ESCITALOPRAM 10 MG FILM-COATED TABLETS

Main information

  • Trade name:
  • ESCITALOPRAM 10 MG FILM-COATED TABLETS
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ESCITALOPRAM 10 MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/083/001
  • Authorization date:
  • 10-09-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Escitalopram10mgFilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgofescitalopramequivalentto12.77mgofescitalopramoxalate.

Eachtabletcontains50.00mgoflactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

EscitalopramRanbaxy10mg:Whitetooff-white,ovalbiconvexfilm-coatedtablets,debossedwith"E”and“8"

oneithersideoftheeyebreaklineononesideandplainontheotherside.

The10mgtabletscanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmajordepressiveepisodes.

Treatmentofpanicdisorderwithorwithoutagoraphobia.

Treatmentofsocialanxietydisorder(socialphobia).

Treatmentofobsessive-compulsivedisorder.

4.2Posologyandmethodofadministration

Safetyofdailydosesabove20mghasnotbeendemonstrated.

Escitalopramisadministeredasasingledailydoseandmaybetakenwithorwithoutfood.

Majordepressiveepisodes

Usualdosageis10mgoncedaily.Dependingonindividualpatientresponse,thedosemaybeincreasedtoamaximum

of20mgdaily.

Usually2to4weeksarenecessarytoobtainantidepressantresponse.Afterthesymptomsresolve,treatmentforatleast

6monthsisrequiredforconsolidationoftheresponse.

Panicdisorderwithorwithoutagoraphobia

Aninitialdoseof5mgisrecommendedforthefirstweekbeforeincreasingthedoseto10mgdaily.Thedosemaybe

furtherincreased,uptoamaximumof20mgdaily,dependentonindividualpatientresponse.

Maximumeffectivenessisreachedafterabout3months.Thetreatmentlastsseveralmonths.

Socialanxietydisorder

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Thedosemaysubsequently,dependingonindividualpatientresponse,bedecreasedto5orincreasedtoamaximumof

20mgdaily.

Socialanxietydisorderisadiseasewithachroniccourse,andtreatmentfor12weeksisrecommendedtoconsolidate

response.Long-termtreatmentofrespondershasbeenstudiedfor6monthsandcanbeconsideredonanindividual

basistopreventrelapse;treatmentbenefitsshouldbere-evaluatedatregularintervals.

Socialanxietydisorderisawell-defineddiagnosticterminologyofaspecificdisorder,whichshouldnotbeconfounded

withexcessiveshyness.Pharmacotherapyisonlyindicatedifthedisorderinterferessignificantlywithprofessionaland

socialactivities.

Theplaceofthistreatmentcomparedtocognitivebehaviouraltherapyhasnotbeenassessed.Pharmacotherapyispart

ofanoveralltherapeuticstrategy.

Obsessive-compulsivedisorder

Initialdosageis10mgoncedaily.Dependingontheindividualpatientresponse,thedosemaybeincreasedtoa

maximumof20mgdaily.

Asobsessive-compulsivedisorder(OCD)isachronicdisease,patientsshouldbetreatedforasufficientperiodto

ensurethattheyaresymptomfree.

Treatmentbenefitsanddoseshouldbere-evaluatedatregularintervals(seesection5.1).

Elderlypatients(>65yearsofage)

Initialtreatmentwithhalftheusuallyrecommendeddoseandalowermaximumdoseshouldbeconsidered(seesection

5.2).

TheefficacyofEscitalopraminsocialanxietydisorderhasnotbeenstudiedinelderlypatients.

Childrenandadolescents(<18years)

Escitalopramshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years(seesection

4.4).

Reducedrenalfunction

Dosageadjustmentisnotnecessaryinpatientswithmildormoderaterenalimpairment.Cautionisadvisedinpatients

withseverelyreducedrenalfunction(CL

lessthan30ml/min.)(seesection5.2).

Reducedhepaticfunction

Aninitialdoseof5mgdailyforthefirsttwoweeksoftreatmentisrecommendedinpatientswithmildormoderate

hepaticimpairment.Dependingonindividualpatientresponse,thedosemaybeincreasedto10mgdaily.Cautionand

extracarefuldosetitrationisadvisedinpatientswithseverelyreducedhepaticfunction(seesection5.2).

PoormetabolisersofCYP2C19

ForpatientswhoareknowntobepoormetaboliserswithrespecttoCYP2C19,aninitialdoseof5mgdailyduringthe

firsttwoweeksoftreatmentisrecommended.Dependingonindividualpatientresponse,thedosemaybeincreasedto

10mgdaily(seesection5.2).

Discontinuationsymptomsseenwhenstoppingtreatment

Abruptdiscontinuationshouldbeavoided.

Whenstoppingtreatmentwithescitalopramthedoseshouldbegraduallyreducedoveraperiodofatleastonetotwo

weeksinordertoreducetheriskofdiscontinuationsymptoms(seesection4.4and4.8).Ifintolerablesymptomsoccur

followingadecreaseinthedoseorupondiscontinuationoftreatment,thenresumingthepreviouslyprescribeddose

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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.Suicide-related

behaviours(suicideattemptandsuicidalthoughts),andhostility(predominantlyaggression,oppositionalbehaviourand

anger)weremorefrequentlyobservedinclinicaltrialsamongchildrenandadolescentstreatedwithantidepressants

comparedtothosetreatedwithplacebo.If,basedonclinicalneed,adecisiontotreatisneverthelesstaken,thepatient

shouldbecarefullymonitoredfortheappearanceofsuicidalsymptoms.Inaddition,long-termsafetydatainchildren

andadolescentsconcerninggrowth,maturationandcognitiveandbehaviouraldevelopmentarelacking.

Paradoxicalanxiety

Somepatientswithpanicdisordermayexperienceincreasedanxietysymptomsatthebeginningoftreatmentwith

antidepressants.Thisparadoxicalreactionusuallysubsideswithintwoweeksduringcontinuedtreatment.Alow

startingdoseisadvisedtoreducethelikelihoodofananxiogeniceffect(seesection4.2).

Seizures

Themedicinalproductshouldbediscontinuedinanypatientwhodevelopsseizures.SSRIsshouldbeavoidedin

patientswithunstableepilepsyandpatientswithcontrolledepilepsyshouldbecarefullymonitored.SSRIsshouldbe

discontinuedifthereisanincreaseinseizurefrequency.

Mania

SSRIsshouldbeusedwithcautioninpatientswithahistoryofmania/hypomania.SSRIsshouldbediscontinuedinany

patiententeringamanicphase.

Diabetes

Inpatientswithdiabetes,treatmentwithanSSRImayalterglycaemiccontrol(hypoglycaemiaorhyperglycaemia).

Insulinand/ororalhypoglycaemicdosagemayneedtobeadjusted.

Suicide/suicidalthoughtsorclinicalworsening

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suicide-relatedevents).This

riskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthefirstfewweeksormoreof

treatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneralclinicalexperiencethatthe

riskofsuicidemayincreaseintheearlystagesofrecovery.

Otherpsychiatricconditionsforwhichescitalopramisprescribedcanalsobeassociatedwithanincreasedriskof

thoughts/behaviorssuicide-related.Inaddition,theseconditionsmaybeco-morbidwithmajordepressivedisorder.

Thesameprecautionsobservedwhentreatingpatientswithmajordepressivedisordershouldthereforebeobserved

whentreatingpatientswithotherpsychiatricdisorders.

Patientswithahistoryofthoughts/behaviorssuicide-related,orthoseexhibitingasignificantdegreeofsuicidalideation

priortocommencementoftreatment,areknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,and

shouldreceivecarefulmonitoringduringtreatment.Ametaanalysisofplacebocontrolledclinicaltrialsof

antidepressantdrugsinadultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwith

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Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patientsandcaregiversofpatientsshouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Akathisia/psychomotorrestlessness

TheuseofSSRIs/SNRIshasbeenassociatedwiththedevelopmentofakathisia,characterisedbyasubjectively

unpleasantordistressingrestlessnessandneedtomoveoftenaccompaniedbyaninabilitytositorstandstill.Thisis

mostlikelytooccurwithinthefirstfewweeksoftreatment.Inpatientswhodevelopthesesymptoms,increasingthe

dosemaybedetrimental.

Hyponatraemia

Hyponatraemia,probablyduetoinappropriateantidiuretichormonesecretion(SIADH),hasbeenreportedrarelywith

theuseofSSRIsandgenerallyresolvesondiscontinuationoftherapy.Cautionshouldbeexercisedinpatientsatrisk,

suchaselderly,cirrhoticpatientsorpatientsconcomitantlytreatedwithmedicationsknowntocausehyponatraemia.

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%ofpatientstreated

withescitalopramand15%ofpatientstakingplacebo.

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

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Generallythesesymptomsareself-limitingandusuallyresolvewithin2weeks,thoughinsomeindividualstheymay

beprolonged(2-3monthsormore).Itisthereforeadvisedthatescitalopramshouldbegraduallytaperedwhen

discontinuingtreatmentoveraperiodofseveralweeksormonths,accordingtothepatient'sneeds(see

“Discontinuationsymptomsseenwhenstoppingtreatment”,section4.2).

Coronaryheartdisease

Duetolimitedclinicalexperience,cautionisadvisedinpatientswithcoronaryheartdisease(seesection5.3).

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Pharmacodynamicinteractions

Contra-indicatedcombinations:

Irreversiblenon-selectiveMAOIs

CasesofseriousreactionshavebeenreportedinpatientsreceivinganSSRIincombinationwithanon-selective,

irreversiblemonoamineoxidaseinhibitor(MAOI),andinpatientswhohaverecentlydiscontinuedSSRItreatment

andhavebeenstartedonsuchMAOItreatment(seesection4.3).Insomecases,thepatientdevelopedserotonin

syndrome(seesection4.8).

Escitalopramiscontra-indicatedincombinationwithnon-selective,irreversibleMAOIs.Escitaloprammaybestarted

14daysafterdiscontinuingtreatmentwithanirreversibleMAOI.Atleast7daysshouldelapseafterdiscontinuing

escitalopramtreatment,beforestartinganon-selective,irreversibleMAOI.

Reversible,selectiveMAO-Ainhibitor(moclobemide)

Duetotheriskofserotoninsyndrome,thecombinationofescitalopramwithaMAO-Ainhibitorsuchas

moclobemideiscontraindicated(seesection4.3).Ifthecombinationprovesnecessary,itshouldbestartedatthe

minimumrecommendeddosageandclinicalmonitoringshouldbereinforced.

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

serotoninsyndrome.

Medicinalproductsloweringtheseizurethreshold

SSRIscanlowertheseizurethreshold.Cautionisadvisedwhenconcomitantlyusingothermedicinalproducts

capableofloweringtheseizurethreshold[e.gantidepressants(tricyclics,SSRIs),neuroleptics(phenothiazines,

thioxanthenesandbutyrophenones),mefloquine,bupropionandtramadol].

Lithium,tryptophan

TherehavebeenreportsofenhancedeffectswhenSSRIshavebeengiventogetherwithlithiumortryptophan,

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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(demethylated

escitalopram)seemstobepartlycatalysedbyCYP2D6.

Co-administrationofescitalopramwithomeprazole30mgoncedaily(aCYP2C19inhibitor)resultedinmoderate

(approximately50%)increaseintheplasmaconcentrationsofescitalopram.

Co-administrationofescitalopramwithcimetidine400mgtwicedaily(moderatelypotentgeneralenzyme-inhibitor)

resultedinamoderate(approximately70%)increaseintheplasmaconcentrationsofescitalopram.

Thus,cautionshouldbeexercisedwhenusedconcomitantlywithCYP2C19inhibitors(e.g.omeprazole,

esomeprazole,fluvoxamine,lansoprazole,ticlopidine)orcimetidine.Areductioninthedoseofescitaloprammaybe

necessarybasedonmonitoringofside-effectsduringconcomitanttreatment.

Effectofescitalopramonthepharmacokineticsofothermedicinalproducts

EscitalopramisaninhibitoroftheenzymeCYP2D6.Cautionisrecommendedwhenescitalopramisco-administered

withmedicinalproductsthataremainlymetabolisedbythisenzyme,andthathaveanarrowtherapeuticindex,e.g.

flecainide,propafenoneandmetoprolol(whenusedincardiacfailure),orsomeCNSactingmedicinalproductsthat

aremainlymetabolisedbyCYP2D6,e.g.antidepressantssuchasdesipramine,clomipramineandnortriptylineor

antipsychoticslikerisperidone,thioridazineandhaloperidol.Dosageadjustmentmaybewarranted.

Co-administrationwithdesipramineormetoprololresultedinbothcasesinatwofoldincreaseintheplasmalevelsof

thesetwoCYP2D6substrates.

InvitrostudieshavedemonstratedthatescitaloprammayalsocauseweakinhibitionofCYP2C19.Cautionis

recommendedwithconcomitantuseofmedicinalproductsthataremetabolisedbyCYP2C19.

4.6Fertility,pregnancyandlactation

Pregnancy

Forescitalopramonlylimitedclinicaldataareavailableregardingexposedpregnancies.

Inreproductivetoxicitystudiesperformedinratswithescitalopram,embryo-fetotoxiceffects,butnoincreased

incidenceofmalformations,wereobserved(seesection5.3).EcitalopramRanbaxyshouldnotbeusedduring

pregnancyunlessclearlynecessaryandonlyaftercarefulconsiderationoftherisk/benefit.

NeonatesshouldbeobservedifmaternaluseofEscitalopramRanbaxycontinuesintothelaterstagesofpregnancy,

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ThefollowingsymptomsmayoccurintheneonateaftermaternalSSRI/SNRIuseinlaterstagesofpregnancy:

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

hypertonia,hypotonia,hyperreflexia,tremor,agitation,irritability,lethargy,constantcrying,somnolenceanddifficulty

sleeping.Thesesymptomscouldbeduetoeitherserotonergiceffectsordiscontinuationsymptoms.Inamajorityof

instancesthecomplicationsbeginimmediatelyorsoon(<24hours)afterdelivery.

EpidemiologicaldatahavesuggestedthattheuseofSSRIsinpregnancy,particularinlatepregnancy,mayincreasethe

riskofpersistentpulmonaryhypertensioninthenewborn(PPHN).Theobservedriskwasapproximately5casesper

1000pregnancies.Inthegeneralpopulation1to2casesofPPHNper1000pregnanciesoccur.

Lactation

Itisexpectedthatescitalopramwillbeexcretedintohumanmilk.

Consequently,breast-feedingisnotrecommendedduringtreatment.

4.7Effectsonabilitytodriveandusemachines

Althoughescitalopramhasbeenshownnottoaffectintellectualfunctionorpsychomotorperformance,any

psychoactivemedicinalproductmayimpairtheabilityofwisdomorexpertisetodevelopanactivity.Patientsshouldbe

cautionedaboutthepotentialriskofaninfluenceontheirabilitytodriveacarandoperatemachinery.

4.8Undesirableeffects

Adversereactionsaremostfrequentduringthefirstorsecondweekoftreatmentandusuallydecreaseinintensityand

frequencywithcontinuedtreatment.

AdversedrugreactionsknownforSSRIsandalsoreportedforescitalopramineitherplacebo-controlledclinicalstudies

orasspontaneouspost-marketingeventsarelistedbelowbysystemorganclassandfrequency.

Frequenciesaretakenfromclinicalstudies;theyarenotplacebo-corrected.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).

Very

common

(1/10) Common

(1/100 to

<1/10) Uncommon

(1/1000 to

<1/100) Rare(1/10000

to<1/1000) Not known

(cannot be

estimated from

the available

data)

Investigations Weightincreased Weight

decreased Liverfunctiontest

abnormal

Cardiac

disorders Tachycardia Bradycardia

Blood and

lymphatic

disorders Thrombocytopenia

Nervoussystem

disorders Insomnia,

Somnolence,Dizziness,

Paraesthesia,

Tremor Taste

disturbance,

Sleepdisorder,

Syncope Serotonin

syndrome Dyskinesia,

Movement

disorder,

Convulsion

Eyedisorders Mydriasis,

Visual

disturbance

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Casesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringescitalopramtherapyorearlyafter

disorders

Respiratory,

thoracic and

mediastinal

disorders Sinusitis,

Yawning Epistaxis

Gastrointestinal

disorders Nausea Diarrhoea,

Constipation,

Vomiting,

Drymouth Gastrointestinal

haemorrhages

(including

rectal

haemorrhage)

Renal and

urinary

disorders Urinaryretention

Skin and

subcutaneous

tissuedisorders Sweating

increased Urticaria,

Alopecia,

Rash,

Pruritus Ecchymosis,

Angioedema

Musculoskeleta,

connective

tissueandbone

disorders Arthralgia,

Myalgia

Endocrine

disorders Inappropriate

ADHsecretion

Metabolismand

nutrition

disorders Decreased

appetite,

Increased

appetite Hyponatraemia

Vascular

disorders Orthostatic

hypotension

General

disorders and

administration

siteconditions Fatigue,Pyrexia Oedema

Immunesystem

disorders Anaphylactic

reaction

Hepatobiliary

disorders Hepatitis

Reproductive

system and

breastdisorders Male:

Ejaculation

disorder,

Impotence Female:

Metrorrhagia,

Menorrhagia Male:

Priapism

Galactorrhoea

Psychiatric

disorders Anxiety,

Restlessness,Abnormal

dreams

Female and

male:

Libidodecreased

Female:

Anorgasmia Bruxism,

Agitation,

Nervousness,

Panic attack,

Confusional

state Aggression,

Depersonalisation,

Hallucination Mania,

Suicidalideation,

Suicidal

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ThefollowingadversedrugreactionshavebeenreportedforthetherapeuticclassofSSRIs:psychomotor

restlessness/akathisia(seesection4.4)andanorexia.

CasesofQT-prolongationhavebeenreportedduringthepost-marketingperiod,predominantlyinpatientswithpre-

existingcardiacdisease.

Nocausalrelationshiphasbeenestablished.

Epidemiologicalstudies,mainlyconductedinpatients50yearsofageandolder,showanincreasedriskofbone

fracturesinpatientsreceivingSSRIsandTCAs.Themechanismleadingtothisriskisunknown.

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

supportivemeasures.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:antidepressants,selectiveserotoninreuptakeinhibitors

ATC-code:N06AB10

Mechanismofaction

Escitalopramisaselectiveinhibitorofserotonin(5-HT)re-uptakewithhighaffinityfortheprimarybindingsite.Italso

bindstoanallostericsiteontheserotonintransporter,witha1000foldloweraffinity.

Escitalopramhasnoorlowaffinityforanumberofreceptorsincluding5-HT

,5-HT

,DAD

andD

receptors,

adrenoceptors,histamineH

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Theinhibitionof5-HTre-uptakeistheonlylikelymechanismofactionexplainingthepharmacologicalandclinical

effectsofescitalopram.

Clinicalefficacy

Majordepressiveepisodes

Escitalopramhasbeenfoundtobeeffectiveintheacutetreatmentofmajordepressiveepisodesinthreeoutoffour

double-blind,placebocontrolledshort-term(8-week)studies.Inalong-termrelapsepreventionstudy,274patientswho

hadrespondedduringaninitial8-weekopenlabeltreatmentphasewithescitalopram10or20mg/day,were

randomisedtocontinuationwithescitalopramatthesamedose,ortoplacebo,forupto36weeks.Inthisstudy,patients

receivingcontinuedescitalopramexperiencedasignificantlylongertimetorelapseoverthesubsequent36weeks

comparedtothosereceivingplacebo.

Socialanxietydisorder

Escitalopramwaseffectiveinboththreeshort-term(12-week)studiesandinrespondersina6monthsrelapse

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

hasbeendemonstrated.

Generalisedanxietydisorder

Escitalopramindosesof10mgand20mg/daywaseffectiveinfouroutoffourplacebo-controlledstudies.Inpooled

datafromthreestudieswithsimilardesigncomprising421escitalopram-treatedpatientsand419placebo-treated

patientstherewere47.5%and28.9%respondersrespectivelyand37.1%and20.8%remitters.Sustainedeffectwas

seenfromweek1.

Maintenanceofefficacyofescitalopram20mg/daywasdemonstratedina24to76week,randomised,maintenanceof

efficacystudyin373patientswhohadrespondedduringtheinitial12weekopen-labeltreatment.

Obsessive-compulsivedisorder

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

scoreafter12weeks.After24weeks,both10and20mg/dayescitalopramweresuperiorascomparedtoplacebo.

Preventionofrelapsewasdemonstratedfor10and20mg/dayescitalopraminpatientswhorespondedtoescitalopram

ina16-weekopen-labelperiodandwhoentereda24-week,randomised,double-blind,placebocontrolledperiod.

5.2Pharmacokineticproperties

Absorption

Absorptionisalmostcompleteandindependentoffoodintake.(Meantimetomaximumconcentration(meanT

)is

4hoursaftermultipledosing).Aswithracemiccitalopram,theabsolutebio-availabilityofescitalopramisexpectedto

beabout80%.

Distribution

Theapparentvolumeofdistribution(V

,/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.

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Theeliminationhalf-life(t

)aftermultipledosingisabout30hoursandtheoralplasmaclearance(Cl

oral )isabout0.6

L/min.Themajormetaboliteshaveasignificantlylongerhalf-life.Escitalopramandmajormetabolitesareassumedto

beeliminatedbyboththehepatic(metabolic)andtherenalroutes,withthemajorpartofthedoseexcretedas

metabolitesintheurine.

Thereislinearpharmacokinetics.Steady-stateplasmalevelsareachievedinabout1week.Averagesteady-state

concentrationsof50nmol/L(range20to125nmol/L)areachievedatadailydoseof10mg.

Elderlypatients(>65years)

Pappearstobeeliminatedmoreslowlyinelderlypatientscomparedtoyoungerpatients.Systemicexposure(AUC)is

about50%higherinelderlycomparedtoyounghealthyvolunteers(seesection4.2).

Reducedhepaticfunction

Inpatientswithmildormoderatehepaticimpairment(Child-PughCriteriaAandB),thehalf-lifeofescitalopramwas

abouttwiceaslongandtheexposurewasabout60%higherthaninsubjectswithnormalliverfunction(seesection

4.2).

Reducedrenalfunction

Withracemiccitalopram,alongerhalf-lifeandaminorincreaseinexposurehavebeenobservedinpatientswith

reducedkidneyfunction(CL

10-53ml/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

hemodynamiceffects(reductionincoronaryflow)andischaemia.However,theexactmechanismofcardiotoxicityin

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

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Intragranularexcipients

Microcrystallinecellulose

Lactosemonohydrate

Copovidone

Maize-starch

Extragranularexcipients

Silicifiedmicrocrystallinecellulose

Croscarmellosesodium

Talc

Colloidalanhydroussilica

Magnesiumstearate

Tabletcoating

OpadryOY-S-58910:

Hypromellose

Titaniumdioxide(E171)

Macrogol400

Talc

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Polyamide/Alu/PVC/Alublister:14,20,28,30,50,56,100film-coatedtablets;

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLimited

Spafield

CorkRoad

Cashel

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8MARKETINGAUTHORISATIONNUMBER

PA408/83/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10thSeptember2010

10DATEOFREVISIONOFTHETEXT

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