AROMASIN 25 Milligram Coated Tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
EXEMESTANE
Available from:
Haemato Pharm AG
ATC code:
L02BG06
INN (International Name):
EXEMESTANE
Dosage:
25 Milligram
Pharmaceutical form:
Coated Tablets
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Aromatase inhibitors
Authorization status:
Authorised
Authorization number:
PPA1841/001/001
Authorization date:
2012-11-30

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Aromasin25mgcoatedtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

ActiveSubstance:exemestane

Eachcoatedtabletcontains25mgexemestane.

Eachtabletcontains30.2mgofsucroseand0.003mgofmethylparahydroxybenzoate(E218).

ForafulllistofExcipients,seesection6.1

3PHARMACEUTICALFORM

Coatedtablet

ProductimportedfromItaly:

Round,biconvex,off-whitecoatedtabletmarked7663ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Aromasinisindicatedfortheadjuvanttreatmentofpostmenopausalwomenwithoestrogenreceptorpositiveinvasive

earlybreastcancer,following2–3yearsofinitialadjuvanttamoxifentherapy.

Aromasinisindicatedforthetreatmentofadvancedbreastcancerinwomenwithnaturalorinducedpostmenopausal

statuswhosediseasehasprogressedfollowinganti-oestrogentherapy.Efficacyhasnotbeendemonstratedinpatients

withoestrogenreceptornegativestatus.

4.2Posologyandmethodofadministration

Adultandelderlypatients

TherecommendeddoseofAromasinisone25mgtablettobetakenoncedaily,preferablyafterameal.

Inpatientswithearlybreastcancer,treatmentwithAromasinshouldcontinueuntilcompletionoffiveyearsof

combinedsequentialadjuvanthormonaltherapy(tamoxifenfollowedbyAromasin),orearlieriftumourrelapseoccurs.

Inpatientswithadvancedbreastcancer,treatmentwithAromasinshouldcontinueuntiltumourprogressionisevident.

Nodoseadjustmentsarerequiredforpatientswithhepaticorrenalinsufficiency(seesection5.2,Pharmacokinetic

Properties).

Children

Notrecommendedforuseinchildren.

4.3Contraindications

Aromasintabletsarecontraindicatedinpatientswithaknownhypersensitivitytotheactivesubstanceortoanyofthe

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4.4Specialwarningsandprecautionsforuse

Aromasinshouldnotbeadministeredtowomenwithpre-menopausalendocrinestatus.Therefore,wheneverclinically

appropriate,thepost-menopausalstatusshouldbeascertainedbyassessmentofLH,FSHandoestradiollevels.

Aromasinshouldbeusedwithcautioninpatientswithhepaticorrenalimpairment.

Aromasintabletscontainsucroseandshouldnotbeadministeredtopatientswithrarehereditaryproblemsoffructose

intolerance,glucose-galactosemalabsorptionorsucrase-isomaltaseinsufficiency.

Aromasintabletscontainmethyl-p-hydroxybenzoatewhichmaycauseallergicreactions(possiblydelayed).

Aromasinisapotentoestrogenloweringagent,andareductioninbonemineraldensityandanincreasedfracturerate

hasbeenobservedfollowingadministration(seesection5.1,Pharmacodynamicproperties).Duringadjuvanttreatment

withAromasin,womenwithosteoporosisoratriskofosteoporosisshouldhavetheirbonemineraldensityformally

assessedbybonedensitometryatthecommencementoftreatment.Althoughadequatedatatoshowtheeffectsof

therapyinthetreatmentofthebonemineraldensitylosscausedbyAromasinarenotavailable,treatmentfor

osteoporosisshouldbeinitiatedinatriskpatients.PatientstreatedwithAromasinshouldbecarefullymonitored.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

InvitroevidenceshowedthatthedrugismetabolisedthroughcytochromeP450(CYP)3A4andaldoketoreductases

(seesection5.2,PharmacokineticProperties)anddoesnotinhibitanyofthemajorCYPisoenzymes.Inaclinical

pharmacokineticstudy,thespecificinhibitionofCYP3A4byketoconazoleshowednosignificanteffectsonthe

pharmacokineticsofexemestane.

Inaninteractionstudywithrifampicin,apotentCYP450inducer,atadoseof600mgdailyandasingledoseof

exemestane25mg,theAUCofexemestanewasreducedby54%andCmaxby41%.Sincetheclinicalrelevanceofthis

interactionhasnotbeenevaluated,theco-administrationofdrugs,suchasrifampicin,anticonvulsants(e.g.phenytoin

andcarbamazepine)andherbalpreparationscontaininghypericumperforatum(StJohn’sWort)knowntoinduce

CYP3A4mayreducetheefficacyofAromasin.Aromasinshouldbeusedcautiouslywithdrugsthataremetabolised

viaCYP3A4andhaveanarrowtherapeuticwindow.Thereisnoclinicalexperienceoftheconcomitantuseof

Aromasinwithotheranticancerdrugs.

Aromasinshouldnotbecoadministeredwithoestrogen-containingmedicinesasthesewouldnegateitspharmacological

action.

4.6Fertility,pregnancyandlactation

Pregnancy

NoclinicaldataonexposedpregnanciesareavailablewithAromasin.Studiesonanimalshaveshownreproductive

toxicity(seesection5.3,Preclinicalsafetydata).Aromasinisthereforecontraindicatedinpregnantwomen.

Lactation

Itisnotknownwhetherexemestaneisexcretedintohumanmilk.Aromasinshouldnotbeadministeredtolactating

woman.

Womenofperimenopausalstatusorchild-bearingpotential

Thephysicianneedstodiscussthenecessityofadequatecontraceptionwithwomenwhohavethepotentialtobecome

pregnantincludingwomenwhoareperimenopausalorwhohaverecentlybecomepostmenopausal,untiltheir

postmenopausalstatusisfullyestablished(seesections4.3Contraindicationsand4.4Specialwarningsand

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4.7Effectsonabilitytodriveandusemachines

Drowsiness,somnolence,astheniaanddizzinesshavebeenreportedwiththeuseofthedrug.Patientsshouldbeadvised

that,iftheseeventsoccur,theirphysicaland/ormentalabilitiesrequiredforoperatingmachineryordrivingacarmay

beimpaired.

4.8Undesirableeffects

AromasinwasgenerallywelltoleratedacrossallclinicalstudiesconductedwithAromasinatastandarddoseof25

mg/day,andundesirableeffectswereusuallymildtomoderate.

Thewithdrawalrateduetoadverseeventswas7.4%inpatientswithearlybreastcancerreceivingadjuvanttreatment

withAromasinfollowinginitialadjuvanttamoxifentherapy .

Themostcommonlyreportedadversereactionswerehotflushes(22%),arthralgia(18%)andfatigue(16%).

Thewithdrawalrateduetoadverseeventswas2.8%intheoverallpatientpopulationwithadvancedbreastcancer.The

mostcommonlyreportedadversereactionswerehotflushes(14%)andnausea(12%).

Mostadversereactionscanbeattributedtothenormalpharmacologicalconsequencesofoestrogendeprivation(e.g.hot

flushes).

Thereportedadversereactionsarelistedbelowbysystemorganclassandbyfrequency.

Frequenciesaredefinedas:verycommon(>10%),common(>1%,<10%),uncommon(>0.1%,<1%),rare(>

0.01%,<0.1%).

Metabolismandnutritiondisorders:

Common Anorexia

Psychiatricdisorders:

Verycommon Insomnia

Common Depression

Nervoussystemdisorders:

Verycommon Headache

Common Dizziness,carpaltunnelsyndrome

Uncommon Somnolence

Vasculardisorders:

Verycommon Hotflushes

Gastrointestinaldisorders:

Verycommon Nausea

Common Abdominalpain,vomiting,constipation,dyspepsia,

diarrhoea

Skinandsubcutaneoustissuedisorders:

Verycommon Increasedsweating

Common Rash,alopecia

Musculoskeletalandbonedisorders:

Verycommon

Jointandmusculoskeletalpain (*)

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Includes:arthralgia,andlessfrequentlypaininlimb,osteoarthritis,backpain,arthritis,myalgiaandjointstiffness

Bloodandlymphaticsystemdisorders

Inpatientswithadvancedbreastcancerthrombocytopeniaandleucopeniahavebeenrarelyreported.Anoccasional

decreaseinlymphocyteshasbeenobservedinapproximately20%ofpatientsreceivingAromasin,particularlyin

patientswithpre-existinglymphopenia;however,meanlymphocytevaluesinthesepatientsdidnotchange

significantlyovertimeandnocorrespondingincreaseinviralinfectionswasobserved.Theseeffectshavenotbeen

observedinpatientstreatedinearlybreastcancerstudies.

Hepatobiliarydisorders

Elevationofliverfunctiontestparametersincludingenzymes,bilirubinandalkalinephosphatasehavebeenobserved.

Thetablebelowpresentsthefrequencyofpre-specifiedadverseeventsandillnessesintheearlybreastcancerstudy

(IES),irrespectiveofcausality,reportedinpatientsreceivingtrialtherapyandupto30daysaftercessationoftrial

therapy.

IntheIESstudy,thefrequencyofischemiccardiaceventsintheexemestaneandtamoxifentreatmentarmswas4.5%

versus4.2%,respectively.Nosignificantdifferencewasnotedforanyindividualcardiovasculareventincluding

hypertension(9.9%versus8.4%),myocardialinfarction(0.6%versus0.2%)andcardiacfailure(1.1%versus0.7%).

IntheIESstudy,exemestanewasassociatedwithagreaterincidenceofhypercholesterolemiacomparedwith

tamoxifen(3.7%vs.2.1%).

Inaseparatedoubleblinded,randomizedstudyofpostmenopausalwomenwithearlybreastcanceratlowrisktreated

withexemestane(N=73)orplacebo(N=73)for24months,exemestanewasassociatedwithanaverage7-9%mean

reductioninplasmaHDL-cholesterol,versusa1%increaseonplacebo.Therewasalsoa5-6%reductionin

Generaldisordersandadministrationsiteconditions:

Verycommon Fatigue

Common Pain,peripheraloedema

Uncommon Asthenia

Adverseeventsand

illnesses Exemestane

(N=2249) Tamoxifen

(N=2279)

Hotflushes 491(21.8%) 457(20.1%)

Fatigue 367(16.3%) 344(15.1%)

Headache 305(13.6%) 255(11.2%)

Insomnia 290(12.9%) 204(9.0%)

Sweatingincreased 270(12.0%) 242(10.6%)

Gynaecological 235(10.5%) 340(14.9%)

Dizziness 224(10.0%) 200(8.8%)

Nausea 200(8.9%) 208(9.1%)

Osteoporosis 116(5.2%) 66(2.9%)

Vaginalhaemorrhage 90(4.0%) 121(5.3%)

Otherprimarycancer 84(3.6%) 125(5.3%)

Vomiting 50(2.2%) 54(2.4%)

Visualdisturbance 45(2.0%) 53(2.3%)

Thromboembolism 16(0.7%) 42(1.8%)

Osteoporoticfracture 14(0.6%) 12(0.5%)

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Theeffectontheotherlipidparametersanalysed(totalcholesterol,LDLcholesterol,triglycerides,apolipoprotein-B

andlipoprotein-a)wasverysimilarinthetwotreatmentgroups.Theclinicalsignificanceoftheseresultsisunclear.

IntheIESstudy,gastriculcerwasobservedatahigherfrequencyintheexemestanearmcomparedtotamoxifen(0.7%

versus<0.1%).Themajorityofpatientsonexemestanewithgastriculcerreceivedconcomitanttreatmentwithnon-

steroidalanti-inflammatoryagentsand/orhadapriorhistory.

Adversereactionsfrompost-marketingexperience

Hepatobiliarydisorders:Hepatitis,cholestatichepatitis

Becausereactionsarereportedvoluntarilyfromapopulationofuncertainsize,itisnotalwayspossibletoreliably

estimatetheirfrequencyorestablishacausalrelationshiptodrugexposure.

4.9Overdose

ClinicaltrialshavebeenconductedwithAromasingivenupto800mginasingledosetohealthyfemalevolunteersand

upto600mgdailytopostmenopausalwomenwithadvancedbreastcancer;thesedosageswerewelltolerated.The

singledoseofAromasinthatcouldresultinlife-threateningsymptomsisnotknown.Inratsanddogs,lethalitywas

observedaftersingleoraldosesequivalentrespectivelyto2000and4000timestherecommendedhumandoseona

mg/m2basis.Thereisnospecificantidotetooverdosageandtreatmentmustbesymptomatic.Generalsupportivecare,

includingfrequentmonitoringofvitalsignsandcloseobservationofthepatient,isindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:steroidalaromataseinhibitor;anti-neoplasticagent

ATC:L02BG06

Exemestaneisanirreversible,steroidalaromataseinhibitor,structurallyrelatedtothenaturalsubstrate

androstenedione.Inpost-menopausalwomen,oestrogensareproducedprimarilyfromtheconversionofandrogensinto

oestrogensthroughthearomataseenzymeinperipheraltissues.Oestrogendeprivationthrougharomataseinhibitionis

aneffectiveandselectivetreatmentforhormonedependentbreastcancerinpostmenopausalwomen.In

postmenopausalwomen,Aromasinp.o.significantlyloweredserumoestrogenconcentrationsstartingfroma5mg

dose,reachingmaximalsuppression( >

90%)withadoseof10-25mg.Inpostmenopausalbreastcancerpatientstreated

withthe25mgdailydose,wholebodyaromatizationwasreducedby98%.

Exemestanedoesnotpossessanyprogestogenicoroestrogenicactivity.Aslightandrogenicactivity,probablydueto

the17-hydroderivative,hasbeenobservedmainlyathighdoses.Inmultipledailydosestrials,Aromasinhadno

detectableeffectsonadrenalbiosynthesisofcortisoloraldosterone,measuredbeforeorafterACTHchallenge,thus

demonstratingitsselectivitywithregardtotheotherenzymesinvolvedinthesteroidogenicpathway.

Glucocorticoidormineralocorticoidreplacementsarethereforenotneeded.Anondose-dependentslightincreasein

serumLHandFSHlevelshasbeenobservedevenatlowdoses:thiseffectis,however,expectedforthe

pharmacologicalclassandisprobablytheresultoffeedbackatthepituitarylevelduetothereductioninoestrogen

levelsthatstimulatethepituitarysecretionofgonadotropinsalsoinpostmenopausalwomen.

AdjuvantTreatmentofEarlyBreastCancer

Inamulticentre,randomised,double-blindstudy,conductedin4724postmenopausalpatientswithoestrogen-receptor-

positiveorunknownprimarybreastcancer,patientswhohadremaineddisease-freeafterreceivingadjuvanttamoxifen

therapyfor2to3yearswererandomisedtoreceive3to2yearsofAromasin(25mg/day)ortamoxifen(20or30

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Afteramediandurationoftherapyofabout30monthsandamedianfollow-upofabout52months,resultsshowedthat

sequentialtreatmentwithAromasinafter2to3yearsofadjuvanttamoxifentherapywasassociatedwithaclinically

andstatisticallysignificantimprovementindisease-freesurvival(DFS)comparedwithcontinuationoftamoxifen

therapy.AnalysisshowedthatintheobservedstudyperiodAromasinreducedtheriskofbreastcancerrecurrenceby

24%comparedwithtamoxifen(hazardratio0.76;p=0.00015).Thebeneficialeffectofexemestaneovertamoxifenwith

respecttoDFSwasapparentregardlessofnodalstatusorpriorchemotherapy.

Aromasinalsosignificantlyreducedtheriskofcontralateralbreastcancer(hazardratio0.57,p=0.04158).

Inthewholestudypopulation,atrendforimprovedoverallsurvivalwasobservedforexemestane(222deaths)

comparedtotamoxifen(262deaths)withahazardratio0.85(log-ranktest:p=0.07362),representinga15%reduction

intheriskofdeathinfavorofexemestane.Astatisticallysignificant23%reductionintheriskofdying(hazardratio

foroverallsurvival0.77;Waldchisquaretest:p=0.0069)wasobservedforexemestanecomparedtotamoxifenwhen

adjustingforthepre -specifiedprognosticfactors(i.e.,ERstatus,nodalstatus,priorchemotherapy,useofHRTanduse

ofbisphosphonates).

Mainefficacyresultsinallpatients(intentiontotreatpopulation)andoestrogenreceptorpositivepatientsare

summarisedinthetablebelow:

*Log-ranktest;ER+patients=oestrogenreceptorpositivepatients;

Disease-freesurvivalisdefinedasthefirstoccurrenceoflocalordistantrecurrence,contralateralbreastcancer,or

deathfromanycause;

Breastcancerfreesurvivalisdefinedasthefirstoccurrenceoflocalordistantrecurrence,contralateralbreast

cancerorbreastcancerdeath;

Distantrecurrencefreesurvivalisdefinedasthefirstoccurrenceofdistantrecurrenceorbreastcancerdeath;

Overallsurvivalisdefinedasoccurrenceofdeathfromanycause.

Intheadditionalanalysisforthesubsetofpatientswithoestrogenreceptorpositiveorunknownstatus,theunadjusted

overallsurvivalhazardratiowas0.83(log-ranktest:p=0.04250),representingaclinicallyandstatisticallysignificant

17%reductionintheriskofdying.

ResultsfromabonesubstudydemonstratedthatwomentreatedwithAromasinfollowing2to3yearsoftamoxifen

treatmentexperiencedmoderatereductioninbonemineraldensity.Intheoverallstudy,thetreatmentemergentfracture

incidenceevaluatedduringthe30monthstreatmentperiodwashigherinpatientstreatedwithAromasincomparedwith

Endpoint

Population Exemestane

Events/N(%) Tamoxifen

Events/N(%) HazardRatio

(95%CI) p-value*

Disease-freesurvivala

Allpatients 354/2352(15.1%) 453/2372(19.1%) 0.76(0.67-0.88) 0.00015

ER+patients 289/2023(14.3%) 370/2021(18.3%) 0.75(0.65-0.88) 0.00030

Contralateralbreastcancer

Allpatients 20/2352(0.9%) 35/2372(1.5%) 0.57(0.33-0.99) 0.04158

ER+patients 18/2023(0.9%) 33/2021(1.6%) 0.54(0.30-0.95) 0.03048

Breastcancerfreesurvivalb

Allpatients 289/2352(12.3%) 373/2372(15.7%) 0.76(0.65-0.89) 0.00041

ER+patients 232/2023(11.5%) 305/2021(15.1%) 0.73(0.62-0.87) 0.00038

Distantrecurrencefreesurvivalc

Allpatients 248/2352(10.5%) 297/2372(12.5%) 0.83(0.70-0.98) 0.02621

ER+patients 194/2023(9.6%) 242/2021(12.0%) 0.78(0.65-0.95) 0.01123

Overallsurvivald

Allpatients 222/2352(9.4%) 262/2372(11.0%) 0.85(0.71-1.02) 0.07362

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Resultsfromanendometrialsubstudyindicatethatafter2yearsoftreatmenttherewasamedian33%reductionof

endometrialthicknessintheAromasin-treatedpatientscomparedwithnonotablevariationinthetamoxifen-treated

patients.Endometrialthickening,reportedatthestartofstudytreatment,wasreversedtonormal(<5mm)for54%of

patientstreatedwithAromasin.

TreatmentofAdvancedBreastCancer

Inarandomisedpeerreviewedcontrolledclinicaltrial,Aromasinatthedailydoseof25mghasdemonstrated

statisticallysignificantprolongationofsurvival,TimetoProgression(TTP),TimetoTreatmentFailure(TTF)as

comparedtoastandardhormonaltreatmentwithmegestrolacetateinpostmenopausalpatientswithadvancedbreast

cancerthathadprogressedfollowing,orduring,treatmentwithtamoxifeneitherasadjuvanttherapyorasfirst-line

treatmentforadvanceddisease.

5.2Pharmacokineticproperties

Absorption:

AfteroraladministrationofAromasintablets,exemestaneisabsorbedrapidly.Thefractionofthedoseabsorbedfrom

thegastrointestinaltractishigh.Theabsolutebioavailabilityinhumansisunknown,althoughitisanticipatedtobe

limitedbyanextensivefirstpasseffect.Asimilareffectresultedinanabsolutebioavailabilityinratsanddogsof5%.

Afterasingledoseof25mg,maximumplasmalevelsof18ng/mlarereachedafter2hours.Concomitantintakewith

foodincreasesthebioavailabilityby40%.

Distribution:

Thevolumeofdistributionofexemestane,notcorrectedfortheoralbioavailability,isca20000l.Thekineticsislinear

andtheterminaleliminationhalf-lifeis24h.Bindingtoplasmaproteinsis90%andisconcentrationindependent.

Exemestaneanditsmetabolitesdonotbindtoredbloodcells.

Exemestanedoesnotaccumulateinanunexpectedwayafterrepeateddosing.

Metabolismandexcretion:

Exemestaneismetabolisedbyoxidationofthemethylenemoietyonthe6positionbyCYP3A4isoenzymeand/or

reductionofthe17-ketogroupbyaldoketoreductasefollowedbyconjugation.Theclearanceofexemestaneisca500

l/h,notcorrectedfortheoralbioavailability.

Themetabolitesareinactiveortheinhibitionofaromataseislessthantheparentcompound.

Theamountexcretedunchangedinurineis1%ofthedose.Inurineandfaecesequalamounts(40%)of 14

C-labeled

exemestanewereeliminatedwithinaweek.

Specialpopulations

Age:NosignificantcorrelationbetweenthesystemicexposureofAromasinandtheageofsubjectshasbeenobserved.

Renalinsufficiency:

Inpatientswithsevererenalimpairment(CL

<30ml/min)thesystemicexposuretoexemestanewas2timeshigher

comparedwithhealthyvolunteers.

Giventhesafetyprofileofexemestane,nodoseadjustmentisconsideredtobenecessary.

Hepaticinsufficiency:

Inpatientswithmoderateorseverehepaticimpairmenttheexposureofexemestaneis2-3foldhighercomparedwith

healthyvolunteers.Giventhesafetyprofileofexemestane,nodoseadjustmentisconsideredtobenecessary.

5.3Preclinicalsafetydata

Toxicologicalstudies:

Findingsintherepeatdosetoxicologystudiesinratanddogweregenerallyattributabletothepharmacologicalactivity

ofexemestane,suchaseffectsonreproductiveandaccessoryorgans.Othertoxicologicaleffects(onliver,kidneyor

centralnervoussystem)wereobservedonlyatexposuresconsideredsufficientlyinexcessofthemaximumhuman

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Mutagenicity:

Exemestanewasnotgenotoxicinbacteria(Amestest),inV79Chinesehamstercells,inrathepatocytesorinthemouse

micronucleusassay.Althoughexemestanewasclastogenicinlymphocytesinvitro,itwasnotclastogenicintwoinvivo

studies.

Reproductivetoxicology:

Exemestanewasembryotoxicinratsandrabbitsatsystemicexposurelevelssimilartothoseobtainedinhumansat25

mg/day.Therewasnoevidenceofteratogenicity.

Carcinogenicity:

Inatwo-yearcarcinogenicitystudyinfemalerats,notreatment-relatedtumorswereobserved.Inmaleratsthestudy

wasterminatedonweek92,becauseofearlydeathbychronicnephropathy.Inatwo-yearcarcinogenicitystudyin

mice,anincreaseintheincidenceofhepaticneoplasmsinbothgenderswasobservedattheintermediateandhigh

doses(150and450mg/kg/day).Thisfindingisconsideredtoberelatedtotheinductionofhepaticmicrosomal

enzymes,aneffectobservedinmicebutnotinclinicalstudies.Anincreaseintheincidenceofrenaltubularadenomas

wasalsonotedinmalemiceatthehighdose(450mg/kg/day).Thischangeisconsideredtobespecies-andgender-

specificandoccurredatadosewhichrepresents63-foldgreaterexposurethanoccursatthehumantherapeuticdose.

Noneoftheseobservedeffectsisconsideredtobeclinicallyrelevanttothetreatmentofpatientswithexemestane.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Silica,colloidalhydrated

Crospovidone

Hypromellose

Magnesiumstearate

Mannitol

Microcrystallinecellulose

Sodiumstarchglycolate(typeA)

Polysorbate

Sugar-coating:

Hypromellose

Polyvinylalcohol

Simeticone

Macrogol

Sucrose;

Magnesiumcarbonate,light

Titaniumdioxide(E171)

MethylParahydroxybenzoate(E218)

Cetylesterswax

Talc

Carnaubawax

Printingink:

Ethylalcohol

Shellac

Ironoxides(E172)

Titaniumoxide(E171)

6.2Incompatibilities

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6.3Shelflife

Theshelflifeexpirydateofthisproductisthedateshownonthecontainerandoutercartonoftheproductasmarketed

inthecountryoforigin.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

30tabletsinblisterpacks(Aluminium-PVDC/PVC-PVDC)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

HaematoPharmGmbH

Lilienthalstr.5c

D012529Schonefeld

Germany

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1841/001/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:30 th

November2012

10DATEOFREVISIONOFTHETEXT

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