DOMPERIDONE

Main information

  • Trade name:
  • DOMPERIDONE Orodispersible Tablet 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Orodispersible Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOMPERIDONE Orodispersible Tablet 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1287/002/001
  • Authorization date:
  • 12-09-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DomperidonePierreFabre10mgOrodispersibleTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Oneorodispersibletabletcontainsdomperidone10mg.

Excipient:sulphurdioxide.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Orodispersibletablet.

Uniformlywhiteoralmostwhite,biconvex,roundorodispersibletabletwithacharacteristicodorofmint.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Adults

Thereliefofthesymptomsofnauseaandvomiting,epigastricsenseoffullness,upperabdominaldiscomfortand

regurgitationofgastriccontents.

Adolescents(over12yearsandweighing35kgormore)

Thereliefofthesymptomsofnauseaandvomiting.

4.2Posologyandmethodofadministration

Itisrecommendedtotakethismedicinebeforemeals.Iftakenaftermeals,absorptionofthedrugissomewhatdelayed.

Theinitialdurationoftreatmentisfourweeks.Patientsshouldbere-evaluatedafterfourweeksandtheneedfor

continuedtreatmentre-assessed.

Adultsandadolescents(over12yearsandweighing35kgormore)

1to2ofthe10mgtabletsthreetofourtimesperdaywithamaximumdailydoseof80mg.

Theorodispersibletabletisatabletwhichdissolvesrapidlyinthemouthwiththehelpofthesaliva.

Placethetabletonthetongueandletitdissolveinthemouthbeforeswallowing.Drinkaglassofwaterafterthetablet

intake.

Paediatricpopulation

Orodispersibletabletsareunsuitableforuseinchildrenunder12yearsofageandweighinglessthan35kg.

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Additionalinformationonspecialpopulations

Useinpatientswithliverinsufficiency

Sincedomperidoneishighlymetabolisedintheliver,thismedicineshouldbeusedwithcautioninpatientswith

hepaticimpairment,seesection4.4.

Useinpatientswithrenalinsufficiency

Giventherenalexcretionofdomperidone,andincaseofprolongedtherapy,thedoseofthemedicineshouldbe

reducedtoonceortwicedailyinpatientswithrenalinsufficiency.Moreover,suchpatientsonprolongedtherapy

shouldbereviewedregularly.(seesections4.4,5.2).

4.3Contraindications

Thismedicineiscontraindicatedinthefollowingsituations:

Knownhypersensitivitytodomperidoneoranyoftheexcipients.

Prolactin-releasingpituitarytumour(prolactinoma).

Thismedicineshouldnotbeusedwhenstimulationofthegastricmotilitycouldbeharmful:gastro-intestinal

haemorrhage,mechanicalobstructionordigestiveperforation.

4.4Specialwarningsandprecautionsforuse

Useduringlactation

Thetotalamountofdomperidoneexcretedinhumanbreastmilkisexpectedtobelessthan7µgperdayatthehighest

recommendeddosingregimen.Itisnotknownwhetherthisisharmfultothenewborn.Thereforethismedicineisnot

recommendedinbreast-feedingwomen.

Useinliverdisorders

Sincedomperidoneishighlymetabolisedintheliver,cautionisrecommendedinpatientswithhepaticimpairment.

(seesections4.2,5.2).

Renalinsufficiency

Inpatientswithsevererenalinsufficiency(serumcreatinine>6mg/100mL,i.e.>0.6mmol/L),theposologyshouldbe

adjusted(seesection4.2)duetoareducedelimination(seesection5.2).Suchpatientsonprolongedtherapyshouldbe

reviewedregularly.

UsewithpotentCYP3A4inhibitors

Co-administrationwithoralketoconazole,erythromycinorotherpotentCYP3A4inhibitorsthatprolongtheQTc

intervalshouldbeavoided(seesection4.5interactionwithothermedicinalproductsandotherformsofinteraction).

Useininfantsandchildren

Neurologicalsideeffectsarerare(seesection4.8)

Sincemetabolicfunctionsandtheblood-brainbarrierarenotfullydevelopedinthefirstmonthsoflifetheriskof

neurologicalsideeffectsishigherinyoungchildren.Therefore,itisrecommendedthatthedosebedetermined

accuratelyandfollowedstrictlyinneonates,infants,toddlersandsmallchildren.

Overdosingmaycauseextrapyramidalsymptomsininfantsandchildren,butothercausesshouldbetakeninto

consideration.

ThismedicinalproductcontainsSulphurdioxide.TheSulphurdioxidemayrarelycauseseverehypersensitivity

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ThemainmetabolicpathwayofdomperidoneisthroughCYP3A4.Invitrodatasuggestthattheconcomitantuseof

drugsthatsignificantlyinhibitthisenzymemayresultinincreasedplasmalevelsofdomperidone.

Separateinvivopharmacokinetic/pharmacodynamicinteractionstudieswithoralketoconazoleororalerythromycinin

healthysubjectsconfirmedamarkedinhibitionofdomperidone'sCYP3A4mediatedfirstpassmetabolismbythese

drugs.

Withthecombinationoforaldomperidone10mgfourtimesdailyandketoconazole200mgtwicedaily,ameanQTc

prolongationof9.8msecwasseenovertheobservationperiod,withchangesatindividualtimepointsrangingfrom1.2

to17.5msec.Withthecombinationofdomperidone10mgfourtimesdailyandoralerythromycin500mgthreetimes

daily,meanQTcovertheobservationperiodwasprolongedby9.9msec,withchangesatindividualtimepoints

rangingfrom1.6to14.3msec.BoththeCmaxandAUCofdomperidoneatsteadystatewereincreasedapproximately

three-foldineachoftheseinteractionstudies.Inthesestudiesdomperidonemonotherapyat10mggivenorallyfour

timesdailyresultedinincreasesinmeanQTcof1.6msec(ketoconazolestudy)and2.5msec(erythromycinstudy),

whileketoconazolemonotherapy(200mgtwicedaily)anderythromycinmonotherapy(500mgthreetimesdaily)ledto

increasesinQTcof3.8and4.9msec,respectively,overtheobservationperiod.

4.6Fertility,pregnancyandlactation

Therearelimitedpost-marketingdataontheuseofdomperidoneinpregnantwomen.Astudyinratshasshown

reproductivetoxicityatahigh,maternallytoxicdose(seesection5.3).Thepotentialriskforhumansisunknown.

Therefore,thismedicineshouldonlybeusedduringpregnancywhenjustifiedbytheanticipatedtherapeuticbenefit.

Thedrugisexcretedinbreastmilkoflactatingrats(mostlyasmetabolites:peakconcentrationof40and800ng/ml

afteroralandi.v.administrationof2.5mg/kgrespectively).Domperidoneconcentrationsinbreastmilkoflactating

womenare10to50%ofthecorrespondingplasmaconcentrationsandexpectednottoexceed10ng/ml.Thetotal

amountofdomperidoneexcretedinhumanbreastmilkisexpectedtobelessthan7µgperdayatthehighest

recommendeddosingregimen.Itisnotknownwhetherthisisharmfultothenewborn.Thereforethismedicineisnot

recommendedinbreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Thismedicinehasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

Theadversedrugreactionsarerankedbelowbyfrequency,usingthefollowingconvention:verycommon(1/10),

common(1/100,<1/10),uncommon(1/1,000,<1/100),rare(1/10,000,<1/1,000),veryrare(<1/10,000),not

known(cannotbeestimatedfromtheavailabledata).

Systemorganclass

(MedDRAclassification) Rare(1/10,000,<1/1,000), Veryrare(<10,000), NotKnown(cannot

beestimatedfrom

availabledata)

ImmuneSystemDisorder: allergicreactionsincluding

anaphylaxis,anaphylacticshock,

anaphylacticreactionand

angioedema

Endocrinedisorder: increasedprolactinlevels 1

Psychiatricsystem

disorders Agitation 3

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1

Asthehypophysisisoutsidethebloodbrainbarrier,domperidonemaycauseanincreaseinprolactinlevels.Inrare

casesthishyperprolactinaemiamayleadtoneuro-endocrinologicalsideeffectssuchasgalactorrhoea,gynaecomastia

andamenorrhoea.

2

Extrapyramidalsideeffectsareveryrareinneonatesandinfants,andexceptionalinadults.Thesesideeffectsreverse

spontaneouslyandcompletelyassoonasthetreatmentisstopped.

3

Othercentralnervoussystem-relatedeffectsofconvulsion,agitation,andsomnolencealsoareveryrareandprimarily

reportedininfantsandchildren.

4.9Overdose

Symptoms

Symptomsofoverdosagemayincludedrowsiness,disorientationandextrapyramidalreactions,especiallyinchildren.

Treatment

Thereisnospecificantidotetodomperidone,butintheeventofoverdose,gastriclavageaswellastheadministration

ofactivatedcharcoal,maybeuseful.Closemedicalsupervisionandsupportivetherapyisrecommended.

Anticholinergic,anti-parkinsondrugsmaybehelpfulincontrollingtheextrapyramidalreactions.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Propulsives,ATCcode:A03FA03.

Domperidoneisadopamineantagonistwithanti-emeticproperties,Domperidonedoesnotreadilycrosstheblood-

brainbarrier.

Indomperidoneusers,especiallyinadults,extrapyramidalsideeffectsareveryrare,butdomperidonepromotesthe

releaseofprolactinfromthepituitary.Itsanti-emeticeffectmaybeduetoacombinationofperipheral(gastrokinetic)

effectsandantagonismofdopaminereceptorsinthechemoreceptortriggerzone,whichliesoutsidetheblood-brain

barrierintheareapostrema.Animalstudies,togetherwiththelowconcentrationsfoundinthebrain,indicatea

predominantlyperipheraleffectofdomperidoneondopaminereceptors.

Studiesinmanhaveshownoraldomperidonetoincreaseloweroesophaegealpressure,improveantroduodenalmotility

Nervoussystemdisorders extrapyramidalsideeffects 2

,

convulsion 3

,somnolence 3

,headache

Gastrointestinaldisorders: gastro-intestinaldisorders,including

veryraretransientintestinalcramps; diarrhoea.

Skinandsubcutaneous

tissuedisorders urticaria,pruritus,rash.

Reproductivesystemand

breastdisorders: galactorrhoea,gynaecomastia,

amenorrhea.

Cardiacdisorders: ventriculararrhythmias. QTcprolongation

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5.2Pharmacokineticproperties

Absorption

Infastingsubjects,domperidoneisrapidlyabsorbedafteroraladministration,withpeakplasmaconcentrationsat30to

60minutes.Thelowabsolutebioavailabilityoforaldomperidone(approximately15%)isduetoanextensivefirst-pass

metabolisminthegutwallandliver.

Althoughdomperidone’sbioavailabilityisenhancedinnormalsubjectswhentakenafterameal,patientswithgastro-

intestinalcomplaintsshouldtakedomperidone15-30minutesbeforeameal.Reducedgastricacidityimpairsthe

absorptionofdomperidone.Oralbioavailabilityisdecreasedbypriorconcomitantadministrationofcimetidineand

sodiumbicarbonate.

ThetimeofpeakabsorptionisslightlydelayedandtheAUCsomewhatincreasedwhentheoraldrugistakenaftera

meal.

Distribution

Oraldomperidonedoesnotappeartoaccumulateorinduceitsownmetabolism;apeakplasmalevelafter90minutesof

21ng/mlaftertwoweeksoraladministrationof30mgperdaywasalmostthesameasthatof18ng/mlafterthefirst

dose.Domperidoneis91-93%boundtoplasmaproteins.

Metabolism

DomperidoneundergoesrapidandextensivehepaticmetabolismbyhydroxylationandN-dealkylation.Invitro

metabolismexperimentswithdiagnosticinhibitorsrevealedthatCYP3A4isamajorformofcytochromeP-450

involvedintheN-dealkylationofdomperidone,whereasCYP3A4,CYP1A2andCYP2E1areinvolvedindomperidone

aromatichydroxylation.

Excretion

Urinaryandfaecalexcretionsamountto31and66%oftheoraldoserespectively.Theproportionofthedrugexcreted

unchangedissmall(10%offaecalexcretionandapproximately1%ofurinaryexcretion).Theplasmahalf-lifeaftera

singleoraldoseis7-9hoursinhealthysubjectsbutisprolongedinpatientswithsevererenalinsufficiency.

Specialpatientgroups

Liverimpairment

Nopharmacokineticstudiesinpatientswithhepaticimpairmentareavailable.

Domperidoneiseliminatedmainlybymetabolismandtherefore,cautionisrecommendedinpatientswithhepatic

impairment,seesections4.2,4.4.

Renalimpairment

Inpatientswithsevererenalinsufficiency(serumcreatinine>6mg/100mL,i.e.>0.6mmol/L)theeliminationhalf-

lifeofdomperidonewasincreasedfrom7.4to20.8hours,butplasmadruglevelswerelowerthaninhealthy

volunteers.

Sinceverylittleunchangeddrugisexcretedviathekidneys,itisunlikelythatthedoseofasingleadministrationneeds

tobeadjustedinpatientswithrenalinsufficiency.However,onrepeatedadministration,thedosingfrequencyshould

bereducedtoonceortwicedailydependingontheseverityoftheimpairment,andthedosemayneedtobereduced.

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5.3Preclinicalsafetydata

ElectrophysiologicalinvitroandinvivostudiesindicateanoverallmoderateriskofdomperidonetoprolongtheQT

intervalinhumans.IninvitroexperimentsonisolatedcellstransfectedwithHERGandonisolatedguineapig

myocytes,exposureratiosrangedbetween5-and30-fold,basedonIC50valuesinhibitingcurrentsthroughIKrion

channelsincomparisontothefreeplasmaconcentrationsinhumansafteradministrationofthemaximumdailydoseof

20mg(q.i.d.).Exposuremarginsforprolongationofactionpotentialdurationininvitroexperimentsonisolated

cardiactissuesexceededthefreeplasmaconcentrationsinhumansatmaximumdailydose(20mgq.i.d.)by17-fold.

However,safetymarginsininvitropro-arrhythmicmodels(isolatedLangendorffperfusedheart)andininvivomodels

(dog,guineapig,rabbitssensitisedfortorsadesdepoints)exceededthefreeplasmaconcentrationsinhumansat

maximumdailydose(20mgq.i.d.)bymorethan17-fold.InthepresenceofinhibitionofthemetabolismviaCYP3A4

freeplasmaconcentrationsofdomperidonecanriseupto10-fold.

Atahigh,maternallytoxicdose(morethan40timestherecommendedhumandose),teratogeniceffectswereseenin

therat.Noteratogenicitywasobservedinmiceandrabbits.

Distributionstudieswithradiolabelleddruginanimalshaveshownwidetissuedistribution,butlowbrain

concentration.

Smallamountsofdrugcrosstheplacentainrats.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Coretablet:

Mannitol,

Maltodextrin

Croscarmellose,sodium

Cellulose,microcrystalline

Magnesiumstearate

Acesulfamepotassium

Flavouringagent:

Peppermintflavourpowdern°SN13627517(essentialoilofstaranise,cloveoil,essentialoilofcornmint,peppermint

oil,L-menthol,maltodextrin,arabicgum,sulphurdioxide),ammoniumglycyrrhizate.

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Thismedicinedoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

10or30orodispersibletabletsinheat-formedblisterpacks(PVC/PE/PVDC/Aluminum).

30orodispersibletabletsinheat-formedblisterpacks(PVC/PE/PVDC/Aluminum).

6.6Specialprecautionsfordisposal

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7MARKETINGAUTHORISATIONHOLDER

PierreFabreLtd

HydeAbbeyHouse,

23AbbeyStreet,

Winchester,

HampshireSO237DR

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1287/2/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12thSeptember2008

Dateoflastrenewal:17thFebruary2011

10DATEOFREVISIONOFTHETEXT

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