseisexcretedinurineasunchangedcitalopram.Hepatic(residual)clearanceisabout0.35L/minandrenalclearance

about0.068L/min.

Thekineticsislinear.Steadystateplasmalevelsareachievedin1-2weeks.Averageconcentrationsof250nmol/L

(100-500nmol/L)areachievedatadailydoseof40mg.Thereisnoclearrelationshipbetweencitalopramplasma

levelsandtherapeuticresponseorsideeffects.

Elderlypatients(=65years):Longerhalflivesanddecreasedclearancevaluesduetoareducedrateofmetabolism

havebeendemonstratedinelderlypatients.

Reducedhepaticfunction:Citalopramiseliminatedmoreslowlyforpatientswithreducedhepaticfunction.Thehalf

lifeofcitalopramisabouttwiceaslongandsteadystatecitalopramconcentrationsatagivendosewillbeabouttwice

ashighasinpatientswithnormalliverfunction.

Reducedrenalfunction:Citalopramiseliminatedmoreslowlyinpatientswithmildtomoderatereductionofrenal

function,withoutanymajorimpactonthepharmacokineticsofcitalopram.Atpresentnoinformationisavailablefor

treatmentofpatientswithseverelyreducedrenalfunction(creatinineclearance<20mL/min).

Preclinicalsafetydata:Citalopramhaslowacutetoxicity.Inchronictoxicitystudiestherewerenofindingsofconcern

forthetherapeuticuseofcitalopram.Basedondatafromreproductiontoxicitystudies(segmentI,IIandIII)thereis

noreasontohavespecialconcernfortheuseofcitalopraminwomenofchild-bearingpotentialCitalopramhasno

mutagenicorcarcinogenicpotential.

5.3Preclinicalsafetydata

Inlaboratoryanimalsnoevidenceforaspecialhazardforhumanswasfound.Thisisbasedonconventionalstudiesof

safetypharmacology,repeateddosetoxicity,genotoxicityandcarcinogenicpotential.

Phospholipidosisinseveralorganswasobservedinrepeateddosetoxicitystudiesinrats.Thisreversibleeffectis

knownforseverallipophilicaminesandwasnotconnectedwithmorphologicalandfunctionaleffects.Theclinical

relevanceisnotclear.

Embryotoxicitystudiesinratshaveshownskeletalanomalitesatmaternaltoxicdoses.Theeffectsmayberelatedto

thepharmacologicalactivityorcouldbeanindirecteffectduetomaternaltoxicity.Peri-andpostnatalstudieshave

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

Lactosemonohydrate

MaizeStarch

MicrocrystallineCellulose

Povidone

Crospovidone

MagnesiumStearate

TabletCoat

TitaniumDioxide(E171)

Lactosemonohydrate

Macrogol4000

Hypromellose(E464)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

PVC/PVdCblisterssealedwithaluminiumfoil(alsoincludesunitdosepacks).Packsizesof12,14,20,28,30,49,50,

56,60,98,100or500tablets.

PVC/PVdCblisterssealedwithaluminiumfoil.Calendarpacksizeof28tablets.

HighDensityPolyethylene(HDPE)tabletcontainerswithpolypropylene(PP)caps.Packsizesof12,14,20,28,50,

100or250tablets.

Polypropylenetabletcontainerswithpolyethylenecaps.Packsizesof12,14,20,28,50,100or250tablets.

Notallpacksizesmaybeavailable.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Irish Medicines Board

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Date Printed 22/09/2007 CRN 2024541 page number: 10

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLtd.

T/AGerardLaboratories

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA577/72/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13thOctober2005

Dateoflastrenewal:9thJanuary2007

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 22/09/2007 CRN 2024541 page number: 11