DOTHEP

Main information

  • Trade name:
  • DOTHEP Film Coated Tablet 75 Milligram
  • Dosage:
  • 75 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOTHEP Film Coated Tablet 75 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/020/001
  • Authorization date:
  • 05-09-1997
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dothep75mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains75mgDosulepinHydrochloride(DothiepinHydrochloride).

Excipient:Eachtabletcontains115mgLactosemonohydrateand1.75mgPonceau4R(E124)

Forafulllistofexcipient,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

Redfilm-coated8.5mmnormalconvextabletsembossedDN/75ononesideandGontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dotheptabletsareindicatedinthetreatmentofsymptomsofdepressiveillness,inparticular,whereananti-anxiety

effectisrequired.

4.2Posologyandmethodofadministration

Dotheptabletsareadministeredorally.

Recommendeddosageschedules:

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

certaincircumstances,e.g.inhospitaluse,dosagesupto225mgdailyhavebeenused.Suggesteddosageregimen:25

to50mgthreetimesdailyor,alternatively,75or150mgasasingledoseatnight.

Elderly:50–75mgdailyinitially.Aswithanyantidepressant,theinitialdoseshouldbeincreasedwithcautionunder

closesupervision.Halfthenormaladultdosemaybesufficienttoproduceasatisfactoryclinicalresponse.

Children:Notrecommended.

4.3Contraindications

Dotheptabletsarecontra-indicatedinpatientswith:

Closedangleglaucoma,existingurinaryretention,recentmyocardialinfarction,anydegreeofheartblockorother

cardiacarrhythmia’s,acutepsychoses,severeliverdisease,womenwhoarebreast-feeding,orpatientscurrently

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4.4Specialwarningsandprecautionsforuse

Specialprecautionsforuse:

Dothiepinshouldnotbeusedinthetreatmentofchildrenandadolescentsundertheageof18years.Studiesin

depressioninthisagegroupdidnotshowabeneficialeffectfortricyclicantidepressants.Studieswithotherclassesof

antidepressantshaveshownariskofsuicidality,selfharmandhostilityrelatedtothesecompounds.Thisriskcannotbe

excludedwithDothiepin.Inaddition,Dothiepinisassociatedwithariskofcardiovascularadverseeventsinallage

groups.Furthermore,longtermsafetydatainchildrenandadolescentsconcerninggrowth,maturationandcognitive

andbehaviouraldevelopmentarenotavailable(seealsosection4.8Undesirableeffectsandsection4.9Overdose).

Theelderlyareparticularlyliabletoexperienceadversereactionstoantidepressants,especiallyagitation,confusion,

andposturalhypotension.Patientsposingahighsuicidalriskrequireclosesupervision.

Dothiepinshouldbegivenonlywithcautiontoepilepticpatientsandtothosewithcardiovasculardisorders.

Itsuseshouldbeavoidedinpatientswithsymptomssuggestiveofprostatichypertrophyandahistoryofepilepsy.

Tricyclicantidepressantspotentiatethecentralnervousdepressantactionofalcohol.Anaestheticsgivenduringthe

tri/tetracyclicantidepressanttherapymayincreasetheriskofarrhythmia’sandhypotension.Ifsurgeryisnecessary,the

anaesthetistshouldbeinformedthatapatientisbeingsotreated.

Itmaybetwotofourweeksfromthestartoftreatmentbeforethereisanimprovementinthepatient’sdepression.The

patientshouldbemonitoredcloselyduringthisperiod.Theanxiolyticeffectmaybeobservedwithinafewdaysof

commencingtreatment.Initially,Dothiepinmayimpairalertness;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

Dothiepinshouldnotbegivenconcurrentlywithmonoamineoxidaseinhibitors(MAOI’s);orwithin14daysof

stoppingsuchtreatment.Dothiepinmayalterthepharmacologicaleffectsofsomeconcurrentlyadministereddrugs,

includingCNSdepressantssuchasalcoholandnarcoticanalgesics.Theeffectsofthesewillbepotentiated,aswillthe

effectsofadrenalineandnoradrenaline.

Thehypotensiveactivityofcertainanti-hypertensiveagents,e.g.bethanidine,debrisoquine,guanethidine,maybe

reducedbyDothiepin.Itisadvisabletoreviewallanti-hypertensivetherapyduringtreatmentwithDothiepin.

Anaestheticsgivenduringtri/tetracyclicanti-depressanttherapymayincreasetheriskofarrhythmiasandhypotension.

Ifsurgeryisnecessary,theanaesthetistshouldbeinformedthatapatientisbeingsotreated.

BarbituratesmaydecreaseandmethylphenidatemayincreasetheserumconcentrationofDothiepinandthusaffectits

antidepressantaction.

4.6Pregnancyandlactation

ThereisnoevidenceastothesafetyofDothiepininhumanpregnancynoristhereevidencefromanimalworkthatitis

freefromhazard.Itshouldonlybeusedinpregnancy,inparticular,inthefirstandlasttrimesters,ifthereare

compellingreasons.

Dothiepinisexcretedinbreastmilk;thereforeitisnotrecommendedforuseduringlactation.

4.7Effectsonabilitytodriveandusemachines

Noadverseeffectsexpected.

4.8Undesirableeffects

Thefollowingadverseeffects,althoughnotallreportedwithDothiepin,haveoccurredwithothertricyclic

antidepressants.

Atropine-likesideeffectsincludingdrymouth,disturbancesofaccommodation,tachycardia,constipationand

hesitancyofmicturitionarecommoninearlytreatment,butusuallydiminish.Otheradverseeffectsincludedrowsiness,

sweating,posturalhypotension,tremorandskinrashes.Interferencewithsexualfunctionmayoccur.

Seriousadverseeffectsarerare.Theseincludedepressionofthebonemarrow,agranulocytosis,cholestaticjaundice,

hypomaniaandconvulsions.Psychoticmanifestations,includingmaniaandparanoiddelusionsmaybeexacerbated

duringtreatmentwithtricyclicantidepressants.

Cardiacarrhythmia’sandseverehypotensionarelikelytooccurwithhighdosageorindeliberateoverdosage.They

mayalsooccurin-patientswithpre-existingheartdiseasetakinganormaldose.

CasesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringDosulepintherapyorearlyaftertreatment

discontinuation(seesection4.4).

Classeffects

Epidemiologicalstudies,mainlyconductedinpatients50yearsofageandolder,showanincreasedriskofbone

fracturesinpatientsreceivingSSRIsandTCAs.Themechanismleadingtothisriskisunknown.

4.9Overdose

ThereisnospecificantidoteforDothiepin.Gastriclavageisrecommended.Whenthepatientisunconsciousorthe

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Repeatedgastric/intestinalaspirationorrepeatedadministrationofactivatedcharcoalmayremovedrugandmetabolites

excretedintothegutviathebile.ContinuousECGmonitoringisadvisable.Abnormalitiesofcardiacrhythmand

epilepticconvulsionsmayoccurandshouldbetreatedaccordingly.Forceddiuresisisnotrecommended.Bedrestis

advisable,evenafterrecovery.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

DothiepinHClisatricyclicantidepressantwithactionsandusessimilartothoseofamitriptyline.

5.2Pharmacokineticproperties

DothiepinHClisreadilyabsorbedfromthegastrointestinaltractandextensivelydemethylatedbyfirst-pass

metabolisminthelivertoitsprimaryactivemetabolite,desmethyldothiepin(northiaden).Dothiepinisexcretedinthe

urine,mainlyintheformofitsmetabolites;smallamountsarealsoexcretedinthefaeces.Thehalf-lifeis

approximately19–33hours.

5.3Preclinicalsafetydata

Nofurtherinformationavailable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maizestarch

Povidone

Sodiumstarchglycolate

Talc

Magnesiumstearate

Filmcoating

Polyvinylalcohol

Ponceau4R(E124)

Purifiedtalc

Titaniumdioxide(E171)

Lecithin

Xanthangum

Carnaubawax

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

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6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalpackageorcontainer.

6.5Natureandcontentsofcontainer

Dothep75mgtabletsareavailableinpacksizesof28,30,100,250and500andarepackagedinPVCblistersor

polypropylenesecuritainers.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratories(tradingasGerardLaboratories)

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

8MARKETINGAUTHORISATIONNUMBER

PA577/20/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 05September1997

Datelastrenewal: 05September2007

10DATEOFREVISIONOFTHETEXT

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