DOTHEP

Main information

  • Trade name:
  • DOTHEP Capsules Hard 25 Milligram
  • Dosage:
  • 25 Milligram
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOTHEP Capsules Hard 25 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/020/002
  • Authorization date:
  • 12-05-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dothep25mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachhardcapsulecontains25mgofdosulepinhydrochloride.

Excipients-ContainsLactoseMonohydrate94.0mgandPonceau4R(E124)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Capsule,hard

Brown/redhardcapsule,marked‘GDN25’inblackink.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dosulepinisindicatedinthetreatmentofsymptomsofdepressiveillness-inparticularwhereananti-anxietyeffectis

required.

4.2Posologyandmethodofadministration

Dothepcapsulesareadministeredorally.

Recommendeddosageschedules:

Adults:Initially75mg/dayindivideddoses(ascapsules)orasasingledoseatnight,increasingto150mg/day.In

certaincircumstancese.g.inhospitaluse,dosagesupto225mgdailyhavebeenused.Suggesteddosageregimen:25to

50mgthreetimesdailyor,alternatively,75or150mgasasingledoseatnight.

Elderly:50-75mgdailyinitially.Aswithanyantidepressant,theinitialdoseshouldbeincreasedwithcautionunder

closesupervision.Halfthenormaladultdosemaybesufficienttoproduceasatisfactoryclinicalresponse.

Children:Notrecommended.

4.3Contraindications

Dothepcapsulesarecontraindicatedinpatientswith:

Closedangleglaucoma.

Existingurinaryretention.

Recentmyocardialinfarction.

Anydegreeofheartblockorothercardiacarrhythmias.

Mania.

Severeliverdisease.

Womenwhoarebreast-feeding.

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4.4Specialwarningsandprecautionsforuse

Specialprecautionsforuse:

Dosulepinshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years.Studiesin

depressioninthisagegroupdidnotshowabeneficialeffectfortricyclicantidepressants.Studieswithotherclassesof

antidepressantshaveshownariskofsuicidality,selfharmandhostilityrelatedtothesecompounds.Thisriskcannotbe

excludedwithDosulepin.Inaddition,Dosulepinisassociatedwithariskofcardiovascularadverseeventsinallage

groups.Furthermore,longtermsafetydatainchildrenandadolescentsconcerninggrowth,maturationandcognitive

andbehaviouraldevelopmentarenotavailable(seealsosection4.8Undesirableeffectsandsection4.9Overdose).

Theelderlyareparticularlyliabletoexperienceadversereactionstoantidepressants,especiallyagitation,confusionand

posturalhypotension.Patientsposingahighsuicidalriskrequireclosesupervision.

Dosulepinshouldbegivenonlywithcautiontoepilepticpatientsandtothosewithcardiovasculardisorders.Itsuse

shouldbeavoidedinpatientswithsymptomssuggestiveofprostatichypertrophyandahistoryofepilepsy.Tricyclic

antidepressantspotentiatethecentralnervousdepressantactionofalcohol.Anaestheticsgivenduringtri/tetracyclic

antidepressanttherapymayincreasetheriskofarrhythmiasandhypotension.Ifsurgeryisnecessary,theanaesthetist

shouldbeinformedthatapatientisbeingsotreated.

Itmaybetwotofourweeksfromthestartoftreatmentbeforethereisanimprovementinthepatient'sdepression;the

patientshouldbemonitoredcloselyduringthisperiod.Theanxiolyticeffectmaybeobservedwithinafewdaysof

commencingtreatment.Initially,Dosulepinmayimpairalertness;patientslikelytodrivevehiclesoroperatemachinery

shouldbewarnedofthispossibility.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Withdrawalsymptomsmayoccuronabruptcessationoftricyclictherapyandincludeinsomnia,irritabilityand

excessiveperspiration.Similarsymptomsinneonateswhosemothersreceivedtricyclicantidepressantsduringthethird

trimesterhavealsobeenreported,althoughthishasnotbeenobservedfollowingtreatmentwithDothiepin.Itis

recommendedthatantidepressantsshouldbewithdrawngradually.

Suicide/suicidalthoughtsorclinicalworsening

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suicide-relatedevents).This

riskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthefirstfewweeksormoreof

treatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneralclinicalexperiencethatthe

riskofsuicidemayincreaseintheearlystagesofrecovery.

Patientswithahistoryofsuicide-relatedevents,orthoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatmentareknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,andshouldreceive

carefulmonitoringduringtreatment.Ameta-analysisofplacebo-controlledclinicaltrialsofantidepressantdrugsin

adultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwithantidepressantscompared

toplaceboinpatientslessthan25yearsold.

Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patients(andcaregiversofpatients)shouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Specialwarnings:

Dependence-withdrawalsymptomsmayoccuronabruptcessationoftreatment.

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Dosulepinshouldnotbegivenconcurrentlywithmonoamineoxidaseinhibitors(MAOI's);norwithin14daysof

stoppingsuchtreatment.Dosulepinmayalterthepharmacologicaleffectsofsomeconcurrentlyadministereddrugs

includingCNSdepressantssuchasalcoholandnarcoticanalgesics.Theeffectsofthesewillbepotentiated,aswillthe

effectsofadrenalineandnoradrenaline.

Thehypotensiveactivityofcertainantihypertensiveagents,e.g.bethanidine,debrisoquine,guanethidine,maybe

reducedbyDosulepin.Anaestheticsgivenduringtri/tetracyclicanti-depressanttherapymayincreasetheriskof

arrhythmiasandhypotension.Ifsurgeryisnecessary,theanaesthetistshouldbeinformedthatapatientisbeingso

treated.

ItisadvisabletoreviewallantihypertensivetherapyduringtreatmentwithDosulepin.

BarbituratesmaydecreaseandmethylphenidatemayincreasetheserumconcentrationofDosulepinandthusaffectits

antidepressantaction.

4.6Fertility,pregnancyandlactation

ThereisnoevidenceastothesafetyofDosulepininhumanpregnancynoristhereevidencefromanimalworkthatitis

freefromhazard.Itshouldonlybeusedinpregnancy,inparticularinthefirstandlasttrimesters,ifthereare

compellingreasons.

Dosulepinisexcretedinbreastmilk;thereforeitisnotrecommendedforuseduringlactation.

4.7Effectsonabilitytodriveandusemachines

Initially,Dosulepinmayimpairalertness,patientslikelytodrivevehiclesoroperatemachineryshouldbewarnedof

thispossibility.

4.8Undesirableeffects

Thefollowingadverseeffects,althoughnotallreportedwithDosulepinhaveoccurredwithothertricyclic

antidepressants.

Atropine-likesideeffectsincludingdrymouth,disturbancesofaccommodation,tachycardia,constipationand

hesitancyofmicturitionarecommonearlyintreatment,butusuallydiminish.Otheradverseeffectsincludedrowsiness,

sweating,posturalhypotension,tremorandskinrashes.Interferencewithsexualfunctionmayoccur.

Seriousadverseeffectsarerare.Theseincludedepressionofthebonemarrow,agranulocytosis,cholestaticjaundice,

hypomaniaandconvulsions.Psychoticmanifestations,includingmaniaandparanoiddelusionsmaybeexacerbated

duringtreatmentwithtricyclicantidepressants.

Withdrawalsymptomsmayoccuronabruptcessationoftricyclictherapyandincludeinsomnia,irritabilityand

excessiveperspiration.Similarsymptomsinneonateswhosemothersreceivedtricyclicantidepressantsduringthethird

trimesterhavealsobeenreported,althoughthishasnotbeenreportedfollowingtreatmentwithDosulepin.

Cardiacarrhythmiasandseverehypotensionarelikelytooccurwithhighdosageorindeliberateoverdosage.Theymay

alsooccurinpatientswithpre-existingheartdiseasetakinganormaldose.

CasesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringDosulepintherapyorearlyaftertreatment

discontinuation(seesection4.4).

Classeffects

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fracturesinpatientsreceivingSSRlsandTeAs.Themechanismleadingtothisriskisunknown.

4.9Overdose

ThereisnospecificantidoteforDosulepin.Gastriclavageisrecommended.Whenthepatientisunconsciousorthe

coughreflexdepressedthelungsshouldbeprotectedbyacuffedendotrachaeltube.

Repeatedgastric/intestinalaspirationorrepeatedadministrationofactivatedcharcoalmayremovedrugandmetabolites

excretedintothegutviathebile.ContinuousECGmonitoringisadvisable.Abnormalitiesofcardiacrhythmand

epilepticconvulsionsmayoccurandshouldbetreatedaccordingly.Forceddiuresisisnotrecommended.Bedrestis

advisable,evenafterrecovery.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

PharmacotherapeuticGroup:Non-selectivemonoaminereuptakeinhibitor.ATCcode:N06AA16

DosulepinHClisatricyclicantidepressantwithactionsandusessimilartothoseofamitriptyline.

5.2Pharmacokineticproperties

DosulepinHClisreadilyabsorbedfromthegastrointestinaltractandextensivelydemethylatedbyfirst-pass

metabolisminthelivertoitsprimaryactivemetabolite-desmethyldothiepin(northiaden).Dosulepinisexcretedinthe

urine,mainlyintheformofitsmetabolites;smallamountsarealsoexcretedinthefaeces.Thehalflifeisapprox.19-33

hours.

5.3Preclinicalsafetydata

Nofurtherinformationavailable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Capsulecontents:

Lactosemonohydrate

Povidone

SodiumstarchglycolateTypeA

Magnesiumstearate

Purifiedtalc

Capsuleshells:

Gelatin

Redironoxide(E172)

Yellowironoxide(E172)

Blackironoxide(E172)

Titaniumdioxide(E171)

Ponceau4R(E124)

Printingink:

Blackironoxide(E172)

Propyleneglycol(E1520)

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6.2Incompatibilities

Notapplicable.

6.3ShelfLife

4years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

PVC/A1blistersinstripspackedincartonscontaining28,56,60,84,100,250,500or1000capsules.

Polypropylenetabletcontainerwithpolyethylenecapcontaining28,56,60,84,100,250,500and1000capsules.

Notallpacksizeswillbemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLtd.T/AGerardLaboratories

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

8MARKETINGAUTHORISATIONNUMBER

PA577/20/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12May2000

Dateoflastrenewal:12May2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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