EXEMESTANE PFIZER

Main information

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

Documents

Localization

  • Available in:
  • EXEMESTANE PFIZER
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/071/001
  • Authorization date:
  • 10-06-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ExemestanePfizer25mgcoatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Activesubstance:exemestane

Eachcoatedtabletcontains25mgexemestane.

Eachtabletcontains30.2mgofsucroseand0.003mgofmethylparahydroxybenzoate(E218).Forfulllistofexcipients,see

section6.1.

3PHARMACEUTICALFORM

Coatedtablet

Round,biconvex,off-whitecoatedtabletmarked7663ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ExemestanePfizerisindicatedfortheadjuvanttreatmentofpostmenopausalwomenwithoestrogenreceptorpositive

invasiveearlybreastcancer,following2–3yearsofinitialadjuvanttamoxifentherapy.

ExemestanePfizerisindicatedforthetreatmentofadvancedbreastcancerinwomenwithnaturalorinduced

postmenopausalstatuswhosediseasehasprogressedfollowinganti-oestrogentherapy.Efficacyhasnotbeendemonstrated

inpatientswithoestrogenreceptornegativestatus.

4.2Posologyandmethodofadministration

Adultandelderlypatients

TherecommendeddoseofExemestanePfizerisone25mgtablettobetakenoncedailyafterameal.

Inpatientswithearlybreastcancer,treatmentwithExemestanePfizershouldcontinueuntilcompletionoffiveyearsof

combinedsequentialadjuvanthormonaltherapy(tamoxifenfollowedbyExemestanePfizer),orearlieriftumour

relapseoccurs.

Inpatientswithadvancedbreastcancer,treatmentwithExemestanePfizershouldcontinueuntiltumourprogressionis

evident.

Nodoseadjustmentsarerequiredforpatientswithhepaticorrenalinsufficiency(see5.2).

Children

Notrecommendedforuseinchildren

4.3Contraindications

ExemestanePfizertabletsarecontraindicatedinpatientswithaknownhypersensitivitytotheactivesubstanceortoanyof

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4.4Specialwarningsandprecautionsforuse

ExemestanePfizershouldnotbeadministeredtowomenwithpre-menopausalendocrinestatus.Therefore,whenever

clinicallyappropriate,thepost-menopausalstatusshouldbeascertainedbyassessmentofLH,FSHandoestradiollevels.

ExemestanePfizershouldbeusedwithcautioninpatientswithhepaticorrenalimpairment.

ExemestanePfizertabletscontainsucroseandshouldnotbeadministeredtopatientswithrarehereditaryproblemsof

fructoseintolerance,glucose-galactosemalabsorptionorsucrase-isomaltaseinsufficiency.

ExemestanePfizertabletscontainmethyl-p-hydroxybenzoatewhichmaycauseallergicreactions(possiblydelayed).

ExemestanePfizerisapotentoestrogenloweringagent,andareductioninbonemineraldensityandanincreased

fractureratehasbeenobservedfollowingadministration(seesection5.1).DuringadjuvanttreatmentwithExemestane

Pfizer,womenwithosteoporosisoratriskofosteoporosisshouldhavetheirbonemineraldensityformallyassessedby

bonedensitometryatthecommencementoftreatment.Althoughadequatedatatoshowtheeffectsoftherapyinthe

treatmentofthebonemineraldensitylosscausedbyExemestanePfizerarenotavailable,treatmentforosteoporosis

shouldbeinitiatedinatriskpatients.PatientstreatedwithExemestanePfizershouldbecarefullymonitored.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

InvitroevidenceshowedthatthedrugismetabolisedthroughcytochromeP450(CYP)3A4andaldoketoreductases

(see5.2)anddoesnotinhibitanyofthemajorCYPisoenzymes.Inaclinicalpharmacokineticstudy,thespecific

inhibitionofCYP3A4byketoconazoleshowednosignificanteffectsonthepharmacokineticsofexemestane.

Inaninteractionstudywithrifampicin,apotentCYP450inducer,atadoseof600mgdailyandasingledoseof

exemestane25mg,theAUCofexemestanewasreducedby54%andCmaxby41%.Sincetheclinicalrelevanceofthis

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

andcarbamazepine)andherbalpreparationscontaininghypericumperforatum(StJohn’sWort)knowntoinduce

CYP3A4mayreducetheefficacyofExemestanePfizer.

ExemestanePfizershouldbeusedcautiouslywithdrugsthataremetabolisedviaCYP3A4andhaveanarrow

therapeuticwindow.ThereisnoclinicalexperienceoftheconcomitantuseofExemestanePfizerwithotheranticancer

drugs.

ExemestanePfizershouldnotbecoadministeredwithoestrogen-containingmedicinesasthesewouldnegateits

pharmacologicalaction.

4.6Fertility,pregnancyandlactation

Pregnancy

NoclinicaldataonexposedpregnanciesareavailablewithExemestanePfizer.Studiesonanimalshaveshown

reproductivetoxicity(Seesection5.3).ExemestanePfizeristhereforecontraindicatedinpregnantwomen.

Lactation

Itisnotknownwhetherexemestaneisexcretedintohumanmilk.ExemestanePfizershouldnotbeadministeredto

lactatingwoman.

Womenofperimenopausalstatusorchild-bearingpotential

Thephysicianneedstodiscussthenecessityofadequatecontraceptionwithwomenwhohavethepotentialtobecome

pregnantincludingwomenwhoareperimenopausalorwhohaverecentlybecomepostmenopausal,untiltheir

postmenopausalstatusisfullyestablished(seesections4.3Contraindicationsand4.4Specialwarningsandprecautions

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4.7Effectsonabilitytodriveandusemachines

Drowsiness,somnolence,astheniaanddizzinesshavebeenreportedwiththeuseofthedrug.Patientsshouldbeadvised

that,iftheseeventsoccur,theirphysicaland/ormentalabilitiesrequiredforoperatingmachineryordrivingacarmaybe

impaired.

4.8Undesirableeffects

ExemestanePfizerwasgenerallywelltoleratedacrossallclinicalstudiesconductedwithExemestanePfizeratastandard

doseof25mg/day,andundesirableeffectswereusuallymildtomoderate.

Thewithdrawalrateduetoadverseeventswas7.4%inpatientswithearlybreastcancerreceivingadjuvanttreatment

withExemestanePfizerfollowinginitialadjuvanttamoxifentherapy . Themostcommonlyreportedadversereactions

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

Thewithdrawalrateduetoadverseeventswas2.8%intheoverallpatientpopulationwithadvancedbreastcancer.The

mostcommonlyreportedadversereactionswerehotflushes(14%)andnausea(12%).

Mostadversereactionscanbeattributedtothenormalpharmacologicalconsequencesofoestrogendeprivation(eghot

flushes).

Thereportedadversereactionsarelistedbelowbysystemorganclassandbyfrequency.

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

0.01%,<0.1%).

*Includes:arthralgiaandlessfrequentlypaininlimb,osteoarthritis,backpain,

arthritis,myalgiaandjointstiffness

Bloodandlymphaticsystemdisorders

Inpatientswithadvancedbreastcancerthrombocytopeniaandleucopeniahavebeenrarelyreported.Anoccasional

decreaseinlymphocyteshasbeenobservedinapproximately20%ofpatientsreceivingExemestanePfizer,particularly

inpatientswithpre-existinglymphopenia;however,meanlymphocytevaluesinthesepatientsdidnotchange

significantlyovertimeandnocorrespondingincreaseinviralinfectionswasobserved.Theseeffectshavenotbeen

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(*)

Common Osteoporosis,fracture

Generaldisordersandadministrationsiteconditions:

Verycommon Fatigue

Common Pain,peripheraloedema

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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

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

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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4.9Overdose

ClinicaltrialshavebeenconductedwithExemestanePfizergivenupto800mginasingledosetohealthyfemale

volunteersandupto600mgdailytopostmenopausalwomenwithadvancedbreastcancer;thesedosageswerewell

tolerated.ThesingledoseofExemestanePfizerthatcouldresultinlife-threateningsymptomsisnotknown.Inratsand

dogs,lethalitywasobservedaftersingleoraldosesequivalentrespectivelyto2000and4000timestherecommended

humandoseonamg/m 2

basis.Thereisnospecificantidotetooverdosageandtreatmentmustbesymptomatic.General

supportivecare,includingfrequentmonitoringofvitalsignsandcloseobservationofthepatient,isindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:steroidalaromataseinhibitor;anti-neoplasticagent

ATC:L02BG06

Exemestaneisanirreversible,steroidalaromataseinhibitor,structurallyrelatedtothenaturalsubstrate

androstenedione.Inpost-menopausalwomen,oestrogensareproducedprimarilyfromtheconversionofandrogensinto

oestrogensthroughthearomataseenzymeinperipheraltissues.Oestrogendeprivationthrougharomataseinhibitionis

aneffectiveandselectivetreatmentforhormonedependentbreastcancerinpostmenopausalwomen.In

postmenopausalwomen,ExemestanePfizerp.o.significantlyloweredserumoestrogenconcentrationsstartingfroma5

mgdose,reachingmaximalsuppression( >

90%)withadoseof10-25mg.Inpostmenopausalbreastcancerpatients

treatedwiththe25mgdailydose,wholebodyaromatizationwasreducedby98%.

Exemestanedoesnotpossessanyprogestogenicoroestrogenicactivity.Aslightandrogenicactivity,probablydueto

the17-hydroderivative,hasbeenobservedmainlyathighdoses.Inmultipledailydosestrials,ExemestanePfizerhad

nodetectableeffectsonadrenalbiosynthesisofcortisoloraldosterone,measuredbeforeorafterACTHchallenge,thus

demonstratingitsselectivitywithregardtotheotherenzymesinvolvedinthesteroidogenicpathway.

Glucocorticoidormineralocorticoidreplacementsarethereforenotneeded.Anondose-dependentslightincreasein

serumLHandFSHlevelshasbeenobservedevenatlowdoses:thiseffectis,however,expectedforthe

pharmacologicalclassandisprobablytheresultoffeedbackatthepituitarylevelduetothereductioninoestrogen

levelsthatstimulatethepituitarysecretionofgonadotropinsalsoinpostmenopausalwomen.

AdjuvantTreatmentofEarlyBreastCancer

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

positiveorunknownprimarybreastcancer,patientswhohadremaineddisease-freeafterreceivingadjuvanttamoxifen

therapyfor2to3yearswererandomisedtoreceive3to2yearsofExemestanePfizer(25mg/day)ortamoxifen(20or

30mg/day)tocompleteatotalof5yearsofhormonaltherapy.

Afteramediandurationoftherapyofabout30monthsandamedianfollow-upofabout52months,resultsshowedthat

sequentialtreatmentwithExemestanePfizerafter2to3yearsofadjuvanttamoxifentherapywasassociatedwitha

clinicallyandstatisticallysignificantimprovementindisease-freesurvival(DFS)comparedwithcontinuationof

tamoxifentherapy.AnalysisshowedthatintheobservedstudyperiodExemestanePfizerreducedtheriskofbreast

cancerrecurrenceby24%comparedwithtamoxifen(hazardratio0.76;p=0.00015).Thebeneficialeffectof

exemestaneovertamoxifenwithrespecttoDFSwasapparentregardlessofnodalstatusorpriorchemotherapy.

ExemestanePfizeralsosignificantlyreducedtheriskofcontralateralbreastcancer(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

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Mainefficacyresultsinallpatients(intentiontotreatpopulation)andoestrogenreceptorpositivepatientsare

summarisedinthetablebelow:

*Log-ranktest;ER+patients=oestrogenreceptorpositivepatients;

Disease-freesurvivalisdefinedasthefirstoccurrenceoflocalordistantrecurrence,contralateralbreastcancer,or

deathfromanycause;

Breastcancerfreesurvivalisdefinedasthefirstoccurrenceoflocalordistantrecurrence,contralateralbreastcancer

orbreastcancerdeath;

Distantrecurrencefreesurvivalisdefinedasthefirstoccurrenceofdistantrecurrenceorbreastcancerdeath;

Overallsurvivalisdefinedasoccurrenceofdeathfromanycause.

Intheadditionalanalysisforthesubsetofpatientswithoestrogenreceptorpositiveorunknownstatus,theunadjusted

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

17%reductionintheriskofdying.

ResultsfromabonesubstudydemonstratedthatwomentreatedwithExemestanePfizerfollowing2to3yearsof

tamoxifentreatmentexperiencedmoderatereductioninbonemineraldensity.Intheoverallstudy,thetreatment

emergentfractureincidenceevaluatedduringthe30monthstreatmentperiodwashigherinpatientstreatedwith

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

Resultsfromanendometrialsubstudyindicatethatafter2yearsoftreatmenttherewasamedian33%reductionof

endometrialthicknessintheExemestanePfizer-treatedpatientscomparedwithnonotablevariationinthetamoxifen-

treatedpatients.Endometrialthickening,reportedatthestartofstudytreatment,wasreversedtonormal(<5mm)for

Endpoint

Population Exemestane

Events/N(%) Tamoxifen

Events/N(%) HazardRatio

(95%CI) p-value*

Disease-freesurvival a

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

Breastcancerfreesurvival b

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

Distantrecurrencefreesurvival c

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

Overallsurvival d

Allpatients

222/2352(9.4%) 262/2372

(11.0%) 0.85(0.71-

1.02) 0.07362

ER+patients

178/2023(8.8%) 211/2021

(10.4%) 0.84(0.68-

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TreatmentofAdvancedBreastCancer

Inarandomisedpeerreviewedcontrolledclinicaltrial,ExemestanePfizeratthedailydoseof25mghasdemonstrated

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

comparedtoastandardhormonaltreatmentwithmegestrolacetateinpostmenopausalpatientswithadvancedbreast

cancerthathadprogressedfollowing,orduring,treatmentwithtamoxifeneitherasadjuvanttherapyorasfirst-line

treatmentforadvanceddisease.

5.2Pharmacokineticproperties

Absorption:

AfteroraladministrationofExemestanePfizertablets,exemestaneisabsorbedrapidly.Thefractionofthedose

absorbedfromthegastrointestinaltractishigh.Theabsolutebioavailabilityinhumansisunknown,althoughitis

anticipatedtobelimitedbyanextensivefirstpasseffect.Asimilareffectresultedinanabsolutebioavailabilityinrats

anddogsof5%.Afterasingledoseof25mg,maximumplasmalevelsof18ng/mlarereachedafter2hours.

Concomitantintakewithfoodincreasesthebioavailabilityby40%.

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:NosignificantcorrelationbetweenthesystemicexposureofExemestanePfizerandtheageofsubjectshasbeen

observed.

Renalinsufficiency:

Inpatientswithsevererenalimpairment(CL

<30ml/min)thesystemicexposuretoexemestanewas2timeshigher

comparedwithhealthyvolunteers.

Giventhesafetyprofileofexemestane,nodoseadjustmentisconsideredtobenecessary.

Hepaticinsufficiency:

Inpatientswithmoderateorseverehepaticimpairmenttheexposureofexemestaneis2-3foldhighercomparedwith

healthyvolunteers.Giventhesafetyprofileofexemestane,nodoseadjustmentisconsideredtobenecessary.

5.3Preclinicalsafetydata

Toxicologicalstudies:Findingsintherepeatdosetoxicologystudiesinratanddogweregenerallyattributabletothe

pharmacologicalactivityofexemestane,suchaseffectsonreproductiveandaccessoryorgans.Othertoxicological

effects(onliver,kidneyorcentralnervoussystem)wereobservedonlyatexposuresconsideredsufficientlyinexcess

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Mutagenicity:Exemestanewasnotgenotoxicinbacteria(Amestest),inV79Chinesehamstercells,inrathepatocytes

orinthemousemicronucleusassay.Althoughexemestanewasclastogenicinlymphocytesinvitro,itwasnot

clastogenicintwoinvivostudies.

Reproductivetoxicology

:Exemestanewasembryotoxicinratsandrabbitsatsystemicexposurelevelssimilartothoseobtainedinhumansat25

mg/day.Therewasnoevidenceofteratogenicity.

Carcinogenicity:Inatwo-yearcarcinogenicitystudyinfemalerats,notreatment-relatedtumorswereobserved.In

maleratsthestudywasterminatedonweek92,becauseofearlydeathbychronicnephropathy.Inatwo-year

carcinogenicitystudyinmice,anincreaseintheincidenceofhepaticneoplasmsinbothgenderswasobservedatthe

intermediateandhighdoses(150and450mg/kg/day).Thisfindingisconsideredtoberelatedtotheinductionof

hepaticmicrosomalenzymes,aneffectobservedinmicebutnotinclinicalstudies.Anincreaseintheincidenceof

renaltubularadenomaswasalsonotedinmalemiceatthehighdose(450mg/kg/day).Thischangeisconsideredtobe

species-andgender-specificandoccurredatadosewhichrepresents63-foldgreaterexposurethanoccursatthehuman

therapeuticdose.Noneoftheseobservedeffectsisconsideredtobeclinicallyrelevanttothetreatmentofpatientswith

exemestane.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:Silicacolloidalhydrated;Crospovidone;Hypromellose;Magnesiumstearate;Mannitol;Microcrystalline

cellulose;Sodiumstarchglycolate(TypeA);polysorbate

Sugar-coating:Hypromellose;Polyvinylalcohol;Simeticone;Macrogol:Sucrose;Magnesiumcarbonate,light;

Titaniumdioxide(E171);MethylParahydroxybenzoate(E218);Cetylesterswax;Talc;Carnaubawax.

Printingink:Shellac;Ironoxides(E172),Titaniumoxide(E171)

6.2Incompatibilities

Notapplicable

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

15,20,30,90,100and120tabletsinblisterpacks(Aluminium-PVDC/PVC-PVDC)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

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7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/71/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10June2011

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