ANASTROZOLE ARROW

Main information

  • Trade name:
  • ANASTROZOLE ARROW
  • Dosage:
  • 1 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ANASTROZOLE ARROW
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1130/015/001
  • Authorization date:
  • 06-03-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AnastrozoleArrow1mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains1mganastrozole.

Excipient(s):Eachtabletcontains65mgoflactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

White,roundfilm-coatedtablet

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofadvancedbreastcancerinpostmenopausalwomen.Theefficacyofanastrozolehasnotbeendemonstrated

inoestrogen-receptornegativepatients,unlesstheyhavehadapreviouspositiveclinicalresponsetotamoxifen.

4.2Posologyandmethodofadministration

Adultsincludingtheelderly:

Onefilm-coatedtablet(1mg)tobetakenorallyonceaday.

Children:

Anastrozoleisnotrecommendedforuseinchildrenduetoinsuffieientdataonsafetyandefficacy(seesection4.4and

5.1).

Renalimpairment:Nodosechangeisrecommendedinpatientswithmildormoderaterenalimpairment.

Hepaticimpairment:Nodosechangeisrecommendedinpatientswithmildhepaticdisease.

4.3Contraindications

Anastrozoleiscontraindicatedin:

premenopausalwomen.

pregnantorlactatingwomen.

patientswithsevererenalimpairment(creatinineclearancelessthan20ml/min).

patientswithmoderateorseverehepaticdisease.

patientswithhypersensitivitytoanastrozoleortoanyoftheexcipientsasreferencedinsection6.1.

Oestrogen-containingtherapiesshouldnotbeco-administeredwithanastrozoleastheywouldnegateits

pharmacologicalaction.

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4.4Specialwarningsandprecautionsforuse

Anastrozoleisnotrecommendedforuseinchildrenasitssafetyandefficacyhavenotbeenestablishedyetinthis

groupofpatients(seesection5.1).

Anastrozoleshouldnotbeusedinboyswithgrowthhormonedeficiencyinadditiontogrowthhormonetreatment.In

thepivotalclinicaltrial,efficacywasnotdemonstratedandsafetywasnotestablished(seesection5.1).Since

anastrozolereducesoestradiollevels,anastrozolemustnotbeusedingirlswithgrowthhormonedeficiencyinaddition

togrowthhormonetreatment.Longtermsafetydatainchildrenandadolescentsarenotavailable.

Theonsetofthemenopausemustbeconfirmedbiochemicallyifthehormonalstatusofthepatientcannotbe

establishedwithclinicalmethods.

Therearenodatatosupportthesafeuseofanastrozoleinpatientswithmoderateorseverehepaticimpairment,or

patientswithsevereimpairmentofrenalfunction(creatinineclearancebelow20ml/min).

Womenwithosteoporosisoratriskofthatdisease,shouldhavetheirbonemineraldensityformallyassessedbybone

densitometrye.g.DEXAscanningatthecommencementoftreatmentandatregularintervalsthereafter.Treatmentor

prophylaxisforosteoporosisshouldbeinitiatedasappropriateandcarefullymonitored.

TherearenodataareavailablefortheuseofanastrozolewithLHRHanalogues;therefore,thiscombinationis

restrictedforuseonlyinclinicalstudies.

Asanastrozolelowerscirculatingoestrogenlevelsitmaycauseareductioninbonemineraldensity.Theuseof

bisphosphonatesmaystopfurtherbone

minerallosscausedbyanastrozoleinpostmenopausalwomenandcouldbeconsidered.

Thisproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Antipyrineandcimetidineclinicalinteractionstudiesindicatethatthecoadministrationofanastrozolewithotherdrugs

isunlikelytoresultinclinically

significantdruginteractionsmediatedbycytochromeP450.

Areviewoftheclinicaltrialsafetydatabasedidnotrevealevidenceofclinicallysignificantinteractioninpatients

treatedwithanastrozolewhoalsoreceivedothercommonlyprescribeddrugs.Therewerenoclinicallysignificant

interactionswithbisphosphonates(seesection5.1).

Oestrogen-containingtherapiesshouldnotbeco-administeredwithanastrozoleastheywouldnegateits

pharmacologicalaction.

Tamoxifenshouldnotbeco-administeredwithanastrozole,asthismaydiminishitspharmacologicalaction(see

section4.3).

4.6Pregnancyandlactation

Anastrozoleiscontraindicatedinpregnantandlactatingwomen(seesection4.3).

4.7Effectsonabilitytodriveandusemachines

Anastrazoleisunlikelytoimpairtheabilityofpatientstodriveandoperatemachinery.However,astheniaand

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machinerywhilesuchsymptomspersist.

4.8Undesirableeffects

SystemOrganClass Frequency Adversereaction

Metabolismandnutrition

Common(1/100to1/10) Anorexia,mainlymildinnature

Hypercholesterolaemia,mainlymild

ormoderateinnature

Nervoussystem Verycommon(1/10)

Headache,mainlymildormoderatein

nature

Common(1/100to1/10) Somnolence,mainlymildormoderate

innature

Carpaltunnelsyndrome

Vasculardisorders Verycommon(1/10)

Hotflushes,mainlymildormoderate

innature

Gastrointestinaldisorders

Verycommon(1/10)

Nausea,mainlymildormoderatein

nature

Common(1/100to1/10) Diarrhoea,mainlymildormoderatein

nature

Vomiting,mainlymildormoderatein

nature

Hepatobiliarydisorders

Common(1/100to1/10) Increasesinalkalinephosphatase,

alanineaminotransferaseand

aspartateaminotransferase

Uncommon(1/1000to

1/100) Increasesingamma-GTandbilirubin

Hepatitis

Skinandsubcutaneous

disorders Verycommon(1/10)

Rash,mainlymildormoderatein

nature

Common(1/100to1/10) Hairthinning(Alopecia),mainlymild

ormoderateinnature

Allergicreactions

Uncommon(1/1000to

1/100) Urticaria

Rare(1/10,000to

1/1000) Erythemamultiforme

Anaphylactoidreaction

Notknown Stevens-JohnsonSyndrome**

Angioedema**

Musculoskeletal

disordersandconnective

tissuedisorders Verycommon(1/10) Jointpain/stiffness,mainlymildor

moderateinnature

Arthritis

Common(1/100to

1/10) Bonepain

Uncommon(1/1000to

1/100) Triggerfinger

Reproductivesystemand

breastdisorders Common(1/100to

1/10) Vaginaldryness,mainlymildor

moderateinnature

Vaginalbleeding,mainlymildor

moderateinnature*

Generaldisordersand

administrationsite

conditions Verycommon(1/10) Asthenia,mainlymildormoderatein

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*Vaginalbleedinghasbeenreporteduncommonly,mainlyinpatientswithadvancedbreastcancerduringthefirstfew

weeksafterchangingfromexistinghormonaltherapytotreatmentwithanastrozole.Ifbleedingpersists,further

evaluationshouldbeconsidered.

AsAnastrozolelowerscirculatingoestrogenlevels,itmaycauseareductioninbonemineraldensityplacingsome

patientsatahigherriskoffracture(seesection4.4).

**Cannotbeestimatedfromtheavailabledata.

Duetothepharmacologicalactionsofanastrozole,hotflushes,vaginaldrynessand

hairthinningmaydevelop.Duringtheuseofanastrozolegastrointestinalcomplaints

(anorexia,nausea,vomitinganddiarrhoea),asthenia,jointpain/stiffness,somnolence,

headacheandmildrashesmayoccur,includingrareformsofmucodermaldisorders,

suchaserythemamultiformeandStevens-Johnsonsyndrome.

Thetablebelowpresentsthefrequencyofpre-specifiedadverseeventsintheATAC

study,irrespectiveofcausality,reportedinpatientsreceivingtrialtherapyandupto

14daysaftercessationoftrialtherapy.

Fractureratesof22per1000patient-yearsand15per1000patient-yearswereobservedfortheanastrozoleand

tamoxifengroups,respectively,afteramedianfollow-upof68months.

Theobservedfracturerateforanastrozoleissimilartotherangereportedinagematchedpostmenopausalpopulations.

IthasnotbeendeterminedwhethertheratesoffractureandosteoporosisseeninATACinpatientsonanastrozole

treatmentreflectaprotectiveeffectoftamoxifen,aspecificeffectofanastrozole,orboth.

Theincidenceofosteoporosiswas10.5%inpatientstreatedwithanastrozoleand7.3%inpatientstreatedwith

Adverseeffects Anastrozole

(N=3092) Tamoxifen

(N=3094)

Hotflushes 1104(35.7%) 1264(40.9%)

Jointpain/stiffness 1100(35.6%) 911(29.4%)

Mooddisturbances 597(19.3%) 554(17.9%)

Fatigue/asthenia 575(18.6%) 544(17.6%)

Nauseaandvomiting 393(12.7%) 384(12.4%)

Fractures 315(10.2%) 209(6.8%)

Fracturesofthespine,hip,orwrist/Colles 133(4.3%) 91(2.9%)

Wrist/Collesfractures 67(2.2%) 50(1.6%)

Spinefractures 43(1.4%) 22(0.7%)

Hipfractures 28(0.9%) 26(0.8%)

Cataracts 182(5.9%) 213(6.9%)

Vaginalbleeding 167(5.4%) 317(10.2%)

Ischaemiccardiovasculardisease 127(4.1%) 104(3.4%)

Anginapectoris 71(2.3%) 51(1.6%)

Myocardialinfarct 37(1.2%) 34(1.1%)

Coronaryarterydisorder 25(0.8%) 23(0.7%)

Myocardialischaemia 22(0.7%) 14(0.5%)

Vaginaldischarge 109(3.5%) 408(13.2%)

Anyvenousthromboembolicevent 87(2.8%) 140(4.5%)

Deepvenousthromboembolicevents

includingPE 48(1.6%) 74(2.4%)

Ischaemiccerebrovascularevents 62(2.0%) 88(2.8%)

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4.9Overdose

Thereislimitedclinicalexperienceofoverdoseofanastrozole.

Inanimalstudies,anastrozoledemonstratedlowacutetoxicity.

Clinicaltrialshavebeenconductedwithvariousdosagesofanastrozole,upto60mginasingledosegiventohealthy

malevolunteersandupto10mgdailygiventopostmenopausalwomenwithadvancedbreastcancer;thesedosages

werewelltolerated.Asingledoseofanastrozolethatresultsinlife-threateningsymptomshasnotbeenestablished.

Thereisnospecificantidotetoanoverdoseandtreatmentmustbesymptomatic.

Inthemanagementofanoverdose,considerationshouldbegiventothepossibilitythatmultipleagentsmayhavebeen

takensimultaneously.Ifthepatientisalert,itisrecommendedtoinducevomiting.

Dialysismaybehelpfulbecauseanastrozoleisnothighlyproteinbound.

Generalsupportivecare,includingfrequentmonitoringofvitalsignsandcloseobservationofthepatient,is

recommended.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:EnzymeInhibitors,ATCcode:L02BG03

Anastrozoleisapotentandhighlyselectivenon-steroidalaromataseinhibitor.Inpostmenopausalwomen,estradiolis

producedprimarilyfromtheconversionofandrostenedionetoestronethroughthearomataseenzymecomplexpresent

inperipheraltissues.Estroneissubsequentlyconvertedtoestradiol.

Reducingthelevelsofcirculatingestradiolhasbeenshowntoproduceabeneficialeffectinwomenwithbreastcancer.

Inpostmenopausalwomen,anastrozoleatadailydoseof1mgsuppressedestradiollevelsbymorethan80%.

Anastrozoledoesnotpossessanyprogestogenic,androgenicoroestrogenicactivity.

Regulardailydosesofanastrozoleupto10mgdidnothaveanyeffectoncortisoloraldosteronesecretion,measured

beforeorafterstandardACTHchallengetesting.Corticoidsupplementsarethereforenotneededduringits

administration.

Aswithalltreatmentdecisions,womenwithbreastcancerandtheirphysicianshouldassesstherelativebenefitsand

risksofthetreatment.

Studyofanastrozolewiththebisphosphonaterisedronate(SABRE)

BoneMineralDensity(BMD)

InthephaseIII/IVSABREstudy,234postmenopausalwomenwithhormonereceptorpositiveearlybreastcancer

scheduledfortreatmentwithanastrozole1mg/daywerestratifiedtolow,moderateandhighriskgroupsaccordingto

theirexistingriskoffragilityfracture.Theprimaryefficacyparameterwastheanalysisoflumbarspinebonemass

densityusingDEXAscanning.AllpatientsreceivedtreatmentwithvitaminDandcalcium.Patientsinthelowrisk

groupreceivedanastrozolealone(N=42),thoseinthemoderategroupwererandomisedtoanastrozoleplusrisedronate

35mgonceaweek(N=77)oranastrozoleplusplacebo(N=77)andthoseinthehighriskgroupreceived

anastrozoleplusrisedronate35mgonceaweek(N=38).Theprimaryendpointwaschangefrombaselineinlumbar

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The12-monthmainanalysishasshownthatpatientsalreadyatmoderatetohighriskoffragilityfractureshowedno

decreaseintheirbonemassdensity(assessedbylumbarspinebonemineraldensityusingDEXAscanning)when

managedbyusinganastrozole1mg/dayincombinationwithrisedronate35mgonceaweek.Inaddition,adecreasein

BMDwhichwasnotstatistically

significantwasseeninthelowriskgrouptreatedwithanastrozole1mg/dayalone.Thesefindingsweremirroredinthe

secondaryefficacyvariableofchangefrombaselineintotalhipBMDat12months.

Thisstudyprovidesevidencethattheuseofbisphosphonatesshouldbeconsideredinthemanagementofpossiblebone

minerallossinpostmenopausalwomenwithearlybreastcancerscheduledtobetreatedwithanastrozole.

Lipids

IntheSABREstudytherewasaneutraleffectonplasmalipidsinthosepatientstreatedwithanastrozoleplus

risedronate.

Paediatrics

Anastrozoleisnotindicatedforuseinchildren.Efficacyhasnotbeenestablishedinthepaediatricpopulationsstudied

(seebelow).Thenumberofchildrentreatedwastoolimitedtodrawanyreliableconclusionsonsafety.Nodataonthe

potentiallong-termeffectsofanastrozoletreatmentinchildrenareavailable(seealsosection5.3).

Shortstatureduetogrowthhormonedeficiency

Arandomised,double-blind,multi-centrestudyevaluated52pubertalboys(aged11-16yearsinclusive)withGHD

treatedfor12to36monthswithanastrozole1mg/dayorplaceboincombinationwithgrowthhormone.Only14

subjectsonanastrozolecompleted36months.

After3yearsanastrozolewasfoundtostatisticallysignificantlyslowbonematurationinpubertalboysongrowth

hormonetherapy.Nostatisticallysignificantdifferencewithplacebowasobservedforthegrowthrelatedparametersof

predictedadultheight,height,heightSDS,andheightvelocity.

Finalheightdatawerenotavailable.Whilethenumberofchildrentreatedwastoolimitedtodrawanyreliable

conclusionsonsafety,therewasanincreasedfracturerateandatrendtowardsreducedbonemineraldensityinthe

anastrozolearmcomparedtoplacebo.

Testotoxicosis

Anopen-label,non-comparative,multi-centrestudyevaluated14malepatients(aged2-9)withfamilialmale-limited

precociouspuberty,alsoknownastestotoxicosis,treatedwithcombinationofanastrozoleandbicalutamide.The

primaryobjectivewastoassesstheefficacyandsafetyofthiscombinationregimenover12months.Thirteenoutofthe

14patientsenrolledcompleted12monthsofcombinationtreatment(onepatientwaslosttofollow-up).Therewasno

significantdifferenceingrowthrateafter12monthsoftreatment,relativetothegrowthrateduringthe6monthsprior

toenteringthestudy.

Gynaecomastiastudies

Trial0006wasarandomised,double-blind,multi-centrestudyof82pubertalboys(aged11-18yearsinclusive)with

gynaecomastiaofgreaterthan12monthsdurationtreatedwithanastrozole1mg/dayorplacebodailyforupto6

months.Nosignificantdifferenceinthenumberofpatientswhohada50%orgreaterreductionintotalbreastvolume

after6monthsoftreatmentwasobservedbetweentheanastrozole1mgtreatedgroupandtheplacebogroup.

Trial0001wasanopen-label,multiple-dosepharmacokineticstudyofanastrozole1mg/dayin36pubertalboyswith

gynaecomastiaoflessthan12monthsduration.Thesecondaryobjectivesweretoevaluatetheproportionofpatients

withreductionsfrombaselineinthecalculatedvolumeof

gynaecomastiaofbothbreastscombinedofatleast50%betweenday1andafter6monthsofstudytreatment,and

patienttolerabilityandsafety.

Apharmacodynamicsubpopulationof25boyswasselectedinthisstudytoexplorethepotentialbenefitsof

anastrozole.Itwasnotedadecreaseintotalbreastvolumeof50%orgreaterat6monthswasseenin55.6%(as

measuredbyultrasound)and77.8%(asmeasuredbycaliper)oftheboys(observationaldataonly,nostatistical

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McCune-AlbrightSyndromestudy

Trial0046wasaninternational,multi-centre,open-labelexploratorytrialofanastrozolein28girls(aged2to10years)

withMcCune-AlbrightSyndrome(MAS).Theprimaryobjectivewastoevaluatethesafetyandefficacyofanastrozole

1mg/dayinpatientswithMAS.Theefficacyofstudytreatmentwasbasedontheproportionofpatientsfulfilling

definedcriteriarelatingtovaginalbleeding,boneage,andgrowthvelocity.

Nostatisticallysignificantchangeinthefrequencyofvaginalbleedingdaysontreatmentwasobserved.Therewereno

clinicallysignificantchangesinTannerstaging,meanovarianvolumeormeanuterinevolume.Nostatistically

significantchangeintherateofincreaseinboneageontreatmentcomparedtotherateduringbaselinewasobserved.

Growthrate(incm/year)wassignificantlyreduced(p<0.05)frompre-treatmentthroughmonth0tomonth12,and

frompre-treatmenttothesecond6months(month7tomonth12).Ofthepatientswithbaselinevaginalbleeding,28%

experienceda50%reductioninthefrequencyofbleedingdaysontreatment;40%experiencedacessationovera6-

monthperiod,and12%experiencedacessationovera12-monthperiod.

Theoverallassessmentoftheadverseeventsinchildrenlessthan18yearsofageraisednosafetyortolerability

concerns.

5.2Pharmacokineticproperties

Absorptionofanastrozole,theactivesubstanceofAnastrozoleTabletsisrapid.Maximumplasmaconcentrations

typicallyoccurwithintwohoursofdosingifthemedicineisgivenunderfastingconditions.

Anastrozoleiseliminatedslowlywithaplasmaeliminationhalf-lifeof40-50hours.Foodcausesaslightdecreasein

theratebutnotintheextentofabsorption.Thesmallchangeintherateofabsorptionisnotexpectedtoresultina

clinicallysignificanteffectonthesteady-stateplasmaconcentrationsduringoncedailydosingofAnastrozoleTablets.

After7dailydoses,theplasmaanastrozoleconcentrationsattainedare90-95%ofthesteady-stateconcentration.

Thereisnoevidenceofatimeordose-dependencyofthepharmacokineticparametersofanastrozole.

Thepharmacokineticsofanastrozoleareindependentofageinpostmenopausalwomen.

Inboyswithpubertalgynaecomastia,anastrozolewasrapidlyabsorbed,waswidelydistributed,andwaseliminated

slowlywithahalf-lifeofapproximately2days.Clearanceofanastrozolewasloweringirlsthaninboysandexposure

higher.Anastrozoleingirlswaswidelydistributedandslowlyeliminated,withanestimatedhalf-lifeofapproximately

0.8days.

Anastrozoleis40%boundtoplasmaproteins.

Anastrozoleisextensivelymetabolisedbypostmenopausalwomen,withlessthan10%ofthedoseexcretedunchanged

intheurinewithin72hoursofdosing.MetabolismofanastrozoleoccursbyN-dealkylation,hydroxylationand

glucuronidation.Themetabolitesareexcretedprimarilyviatheurine.

Triazole,themajormetaboliteofanastrozoleinplasma,doesnotinhibitthearomataseenzyme.

Theapparentoralclearanceofanastrozoleinvolunteerswithstablehepaticcirrhosisorrenalimpairmentwasinthe

rangeobservedinhealthyvolunteers.

5.3Preclinicalsafetydata

Acutetoxicity

Inacutetoxicitystudiesinrodents,themedianlethaldoseofanastrozolewasgreaterthan100mg/kg/daybytheoral

routeandgreaterthan50mg/kg/daybytheintraperitonealroute.Inanoralacutetoxicitystudyinthedog,themedian

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Chronictoxicity

Multipledosetoxicitystudiesutilizedratsanddogs.Nono-effectlevelswereestablishedforanastrozoleinthetoxicity

studies,butthoseeffectsthatwereobservedatthelowdoses(1mg/kg/day)andmiddoses(dog3mg/kg/day;rat5

mg/kg/day)wererelatedtoeitherthepharmacologicalorenzymeinducingpropertiesofanastrozoleandwere

unaccompaniedbysignificanttoxicordegenerativechanges.

Mutagenicity

Genetictoxicologystudieswithanastrozoleshowthatitisnotamutagenoraclastogen.

Reproductivetoxicology

Oraladministrationofanastrozoletofemaleratsproducedahighincidenceofinfertilityat1mg/kg/dayandincreased

pre-implantationlossat0.02mg/kg/day.Theseeffectsoccurredatclinicallyrelevantdoses.Aneffectinmancannotbe

excluded.Theseeffectswererelatedtothepharmacologyofthecompoundandwerecompletelyreversedaftera5-

weekcompoundwithdrawalperiod.

Oraladministrationofanastrozoletopregnantratsandrabbitscausednoteratogeniceffectsatdosesupto1.0and0.2

mg/kg/dayrespectively.Thoseeffectsthatwereseen(placentalenlargementinratsandpregnancyfailureinrabbits)

wererelatedtothepharmacologyofthecompound.

Thesurvivaloflittersborntoratsgivenanastrozoleat0.02mg/kg/dayandabove(fromday17ofpregnancytoday22

post-partum)wascompromised.Theseeffectswererelatedtothepharmacologicaleffectsofthecompoundon

parturition.Therewerenoadverseeffectsonbehaviourorreproductiveperformanceofthefirstgenerationoffspring

attributabletomaternaltreatmentwithanastrozole.

Inafertilitystudyweanlingmaleratsweredosedorallywith50or400mg/lanastrozoleviatheirdrinkingwaterfor10weeks.

Measuredmeanplasmaconcentrationswere44.4(±14.7)ng/mland165(±90)ng/mlrespectively.Matingindiceswereadversely

affectedinbothdosegroups,whilstareductioninfertilitywasevidentonlyatthe400mg/ldoselevel.Thereductionwas

transientasallmatingandfertilityparametersweresimilartocontrolgroup

valuesfollowinga9-weektreatment-freerecoveryperiod.

Carcinogenicity

Atwoyearratoncogenicitystudyresultedinanincreaseinincidenceofhepaticneoplasmsanduterinestromalpolyps

infemalesandthyroidadenomasinmalesatthehighdose(25mg/kg/day)only.Thesechangesoccurredatadose

whichrepresents100-foldgreaterexposurethanoccursathumantherapeuticdoses,andareconsiderednottobe

clinicallyrelevanttothetreatmentofpatientswithanastrozole.

Atwoyearmouseoncogenicitystudyresultedintheinductionofbenignovariantumoursandadisturbanceinthe

incidenceoflymphoreticularneoplasms(fewerhistiocyticsarcomasinfemalesandmoredeathsasaresultof

lymphomas).Thesechangesareconsideredtobemouse-specificeffectsofaromataseinhibitionandnotclinically

relevanttothetreatmentofpatientswithanastrozole.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Maizestarch

Povidone

Microcrystallinecellulose

SodiumstarchglycolateTypeA

Colloidalanhydroussilica

Magnesiumstearate

Talc

Film-coating:

Hypromellose

Macrogol

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Talc

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

4years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

PVC/Aluminiumblistersof10,14,20,28,30,98or100film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ArrowGenericsLtd

Unit2

EastmanWay

Stevenage

Hertfordshire

SG14SZ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1130/15/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:6March2009

10DATEOFREVISIONOFTHETEXT

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