AROMASIN

Main information

  • Trade name:
  • AROMASIN Coated Tablets 25 Milligram
  • Dosage:
  • 25 Milligram
  • Pharmaceutical form:
  • Coated Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AROMASIN Coated Tablets 25 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1659/042/001
  • Authorization date:
  • 12-08-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Aromasin25mgCoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Theactivesubstanceisexemestane;eachcoatedtabletcontains25mgexemestane.

Excipients:eachtabletcontainssucroseandmethylparahydroxybenzoate(E218).

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

CoatedTablet

ProductimportedfromtheUK:

Round,biconvex,off-whitecoatedtabletmarked7663ononeside

4CLINICALPARTICULARS

4.1TherapeuticIndications

Aromasin ®

isindicatedfortheadjuvanttreatmentofpostmenopausalwomenwithoestrogenreceptorpositive

invasiveearlybreastcancer,following2–3yearsofinitialadjuvanttamoxifentherapy.

Aromasin ®

isindicatedforthetreatmentofadvancedbreastcancerinwomenwithnaturalorinducedpostmenopausal

statuswhosediseasehasprogressedfollowinganti-oestrogentherapy.Efficacyhasnotbeendemonstratedinpatients

withoestrogenreceptornegativestatus.

4.2Posologyandmethodofadministration

Adultandelderlypatients

TherecommendeddoseofAromasin ®

isone25mgtablettobetakenoncedaily,preferablyafterameal.

Inpatientswithearlybreastcancer,treatmentwithAromasin ®

shouldcontinueuntilcompletionoffiveyearsof

combinedsequentialadjuvanthormonaltherapy(tamoxifenfollowedbyAromasin ®

),orearlieriftumourrelapse

occurs.

Inpatientswithadvancedbreastcancer,treatmentwithAromasin ®

shouldcontinueuntiltumourprogressionisevident.

Nodoseadjustmentsarerequiredforpatientswithhepaticorrenalinsufficiency(seesection5.2,Pharmacokinetic

Properties).

Children

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4.3Contraindications

Aromasin ®

tabletsarecontraindicatedinpatientswithaknownhypersensitivitytotheactivesubstanceortoanyofthe

excipients,inpre-menopausalwomenandinpregnantorlactatingwomen.

4.4Specialwarningsandprecautionsforuse

Aromasin ®

shouldnotbeadministeredtowomenwithpre-menopausalendocrinestatus.Therefore,whenever

clinicallyappropriate,thepost-menopausalstatusshouldbeascertainedbyassessmentofLH,FSHandoestradiol

levels.

Aromasin ®

shouldbeusedwithcautioninpatientswithhepaticorrenalimpairment.

Aromasin®tabletscontainsucroseandshouldnotbeadministeredtopatientswithrarehereditaryproblemsoffructose

intolerance,glucose-galactosemalabsorptionorsucrase-isomaltaseinsufficiency.

Aromasin ®

tabletscontainmethylparahydroxybenzoatewhichmaycauseallergicreactions(possiblydelayed).

Aromasin ®

isapotentoestrogenloweringagent,andareductioninbonemineraldensityandanincreasedfracturerate

hasbeenobservedfollowingadministration(seesection5.1,Pharmacodynamicproperties).Duringadjuvanttreatment

withAromasin ®

,womenwithosteoporosisoratriskofosteoporosisshouldhavetheirbonemineraldensityformally

assessedbybonedensitometryatthecommencementoftreatment.Althoughadequatedatatoshowtheeffectsof

therapyinthetreatmentofthebonemineraldensitylosscausedbyAromasin ®

arenotavailable,treatmentfor

osteoporosisshouldbeinitiatedinatriskpatients.PatientstreatedwithAromasin ®

shouldbecarefullymonitored.

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 ®

.Aromasin ®

shouldbeusedcautiouslywithdrugsthatare

metabolisedviaCYP3A4andhaveanarrowtherapeuticwindow.Thereisnoclinicalexperienceoftheconcomitant

useofAromasin ®

withotheranticancerdrugs.

Aromasin ®

shouldnotbecoadministeredwithoestrogen-containingmedicinesasthesewouldnegateits

pharmacologicalaction.

4.6Fertility,pregnancyandlactation

Pregnancy

NoclinicaldataonexposedpregnanciesareavailablewithAromasin ®

.Studiesonanimalshaveshownreproductive

toxicity(seesection5.3,Preclinicalsafetydata).Aromasin ®

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Lactation

Itisnotknownwhetherexemestaneisexcretedintohumanmilk.Aromasin ®

shouldnotbeadministeredtolactating

woman.

Womenofperimenopausalstatusorchild-bearingpotential

Thephysicianneedstodiscussthenecessityofadequatecontraceptionwithwomenwhohavethepotentialtobecome

pregnantincludingwomenwhoareperimenopausalorwhohaverecentlybecomepostmenopausal,untiltheir

postmenopausalstatusisfullyestablished(seesections4.3Contraindicationsand4.4Specialwarningsand

precautionsforuse).

4.7Effectsonabilitytodriveandusemachines

Drowsiness,somnolence,astheniaanddizzinesshavebeenreportedwiththeuseofthedrug.Patientsshouldbe

advisedthat,iftheseeventsoccur,theirphysicaland/ormentalabilitiesrequiredforoperatingmachineryordrivinga

carmaybeimpaired.

4.8Undesirableeffects

Aromasin ®

wasgenerallywelltoleratedacrossallclinicalstudiesconductedwithAromasin ®

atastandarddoseof25

mg/day,andundesirableeffectswereusuallymildtomoderate.

Thewithdrawalrateduetoadverseeventswas7.4%inpatientswithearlybreastcancerreceivingadjuvanttreatment

withAromasin ®

followinginitialadjuvanttamoxifentherapy . Themostcommonlyreportedadversereactionswere

hotflushes(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

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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

Musculoskeletalandbonedisorders:

Verycommon

Jointandmusculoskeletalpain (*)

Common Osteoporosis,fracture

Generaldisordersandadministrationsiteconditions:

Verycommon Fatigue

Common Pain,peripheraloedema

Uncommon Asthenia

Adverseeventsandillnesses 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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Inaseparatedoubleblinded,randomizedstudyofpostmenopausalwomenwithearlybreastcanceratlowrisktreated

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

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

apolipoproteinA1intheexemestanegroupversus0-2%forplacebo.Theeffectontheotherlipidparametersanalysed

(totalcholesterol,LDLcholesterol,triglycerides,apolipoprotein-Bandlipoprotein-a)wasverysimilarinthetwo

treatmentgroups.Theclinicalsignificanceoftheseresultsisunclear.

IntheIESstudy,gastriculcerwasobservedatahigherfrequencyintheexemestanearmcomparedtotamoxifen(0.7%

versus<0.1%).Themajorityofpatientsonexemestanewithgastriculcerreceivedconcomitanttreatmentwithnon-

steroidalanti-inflammatoryagentsand/orhadapriorhistory.

Adversereactionsfrompost-marketingexperience

Hepatobiliarydisorders:Hepatitis,cholestatichepatitis

Becausereactionsarereportedvoluntarilyfromapopulationofuncertainsize,itisnotalwayspossibletoreliably

estimatetheirfrequencyorestablishacausalrelationshiptodrugexposure.

4.9Overdose

ClinicaltrialshavebeenconductedwithAromasin ®

givenupto800mginasingledosetohealthyfemalevolunteers

andupto600mgdailytopostmenopausalwomenwithadvancedbreastcancer;thesedosageswerewelltolerated.The

singledoseofAromasin ®

thatcouldresultinlife-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,Aromasin ®

p.o.significantlyloweredserumoestrogenconcentrationsstartingfroma5mg

dose,reachingmaximalsuppression( >

90%)withadoseof10-25mg.Inpostmenopausalbreastcancerpatientstreated

withthe25mgdailydose,wholebodyaromatizationwasreducedby98%.

Exemestanedoesnotpossessanyprogestogenicoroestrogenicactivity.Aslightandrogenicactivity,probablydueto

the17-hydroderivative,hasbeenobservedmainlyathighdoses.Inmultipledailydosestrials,Aromasin ®

hadno

detectableeffectsonadrenalbiosynthesisofcortisoloraldosterone,measuredbeforeorafterACTHchallenge,thus

demonstratingitsselectivitywithregardtotheotherenzymesinvolvedinthesteroidogenicpathway.

Glucocorticoidormineralocorticoidreplacementsarethereforenotneeded.Anondose-dependentslightincreasein

serumLHandFSHlevelshasbeenobservedevenatlowdoses:thiseffectis,however,expectedforthe

pharmacologicalclassandisprobablytheresultoffeedbackatthepituitarylevelduetothereductioninoestrogen

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AdjuvantTreatmentofEarlyBreastCancer

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

positiveorunknownprimarybreastcancer,patientswhohadremaineddisease-freeafterreceivingadjuvanttamoxifen

therapyfor2to3yearswererandomisedtoreceive3to2yearsofAromasin ®

(25mg/day)ortamoxifen(20or30

mg/day)tocompleteatotalof5yearsofhormonaltherapy.

Afteramediandurationoftherapyofabout30monthsandamedianfollow-upofabout52months,resultsshowedthat

sequentialtreatmentwithAromasin ®

after2to3yearsofadjuvanttamoxifentherapywasassociatedwithaclinically

andstatisticallysignificantimprovementindisease-freesurvival(DFS)comparedwithcontinuationoftamoxifen

therapy.AnalysisshowedthatintheobservedstudyperiodAromasin ®

reducedtheriskofbreastcancerrecurrenceby

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

withrespecttoDFSwasapparentregardlessofnodalstatusorpriorchemotherapy.

Aromasin ®

alsosignificantlyreducedtheriskofcontralateralbreastcancer(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,contralateralbreastcancer

orbreastcancerdeath;

Distantrecurrencefreesurvivalisdefinedasthefirstoccurrenceofdistantrecurrenceorbreastcancerdeath;

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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Intheadditionalanalysisforthesubsetofpatientswithoestrogenreceptorpositiveorunknownstatus,theunadjusted

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

17%reductionintheriskofdying.

ResultsfromabonesubstudydemonstratedthatwomentreatedwithAromasin ®

following2to3yearsoftamoxifen

treatmentexperiencedmoderatereductioninbonemineraldensity.Intheoverallstudy,thetreatmentemergentfracture

incidenceevaluatedduringthe30monthstreatmentperiodwashigherinpatientstreatedwithAromasin ®

compared

withtamoxifen(4.5%and3.3%correspondingly,p=0.038).

Resultsfromanendometrialsubstudyindicatethatafter2yearsoftreatmenttherewasamedian33%reductionof

endometrialthicknessintheAromasin ®

-treatedpatientscomparedwithnonotablevariationinthetamoxifen-treated

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

patientstreatedwithAromasin ®

TreatmentofAdvancedBreastCancer

Inarandomisedpeerreviewedcontrolledclinicaltrial,Aromasin ®

atthedailydoseof25mghasdemonstrated

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

comparedtoastandardhormonaltreatmentwithmegestrolacetateinpostmenopausalpatientswithadvancedbreast

cancerthathadprogressedfollowing,orduring,treatmentwithtamoxifeneitherasadjuvanttherapyorasfirst-line

treatmentforadvanceddisease.

5.2Pharmacokineticproperties

Absorption:

AfteroraladministrationofAromasin ®

tablets,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:NosignificantcorrelationbetweenthesystemicexposureofAromasin ®

andtheageofsubjectshasbeen

observed.

Renalinsufficiency:

Inpatientswithsevererenalimpairment(CL

<30ml/min)thesystemicexposuretoexemestanewas2timeshigher

comparedwithhealthyvolunteers.

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Hepaticinsufficiency:.

Inpatientswithmoderateorseverehepaticimpairmenttheexposureofexemestaneis2-3foldhighercomparedwith

healthyvolunteers.Giventhesafetyprofileofexemestane,nodoseadjustmentisconsideredtobenecessary.

5.3Preclinicalsafetydata

Toxicologicalstudies:

Findingsintherepeatdosetoxicologystudiesinratanddogweregenerallyattributabletothepharmacologicalactivity

ofexemestane,suchaseffectsonreproductiveandaccessoryorgans.Othertoxicologicaleffects(onliver,kidneyor

centralnervoussystem)wereobservedonlyatexposuresconsideredsufficientlyinexcessofthemaximumhuman

exposureindicatinglittlerelevancetoclinicaluse.

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)

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Talc

Carnaubawax

Printingink:

Ethylalcohol

Shellac

Ironoxides(E172)

Titaniumoxide(E171)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownontheblisterandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.Keepyourtabletsintheoriginalpack.

6.5Natureandcontentsofcontainer

Blisterstripsof15tablets,30tabletstoapack,inanover-labelledoutercarton.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialinstructions

7PARALLELPRODUCTAUTHORISATIONHOLDER

IPSHealthcareLimited

SterlingHouse

501MiddletonRoad

Oldham

Lancashire

OL99LY

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1659/42/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12thAugust2011.

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