ESCITOMAR

Main information

  • Trade name:
  • ESCITOMAR Film Coated Tablet 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ESCITOMAR Film Coated Tablet 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0740/013/001
  • Authorization date:
  • 15-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Escitomar10mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgescitalopram(asoxalate)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmajordepressiveepisodes.

Treatmentofpanicdisorderwithorwithoutagoraphobia.

Treatmentofsocialanxietydisorder(socialphobia).

Treatmentofgeneralisedanxietydisorder.

Treatmentofobsessive-compulsivedisorder.

4.2Posologyandmethodofadministration

Safetyofdailydosesabove20mghasnotbeendemonstrated.

Escitalopramisadministeredasasingledailydoseandmaybetakenwithorwithoutfood.

Majordepressiveepisodes

Usualdosageis10mgoncedaily.Dependingonindividualpatientresponse,thedosemaybeincreasedtoamaximum

of20mgdaily.

Usually2-4weeksarenecessarytoobtainantidepressantresponse.Afterthesymptomsresolve,treatmentforatleast6

monthsisrequiredforconsolidationoftheresponse.

Panicdisorderwithorwithoutagoraphobia

Aninitialdoseof5mgisrecommendedforthefirstweekbeforeincreasingthedoseto10mgdaily.Thedosemaybe

furtherincreased,uptoamaximumof20mgdaily,dependentonindividualpatientresponse.

Film-coatedtablet(tablet)

White,oval,film-coatedtablets,debossedwith‘E9CM’ononesideandontheotherside

scoredanddebossedwith‘10’(onenumberoneachsideofthescoringline).

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Socialanxietydisorder

Usualdosageis10mgoncedaily.Usually2-4weeksarenecessarytoobtainsymptomrelief.Thedosemay

subsequently,dependingonindividualpatientresponse,bedecreasedto5mgorincreasedtoamaximumof20mg

daily.

Socialanxietydisorderisadiseasewithachroniccourse,andtreatmentfor12weeksisrecommendedtoconsolidate

response.Long-termtreatmentofrespondershasbeenstudiedfor6monthsandcanbeconsideredonanindividual

basistopreventrelapse;treatmentbenefitsshouldbere-evaluatedatregularintervals.

Socialanxietydisorderisawell-defineddiagnosticterminologyofaspecificdisorder,whichshouldnotbeconfounded

withexcessiveshyness.Pharmacotherapyisonlyindicatedifthedisorderinterferessignificantlywithprofessionaland

socialactivities.

Theplaceofthistreatmentcomparedtocognitivebehaviouraltherapyhasnotbeenassessed.Pharmacotherapyispart

ofanoveralltherapeuticstrategy.

Generalisedanxietydisorder

Initialdosageis10mgoncedaily.Dependingontheindividualpatientresponse,thedosemaybeincreasedtoa

maximumof20mgdaily.

Longtermtreatmentofrespondershasbeenstudiedforatleast6monthsinpatientsreceiving20mg/day.Treatment

benefitsanddoseshouldbere-evaluatedatregularintervals(seesection5.1).

Obsessive-CompulsiveDisorder

Initialdosageis10mgoncedaily.Dependingontheindividualpatientresponse,thedosemaybeincreasedtoa

maximumof20mgdaily.

AsOCDisachronicdisease,patientsshouldbetreatedforasufficientperiodtoensurethattheyaresymptomfree.

Treatmentbenefitsanddoseshouldbere-evaluatedatregularintervals(seesection5.1).

Elderlypatients(>65yearsofage)

Initialtreatmentwithhalftheusuallyrecommendeddoseandalowermaximumdoseshouldbeconsidered(seesection

5.2).

Theefficacyofescitalopraminsocialanxietydisorderhasnotbeenstudiedinelderlypatients.

Childrenandadolescents(<18years)

Escitalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years(seesection

4.4).

Reducedrenalfunction

Dosageadjustmentisnotnecessaryinpatientswithmildormoderaterenalimpairment.Cautionisadvisedinpatients

withseverelyreducedrenalfunction(CLCRlessthan30ml/min)(seesection5.2).

Reducedhepaticfunction

Aninitialdoseof5mgdailyforthefirsttwoweeksoftreatmentisrecommendedinpatientswithmildormoderate

hepaticimpairment.Dependingonindividualpatientresponse,thedosemaybeincreasedto10mgdaily.Cautionand

extracarefuldosetitrationisadvisedinpatientswithseverelyreducedhepaticfunction(seesection5.2).

PoormetabolisersofCYP2C19

ForpatientswhoareknowntobepoormetaboliserswithrespecttoCYP2C19,aninitialdoseof5mgdailyduringthe

firsttwoweeksoftreatmentisrecommended.Dependingonindividualpatientresponse,thedosemaybeincreasedto

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Discontinuationsymptomsseenwhenstoppingtreatment

Abruptdiscontinuationshouldbeavoided.Whenstoppingtreatmentwithescitalopramthedoseshouldbegradually

reducedoveraperiodofatleastonetotwoweeksinordertoreducetheriskofdiscontinuationsymptoms(seesection

4.4and4.8).Ifintolerablesymptomsoccurfollowingadecreaseinthedoseorupondiscontinuationoftreatment,then

resumingthepreviouslyprescribeddosemaybeconsidered.Subsequently,thephysicianmaycontinuedecreasingthe

dose,butatamoregradualrate.

4.3Contraindications

Hypersensitivitytoescitalopramortoanyoftheexcipients.

Concomitanttreatmentwithnon-selective,irreversiblemonoamineoxidaseinhibitors(MAO-inhibitors)is

contraindicatedduetotheriskofserotoninsyndromewithagitation,tremor,hyperthermiaetc.(seesection4.5).

ThecombinationofescitalopramwithreversibleMAO-Ainhibitors(e.g.moclobemide)orthereversiblenon-selective

MAO-inhibitorlinezolidiscontraindicatedduetotheriskofonsetofaserotoninsyndrome(seesection4.5).

4.4Specialwarningsandprecautionsforuse

ThefollowingspecialwarningsandprecautionsapplytothetherapeuticclassofSSRIs(SelectiveSerotoninRe-uptake

Inhibitors).

Useinchildrenandadolescentsunder18yearsofage

Escitalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years.Suiciderelated

behaviours(suicideattemptandsuicidalthoughts),andhostility(predominatelyaggression,oppositionalbehaviourand

anger)weremorefrequentlyobservedinclinicaltrialsamongchildrenandadolescentstreatedwithantidepressants

comparedtothosetreatedwithplacebo.If,basedonclinicalneed,adecisiontotreatisneverthelesstaken,thepatient

shouldbecarefullymonitoredfortheappearanceofsuicidalsymptoms.Inaddition,long-termsafetydatainchildren

andadolescentsconcerninggrowth,maturationandcognitiveandbehaviouraldevelopmentarelacking.

Paradoxicalanxiety

Somepatientswithpanicdisordermayexperienceincreasedanxietysymptomsatthebeginningoftreatmentwith

antidepressants.Thisparadoxicalreactionusuallysubsideswithintwoweeksduringcontinuedtreatment.Alow

startingdoseisadvisedtoreducethelikelihoodofananxiogeniceffect(seesection4.2).

Seizures

Escitalopramshouldbediscontinuedifapatientdevelopsseizuresforthefirsttime,orifthereisanincreaseinseizure

frequency(inpatientswithapreviousdiagnosisofepilepsy).SSRIsshouldbeavoidedinpatientswithunstable

epilepsyandpatientswithcontrolledepilepsyshouldbecloselymonitored.

Mania

SSRIsshouldbeusedwithcautioninpatientswithahistoryofmania/hypomania.SSRIsshouldbediscontinuedinany

patiententeringamanicphase.

Diabetes

Inpatientswithdiabetes,treatmentwithanSSRImayalterglycaemiccontrol(hypoglycaemiaorhyperglycaemia).

Insulinand/ororalhypoglycaemicdosagemayneedtobeadjusted.

Suicide/suicidalthoughtsorclinicalworsening

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suicide-relatedevents).This

riskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthefirstfewweeksormoreof

treatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneralclinicalexperiencethatthe

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Otherpsychiatricconditionsforwhichescitalopramisprescribedcanalsobeassociatedwithanincreasedriskof

suicide-relatedevents.Inaddition,theseconditionsmaybeco-morbidwithmajordepressivedisorder.Thesame

precautionsobservedwhentreatingpatientswithmajordepressivedisordershouldthereforebeobservedwhentreating

patientswithotherpsychiatricdisorders.

Patientswithahistoryofsuicide-relatedevents,orthoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatment,areknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,andshould

receivecarefulmonitoringduringtreatment.Ametaanalysisofplacebocontrolledclinicaltrialsofantidepressant

drugsinadultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwithantidepressants

comparedtoplaceboinpatientslessthan25yearsold.

Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patients(andcaregiversofpatients)shouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Akathisia/psychomotorrestlessness

TheuseofSSRIs/SNRIshasbeenassociatedwiththedevelopmentofakathisia,characterisedbyasubjectively

unpleasantordistressingrestlessnessandneedtomoveoftenaccompaniedbyaninabilitytositorstandstill.Thisis

mostlikelytooccurwithinthefirstfewweeksoftreatment.Inpatientswhodevelopthesesymptoms,increasingthe

dosemaybedetrimental.

Hyponatraemia

Hyponatraemia,probablyduetoinappropriateantidiuretichormonesecretion(SIADH),hasbeenreportedrarelywith

theuseofSSRIsandgenerallyresolvesondiscontinuationoftherapy.Cautionshouldbeexercisedinpatientsatrisk,

suchastheelderly,orpatientswithcirrhosis,orifusedincombinationwithothermedicationsknowntocause

hyponatraemia.

Haemorrhage

Therehavebeenreportsofcutaneousbleedingabnormalities,suchasecchymosesandpurpura,withSSRIs.Cautionis

advisedinpatientstakingSSRIs,particularlyinconcomitantusewithoralanticoagulants,withmedicinalproducts

knowntoaffectplateletfunction(e.g.atypicalantipsychoticsandphenothiazines,mosttricyclicantidepressants,

acetylsalicylicacidandnon-steroidalanti-inflammatorymedicinalproducts(NSAIDs),ticlopidineanddipyridamole)

andinpatientswithknownbleedingtendencies.

ECT(electroconvulsivetherapy)

ThereislimitedclinicalexperienceofconcurrentadministrationofSSRIsandECT,thereforecautionisadvisable.

Serotoninsyndrome

Cautionisadvisableifescitalopramisusedconcomitantlywithmedicinalproductswithserotonergiceffectssuchas

sumatriptanorothertriptans,tramadolandtryptophan.

Inrarecases,serotoninsyndromehasbeenreportedinpatientsusingSSRIsconcomitantlywithserotonergicmedicinal

products.Acombinationofsymptoms,suchasagitation,tremor,myoclonusandhyperthermiamayindicatethe

developmentofthiscondition.IfthisoccurstreatmentwiththeSSRIandtheserotonergicmedicinalproductshouldbe

discontinuedimmediatelyandsymptomatictreatmentinitiated.

St.John´sWort

ConcomitantuseofSSRIsandherbalremediescontainingSt.John´sWort(Hypericumperforatum)mayresultinan

increasedincidenceofadversereactions(seesection4.5).

Discontinuationsymptomsseenwhenstoppingtreatment

Discontinuationsymptomswhenstoppingtreatmentarecommon,particularlyifdiscontinuationisabrupt(seesection

4.8).Inclinicaltrialsadverseeventsseenontreatmentdiscontinuationoccurredinapproximately25%ofpatients

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Theriskofdiscontinuationsymptomsmaybedependentonseveralfactorsincludingthedurationanddoseoftherapy

andtherateofdosereduction.Dizziness,sensorydisturbances(includingparaesthesiaandelectricshocksensations),

sleepdisturbances(includinginsomniaandintensedreams),agitationoranxiety,nauseaand/orvomiting,tremor,

confusion,sweating,headache,diarrhoea,palpitations,emotionalinstability,irritability,andvisualdisturbancesarethe

mostcommonlyreportedreactions.Generallythesesymptomsaremildtomoderate;however,insomepatientsthey

maybesevereinintensity.

Theyusuallyoccurwithinthefirstfewdaysofdiscontinuingtreatment,buttherehavebeenveryrarereportsofsuch

symptomsinpatientswhohaveinadvertentlymissedadose.

Generallythesesymptomsareself-limitingandusuallyresolvewithin2weeks,thoughinsomeindividualstheymay

beprolonged(2-3monthsormore).Itisthereforeadvisedthatescitalopramshouldbegraduallytaperedwhen

discontinuingtreatmentoveraperiodofseveralweeksormonths,accordingtothepatient'sneeds(see

“Discontinuationsymptomsseenwhenstoppingtreatment”,section4.2).

Coronaryheartdisease

Duetolimitedclinicalexperience,cautionisadvisedinpatientswithcoronaryheartdisease(seesection5.3).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Pharmacodynamicinteractions

Contra-indicatedcombinations:

Irreversiblenon-selectiveMAOIs

CasesofseriousreactionshavebeenreportedinpatientsreceivinganSSRIincombinationwithanon-selective,

irreversiblemonoamineoxidaseinhibitor(MAOI),andinpatientswhohaverecentlydiscontinuedSSRItreatmentand

havebeenstartedonsuchMAOItreatment(seesection4.3).Insomecases,thepatientdevelopedserotoninsyndrome

(seesection4.8).

Escitalopramiscontra-indicatedincombinationwithnon-selective,irreversibleMAOIs.Escitaloprammaybestarted

14daysafterdiscontinuingtreatmentwithanirreversibleMAOI.Atleast7daysshouldelapseafterdiscontinuing

escitalopramtreatment,beforestartinganon-selective,irreversibleMAOI.

Reversible,selectiveMAO-Ainhibitor(moclobemide)

Duetotheriskofserotoninsyndrome,thecombinationofescitalopramwithaMAO-Ainhibitorsuchasmoclobemide

iscontraindicated(seesection4.3).Ifthecombinationprovesnecessary,itshouldbestartedattheminimum

recommendeddosageandclinicalmonitoringshouldbereinforced.

Reversible,non-selectiveMAO-inhibitor(linezolid)

Theantibioticlinezolidisareversiblenon-selectiveMAO-inhibitorandshouldnotbegiventopatientstreatedwith

escitalopram.Ifthecombinationprovesnecessary,itshouldbegivenwithminimumdosagesandundercloseclinical

monitoring(seesection4.3).

Irreversible,selectiveMAO-Binhibitor(selegiline)

Incombinationwithselegiline(irreversibleMAO-Binhibitor),cautionisrequiredduetotheriskofdeveloping

serotoninsyndrome.Selegilinedosesupto10mg/dayhavebeensafelyco-administeredwithracemiccitalopram.

Combinationsrequiringprecautionsforuse:

Serotonergicmedicinalproducts

Co-administrationwithserotonergicmedicinalproducts(e.g.tramadol,sumatriptanandothertriptans)mayleadto

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Medicinalproductsloweringtheseizurethreshold

SSRIscanlowertheseizurethreshold.Cautionisadvisedwhenconcomitantlyusingothermedicinalproductscapable

ofloweringtheseizurethreshold(e.gantidepressants(tricyclics,SSRIs),neuroleptics(phenothiazines,thioxanthenes

andbutyrophenones),mefloquin,bupropionandtramadol).

Lithium,tryptophan

TherehavebeenreportsofenhancedeffectswhenSSRIshavebeengiventogetherwithlithiumortryptophan,

thereforeconcomitantuseofSSRIswiththesemedicinalproductsshouldbeundertakenwithcaution.

St.John'sWort

ConcomitantuseofSSRIsandherbalremediescontainingSt.John´sWort(Hypericumperforatum)mayresultinan

increasedincidenceofadversereactions(seesection4.4).

Haemorrhage

Alteredanti-coagulanteffectsmayoccurwhenescitalopramiscombinedwithoralanticoagulants.Patientsreceiving

oralanticoagulanttherapyshouldreceivecarefulcoagulationmonitoringwhenescitalopramisstartedorstopped(see

section4.4).

Alcohol

Nopharmacodynamicorpharmacokineticinteractionsareexpectedbetweenescitalopramandalcohol.However,as

withotherpsychotropicmedicinalproducts,thecombinationwithalcoholisnotadvisable.

Pharmacokineticinteractions

Influenceofothermedicinalproductsonthepharmacokineticsofescitalopram

ThemetabolismofescitalopramismainlymediatedbyCYP2C19.CYP3A4andCYP2D6mayalsocontributetothe

metabolismalthoughtoasmallerextent.ThemetabolismofthemajormetaboliteS-DCT(demethylatedescitalopram)

seemstobepartlycatalysedbyCYP2D6.

Co-administrationofescitalopramwithomeprazole30mgoncedaily(aCYP2C19inhibitor)resultedinmoderate

(approximately50%)increaseintheplasmaconcentrationsofescitalopram.

Co-administrationofescitalopramwithcimetidine400mgtwicedaily(moderatelypotentgeneralenzyme-inhibitor)

resultedinamoderate(approximately70%)increaseintheplasmaconcentrationsofescitalopram.

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

fluvoxamine,lansoprazole,ticlopidine)orcimetidine.Areductioninthedoseofescitaloprammaybenecessarybased

onmonitoringofside-effectsduringconcomitanttreatment.

Effectofescitalopramonthepharmacokineticsofothermedicinalproducts

EscitalopramisaninhibitoroftheenzymeCYP2D6.Cautionisrecommendedwhenescitalopramisco-administered

withmedicinalproductsthataremainlymetabolisedbythisenzyme,andthathaveanarrowtherapeuticindex,e.g.

flecainide,propafenoneandmetoprolol(whenusedincardiacfailure),orsomeCNSactingmedicinalproductsthatare

mainlymetabolisedbyCYP2D6,e.g.antidepressantssuchasdesipramine,clomipramineandnortriptylineor

antipsychoticslikerisperidone,thioridazineandhaloperidol.Dosageadjustmentmaybewarranted.

Co-administrationwithdesipramineormetoprololresultedinbothcasesinatwofoldincreaseintheplasmalevelsof

thesetwoCYP2D6substrates.

InvitrostudieshavedemonstratedthatescitaloprammayalsocauseweakinhibitionofCYP2C19.Cautionis

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4.6Pregnancyandlactation

Pregnancy

Forescitalopramonlylimitedclinicaldataareavailableregardingexposedpregnancies.

Inreproductivetoxicitystudiesperformedinratswithescitalopram,embryo-fetotoxiceffects,butnoincreased

incidenceofmalformations,wereobserved(seesection5.3).Escitalopramshouldnotbeusedduringpregnancyunless

clearlynecessaryandonlyaftercarefulconsiderationoftherisk/benefit.

Neonatesshouldbeobservedifmaternaluseofescitalopramcontinuesintothelaterstagesofpregnancy,particularly

inthethirdtrimester.Abruptdiscontinuationshouldbeavoidedduringpregnancy.

ThefollowingsymptomsmayoccurintheneonateaftermaternalSSRI/SNRIuseinlaterstagesofpregnancy:

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

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

difficultysleeping.Thesesymptomscouldbeduetoeitherserotonergiceffectsordiscontinuationsymptoms.Ina

majorityofinstancesthecomplicationsbeginimmediatelyorsoon(<24hours)afterdelivery.

EpidemiologicaldatahavesuggestedthattheuseofSSRIsinpregnancy,particularinlatepregnancy,mayincreasethe

riskofpersistentpulmonaryhypertensioninthenewborn(PPHN).Theobservedriskwasapproximately5casesper

1000pregnancies.Inthegeneralpopulation1to2casesofPPHNper1000pregnanciesoccur.

Lactation

Itisexpectedthatescitalopramwillbeexcretedintohumanmilk.

Consequently,breast-feedingisnotrecommendedduringtreatment.

4.7Effectsonabilitytodriveandusemachines

Althoughescitalopramhasbeenshownnottoaffectintellectualfunctionorpsychomotorperformance,any

psychoactivemedicinalproductmayimpairjudgementorskills.Patientsshouldbecautionedaboutthepotentialriskof

aninfluenceontheirabilitytodriveacarandoperatemachinery.

4.8Undesirableeffects

Adversereactionsaremostfrequentduringthefirstorsecondweekoftreatmentandusuallydecreaseinintensityand

frequencywithcontinuedtreatment.

AdversedrugreactionsknownforSSRIsandalsoreportedforescitalopramineitherplacebo-controlledclinicalstudies

orasspontaneouspost-marketingeventsarelistedbelowbysystemorganclassandfrequency.

Frequenciesaretakenfromclinicalstudies;theyarenotplacebo-corrected.Frequenciesaredefinedas:verycommon

≥1/10),common(≥1/100to<1/10),uncommon(≥1/1000to<1/100),rare(≥1/10,000to<1/1000),veryrare

(<1/10,000),ornotknown(cannotbeestimatedfromtheavailabledata).

Systemorganclass Frequency UndesirableEffect

Bloodandlymphatic

systemdisorders Notknown Thrombocytopenia

Immunesystemdisorders Rare Anaphylacticreaction

Endocrinedisorders Notknown InappropriateADHsecretion

Metabolismandnutrition

disorders Common Decreasedappetite,increasedappetite,

weightincreased

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Notknown Hyponatraemia,anorexia 2

Psychiatricdisorders Common Anxiety,restlessness,abnormaldreams

Femaleandmale:libidodecreased

Female:anorgasmia

Uncommon Bruxism,agitation,nervousness,panic

attack,confusionalstate

Rare Aggression,depersonalisation,hallucination

Notknown Mania,suicidalideation,suicidal

behaviour 1

Nervoussystemdisorders Common Insomnia,somnolence,dizziness,

paraesthesia,tremor

Uncommon Tastedisturbance,sleepdisorder,syncope

Rare Serotoninsyndrome

Notknown Dyskinesia,movementdisorder,

convulsion,akathisia/psychomotor

restlessness 2

Eyedisorders Uncommon Mydriasis,visualdisturbance

Earandlabyrinthdisorders Uncommon Tinnitus

Cardiacdisorders Uncommon Tachycardia

Rare Bradycardia

Vasculardisorders Notknown Orthostatichypotension

Respiratory,thoracicand

mediastinaldisorders Common Sinusitis,yawning

Uncommon Epistaxis

Gastroinstestinaldisorders Verycommon Nausea

Common Diarrhoea,constipation,vomiting,dry

mouth

Uncommon Gastrointestinalhaemorrhages(including

rectalhaemorrhage)

Hepatobiliarydisorders Notknown Hepatitis,liverfunctiontestabnormal

Skinandsubcutaneous

tissuedisorders Common Sweatingincreased

Uncommon Urticaria,alopecia,rash,pruritus

Notknown Ecchymosis,angioedemas

Musculoskeletaland

connectivetissuedisorders Common Arthralgia,myalgia

Renalandurinary

disorders Notknown Urinaryretention

Reproductivesystemand

breastdisorders Common Male:ejaculationdisorder,impotence

Uncommon Female:metrorrhagia,menorrhagia

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1Casesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringescitalopramtherapyorearlyafter

treatmentdiscontinuation(seesection4.4).

2TheseeventshavebeenreportedforthetherapeuticclassSSRIs.

CasesofQT-prolongationhavebeenreportedduringthepost-marketingperiod,predominantlyinpatientswithpre-

existingcardiacdisease.

Classeffects

Epidemiologicalstudies,mainlyconductedinpatients50yearsofageandolder,showan

increasedriskofbonefracturesinpatientsreceivingSSRIsandTCAs.Themechanism

leadingtothisriskisunknown.

Discontinuationsymptomsseenwhenstoppingtreatment

DiscontinuationofSSRIs/SNRIs(particularlywhenabrupt)commonlyleadstodiscontinuationsymptoms.Dizziness,

sensorydisturbances(includingparaesthesiaandelectricshocksensations),sleepdisturbances(includinginsomniaand

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

palpitations,emotionalinstability,irritability,andvisualdisturbancesarethemostcommonlyreportedreactions.

Generallytheseeventsaremildtomoderateandareself-limiting,however,insomepatientstheymaybesevereand/or

prolonged.Itisthereforeadvisedthatwhenescitalopramtreatmentisnolongerrequired,gradualdiscontinuationby

dosetaperingshouldbecarriedout(seesection4.2and4.4).

4.9Overdose

Toxicity

Clinicaldataonescitalopramoverdosearelimitedandmanycasesinvolveconcomitantoverdosesofotherdrugs.Inthe

majorityofcasesmildornosymptomshavebeenreported.Fatalcasesofescitalopramoverdosehaverarelybeen

reportedwithescitalopramalone;themajorityofcaseshaveinvolvedoverdosewithconcomitantmedications.Doses

between400and800mgofescitalopramalonehavebeentakenwithoutanyseveresymptoms.

Symptoms

Symptomsseeninreportedoverdoseofescitalopramincludesymptomsmainlyrelatedtothecentralnervoussystem

(rangingfromdizziness,tremor,andagitationtorarecasesofserotoninsyndrome,convulsion,andcoma),the

gastrointestinalsystem(nausea/vomiting),andthecardiovascularsystem(hypotension,tachycardia,QTprolongation,

andarrhythmia)andelectrolyte/fluidbalanceconditions(hypokalaemia,hyponatraemia).

Treatment

Thereisnospecificantidote.Establishandmaintainanairway,ensureadequateoxygenationandrespiratoryfunction.

Gastriclavageandtheuseofactivatedcharcoalshouldbeconsidered.Gastriclavageshouldbecarriedoutassoonas

possibleafteroralingestion.Cardiacandvitalsignsmonitoringarerecommendedalongwithgeneralsymptomatic

Male:priapism

Generaldisordersand

administrationsite

conditions Common Fatigue,pyrexia

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:antidepressants,selectiveserotoninreuptakeinhibitors

ATC-code:N06AB10

Mechanismofaction

Escitalopramisaselectiveinhibitorofserotonin(5-HT)re-uptakewithhighaffinityfortheprimarybindingsite.Italso

bindstoanallostericsiteontheserotonintransporter,witha1000foldloweraffinity.

Escitalopramhasnoorlowaffinityforanumberofreceptorsincluding5-HT1A,5-HT2,DAD1andD2receptors,1-,

2-,-adrenoceptors,histamineH1,muscarinecholinergic,benzodiazepine,andopioidreceptors.

Theinhibitionof5-HTre-uptakeistheonlylikelymechanismofactionexplainingthepharmacologicalandclinical

effectsofescitalopram.

Clinicalefficacy

MajorDepressiveEpisodes

Escitalopramhasbeenfoundtobeeffectiveintheacutetreatmentofmajordepressiveepisodesinthreeoutoffour

double-blind,placebocontrolledshort-term(8-weeks)studies.Inalong-termrelapsepreventionstudy,274patients

whohadrespondedduringaninitial8-weekopenlabeltreatmentphasewithescitalopram10or20mg/day,were

randomisedtocontinuationwithescitalopramatthesamedose,ortoplacebo,forupto36weeks.Inthisstudy,patients

receivingcontinuedescitalopramexperiencedasignificantlylongertimetorelapseoverthesubsequent36weeks

comparedtothosereceivingplacebo.

SocialAnxietyDisorder

Escitalopramwaseffectiveinboththreeshort-term(12-week)studiesandinrespondersina6monthsrelapse

preventionstudyinsocialanxietydisorder.Ina24-weekdose-findingstudy,efficacyof5,10and20mgescitalopram

hasbeendemonstrated.

Generalisedanxietydisorder

Escitalopramindosesof10and20mg/daywaseffectiveinfouroutoffourplacebo-controlledstudies.

Inpooleddatafromthreestudieswithsimilardesigncomprising421escitalopram-treatedpatientsand419placebo-

treatedpatientstherewere47.5%and28.9%respondersrespectivelyand37.1%and20.8%remitters.Sustainedeffect

wasseenfromweek1.

Maintenanceofefficacyofescitalopram20mg/daywasdemonstratedina24-to76-week,randomised,maintenanceof

efficacystudyin373patientswhohadrespondedduringtheinitial12-weekopen-labeltreatment.

Obsessive-compulsivedisorder

Inarandomized,double-blind,clinicalstudy,20mg/dayescitalopramseparatedfromplaceboontheY-BOCStotal

scoreafter12weeks.After24weeks,both10and20mg/dayescitalopramweresuperiorascomparedtoplacebo.

Preventionofrelapsewasdemonstratedfor10and20mg/dayescitalopraminpatientswhorespondedtoescitalopram

ina16-weekopen-labelperiodandwhoentereda24week,randomized,doubleblind,placebocontrolledperiod.

5.2Pharmacokineticproperties

Absorption

Absorptionisalmostcompleteandindependentoffoodintake.(Meantimetomaximumconcentration(meanT

)is

4hoursaftermultipledosing).Aswithracemiccitalopram,theabsolutebio-availabilityofescitalopramisexpectedto

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Distribution

Theapparentvolumeofdistribution(Vd,/F)afteroraladministrationisabout12to26L/kg.Theplasmaprotein

bindingisbelow80%forescitalopramanditsmainmetabolites.

Biotransformation

Escitalopramismetabolisedinthelivertothedemethylatedanddidemethylatedmetabolites.Bothoftheseare

pharmacologicallyactive.Alternatively,thenitrogenmaybeoxidisedtoformtheN-oxidemetabolite.Bothparent

substanceandmetabolitesarepartlyexcretedasglucuronides.Aftermultipledosingthemeanconcentrationsofthe

demethylanddidemethylmetabolitesareusually28-31%and<5%,respectively,oftheescitalopramconcentration.

BiotransformationofescitalopramtothedemethylatedmetaboliteismediatedprimarilybyCYP2C19.Some

contributionbytheenzymesCYP3A4andCYP2D6ispossible.

Elimination

Theeliminationhalf-life(t½)aftermultipledosingisabout30hoursandtheoralplasmaclearance(Cloral)isabout

0.6L/min.Themajormetaboliteshaveasignificantlylongerhalf-life.Escitalopramandmajormetabolitesareassumed

tobeeliminatedbyboththehepatic(metabolic)andtherenalroutes,withthemajorpartofthedoseexcretedas

metabolitesintheurine.

Thereislinearpharmacokinetics.Steady-stateplasmalevelsareachievedinabout1week.Averagesteady-state

concentrationsof50nmol/L(range20to125nmol/L)areachievedatadailydoseof10mg.

Elderlypatients(>65years)

Escitalopramappearstobeeliminatedmoreslowlyinelderlypatientscomparedtoyoungerpatients.Systemic

exposure(AUC)isabout50%higherinelderlycomparedtoyounghealthyvolunteers(seesection4.2).

Reducedhepaticfunction

Inpatientswithmildormoderatehepaticimpairment(Child-PughCriteriaAandB),thehalf-lifeofescitalopramwas

abouttwiceaslongandtheexposurewasabout60%higherthaninsubjectswithnormalliverfunction(seesection

4.2).

Reducedrenalfunction

Withracemiccitalopram,alongerhalf-lifeandaminorincreaseinexposurehavebeenobservedinpatientswith

reducedkidneyfunction(CLcr10-53ml/min).Plasmaconcentrationsofthemetaboliteshavenotbeenstudied,but

theymaybeelevated(seesection4.2).

Polymorphism

IthasbeenobservedthatpoormetaboliserswithrespecttoCYP2C19havetwiceashighaplasmaconcentrationof

escitalopramasextensivemetabolisers.Nosignificantchangeinexposurewasobservedinpoormetaboliserswith

respecttoCYP2D6(seesection4.2).

5.3Preclinicalsafetydata

Nocompleteconventionalbatteryofpreclinicalstudieswasperformedwithescitalopramsincethebridging

toxicokineticandtoxicologicalstudiesconductedinratswithescitalopramandcitalopramshowedasimilarprofile.

Therefore,allthecitalopraminformationcanbeextrapolatedtoescitalopram.

Incomparativetoxicologicalstudiesinrats,escitalopramandcitalopramcausedcardiactoxicity,includingcongestive

heartfailure,aftertreatmentforsomeweeks,whenusingdosagesthatcausedgeneraltoxicity.Thecardiotoxicity

seemedtocorrelatewithpeakplasmaconcentrationsratherthantosystemicexposures(AUC).Peakplasma

concentrationsatno-effect-levelwereinexcess(8-fold)ofthoseachievedinclinicaluse,whileAUCforescitalopram

wasonly3-to4-foldhigherthantheexposureachievedinclinicaluse.ForcitalopramAUCvaluesfortheS-

enantiomerwere6-to7-foldhigherthanexposureachievedinclinicaluse.Thefindingsareprobablyrelatedtoan

exaggeratedinfluenceonbiogenicaminesi.e.secondarytotheprimarypharmacologicaleffects,resultingin

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ratsisnotclear.Clinicalexperiencewithcitalopram,andtheclinicaltrialexperiencewithescitalopram,donotindicate

thatthesefindingshaveaclinicalcorrelate.

Increasedcontentofphospholipidshasbeenobservedinsometissuese.g.lung,epididymidesandliveraftertreatment

forlongerperiodswithescitalopramandcitalopraminrats.Findingsintheepididymidesandliverwereseenat

exposuressimilartothatinman.Theeffectisreversibleaftertreatmentcessation.Accumulationofphospholipids

(phospholipidosis)inanimalshasbeenobservedinconnectionwithmanycationicamphiphilicmedicines.Itisnot

knownifthisphenomenonhasanysignificantrelevanceforman.

Inthedevelopmentaltoxicitystudyintheratembryotoxiceffects(reducedfoetalweightandreversibledelayof

ossification)wereobservedatexposuresintermsofAUCinexcessoftheexposureachievedduringclinicaluse.No

increasedfrequencyofmalformationswasnoted.Apre-andpostnatalstudyshowedreducedsurvivalduringthe

lactationperiodatexposuresintermsofAUCinexcessoftheexposureachievedduringclinicaluse.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Microcrystallinecellulose

Colloidalanhydroussilica

Talc

Croscarmellosesodium

Magnesiumstearate

Coating:

Hypromellose

Macrogol400

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

36months.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

PVC/PE/PVdC/Aluminiumblister,packwithanoutercarton;10,14,20,28,30,50,56,60,90,98or100tablets-Unit

dose;200x1tablets

oPA/Aluminium/PVC/Aluminiumblister,packwithanoutercarton;10,14,20,28,30,50,56,60,90,98or100

tablets-Unitdose;200x1tablets

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6.6Specialprecautionsfordisposalandotherhandling

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

GenthonBV

Microweg22

6545CMNijmegen

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA740/13/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffistauthorisation:15thOctober2010

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