CITALOPRAM

Main information

  • Trade name:
  • CITALOPRAM Tablets 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CITALOPRAM Tablets 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0585/018/001
  • Authorization date:
  • 09-09-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Citalopram10mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontainscitalopramhydrobromideequivalentto10mgofcitalopram.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Citalopram10mgfilm-coatedtabletsareround,biconvex,white,film-coatedtabletsmarkedwith‘CI’ononesideand

10ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmajordepressiveepisodes.

Treatmentofpanicdisorderwithorwithoutagoraphobia.

4.2Posologyandmethodofadministration

Forthedifferentdosageregimenssuitablestrengthsshouldbeprescribed.

Citalopramtabletsareadministeredasasingledailydose.Citalopramtabletscanbetakenanytimeofthedaywithout

regardtofoodintake.

TreatingMajorDepressiveEpisodes

Citalopramshouldbeadministeredasasingleoraldoseof20mgdaily.Dependentonindividualpatientresponsethis

maybeincreasedtoamaximumof60mgdaily.

Followingtreatmentinitiation,anantidepressanteffectshouldnotbeexpectedforatleasttwoweeks.Atreatment

periodofatleast6monthsisusuallynecessarytoprovideadequatemaintenanceagainstthepotentialforrelapse.

TreatingPanicDisorder

Incommonwithotherpharmacotherapyusedinthispatientgroup,alowstartingdoseisadvisedtoreducethe

likelihoodofaparadoxicalinitialanxiogeniceffect.Asingleoraldoseof10mgdailyisrecommendedforthefirst

weekbeforeincreasingthedoseto20mgdaily.Thedosemaybefurtherincreased,uptoamaximumof60mgdaily

dependentonindividualpatientresponse,howeveranoptimumdoseis20-30mgdaily.

Maximumeffectivenessofcitalopramintreatingpanicdisorderisreachedafterabout3months.Dependenton

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 1

Elderlypatients(>65yearsold)

Treatmentofmajordepressiveepisodes:

Forelderlypatientsthedoseshouldbereducedto10-20mgdaily.Dependingonindividualpatientresponsethedose

maybeincreasedtoamaximumof40mgdaily.

Treatmentofpanicdisorder:

Theinitialdoseis10mgoncedaily.Afteroneweekthedosemaybeincreasedto20mgdaily.Dependingon

individualpatientresponsethedosemaybeincreasedtoamaximumof40mgdaily.

Childrenandadolescentsundertheageof18

Citalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years(seesection4.4).

Reducedhepaticfunction

Dosageshouldberestrictedtothelowerendofthedoserange.Patientswithhepaticimpairmentshouldreceivea

startingdoseof10mgdaily.Thedoseshouldnotexceed30mgperday(seesection4.4).Thesepatientsshouldbe

clinicallymonitored.

Reducedrenalfunction

Dosageadjustmentisnotnecessaryincasesofmildormoderaterenalimpairment.Noinformationisavailablein

casesofsevererenalimpairment(creatinineclearance<20ml/min)(seesection4.4).

Interruptionoftherapy

Toavoidwithdrawalreactionscitalopramshouldbewithdrawnslowly.Itisadvisedthatthedoseisgraduallyreduced

over1-2weekperiods(seesection4.8).

4.3Contraindications

Hypersensitivitytocitalopramortoanyoftheexcipients.

Monoamineoxidaseinhibitors:Casesofseriousandsometimesfatalreactionshavebeenreportedinpatientsreceiving

aselectiveserotoninreuptakeinhibitor(SSRI)incombinationwithmonoamineoxidaseinhibitor(MAOI),including

theselectiveMAOIselegilineandthereversibleMAOI(RIMA)moclobemideandinpatientswhohaverecently

discontinuedanSSRIandhavebeenstartedonaMAOI(seesection4.4).

Somecasespresentedwithfeaturesresemblingserotoninsyndrome.SymptomsofadruginteractionwithaMAOI

include:hyperthermia,rigidity,myoclonus,autonomicinstabilitywithpossiblerapidfluctuationsofvitalsigns,mental

statuschangesthatincludeconfusion,irritabilityandextremeagitationprogressingtodeliriumandcoma.

CitalopramshouldnotbeusedincombinationwithaMAOI.Citalopramshouldnotbegivenforfourteendaysafter

discontinuingtreatmentwithanirreversibleMAOIorforthetimespecifiedafterdiscontinuingtreatmentwitha

reversibleMAOI(RIMA)asstatedintheprescribingtextoftheRIMA.Atleast7daysshouldelapseafter

discontinuingcitalopramtreatmentbeforestartingaMAOIorRIMA.

4.4Specialwarningsandprecautionsforuse

Citalopramshouldnotbeusedconcomitantlywithmedicinalproductswithserotonergiceffectssuchastramadol,

tryptophan,oxitriptan,sumatriptanorothertriptans.

Diabetes-Inpatientswithdiabetes,treatmentwithanSSRImayalterglycaemiccontrol.Insulinandoral

hypoglycaemicdosagemayneedtobeadjusted.

Seizures-Seizuresareapotentialriskwithantidepressantdrugs.Thedrugshouldbediscontinuedinanypatientwho

developsseizures.Citalopramshouldbeavoidedinpatientswithunstableepilepsyandpatientswithcontrolled

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 2

Electroconvulsivetherapy(ECT)-Thereislittleclinicalexperienceofconcurrentadministrationofcitalopramand

ECT,thereforecautionisadvisable.

Mania-Citalopramshouldbeusedwithcautioninpatientswithahistoryofmania/hypomania.Citalopramshouldbe

discontinuedinanypatiententeringamanicphase.

Suicide/suicidalthoughtsorclinicalworsening:

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suiciderelatedevents).This

riskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthefirstfewweeksormoreof

treatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneralclinicalexperiencethatthe

riskofsuicidemayincreaseintheearlystagesofrecovery.

OtherpsychiatricconditionsforwhichCitalopramisprescribedcanalsobeassociatedwithanincreasedriskof

suicide-relatedevents.Inaddition,theseconditionsmaybeco-morbidwithmajordepressivedisorder.Thesame

precautionsobservedwhentreatingpatientswithmajordepressivedisordershouldthereforebeobservedwhentreating

patientswithotherpsychiatricdisorders.

Patientswithahistoryofsuicide-relatedevents,orthoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatmentareknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,andshouldreceive

carefulmonitoringduringtreatment.Ameta-analysisofplacebocontrolledclinicaltrialsofantidepressantdrugsin

adultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwithantidepressantscompared

toplaceboinpatientslessthan25yearsold.

Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patients(andcaregiversofpatients)shouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Haemorrhage-Therehavebeenreportsofbleedingabnormalitiessuchasecchymoses,purpuragynaecological

haemorrhages,gastrintestinalbleedingsandothercutaneousormucousbleedingswithSSRIs.Cautionisadvisedin

patientstakingcitalopram,particularlyinconcomitantusewithoralanticoagulants,activesubstancesknowntoaffect

plateletfunctionorotheractivesubstancesthatmayincreasetheriskofhaemorrhage(e.g.atypicalantipsychoticsand

phenothiazines,mosttricyclicantidepressants,acetylsalicylicacidandnon-steroidalanti-inflammatorydrugs

(NSAIDs)aswellasinpatientswithahistoryofbleedingdisorders.

Serotoninsyndrome-InrarecasesaserotoninsyndromehasbeenreportedinpatientsusingSSRIs.

Acombinationofsymptoms,suchasagitation,tremor,myoclonusandhyperthermiamayindicatethedevelopmentof

thiscondition.Treatmentwithcitalopramshouldbediscontinuedimmediatelyandsymptomatictreatmentinitiated.

Hyponatraemia-Hyponatraemiaandthesyndromeofinappropriateanti-diuretichormonesecretion(SIADH)hasbeen

reportedrarely,predominantlyintheelderly,andgenerallyreversesondiscontinuationoftherapy.

StJohn'swort–Anincreaseinserotoninergiceffects,suchasserotoninsyndrome,mayoccuratconcomitantuseof

citalopramandherbalpreparationscontainingStJohn'swort(Hypericumperforatum).ThereforecitalopramandSt

John'swortpreparationsshouldnotbetakenconcomitantly(seesection4.5).

Psychosis-Treatmentofpsychoticpatientswithdepressiveepisodesmayincreasepsychoticsymptoms.

Experiencewithcitalopramhasnotrevealedanyclinicallyrelevantinteractionswithneuroleptics.

However,aswithotherSSRIs,thepossibilityofapharmacodynamicinteractioncannotbeexcluded.

Considerationshouldbegiventofactorsthatmayaffectthedispositionofaminormetaboliteofcitalopram

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 3

susceptibleindividuals.However,inECGmonitoringofpatientsinclinicaltrials,includingthosepatientswithpre-

existingcardiacconditions,noclinicallysignificantchangeswerenoted.

Somepatientswithpanicdisorderexperienceaninitialanxiogeniceffectwhenstartingpharmacotherapy.Alow

startingdose(seePosology)reducesthelikelihoodofthiseffect.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Theuseofcitalopraminpatientswithsevererenalimpairment(creatinineclearancelessthan20ml/min.)isnot

recommendedasnoinformationisavailableonuseinthesepatients(seesection4.2).

Incasesofimpairedhepaticfunctiondosereductionisrecommended(seesection4.2)andliverfunctionhastobe

closelymonitored.

Useinchildrenandadolescentsunder18yearsofage-CitalopramTabletsshouldnotbeusedinthetreatmentof

childrenandadolescentsundertheageof18years,exceptforpatientswithOCD.Suicide-relatedbehaviours(suicide

attemptandsuicidalthoughts)andhostility(predominantlyaggression,oppositionalbehaviourandanger)weremore

frequentlyobservedinclinicaltrialsamongchildrenandadolescentstreatedwithantidepressantscomparedwiththose

treatedwithplacebo.If,basedonclinicalneed,adecisiontotreatisneverthelesstaken,thepatientshouldbecarefully

monitoredfortheappearanceofsuicidalsymptoms.Inaddition,long-termsafetydatainchildrenandadolescents

concerninggrowth,maturationandcognitiveandbehaviouraldevelopmentarelacking.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Monoamineoxidaseinhibitors(MAOIs)shouldnotbeusedincombinationwithSSRIs(seesection4.3).

ThemetabolismofcitalopramisonlypartlydependentonthehepaticcytochromeP450isozymeCYP2D6and,unlike

someotherSSRIs,citalopramisonlyaweakinhibitorofthisimportantenzymesystemwhichisinvolvedinthe

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

bindingisrelativelylow(<80%).Thesepropertiesgivecitalopramalowpotentialforclinicallysignificantdrug

interactions.

Alcohol-Thecombinationofcitalopramandalcoholisnotadvisable.However,noadversepharmacodynamic

interactionsbetweencitalopramandalcoholhavebeennoted.

Serotonergicdrugs–Co-administrationwithserotonergicdrugs(e.g.tramadol,tryptophan,oxitriptan,sumatriptanand

othertriptans)mayleadtoserotoninsyndrome.Incombinationwithtriptans,thereisapotentialriskofcoronary

vasoconstrictionandhypertensiontoo.Therefore,thesimultaneoususeofcitalopramandtheseactivesubstancesisnot

recommended(seesection4.4).

Lithium-Thereisnopharmacokineticinteractionbetweenlithiumandcitalopram.

HowevertherehavebeenreportsofserotoninsyndromewhenSSRIshavebeengivenwithlithiumandthereforethe

concomitantuseofcitalopramwithlithiumshouldbeundertakenwithcautionandcloserandmorefrequentclinical

monitoringisrequired.

Cautioniswarrantedforpatientswhoarebeingtreatedsimultaneouslywithoralanticoagulants,activesubstances

knowntoaffectplateletfunction,orothermedicinesthatcanincreasetheriskofhaemorrhage(e.g.NSAIDs,

acetylsalicylicacid,dipyridamol,ticlopidine,atypicalantipsychotics,phenothiazines,mosttricyclicdepressants)(see

section4.4).

Co-administrationofcitalopramandmetoprolol(CYP2D6substrate)resultedinatwo-foldincreaseintheplasma

levelsofmetoprolol.Noclinicallysignificanteffectsonbloodpressureorheartratewereobserved.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 4

desipramine,theprimarymetaboliteofimipramine,wasincreased.Whendesipramineiscombinedwithcitalopram,an

increaseofthedesipramineplasmaconcentrationhasbeenobserved.Areductionofthedesipraminedosemaybe

needed.

Cimetidine,aknownenzyme-inhibitor,causedaslightriseintheaveragesteady-statecitalopramlevels.Cautionis

thereforerecommendedwhenadministeringhighdosesofcitalopramincombinationwithhighdosesofcimetidine.

PharmacodynamicinteractionsbetweencitalopramandherbalremedyStJohn'sWort(Hypericumperforatum)can

occurresultinginanincreaseinundesirableeffects(seesection4.4).

Inclinicalstudiesnopharmacodynamicinteractionshavebeennotedwhencitalopramwasgivenconcomitantlywith

benzodiazepines,neuroleptics,analgesics,lithium,antihistamines,antihypertensivedrugs,beta-blockersandother

cardiovasculardrugs.

Theabsorptionandotherpharmacokineticpropertiesofcitalopramhavenotbeenreportedtobeaffectedbyfood.

4.6Pregnancyandlactation

Pregnancy:

Basedonalimitednumberofexposedpregnancies,availabledatadonotgiveindicationofanincreasedriskof

congenitalmalformationsinthenewborn.

Animalstudiesshowedreproductivetoxicity,butdidnotindicatedirectharmfuleffectswithrespecttopregnancy,

embryonic/foetaldevelopment,parturitionorpostnataldevelopment(seesection5.3).

ThefollowingeffectswerereportedinneonateswithSSRIsadministeredtopregnantwomenuntilanimminentdateof

birthoruntilbirth:irritability,tremor,hypertonia,increasedmuscletone,constantcrying,anddifficultyinsucklingor

insleeping.Theymayeitherindicateserotoninergiceffectsorwithdrawalsyndrome.Thetimetooccurandthe

durationofthesesymptomsintheorydependontheeliminationhalf-lifeoftheproduct.

Theuseofcitaloprammaybeconsideredduringpregnancywhennecessary,andneonateshouldbeobservedwhen

prescribinguntilanimminentdateofbirthoruntilbirth.

Atreatmentshouldneverbeabruptlystoppedduringpregnancy.

Lactation:

Citalopramisexcretedinmilkinsmallquantities.Benefitsofbreast-feedingshouldbeweighedagainstthepossible

riskstothechild.

4.7Effectsonabilitytodriveandusemachines

Citalopramdoesnotimpairintellectualfunctionandpsychomotorperformance.However,patientswhoareprescribed

psychotropicmedicationmaybeexpectedtohavesomeimpairmentofgeneralattentionandconcentrationeitherdueto

theillnessitself,themedicationorbothandshouldbecautionedabouttheirabilitytodriveacarandoperate

machinery.

4.8Undesirableeffects

Adverseeffectsobservedwithcitalopramareingeneralmildandtransient.Theyaremostprominentduringthefirst

oneortwoweeksoftreatmentandusuallyattenuateasthedepressivestateimproves.

Incomparativeclinicaltrialswithtricyclicantidepressantstheincidenceofadverseeventsoccurringwithcitalopram

wasfoundtobelowerinallcases.

Withdrawalreactionshavebeenreportedinassociationwithselectiveserotoninreuptakeinhibitors(SSRIs),including

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 5

oftreatmentwithcitalopramshouldbeavoided(seesection4.2).Themajorityofsymptomsexperiencedon

withdrawalofSSRIsarenon-seriousandself-limiting.

Adverseeventsreportedinclinicaltrialswiththefollowingfrequencies:

Verycommon

(>10%) Common

(>1%,<10%) Uncommon

(>0.1%,<1%) Veryrare

(<0.01%,

including

isolatedreports) Frequency

notknown

Psychiatric

disorders Somnolence,

insomnia,

agitation,

nervousness Sleepdisorders,

impaired

concentration,

abnormal

dreaming,

amnesia,

anxiety,

decreased

libido,

increased

appetite,

anorexia,

apathy,

Euphoria,

increasedlibido Hallucinations,

mania,

depersonalisation,

panicattack

(thesesymptoms

maybeduetothe

underlying

disease) Suicidal

ideation

suicidal

behaviour*

Nervoussystem

disorders Headache,

tremor,

dizziness Migraine,

paraesthesia Extrapyramidal

disorder,

convulsions Serotonin

syndrome,

akathisia

Cardiac

disorders Palpitations Tachycardia Bradycardia Supraventricular

&ventricular

arrhythmias

Vascular

disorders Postural

hypotension,

hypotension,

hypertension

Gastrointestinal

disorders Nausea,dry

mouth,

constipation,

diarrhoea Dyspepsia,

vomiting,

abdominal

pain,flatulence,

increased

salivation

Renaland

urinary

disorders Micturition

disorder,

polyuri

Hyponatraemia

Metabolism

andnutrition

disorders Weight

decrease,

weightincrease

Hepato-biliary

disorders Increasedliver

enzymevalues

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 6

*Casesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringcitalopramtherapyorearlyafter

treatmentdiscontinuation(seesection4.4).

4.9Overdose

Citalopramisgiventopatientsatpotentialriskofsuicideandsomereportsofattemptedsuicidehavebeenreceived.

Detailisoftenlackingregardingprecisedoseorcombinationwithotherdrugsand/oralcohol.

Fataldosenotknown.Patientshavesurvivedingestionofupto2gcitalopram.Theeffectswillbepotentiatedby

alcoholtakenatthesametime.PotentialinteractionwithtricyclicantidepressantsandMAOIs.

Symptoms:

Nausea,vomiting,sweating,tachycardia,drowsiness,coma,dystonia,convulsions,hyperventilationandhyperpyrexia

havebeenreported.Cardiacfeaturesthathavebeenobservedincludenodalrhythm,prolongedQTintervalsandwide

disorders Sinusitis

Reproductive

system

disorders Ejaculation

failure,

female

anorgasmia,

dysmenorrhoea,

impotence galactorrhoea

Skindisorders Increased

sweating Rash,

Pruritus Photosensitivityangiodema

Eyedisorders Abnormal

accommodation Abnormalities

ofvision

Specialsenses

Disorders Taste

Abnormalities

Earand

labyrinth

disorders Tinnitus

Musculoskeletal

disorders Myalgia arthralgia

General

disorders Asthenia Fatigue,

yawning Allergic

reactions,

syncope,

malaise,

ecchymosis,

purpura,

gynaecological

haemorrhages,

gastrointestinal

bleedingand

othercutaneous

ormucous

membrane

Anaphylactoid

reactions,

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 7

Rarely,featuresofthe"serotoninsyndrome"mayoccurinseverepoisoning.Thisincludesalterationofmentalstatus,

neuromuscularhyperactivityandautonomicinstability.Theremaybehyperpyrexiaandelevationofserumcreatine

kinase.Rhabdomyolysisisrare.

Treatment:

Thereisnospecificantidote.Treatmentissymptomaticandsupportive.

Iftheamountofmedicineislargeandingestionveryrecent,gastriclavagecanbeconsidered(ifthepatienthaslost

consciousness,intubationmustbeperformedfirst).Otherwise,itisessentialtoadministeractivatedcharcoaltoreduce

furtherabsorption.Speedingupthepassageusingsuitablelaxatives,e.g.,sodiumsulphatecanalsobeconsidered.

Medicalsurveillanceisadvisable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Selectiveserotoninreuptakeinhibitors(SSRI)

ATCcode:N06AB04

Biochemicalandbehaviouralstudieshaveshownthatcitalopramisapotentinhibitoroftheserotonin(5-HT)-uptake.

Tolerancetotheinhibitionof5-HT-uptakeisnotinducedbylong-termtreatmentwithcitalopram.

Citalopramisthemostselectiveserotoninreuptakeinhibitor(SSRI)yetdescribed,withno,orminimal,effecton

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

IncontrasttomanytricyclicantidepressantsandsomeoftheotherSSRI's,citalopramhasnoneorverylowaffinityfor

aseriesofreceptorsincluding5-HT

5-HT

,DAD

andD

receptors,

-,-adrenoceptors,histamineH

muscarinecholinergic,benzodiazepine,andopioidreceptors.Aseriesoffunctionalinvitrotestsinisolatedorgansas

wellasfunctionalinvivotestshaveconfirmedthelackofreceptoraffinity.Thisabsenceofeffectsonreceptorscould

explainwhycitalopramproducesfewerofthetraditionalsideeffectssuchasdrymouth,bladderandgutdisturbance,

blurredvision,sedation,cardiotoxicityandorthostatichypotension.

Suppressionofrapideyemovement(REM)sleepisconsideredapredictorofantidepressantactivity.Liketricyclic

antidepressants,otherSSRI'sandMAOinhibitors,citalopramsuppressesREM-sleepandincreasesdeepslow-wave

sleep.

Althoughcitalopramdoesnotbindtoopioidreceptorsitpotentiatestheanti-nociceptiveeffectofcommonlyused

opioidanalgesics.Therewaspotentiationofd-amphetamine-inducedhyperactivityfollowingadministrationof

citalopram.

ThemainmetabolitesofcitalopramareallSSRIsalthoughtheirpotencyandselectivityratiosarelowerthanthoseof

citalopram.However,theselectivityratiosofthemetabolitesarehigherthanthoseofmanyoftheotherSSRIs.The

metabolitesdonotcontributetotheoverallantidepressanteffect.

5.2Pharmacokineticproperties

Absorption

Absorptionisalmostcompleteandindependentoffoodintake(T

average/mean3.8hours).Oralbioavailabilityis

about80%.

Distribution

Theapparentvolumeofdistribution(V

)isabout12.3L/kg.Theplasmaproteinbindingisbelow80%forcitalopram

anditsmainmetabolites.

Biotransformation

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 8

deaminatedpropionicacidderivative.AlltheactivemetabolitesarealsoSSRIs,althoughweakerthantheparent

compound.Unchangedcitalopramisthepredominantcompoundinplasma.

Elimination

Theeliminationhalf-life(T

)isabout1.5days,thesystemiccitalopramplasmaclearance(Cl

)isabout0.33L/min

(330ml/min),andoralplasmaclearance(Cl

oral )isabout0.41L/min(410ml/min).

Citalopramisexcretedmainlyviatheliver(85%)andtheremainder(15%)viathekidneys.About12-23%ofthedaily

doseisexcretedinurineasunchangedcitalopram.Hepatic(residual)clearanceisabout0.35L/min(350ml/min)and

renalclearanceabout0.068L/min(68ml/min).

Thekineticsislinear.Steadystateplasmalevelsareachievedin1-2weeks.Averageconcentrationsof250nmol/L

(100-500nmol/L)areachievedatadailydoseof40mg.Thereisnoclearrelationshipbetweencitalopramplasma

levelsandtherapeuticresponseorsideeffects.

Elderlypatients(65years)

Longerhalf-livesanddecreasedclearancevaluesduetoareducedrateofmetabolismhavebeendemonstratedin

elderlypatients.

Reducedhepaticfunction

Citalopramiseliminatedmoreslowlyinpatientswithreducedhepaticfunction.Thehalf-lifeofcitalopramisabout

twiceaslongandsteadystatecitalopramconcentrationsatagivendosewillbeabouttwiceashighasinpatientswith

normalliverfunction.

Reducedrenalfunction

Citalopramiseliminatedmoreslowlyinpatientswithmildtomoderatereductionofrenalfunction,withoutanymajor

impactonthepharmacokineticsofcitalopram.Atpresentnoinformationisavailablefortreatmentofpatientswith

severelyreducedrenalfunction(creatinineclearance<20mL/min).

5.3Preclinicalsafetydata

Preclinicaldatarevealednospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,

genotoxicityandcarcinogenicpotential.Phospholipidosishasbeenobservedinseveralorgansfollowingmultiple

administrationinrats.Theeffectwasreversibleatdiscontinuation.Accumulationofphospholipidshasbeenobserved

inlongtermanimalstudieswithmanycation-amphophilicdrugs.Theclinicalrelevanceoftheseresultsisnotclear.

Embryotoxicitystudiesinratshaveshownskeletalanomaliesathighmaternaltoxicdoses.Theeffectsmayberelated

tothepharmacologicalactivityormaybeaconsequenceofmaternaltoxicity.Peri-andpostnatalstudieshaverevealed

reducedsurvivalinoffspringduringthelactationperiod.Thepotentialriskforhumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Maizestarch

Lactosemonohydrate

CroscarmelloseSodium

Glycerol

Copovidone

Magnesiumstearate

Microcystallinecellulose

Tabletcoat:

Hypromellose

Macrogol

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 9

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

PVC/Alublisters

Packsize:10,20,28,50or100tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PlivaPharmaLimited

VisionHouse

BedfordRoad

Petersfield

HampshireGU323QB

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0585/018/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:09September2005

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/04/2010 CRN 2080319 page number: 10