CABASER 4MG TABLETS

Main information

  • Trade name:
  • CABASER 4MG TABLETS
  • Dosage:
  • 4 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CABASER 4MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0187/061/003
  • Authorization date:
  • 29-10-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0187/061/003

CaseNo:2036103

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PharmaciaLaboratoriesLimited

RamsgateRoad,Sandwich,Kent,CT139NJ,England

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cabaser4mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom10/05/2007until28/10/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cabaser4mgTablet

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains4mgcabergolineastheactivesubstance.

Eachtabletalsocontains301.6mgofanhydrouslactose.

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

White,oval,bothsidesconcavetablets,onesidescoredandengraved“7”ontheleftofthebreaklineand“03”onthe

rightofit.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofParkinson'sdisease

Iftreatmentwithadopamineagonistisbeingconsidered.Cabaserisindicatedassecondlinetherapyinpatientswho

areintolerantorfailtreatmentwithanon-ergotcompound,asmonotherapy,orasadjunctivetreatmenttolevodopaplus

dopa-decarboxylaseinhibitor,inthemanagementofthesignsandsymptomsofParkinson’sdisease.

Treatmentshouldbeinitiatedunderspecialistsupervision.Thebenefitofcontinuedtreatmentshouldberegularly

reassessedtakingintoaccounttheriskoffibroticreactionsandvalvulopathy(seesections4.3,4.4&4.8).

4.2Posologyandmethodofadministration

Cabaserisfororaladministration.Sincethetolerabilityofdopaminergicagentsisimprovedwhenadministeredwith

food,itisrecommendedthatCabaserbetakenwithmeals.

Cabaserisintendedforchronic,longtermtreatment.

Adultsandelderlypatients

Asexpectedfordopamineagonists,doseresponseforbothefficacyandsideeffectsappearstobelinkedtoindividual

sensitivity.Optimizationofdoseshouldbeobtainedthroughslowinitialdosetitration,fromstartingdosesof1mg

daily.Thedosageofconcurrentlevodopamaybegraduallydecreased,whilethedosageofCabaserisincreased,until

theoptimumbalanceisdetermined.Inviewofthelonghalf-lifeofthecompound,incrementsofthedailydoseof0.5-

1mgshouldbedoneatweekly(initialweeks)orbi-weeklyintervals,uptooptimaldoses.

Therecommendedtherapeuticdosageis2to6mg/dayasadjuvanttherapytolevodopa/carbidopa.Cabasershouldbe

givenasasingledailydose.

ControlledclinicalstudieshavedemonstratedthatCabaseradministeredoncedailyatanaveragedoseof4mg/day

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Useinchildren

ThesafetyandefficacyofCabaserhavenotbeeninvestigatedinchildrenasParkinson'sdiseasedoesnotaffectthis

population.

4.3Contraindications

HypersentivitytoCabaser,otherergotalkaloidsortoanyoftheexcipients.

Historyofpulmonary,pericardialandretroperitonealfibroticdisorders.

Anatomicalevidenceofcardiacvalvulopathyofanyvalue(e.g.echocardiogramshowingvalveleafletthickening,

valverestriction,valvemixedrestriction-stenosis).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.4Specialwarningsandprecautionsforuse

RenalInsufficiency:NooveralldifferencesinthepharmacokineticsofCabaserwereobservedin12patientshaving

moderate(creatinineclearance31-60ml/min)tosevere(creatinineclearance8-26ml/min)renaldisease.The

pharmacokineticsofCabaserinthesepatientsweresimilartothoseofhealthyvolunteersasexpected,sinceonlya

smallfractionofCabaseriseliminatedrenally.ThepharmacokineticsofCabaserhasnotbeenstudiedinpatients

havingend-stagerenalfailure,orinpatientsonhaemodialysis;thesepatientsshouldbetreatedwithcaution.

HepaticInsufficiency:ThepharmacokineticsofCabaserwasstudiedin12patientshavingvaryingdegreeofhepatic

dysfunction(Child-Pughscore5-11).Followingsingle1mgdoseadministration,Cabaserpharmacokineticsinpatients

withmild-moderatedysfunction(Child-Pughscore<10)weresimilartothosedeterminedinpreviousstudiesin

subjectswithnormalhepaticfunction.However,patientswiththemostseveredysfunction(Child-Pughscore>10)

showedAUCvalues2-foldormoregreaterthanpatientswithlesserdysfunction.Noindicationofprolongedhalf-life

wasfound.TheseresultssuggestpatientswithseverehepaticinsufficiencymayrequirelowerdoseofCabaser.These

patientsshouldbedosedwithcaution,anditisrecommendedthatdailydoseshouldbelimitedtonomorethan1mg.

Respiratory:Pleuraleffusion/pulmonaryfibrosishasbeenreportedinapproximately0.8%ofpatientsfollowinglong

termadministrationofCabaser,andusuallywhengiventopatientspreviouslytreatedwithergolinicDAagonists.

Pleuritisandpleuralfibrosishavealsobeenreportedafterprolongeduseofergotderivatives.ThereforeCabasershould

begivenwithcautiontopatientswithahistoryorclinicalsymptomsofrespiratorydisorderslinkedtofibrotictissue

degeneration.Achestx-rayexaminationisrecommendedifclinicalsymptomsofrespiratorydisordersareobserved.

Wherex-rayexaminationindicatespleuraleffusion/fibrosis,discontinuationofCabaserisrecommendedandis

expectedtoleadtoanimprovementofsymptoms.

Erythrocytesedimentationrate(ESR)hasbeenfoundtobeabnormallyincreasedinassociationwithpleural

effusion/fibrosis.Chestx-rayexaminationisrecommendedincaseofunexplainedESRincreasestoabnormalvalues.

Serumcreatinemeasurementscanalsobeusedtohelpinthediagnosisoffibroticdisorder.Itmaybeappropriateto

performbaselineinvestigationsofESRorotherinflammatorymarkers,lungfunction/chestx-rayandrenalfunction

priortoinitiationoftherapy.

Serumcreatinemeasurementscanalsobeusedtohelpinthediagnosisoffibroticdisorder.Itmaybeappropriateto

performbaselineinvestigationsofESRorotherinflammatorymarkers,lungfunction/chestx-rayandrenalfunction

priortoinitiationoftherapy.

Cardiac:

FibroticandCardiacvalvulopathy

Fibroticandserosalinflammatorydisorderssuchaspleuritis,pleuraleffusion,pleuralfibrosis,pulmonaryfibrosis,

pericarditis,pericardialeffusion,cardiacvalvulopathyinvolvingoneormorevalves(aortic,mitralandtricuspid)or

retroperitonealfibrosishaveoccurredafterprolongedusageofergotderivativessuchasCabaser.Therefore,Cabaser

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degeneration.

Insomecases,symptomsormanifestationsofcardiacvalvulopathyimprovedafterdiscontinuationofcabaser.

Erythrocytesedimentationrate(ESR)hasbeenfoundtobeabnormallyincreasedinassociationwithpleural

effusion/fibrosis.Chestx-rayexaminationisrecommendedincasesofunexplainedESRincreasestoabnormalvalues.

Serumcreatinemeasurementscanalsobeusedtohelpinthediagnosisoffibroticdisorders.

Valvulopathywasassociatedwithcumulativedoses.

Beforeinitiatingtreatment:

Allpatientsshouldundergoacardivascularevaluation,includingechocardiogram,toassessthepotentialpresenceof

asymptomaticvalvulardisease.ItmaybeappropriatetoperformbaselineinvestigationsofESRorotherinflammatory

markers,lungfunction/chestx-rayandrenalfunctionpriortoinitiationoftherapy.Iffibroticvalvulardiseaseis

detected,thepatientshouldnotbetreatedwithCabaser(Seesection4.3).

Duringtreatment:

Fibroticdisorderscanhaveaninsidiousonsetandpatientsshouldberegularlymonitoredforpossiblemanifestationsto

progressivefibrosis.Thereforeduringtreatment,attentionshouldbepaidtothesignsandsymptomsof:

Pleuropulmonarydisease,suchasdyspnoea,shortnessofbreath,persistentcough,orchestpain.

Renalinsufficiencyorureteral/abdominalvascularobstructionthatmayoccurwithpainintheloin/flank,and

lowerlimboedema,aswellasanypossibleabdominalmassesortendernessthatmayindicateretroperitoneal

fibrosis.

Cardiacfailure,ascasesofpericardialfibrosishaveoftenmanifestedascardiacfailure;constrictivepericarditis

shouldbeexcludedifsuchsymptomsappear.

Cardiacfailure,ascasesofvalvularfibrosishaveoftenmanifestedascardiacfailure;valvularfibrosisshouldbe

excludedifsuchsymptomsappear.

Clinicaldiagnosticmonitoringfordevelopmentofvalvulardiseaseorfibrosis,asappropriate,isrecommended.

Followingtreatmentinitiation,the

firstechocardiogramshouldoccurwithin3-6months,thereafter,thefrequencyofechocardiographicmonitoring

shouldbedeterminedbappropriate

individualclinicalassessmentwithparticularemphasisontheabove-mentionedsignsandsymptoms,butshould

occurataleastevery6to12

months.

Cabasershouldbediscontinuedifanechocardiogramrevealsneworworsenedvalvularregurgitation,valvular

restrictionorvalveleafletthickening.(SeeSection4.3)Theneedforotherclinicalmonitoring(e.g.,physical

examination,carefulcardiacauscultation,X-ray,echocardiogram,CTscan)shouldbedeterminedonanindividual

basis.

SymptomatichypotensioncanoccurfollowingadministrationofCabaser:particularattentionshouldbepaidwhen

administeringCabaserconcomitantlywithotherdrugsknowntolowerbloodpressure.Becauseofitseliminationhalf-

lifehypotensiveeffectsmaypersistforafewdaysaftercessationoftherapy.

CNS:Cabaserhasbeenassociatedwithsomnolenceandepisodesofsuddensleeponset,particularlyinpatientswith

Parkinson'sdisease.Suddenonsetofsleepduringactivities,insomecaseswithoutawarenessorwarningsigns,has

beenreporteduncommonly.Patientsmustbeinformedofthisandadvisedtoexercisecautionwhiledrivingor

operatingmachinesduringtreatmentwithCabaser.Patientswhohaveexperiencedsomnolenceand/oranepisodeof

suddensleeponsetmustrefrainfromdrivingoroperatingmachines.Furthermoreareductionofdosageortermination

oftherapymaybeconsidered.

Inaddition,byanalogywithotherergotderivatives,Cabasershouldbegivenwithcautiontopatientssufferingfrom

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particularlypsychoticmentaldisease.

Pathologicalgambling,increasedlibidoandhypersexualtiyhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson’sdisease,includingCabaser.

TheeffectsofalcoholonoveralltolerabilityofCabaserarecurrentlyunknown.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

NopharmacokineticinteractionwithL-dopaorselegilinewasobservedinthestudiescarriedoutinparkinsonian

patients.Theconcomitantuseofotherdrugs,particularlyotherantiparkinsoniannon-dopamine-agonistagents,wasnot

associatedwithdetectableinteractionsmodifyingtheefficacyandsafetyofCabaser.

NootherinformationisavailableaboutpossibleinteractionbetweenCabaserandotherergotalkaloids:thereforethe

concomitantuseofthesemedicationsduringlongtermtreatmentwithCabaserisnotrecommended.

SinceCabaserexertsitstherapeuticeffectbydirectstimulationofdopaminereceptors,itshouldnotbeconcurrently

administeredwithdrugswhichhavedopamineantagonistactivity(suchasphenothiazines,butyrophenones,

thioxanthenes,metoclopramide)sincethesemightreducethetherapeuticeffectofCabaser.

Byanalogywithotherergotderivatives,Cabasershouldnotbeusedinassociationwithmacrolideantibiotics(e.g.

erythromycin)sincethesystemicbioavailabilityofCabaserisincreasedandadverseeffectscouldincrease.

4.6Pregnancyandlactation

Cabaserhasbeenshowntocrosstheplacentainrats:itisunknownwhetherthisoccursalsoinhumans.

Animalstudiesinratsandmicehavenotdemonstratedanyteratogeniceffectoranyeffectofthecompoundonglobal

reproductiveperformance.Inclinicalstudiestherehavebeenover100pregnanciesinwomentreatedwithCabaserfor

hyperprolactinaemicdisorders.Thecompoundwasgenerallytakenduringthefirst8weeksafterconception.

Amongthepregnanciesevaluablesofar,therewereapproximately85%livebirthsandabout10%spontaneous

abortions.Threecasesofcongenitalabnormalities(Down'ssyndrome,hydrocephalus,malformationoflowerlimbs)

whichledtotherapeuticabortionandthreecasesofminorabnormalitiesinlivebirthswereobserved.

Theseincidenceratesarecomparablewiththosequotedfornormalpopulationsandforwomenexposedtoother

ovulation-inducingdrugs.Basedontheabovedata,theuseoftheproductdoesnotappeartobeassociatedwithan

increasedriskofabortion,prematuredelivery,multiplepregnancyorcongenitalabnormalities.

Becauseclinicalexperienceisstilllimitedandthedrughasalonghalf-life,asaprecautionarymeasureitis

recommendedthatwomenseekingpregnancydiscontinueCabaseronemonthbeforeintendedconception,inorderto

preventpossiblefoetalexposuretothedrug.Ifconceptionoccursduringtherapy,treatmentistobediscontinuedas

soonaspregnancyisconfirmed,tolimitfoetalexposuretothedrug.

InratsCabaserand/oritsmetabolitesareexcretedinmilk.Lactationisexpectedtobeinhibited/suppressedbyCabaser,

inviewofitsdopamine-agonistproperties.Therefore,whilenoinformationontheexcretionofCabaserinmaternal

milkinhumansisavailable,puerperalwomenshouldbeadvisednottobreast-feedincaseoffailedlactation

inhibition/suppressionbytheproduct.

4.7Effectsonabilitytodriveandusemachines

DuringtreatmentwithCabaser,patientsshouldbecautionedaboutengaginginactivitiesrequiringrapidandprecise

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PatientsbeingtreatedwithCabaserandpresentingwithsomnolenceand/orsuddensleeponsetepisodesmustbe

informedtorefrainfromdrivingorengaginginactivitieswhereimpairedalertnessmayputthemselvesorothersatrisk

ofseriousinjuryordeath(e.g.operatingmachines)untilsuchepisodesandsomnolencehaveresolved.

4.8Undesirableeffects

About1070parkinsonianpatientshavereceivedCabaserasadjuvanttherapytoL-dopainclinicalstudies;ofthese74%

hadatleastoneadverseevent,mainlyofmildtomoderateseverityandtransientinnature,andrequiring

discontinuationinasmallproportionofcases.

Inthemajorityofcases(51%),eventswererelatedtothenervoussystem:mostfrequentlyreportedeventswere

dyskinesia,hyperkinesia,hallucinationsorconfusion.Thegastrointestinalsystemwasinvolvedin33%ofcases:events

mostfrequentlyreportedwerenausea,vomiting,dyspepsiaandgastritis.Thecardiovascularsystemwasinvolvedin

27%ofcases,mostfrequentlyreportedeventsbeingdizzinessandhypotension.Therespiratorysystemwasinvolved

in13%ofcases,symptomaticpleuraleffusion/fibrosisbeingreportedwithafrequency<2%.

Otheradverseeventsexpectedforthepharmacologicalclass,inviewofthevasoconstrictiveproperties,includeangina

(reportedinabout1%ofthepatientsonCabaser)anderythromelalgia(observedin0.4%ofthepatients).

Similarlyexpectedforthepharmacologicalclass,peripheraloedemaoccurredin6%ofpatients.

Gastricupsetwasmorefrequentinfemalethaninmalepatients,whileCNSeventsweremorefrequentintheelderly.

Abloodpressuredecreaseofclinicalrelevancewasobservedmainlyonstandinginaminorityofpatients.Theeffect

wasmainlyevidentinthefirstweeksoftherapy.NeithermodificationofheartratenorconsistentchangesofECG

tracingwereobservedduringCabasertreatment.

AlterationsinstandardlaboratorytestsareuncommonduringlongtermtherapywithCabaser.Inclinicalstudies,

increaseoftriglyceridesgreaterthan30%abovetheupperlimitofthelaboratoryreferencerangewereobservedin

6.8%oftheCabaser-treatedpatientswhohadvalueswithinthenormalrangeatbaseline.Inmostcasestheincreases

weretransient.Noclearindicationsofincreasesovertimeorsignificantshiftsfromnormaltoabnormalvalueswere

observedintheoverallgroupofpatientstreatedwithCabaser.Aclinicallyrelevantdecreaseinhaemoglobin,

haematocritand/orredbloodcellcount(>15%Vsbaseline)wasobservedatleastoncein6.8%ofclinicalstudy

patientswithnormalvaluesatentry;normalizationwasobservedinonethirdofthesepatients.

Therehavebeenreportsoffibroticandserosalinflammatoryconditions,suchaspleuritis,pleuraleffusion,pleural

fibrosis,pulmonaryfibrosis,pericarditis,pericardialeffusion,cardiacvalvulopathyandretroperitonealfibrosis,in

patientstakingCabaser(See‘Specialwarningsandspecialprecautionsforuse’).Theincidenceofvalvulopathywith

Cabaserisnotknown,howeverbasedonrecentstudiesoftheprevalenceofvalvularregurgitation(themostsensitive

echocardiographicmarkerforrestrictivevalvulopathy),theprevalenceofregurgitation(virtuallyallcases

asymptomatic)potentiallyattributabletoCabasermaybeintherangeof20%orgreater.

Thereislimitedinformationavailableonthereversibilityofthesereactions.

PatientstreatedwithdopamineagonistsfortreatmentofParkinson’sdisease,includingCabaser,especiallyathigh

doses,havebeenreportedasexhibitingsignsofpathologicalgambling,increasedlibidoandhypersexuality,generally

reversibleuponreductionofthedoseortreatmentdiscontinuation.

Post-marketingSurveillance:ThefollowingeventshavebeenreportedinassociationwithCabaser:somnolence,

suddensleeponset.

4.9Overdose

Theacutetoxicitystudiescarriedoutinanimalsindicateverylowtoxicity,withawidesafetymarginwithrespectto

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ThereisnoexperienceinhumansofoverdosagewithCabaserintheproposedindication:itislikelytoleadto

symptomsduetoover-stimulationofdopaminereceptors.Thesemightincludenausea,vomiting,gastriccomplaints,

hypotension,confusion/psychosisorhallucinations.Thevomitingstimulatingpropertiesofdopamineagonistsare

expectedtofavourremovalofunabsorbeddrug.Supportivemeasuresshouldbetakentoremoveunabsorbeddrugand

tomaintainbloodpressure,ifnecessary.Inaddition,incaseofpronouncedcentralnervoussystemeffects

(hallucinations)theadministrationofdopamineantagonistdrugsmaybeadvisable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Cabaserisadopaminergicergolinederivativeendowedwithpotentandlong-lastingdopamineD2receptoragonist

properties.

CabaserhasshowedtobeeffectiveindecreasingdailyfluctuationsinmotorperformanceinParkinsonianpatients

receivinglevodopa/carbidopatherapy.Improvementofmotordeficithasbeendemonstrated,whilesubstantially

decreasingthelevodopa/carbidopadose.

InhealthyvolunteerstheadministrationofCabaseratsingleoraldosesof0.3-2.5mgwasassociatedwithasignificant

decreaseinserumPRLlevels.Theeffectisprompt(within3hoursofadministration)andpersistent(upto7-28days).

ThePRL-loweringeffectisdose-relatedbothintermsofdegreeofeffectanddurationofaction.

ThepharmacodynamicactionsofCabasernotlinkedtothetherapeuticeffectrelateonlytobloodpressuredecrease.

ThemaximalhypotensiveeffectofCabaserasasingledoseusuallyoccursduringthefirst6hoursafterdrugintakeand

isdose-dependentbothintermsofmaximaldecreaseandfrequency.

5.2Pharmacokineticproperties

ThepharmacokineticandmetabolicprofilesofCabaserhavebeenstudiedinhealthyvolunteersofbothsexes,in

femalehyperprolactinaemicpatientsandinparkinsonianpatients.Afteroraladministrationofthelabelledcompound,

radioactivitywasrapidlyabsorbedfromthegastrointestinaltractasthepeakofradioactivityinplasmawasbetween0.5

and4hours.Tendaysafteradministrationabout18/20%and55/72%oftheradioactivedose( 3

H-cabergoline/ 14

cabergoline)wasrecoveredinurineandfaeces,respectively.Unchangeddruginurineaccountedfor2-3%ofthedose.

Inurine,themainmetaboliteidentifiedwas6-allyl-8b-carboxy-ergoline,whichaccountedfor4-6%ofthedose.Three

additionalmetaboliteswereidentifiedinurine,whichaccountedoverallforlessthan3%ofthedose.Themetabolites

havebeenfoundtobemuchlesspotentthanCabaserasD

dopaminereceptoragonists"invitro".

ThelowurinaryexcretionofunchangedCabaserhasbeenconfirmedalsoinstudieswithnon-radioactiveproduct.The

eliminationhalf-lifeofCabaser,estimatedfromurinaryexcretionrates,islong(63-68hoursinhealthyvolunteers,79-

115hoursinhyperprolactinaemicpatients).

ThepharmacokineticsofCabaserseemstobedose-independentbothinhealthyvolunteers(dosesof0.5-1.5mg)and

parkinsonianpatients(steadystateofdailydosesupto7mg/day).

Onthebasisoftheeliminationhalf-life,steadystateconditionsshouldbeachievedafter4weeks,asconfirmedbythe

meanpeakplasmalevelsofCabaserobtainedafterasingledose(37+8pg/ml)andaftera4weekmultiple-regimen

(101+43pg/ml)."Invitro"experimentsshowedthatthedrugatconcentrationsof0.1-10ng/mlis41-42%boundto

plasmaproteins.

FooddoesnotappeartoaffectabsorptionanddispositionofCabaser.

WhilerenalinsufficiencyhasbeenshownnottomodifyCabaserkinetics,hepaticinsufficiencyofseveredegree(>10

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5.3Preclinicalsafetydata

Almostallthefindingsnotedthroughouttheseriesofpreclinicalsafetystudiesareaconsequenceofthecentral

dopaminergiceffectsorthelong-lastinginhibitionofPRLinrodentswithaspecifichormonalphysiologydifferentto

man.

PreclinicalsafetystudiesofCabaserindicateaconsistentsafetymarginforthiscompoundinrodentsandinmonkeys,

aswellasalackofteratogenic,genotoxicorcarcinogenicpotential.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactoseanhydrous

Leucine

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

C.Containersshouldbekepttightlyclosed.

6.5Natureandcontentsofcontainer

Amberglassbottleswithaluminiumtamperresistantscrewcapequippedwithalowdensitypolyethylene/

thermoplasticelastomerplasticundercapactingasacontainerholdingsilicagel,closedbyaplasticcapwithporous

paperatthelowerextremity.

Eachbottlecontains15or16tabletsof4mgstrengthandisenclosedinanoutercardboardcarton.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

BottlesofCabaseraresuppliedwithdesiccantinthecaps.Thisdesiccantmustnotberemoved.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaLaboratoriesLimited

RamsgateRoad

Sandwich

KentCT139NJ

UnitedKingdom

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PA187/61/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:29October1999

Dateoflastrenewal:29October2004

10DATEOFREVISIONOFTHETEXT

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