DERINIK

Main information

  • Trade name:
  • DERINIK Tablets 0.7 Milligram
  • Dosage:
  • 0.7 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DERINIK Tablets 0.7 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1380/106/003
  • Authorization date:
  • 26-11-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Derinik0.7mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Derinik0.7mgtabletscontain0.7mgofpramipexolebase(as1.0mgofpramipexoledihydrochloridemonohydrate).

Pleasenote:

Pramipexoledosesaspublishedintheliteraturerefertothesaltform.

Therefore,doseswillbeexpressedintermsofbothpramipexolebaseandpramipexolesalt(inbrackets).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

White,roundtablets,markedononesidewitha“3”(three),scoredontheothersidewithnodefectsanddimensions

6.0±0.1mmindiameterand3.0mm±0.2mminthickness.Thetabletsarescoredsothetabletcanbedividedinto

equalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

DerinikisindicatedinadultsfortreatmentofthesignsandsymptomsofidiopathicParkinson'sdisease,alone(without

levodopa)orincombinationwithlevodopa,i.e.overthecourseofthedisease,throughtolatestageswhentheeffectof

levodopawearsofforbecomesinconsistentandfluctuationsofthetherapeuticeffectoccur(endofdoseor“onoff”

fluctuations).

4.2Posologyandmethodofadministration

Posology

Parkinson’sdisease

Thedailydoseisadministeredinequallydivideddoses3timesaday.

Initialtreatment

Dosesshouldbeincreasedgraduallyfromastartingdoseof0.264mgofbase(0.375mgofsalt)perdayandthen

increasedevery5-7days.Providingpatientsdonotexperienceintolerableundesirableeffects,thedoseshouldbe

titratedtoachieveamaximaltherapeuticeffect.

Ifafurtherdoseincreaseisnecessarythedailydoseshouldbeincreasedby0.54mgofbase(0.75mgofsalt)atweekly

intervalsuptoamaximumdoseof3.3mgofbase(4.5mgofsalt)perday.

ASCENDINGDOSESCHEDULEOFPRIXOL

Week Dosage

(mgofbase) TotalDailyDose

(mgofbase) Dosage

(mgofsalt) TotalDailyDose

(mgofsalt)

3x0.088 0.264 3x0.125 0.375

3x0.18 0.54 3x0.25 0.75

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 1

(seesection4.8).

Maintenancetreatment

Theindividualdoseofpramipexoleshouldbeintherangeof0.264mgofbase(0.375mgofsalt)toamaximumof3.3

mgofbase(4.5mgofsalt)perday.Duringdoseescalationinpivotalstudies,efficacywasobservedstartingatadaily

doseof1.1mgofbase(1.5mgofsalt).Furtherdoseadjustmentsshouldbedonebasedontheclinicalresponseandthe

occurrenceofadversereactions.Inclinicaltrialsapproximately5%ofpatientsweretreatedatdosesbelow1.1mgof

base(1.5mgofsalt).InadvancedParkinson’sdisease,pramipexoledoseshigherthan1.1mgofbase(1.5mgofsalt)

perdaycanbeusefulinpatientswhereareductionofthelevodopatherapyisintended.Itisrecommendedthatthedose

oflevodopaisreducedduringboththedoseescalationandthemaintenancetreatmentwithpramipexole,dependingon

reactionsinindividualpatients(seesection4.5).

Treatmentdiscontinuation

Abruptdiscontinuationofdopaminergictherapycanleadtothedevelopmentofaneurolepticmalignantsyndrome.

Therefore,pramipexoleshouldbetaperedoffatarateof0.54mgofbase(0.75mgofsalt)perdayuntilthedailydose

hasbeenreducedto0.54mgofbase(0.75mgofsalt).

Thereafterthedoseshouldbereducedby0.264mgofbase(0.375mgofsalt)perday(seesection4.4).

Dosinginpatientswithrenalimpairment

Theeliminationofpramipexoleisdependentonrenalfunction.Thefollowingdosescheduleissuggestedforinitiation

oftherapy:

Patientswithacreatinineclearanceabove50ml/minrequirenoreductionindailydoseordosingfrequency.Inpatients

withacreatinineclearancebetween20and50ml/min,theinitialdailydoseofpramipexoleshouldbeadministeredin

twodivideddoses,startingat0.088mgofbase(0.125mgofsalt)twiceaday(0.176mgofbase/0.25mgofsaltdaily).

Amaximumdailydoseof1.57mgpramipexolebase(2.25mgofsalt)shouldnotbeexceeded.

Inpatientswithacreatinineclearancelessthan20ml/min,thedailydoseofpramipexoleshouldbeadministeredina

singledose,startingat0.088mgofbase(0.125mgofsalt)daily.Amaximumdailydoseof1.1mgpramipexolebase

(1.5mgofsalt)shouldnotbeexceeded.

Ifrenalfunctiondeclinesduringmaintenancetherapythepramipexoledailydoseshouldbereducedbythesame

percentageasthedeclineincreatinineclearance,i.e.ifcreatinineclearancedeclinesby30%,thenthepramipexole

dailydoseshouldbereducedby30%.Thedailydosecanbeadministeredintwodivideddosesifcreatinineclearance

isbetween20and50ml/minandasasingledailydoseifcreatinineclearanceislessthan20ml/min.

Dosinginpatientswithhepaticimpairment

Doseadjustmentinpatientswithhepaticfailureisprobablynotnecessary,asapprox.90%ofabsorbedactivesubstance

isexcretedthroughthekidneys.However,thepotentialinfluenceofhepaticinsufficiencyonpramipexole

pharmacokineticshasnotbeeninvestigated

Paediatricpopulation

Thesafetyandefficacyofpramipexoleinchildrenbelow18yearshasnotbeenestablished.Thereisnorelevantuseof

pramipexoleinthepaediatricpopulationinParkinson’sDisease.

4.3Contraindications

Hypersensitivitytoactivesubstanceortoanyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

WhenprescribingpramipexoleinapatientwithParkinson’sdiseasewithrenalimpairmentareduceddoseissuggested

inlinewithsection4.2.

Hallucinations

Hallucinationsareknownasaside-effectoftreatmentwithdopamineagonistsandlevodopa.Patientsshouldbe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 2

Dyskinesia

InadvancedParkinson’sdisease,incombinationtreatmentwithlevodopa,dyskinesiascanoccurduringtheinitial

titrationofpramipexole.Iftheyoccur,thedoseoflevodopashouldbedecreased.

Suddenonsetofsleepandsomnolence

Pramipexolehasbeenassociatedwithsomnolenceandepisodesofsuddensleeponset,particularlyinpatientswith

Parkinson’sdisease.Suddenonsetofsleepduringdailyactivities,insomecaseswithoutawarenessorwarningsigns,

hasbeenreporteduncommonly.Patientsmustbeinformedofthisandadvisedtoexercisecautionwhiledrivingor

operatingmachinesduringtreatmentwithpramipexole.Patientswhohaveexperiencedsomnolenceand/oranepisode

ofsuddensleeponsetmustrefrainfromdrivingoroperatingmachines.Furthermoreareductionofthedoseor

terminationoftherapymaybeconsidered.Becauseofpossibleadditiveeffects,cautionshouldbeadvisedwhen

patientsaretakingothersedatingmedicinalproductsoralcoholincombinationwithpramipexole(seesections4.5,4.7

andsection4.8).

Impulsecontroldisordersandcompulsivebehaviors

Pathologicalgambling,increasedlibidoandhypersexualityhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson’sdisease,includingpramipexole.Furthermore,patientsandcaregiversshouldbeawareofthe

factthatotherbehaviouralsymptomsofimpulsecontroldisordersandcompulsionssuchasbingeeatingand

compulsiveshoppingcanoccur.Dosereduction/tapereddiscontinuationshouldbeconsidered.

Patientswithpsychoticdisorders

Patientswithpsychoticdisordersshouldonlybetreatedwithdopamineagonistsifthepotentialbenefitsoutweighthe

risks.Co-administrationofantipsychoticmedicinalproductswithpramipexoleshouldbeavoided(seesection4.5).

Ophthalmologicmonitoring

Ophthalmologicmonitoringisrecommendedatregularintervalsorifvisionabnormalitiesoccur.

Severecardiovasculardisease

Incaseofseverecardiovasculardisease,careshouldbetaken.Itisrecommendedtomonitorbloodpressure,especially

atthebeginningoftreatment,duetothegeneralriskofposturalhypotensionassociatedwithdopaminergictherapy.

Neurolepticmalignantsyndrome

Symptomssuggestiveofneurolepticmalignantsyndromehavebeenreportedwithabruptwithdrawalofdopaminergic

therapy(Seesection4.2)

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Plasmaproteinbinding

Pramipexoleisboundtoplasmaproteinstoaverylow(<20%)extent,andlittlebiotransformationisseeninman.

Therefore,interactionswithothermedicinalproductsaffectingplasmaproteinbindingoreliminationby

biotransformationareunlikely.Asanticholinergicsaremainlyeliminatedby

biotransformation,thepotentialforaninteractionislimited,althoughaninteractionwithanticholinergicshasnotbeen

investigated.Thereisnopharmacokineticinteractionwithselegilineandlevodopa.

Inhibitors/competitorsofactiverenaleliminationpathway

Cimetidinereducedtherenalclearanceofpramipexolebyapproximately34%,presumablybyinhibitionofthecationic

secretorytransportsystemoftherenaltubules.Therefore,medicinalproductsthatareinhibitorsofthisactiverenal

eliminationpathwayorareeliminatedbythispathway,suchas

cimetidine,amantadine,andmexiletine,mayinteractwithpramipexoleresultinginreducedclearanceofeitherorboth

medicinalproducts.Reductionofthepramipexoledoseshouldbeconsideredwhenthesemedicinalproductsare

administeredconcomitantlywithpramipexole.

Combinationwithlevodopa

Whenpramipexoleisgivenincombinationwithlevodopa,itisrecommendedthatthedoseoflevodopaisreducedand

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 3

Becauseofpossibleadditiveeffects,cautionshouldbeadvisedwhenpatientsaretakingothersedatingmedicinal

productsoralcoholincombinationwithpramipexole(seesection4.4,4.7,4.8).

Antipsychoticmedicinalproducts

Co-administrationofantipsychoticmedicinalproductswithpramipexoleshouldbeavoided(seesection4.4),e.g.if

antagonisticeffectscanbeexpected.

4.6Fertility,pregnancyandlactation

Pregnancy

Theeffectonpregnancyandlactationhasnotbeeninvestigatedinhumans.Pramipexolewasnotteratogenicinratsand

rabbits,butwasembryotoxicintheratatmaternotoxicdoses(seesection5.3).pramipexoleshouldnotbeusedduring

pregnancyunlessclearlynecessary,i.e.ifthepotentialbenefit

justifiesthepotentialrisktothefoetus.

Brest-feeding

Aspramipexoletreatmentinhibitssecretionofprolactininhumans,inhibitionoflactationisexpected.Theexcretionof

pramipexoleintobreastmilkhasnotbeenstudiedinwomen.Inrats,theconcentrationofactivesubstance-related

radioactivitywashigherinbreastmilkthaninplasma.Intheabsenceofhumandata,pramipexoleshouldnotbeused

duringbreast-feeding.However,ifitsuseisunavoidable,breast-feedingshouldbediscontinued.

Fertility

Nohumanornon-clinicalfertilitydataareavailable.

4.7Effectsonabilitytodriveandusemachines

Pramipexolecanhaveamajorinfluenceontheabilitytodriveandusemachines.

Hallucinationsorsomnolencecanoccur.

Patientsbeingtreatedwithpramipexoleandpresentingwithsomnolenceand/orsuddensleepepisodesmustbe

informedtorefrainfromdrivingorengaginginactivitieswhereimpairedalertnessmayputthemselvesorothersatrisk

ofseriousinjuryordeath(e.g.operatingmachines)untilsuchrecurrentepisodesandsomnolencehaveresolved(see

alsosections4.4,4.5,and4.8).

4.8Undesirableeffects

Expectedadversereactions

Thefollowingadversereactionsareexpectedundertheuseofpramipexole:abnormaldreams,amnesia,behavioural

symptomsofimpulsecontroldisordersandcompulsionssuchasbingeeating,compulsiveshopping,hypersexuality

andpathologicalgambling;confusion,constipation,delusion,dizziness,dyskinesia,dyspnoea,fatigue,hallucinations,

headache,hyperkinesia,hyperphagia,hypotension,insomnia,libidodisorders,nausea,paranoia,peripheraloedema,

pneumonia,pruritus,rashandotherhypersensitivity;restlessness,somnolence,suddenonsetofsleep,syncope,visual

disturbance

includingvisionblurredandvisualacuityreduced,vomiting,weightdecrease,weightincrease.

Basedontheanalysisofpooledplacebo-controlledtrials,comprisingatotalof1,923patientsonpramipexoleand

1,354patientsonplacebo,adversedrugreactionswerefrequentlyreportedforbothgroups.63%ofpatientson

pramipexoleand52%ofpatientsonplaceboreportedatleastoneadversedrugreaction.

Table1displaythefrequencyofadversedrugreactionsfromplacebo-controlledclinicaltrialsinParkinson’sdisease.

Theadversedrugreactionsreportedinthesetablesarethoseeventsthatoccurredin0.1%ormoreofpatientstreated

withpramipexoleandwerereportedsignificantlymoreofteninpatientstakingpramipexolethanplacebo,orwherethe

eventwasconsideredclinicallyrelevant.Themajorityofadversedrugreactionsweremildtomoderate,theyusually

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 4

Withinthesystemorganclasses,adversereactionsarelistedunderheadingsoffrequency(numberofpatientsexpected

toexperiencethereaction),usingthefollowingcategories: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);notknown(cannotbe

estimatedfromtheavailabledata).

Parkinson’sdisease,mostcommonadversereactions

Themostcommonly( ≥5%)reportedadversedrugreactionsinpatientswithParkinson’sdiseasemorefrequentwith

pramipexoletreatmentthanwithplacebowerenausea,dyskinesia,hypotension,dizziness,somnolence,insomnia,

constipation,hallucination,headacheandfatigue.Theincidenceof

somnolenceisincreasedatdoseshigherthan1.5mgpramipexolesaltperday(seesection4.2).Amorefrequent

adversedrugreactionincombinationwithlevodopawasdyskinesia.Hypotensionmayoccuratthebeginningof

treatment,especiallyifpramipexoleistitratedtoofast.

Somnolence

Pramipexoleiscommonlyassociatedwithsomnolenceandhasbeenassociateduncommonlywithexcessivedaytime

somnolenceandsuddensleeponsetepisodes(seealsosection4.4).

Libidodisorders

Pramipexolemaybeassociatedwithlibidodisorders(increasedordecreased).

Impulsecontroldisordersandcompulsivebehaviours

SystemOrganClass AdverseDrugReaction

Infectionsandinfestations

Uncommon pneumonia

Psychiatricdisorders

Common abnormaldreams,behaviouralsymptomsof

impulsecontroldisordersandcompulsions;

confusion,hallucinations,insomnia,restlessness

Uncommon compulsiveshopping,delusion,hypersexuality,

libidodisorder,paranoia,pathologicalgambling

Notknown bingeeating,hyperphagia

Nervoussystemdisorders

Verycommon dizziness,dyskinesia,somnolence

Common amnesia,headache

Uncommon hyperkinesia,suddenonsetofsleep,syncope

Eyedisorders

Common visualdisturbanceincludingvisionblurredand

visualacuityreduced

Vasculardisorders

Verycommon hypotension

Respiratory,thoracic,andmediastinaldisorders

Uncommon dyspnoea

Gastrointestinaldisorders

Verycommon nausea

Common Constipation,vomiting

Skinandsubcutaneoustissuedisorders

Uncommon hypersensitivity,pruritus,rash

Generaldisordersandadministrationsiteconditions

Common fatigue,peripheraloedema

Investigations

Common weigthdecrease

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 5

beenreportedasexhibitingsignsofpathologicalgambling,increasedlibidoandhypersexuality,generallyreversible

uponreductionofthedoseortreatmentdiscontinuation(seealso

section4.4).

Inacross-sectional,retrospectivescreeningandcase-controlstudyincluding3,090Parkinson’sdiseasepatients,13.6%

ofallpatientsreceivingdopaminergicornon-dopaminergictreatmenthadsymptomsofanimpulsecontroldisorder

duringthepastsixmonths.Manifestationsobservedinclude

pathologicalgambling,compulsiveshopping,bingeeating,andcompulsivesexualbehaviour(hypersexuality).Possible

independentriskfactorsforimpulsecontroldisordersincludeddopaminergictreatmentsandhigherdosesof

dopaminergictreatment,youngerage( ≤65years),notbeingmarriedandself-reportedfamilyhistoryofgambling

behaviours.

4.9Overdose

Thereisnoclinicalexperiencewithmassiveoverdose.Theexpectedadversereactionswouldbethoserelatedtothe

pharmacodynamicprofileofadopamineagonist,includingnausea,vomiting,hyperkinesia,hallucinations,agitation

andhypotension.Thereisnoestablishedantidoteforoverdose

ofadopamineagonist.Ifsignsofcentralnervoussystemstimulationarepresent,aneurolepticagentmaybeindicated.

Managementoftheoverdosemayrequiregeneralsupportivemeasures,alongwithgastriclavage,intravenousfluids,

administrationofactivatedcharcoalandelectrocardiogram

monitoring.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

PramipexoleisadopamineagonistthatbindswithhighselectivityandspecificitytotheD2subfamilyofdopamine

receptorsofwhichithasapreferentialaffinitytoD3receptors,andhasfullintrinsicactivity.

Pramipexolealleviatesparkinsonianmotordeficitsbystimulationofdopaminereceptorsinthestriatum.Animal

studieshaveshownthatpramipexoleinhibitsdopaminesynthesis,release,andturnover.

Inhumanvolunteers,adose-dependentdecreaseinprolactinwasobserved.

ClinicaltrialsinParkinson’sdisease

InpatientspramipexolealleviatessignsandsymptomsofidiopathicParkinson’sdisease.Placebocontrolledclinical

trialsincludedapproximately1,800patientsofHoehnandYahrstagesI–Vtreatedwithpramipexole.Outofthese,

approximately1,000wereinmoreadvancedstages,received

concomitantlevodopatherapy,andsufferedfrommotorcomplications.InearlyandadvancedParkinson’sdisease,

efficacyofpramipexoleincontrolledclinicaltrialswasmaintainedforapproximatelysixmonths.Inopencontinuation

trialslastingformorethanthreeyearstherewerenosignsofdecreasingefficacy.

Inacontrolleddoubleblindclinicaltrialof2yearduration,initialtreatmentwithpramipexolesignificantlydelayedthe

onsetofmotorcomplications,andreducedtheiroccurrencecomparedtoinitialtreatmentwithlevodopa.Thisdelayin

motorcomplicationswithpramipexoleshouldbebalancedagainstagreaterimprovementinmotorfunctionwith

levodopa(asmeasuredbythemeanchangeinUPDRS-score).Theoverallincidenceofhallucinationsandsomnolence

wasgenerallyhigherintheescalationphasewiththepramipexolegroup.However,therewasnosignificantdifference

duringthemaintenancephase.Thesepointsshouldbeconsideredwheninitiatingpramipexoletreatmentinpatients

withParkinson’sdisease.

ClinicaltrialinTouretteDisorder

Theefficacyofpramipexole(0.0625-0.5mg/day)withpaediatricpatientsaged6-17yearswithTouretteDisorderwas

evaluatedina6-week,double-blind,randomised,placebo-controlledflexibledosestudy.Atotalof63patientswere

randomised(43onpramipexole,20onplacebo).Theprimary

endpointwaschangefrombaselineontheTotalTicScore(TTS)oftheYaleGlobalTicSeverityScale(YGTSS).No

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 6

secondaryefficacyendpointsincludingYGTSStotalscore,PatientGlobalImpressionofImprovement(PGI-I),

ClinicalGlobalImpressionofImprovement(CGI-I),orClinicalGlobalImpressionsofSeverityofIllness(CGI-S).

Adverseeventsoccurringinatleast5%ofpatientsinthepramipexolegroupandmorecommoninthepramipexole-

treatedpatientsthaninpatientsonplacebowere:headache(27.9%,placebo25.0%),somnolence(7.0%,placebo5.0%),

nausea(18.6%,placebo10.0%),vomiting(11.6%,placebo0.0%),upperabdominalpain(7.0%,placebo5.0%),

orthostatichypotension(9.3%,placebo5.0%),myalgia(9.3%,placebo5.0%),sleepdisorder(7.0%,placebo0.0%),

dyspnoea(7.0%,placebo0.0%)andupperrespiratorytractinfection(7.0%,placebo5.0%).Othersignificantadverse

eventsleadingtodiscontinuationofstudymedicationforpatientsreceivingpramipexolewereconfusionalstate,speech

disorderandaggravatedcondition(seesection4.2).

5.2Pharmacokineticproperties

Pramipexoleisrapidlyandcompletelyabsorbedfollowingoraladministration.Theabsolutebioavailabilityisgreater

than90%andthemaximumplasmaconcentrationsoccurbetween1and3hours.Concomitantadministrationwithfood

didnotreducetheextentofpramipexoleabsorption,buttherateofabsorptionwasreduced.Pramipexoleshowslinear

kineticsandasmallinter-patientvariationofplasmalevels.Inhumans,theproteinbindingofpramipexoleisverylow

(<20%)andthevolumeofdistributionislarge(400l).Highbraintissueconcentrationswereobservedintherat

(approx.8-foldcomparedtoplasma).

Pramipexoleismetabolisedinmanonlytoasmallextent.

Renalexcretionofunchangedpramipexoleisthemajorrouteofelimination.Approximately90%of14C-labelleddose

isexcretedthroughthekidneyswhilelessthan2%isfoundinthefaeces.Thetotalclearanceofpramipexoleis

approximately500ml/minandtherenalclearanceisapproximately

400ml/min.Theeliminationhalf-life(t½)variesfrom8hoursintheyoungto12hoursintheelderly

5.3Preclinicalsafetydata

Repeateddosetoxicitystudiesshowedthatpramipexoleexertedfunctionaleffects,mainlyinvolvingtheCNSand

femalereproductivesystem,andprobablyresultingfromanexaggeratedpharmacodynamiceffectofpramipexole.

Decreasesindiastolicandsystolicpressureandheartratewerenotedintheminipig,andatendencytoahypotensive

effectwasdiscernedinthemonkey.

Thepotentialeffectsofpramipexoleonreproductivefunctionhavebeeninvestigatedinratsandrabbits.Pramipexole

wasnotteratogenicinratsandrabbitsbutwasembryotoxicintheratatmaternallytoxicdoses.Duetotheselectionof

animalspeciesandthelimitedparametersinvestigated,

theadverseeffectsofpramipexoleonpregnancyandmalefertilityhavenotbeenfullyelucidated.

Pramipexolewasnotgenotoxic.Inacarcinogenicitystudy,maleratsdevelopedLeydigcellhyperplasiaandadenomas,

explainedbytheprolactin-inhibitingeffectofpramipexole.Thisfindingisnotclinicallyrelevanttoman.Thesame

studyalsoshowedthat,atdosesof2mg/kg(ofsalt)and

higher,pramipexolewasassociatedwithretinaldegenerationinalbinorats.Thelatterfindingwasnotobservedin

pigmentedrats,norina2-yearalbinomousecarcinogenicitystudyorinanyotherspeciesinvestigated.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Starch,pregelatinised(Starchmaize1500)

Mannitol

Cellulose,microcrystalline

Povidone(27.0-32.4)

Talc

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 7

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

Blister(PA/ALU/PVC-Aluminium):10tabletsperblisterstrips.

Cartonscontaining3or10blisterstrips(30or100tablets)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ActavisGroupPTCehf

Reykjavikurvegi76-78

220Hafnarfjordur

Iceland

8MARKETINGAUTHORISATIONNUMBER

PA1380/106/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:5November2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/04/2011 CRN 2084410 page number: 8