ESTOPAUSE

Main information

  • Trade name:
  • ESTOPAUSE Film Coated Tablet
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ESTOPAUSE Film Coated Tablet
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1201/001/001
  • Authorization date:
  • 07-03-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

EstopauseFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachwhitetabletcontains2mgofOestradiol.Eachpalebluetabletcontains2mgofOestradioland5mgof

MedroxyprogesteroneAcetate.

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Calendarpackconsistingof16round,white,biconvextabletsand12round,pale-blue,biconvextablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hormonereplacementtherapy(HRT)forestrogendeficiencysymptoms.Inpostmenopausalwomenwithan

intactuterus.

Secondlinetherapyforpreventionofosteoporosisinpostmenopausalwomenathighriskoffuturefractureswho

areintolerantof,orcontraindicatedfor,othermedicinalproductsapprovedforthepreventionofosteoporosis.

Theexperienceoftreatingwomenolderthan65yearsislimited.

4.2Posologyandmethodofadministration

Adultsandelderly

EstopauseisacontinuoussequentialcombinedHRTregimen(OestrogenandMedroxyprogesterone).The

oestrogenphase(2mgoestrogen[17 oestradol]isgivenforthefirst16days.Thisisfollowedbyacombined

oestrogenandprogesteroneacetatefor12days.

Theregimenisbasedona28daycyclewhichonetabletistakendailywithoutinterruption.Onetabletof

oestrogen2mgistakendailyforthefirst16days.Thisisfollowedbyonetabletdailyforthefollowing12daysof

combinedtabletcontains(oestrogen2mgandmedroxyprogesterone5mg).Inmenstruatingwomenorwomen

alreadyonHRT,thefirsttabletshouldbetakeninthefifthdayofmenstrualbleeding.Ifmenstruatinghasstopped

orisinfrequentorsporadic,thefirsttabletcanbetakenatanytime.

Tabletsshouldbetakenapproximatelyatthesametimeoftheday.Ifthepatienthasforgottentotakeonetablet,

theforgottentabletistobediscarded.

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Useinchildren

Notbeusedinchildren

Forinitiationandcontinuationoftreatmentofpostmenopausalsymptoms,thelowesteffectivedoseforthe

shortestduration(seealsoSection4.4)shouldbeused.

4.3Contraindications

Known,pastorsuspectedbreastcancer

Knownorsuspectedoestrogen-dependantmalignanttumours(e.g.endometrialcancer)

Undiagnosedgenitalbleeding

Untreatedendometrialhyperplasia

Previousidiopathicorcurrentvenousthromboembolism(deepvenousthrombosis,pulmonaryembolism)

Activeorrecentarterialthromboembolicdisease(e.g.angina,myocardialinfarction)

Acuteliverdisease,orahistoryofliverdiseaseaslongastheliverfunctiontestshavefailedtoreturntonormal

Knownhypersensitivitytotheactivesubstancesortoanyoftheexcipients

Porphyria

4.4Specialwarningsandprecautionsforuse

Medicalexamination/Followup

Forthetreatmentofpostmenopausalsymptoms,HRTshouldonlybeinitiatedforsymptomsthatadverselyaffect

qualityoflife.Forbothindications,acarefulappraisalofrisksandbenefitsshouldbeundertakenatannuallyandHRT

shouldonlybecontinuedaslongasthebenefitoutweighstherisk.

BeforeinitiatingorreinstitutingHRT,acompletepersonalandfamilymedicalhistoryshouldbetaken.Physical

(includingpelvicandbreast)examinationshouldbeguidedbythisandbythecontraindicationsandwarningsforuse.

Duringtreatment,periodiccheck-upsarerecommendedofafrequencyandnatureadaptedtotheindividualwoman.

Womenshouldbeadvisedthatchangesintheirbreastsshouldbereportedtotheirdoctorornurses(seeBreastcancer

below).Investigations,includingmammography,shouldbecarriedoutinaccordancewithcurrentlyaccepted

screeningpractice,modifiedtotheclinicalneedsoftheindividual.

Acarefulappraisaloftherisksandbenefitsshouldbeundertakenovertimeinwomentreatedwithhormone

replacementtherapy.

Conditionswhichneedsupervision

Ifanyofthefollowingconditionsarepresent,haveoccurredpreviously,and/orhavebeenaggravatedduringpregnancy

orprevioushormonetreatment,thepatientshouldbecloselysupervised.Itshouldbetakenintoaccountthatthese

conditionsmayrecurorbeaggravated

duringtreatmentwithEstopause,inparticular:

Leiomyoma(uterinefibroid)orendometriosis

Ahistoryof,orriskfactorsforthromboembolicdisorders

Riskfactorsforoestrogendependanttumours,e.g.1 st

degreehereditaryforbreastcancer

Hypertension

Liverdisorders(e.g.liveradenoma)

Diabetesmellituswithorwithoutvascularinvolvement

Cholelithiasis

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Systemiclupuserythematosis

Ahistoryofendometrialhyperplasia

Epilepsy

Asthma

Otoscerlosis

Reasonsforimmediatewithdrawaloftherapy:

Therapyshouldbediscontinuedincaseswhereacontra-indicationisdiscoveredandinthefollowingsituations:

Jaundiceordeteriorationinliverfunction

Significantincreaseinbloodpressure

Newonsetofmigrainetypeheadache

Pregnancy

EndometrialHyperplasia

Theriskofendometrialhyperplasiaandcarcinomaisincreasedwhenoestrogensareadministeredaloneforprolonged

periods.Theadditionofaprogestagenforatleast12dayspercylce(forcyclicorsequentialproducts)oreverydayin

non-hysterectomisedwomengreatlyreduces,butmaynoteliminate,thisrisk.

Break-throughbleedingandspottingmayoccurduringthefirstmonthsoftreatment.Ifbreak-throughbleedingor

spottingappearsaftersometimeontherapy,orcontinuesaftertreamenthasbeendiscontinued,thereasonshouldbe

investigated,whichmayincludeendometrialbiopsytoexcludeendometrialmalignancy.

BreastCancer

Arandomisedplacebo-controlledtrial,theWoman’sHealthInitiativestudy(WHI),andepidemiologicalstudies,

includingtheMillionWomenStudy(MWS)andotherepidemiologicalstudieshavereportedanincreasedriskofbreast

cancerinwomentakingestrogens,estrogen-progestagencombinationsortiboloneforHRTforseveralyears(see

section4.8).IntheMWS,therelativeriskofbreastcancerwithconjugatedequineoestrogens(CEE)orestradiol(E2)

wasgreaterwhenaprogestagenwasadded,compounds.Eithersequentiallyorcontinuously,andregardlessoftypeof

progestagen.Thereisnoevidenceofadifferenceinriskbetweenthedifferentroutesofadministration.

ForallHRT,anexcessriskbecomesapparentwithinafewyearsofuseandincreaseswiththedurationofintakebut

returnstobaselinewithinafew(atmostfive)yearsafterstoppingtreatment.

Theoestrogen+progestagentreatmentintheWHIstudywasassociatedwithbreastcancersthatwereslightlylargerin

sizeandmorefrequentlyhadlocallymphnodemetastases.

HRT,especiallyoestrogen-progestagentreatment,increasesthedensityofmammographicimageswhichmay

adverselyaffecttheradiologicaldetectionofbreastcancer.

Venousthromboembolism

HRTisassociatedwithahigherrelativeriskofdevelopingvenousthromboembolism(VET),i.e.deepvenous

thrombosisorpulmonaryembolism.Onerandomisedcontrolledtrialandepidemiologicalstudiesfoundatwo-to-

threefoldhigherriskforuserscomparedwithnon-users.Fornon-usersitisestimatedthatthenumberofcasesofVTE

thatwilloccuroverafiveyearperiodisabout3per1000womenaged50-59years.Itisestimatedthatinhealthy

womenwhouseHRTfor5years,thenumberofadditionalcasesofVTEovera5yearperiodwillbebetween2and6

(bestestimate=4)per1000womenaged50-59yearsandbetween5and15(bestestimate=9)per1000womenaged60-

69years.TheoccurrenceofsuchaneventismorelikelyinthefirstyearofHRTthanlater.

GenerallyrecognisedriskfactorsforVTEincludeapersonalhistoryorfamilyhistory,severeobesity(BMI>30kg/m 2

andsystemiclupuserythrematous(SLE).ThereisnoconsensusaboutthepossibleroleofvaricoseveininVTE.

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Personalorstrongfamilyhistoryofthromboembolismorrecurrentspontaneousabortionshouldbeinvestigatedin

orderinordertoexcludeathrombophilicpredisposition.Untilathoroughevaluationofthrombophilicfactorshasbeen

madeoranticoagulanttreatmentinitiated,useofHRTinsuchpatientsshouldbeviewedascontraindicated.Those

womenalreadyonanticoagulanttreatmentrequirecarefulconsiderationofthebenefit-riskuseofHRT.

TheriskofVTEmaybetemporarilyincreasedwithprolongedimmobilisation,majortraumaormajorsurgery.Asin

allpostoperativepatients,scrupulousattentionshouldbegiventoprophylacticmeasurestopreventVTEfollowing

surgery.Whereprolongedimmobilisationisliabletofollowelectivesurgery,particularlyabdominalororthapaedic

surgerytolowerlimbs,considerationshouldbegiventotemporarilyHTR4to6weeksearlier,ifpossible.Treatement

shouldnotberestarteduntilthewomaniscompletelymoblilised.

IfVTEdevelopsafterinitiatingtherapy,thedrugshouldbediscontinued.Patientsshouldbetoldtocontacttheir

doctorsimmediatelywhentheyareawareofpotentialthromboembolicsymptoms(e.g.,painfulswellingofaleg,

suddenpaininthechest,dyspnoea).

Corornaryarterydisease(CAD)

Thereisnoevidencefromrandomisedcontrolledtrialsofcardiovascularbenefitwithcontinuouscombinedconjugated

oestrogenandmedroxyprgestroneacetate(MPA).Twolargeclinicaltrials(WHIandHERSieHeartand

Estrogen/progestinReplacementStudy)showedapossibleincreasedriskofcardiovascularmorbidityinthefirstyear

ofuseandnooverallbenefit.ForotherHRTproductsthereareonlylimiteddatafromrandomisedcontrolledtrials

examiningeffectsincardiovascularmorbidityandmortality.Therefore,itisuncertainwhetherthesefindingsalso

extendtootherHRTproducts.

Stroke

Onelargerandomisedclinicaltrial(WHI-trial)found,asasecondaryoutcome,anincreasedriskofischaemicstrokein

healthywomenduringtreatmentwithcontinuouscombinedconjugatedoestrogensandMPA.Forwomenwhodonot

useHRT,itisestimatedthatthenumberofcasesofstrokethatwilloccurovera5yearperiodis3per1000women

aged50-59yearsand11per1000womenaged60-69years.Itisestimatedthatforwomenwhouseconjugated

oestrogenandMPAfor5years,thenumberofadditionalcaseswillbebetween0and3(bestestimate=1)per1000

usersaged50-59yearsandbetween1and9(bestestimate=4)per1iatedwithanincreasedriskofovariancancerin

some1000usersaged60-69years.ItisunknownwhethertheincreasedriskalsoextendstootherHRTproducts.

Ovariancancer

Long-term(atleast5-10years)useofoestrogenonlyHRTproductsinhysterectomisedwomenhasbeenassociated

withanincreasedriskofovariancancerinsomeepidemiologicalstudies.Itisuncertainwhetherlong-termuseof

combinedHRTconfersdifferentriskthanoestrogen-onlyproducts.

Otherconditions

Oestrogenmaycausefluidretentionand,therefore,patientswithcardiacorrenaldysfunctionshouldbecarefully

observed.Patientswithterminalrenalinsufficiencyshouldbecloselyobserved.Patientswithterminalrenal

insufficiencyshouldbecloselyobserved,sinceitisexpectedthatthelevelofcirculatingactiveingredientsinthe

Estopauseisincreased.

-Womenwithpre-existinghypertriglyceridemiashouldbefollowedcloselyduringoestrogenreplacementorhormone

replacementtherapy,sincerarecasesoflargeincreasesofplasmatriglyceridesleadingtopancreatitishavebeen

reportedwithoestrogentherapyinthiscondition.

Oestrogensincreasethyroidbindingglobulin(TGB),leadingtoincreasedcirculatingtotalthyroidhormone,as

measuredbyprotein-boundiodine(PBI),T4levels(bycolumnorbyradio-immunoassay)orT3(byradio-

immunoassay).T3resinuptakeisdecreased,reflectingtheelevatedTBG.FreeT4andfreeT3concentrationsare

unaltered.Otherbindingproteinsmaybeeleveatedinserum,i.e.corticoidbindingglobulin(CBG),sex-hormone-

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biologicalactivehormoneconcentrationsareunchanged.Otherplasmaproteinsmaybeincreased

(angiotensinogen/renninsubstrate,alpha-I-antitrypsin,ceruloplasmin).

Thereisnoevidenceforimprovementofcognitivefunction.Thereissomeevidenceofincreasedriskofprobable

dementiainwomenolderthan65yearsusingcontinuouscombinedconjugatedoestrogenandMPA.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Themetabolismofoestrogensandprogestagensmaybeincreasedbyconcomitantuseofsubstancesknowntoinduce

drug-metabolisingenzymes,specificallycytochromeP450enzymes,suchasanticonvulsants(e.g.Phenobarbital,

phenytoin,andcarbamazepine)anti-infectives(e.g.rifampicin,rifabutin,nevirapine,efavirenz).

Ritonavirandnelfinavir,althoughknownasstronginhibitors,bycontrastexhibitinducingpropertieswhenused

concomitantlywithsteroidhormones.HerbalpreparationscontainingStJohn’swort(hypericumperforatum)may

inducethemetabolismofoestrogensandprogestogens.

Clinically,anincreasedmetabolismofoestrogensandprogestogansmayleadtodecreasedeffectandchangesinthe

uterinebleedingprofile.

4.6Pregnancyandlactation

Estopauseisnotindicatedduringpregnancy.IfpregnancyoccursduringtreatmentwithEstopause,treatmentshouldbe

withdrawnimmediately.Dataonalimitednumberofexposedpregnanciesindicateadverseeffectsof

medroxyprogesteroneacetateonsexualdifferentiationofthefoetusStudiesinanimalshaveshownreproductive

toxicity(seesection5.3).Thepotentialriskforhumansisunknown.Theresultsofmostepidemiologicalstudiesto

daterelevanttoinadvertentfoetalexposuretocombinationsofestrogensprogestagenindicatenoteratogenicor

foetotoxiceffect.

Theresultsofmostepidemiologicalstudiestodaterelevanttoinadvertentfoetalexposuretocombinationsof

oestrogensandprogestagensindicatenoteratogenicorfetotoxiceffect.

Lactation

Estopauseisnotindicatedduringlactation

4.7Effectsonabilitytodriveandusemachines

Noeffectsonabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

ThemostfrequentlyreportedundesirableeffectduringEstopausetreatmentwasbreasttenderness,whichoccurredin

10.6%ofusers.UndesirableeffectsaccordingtosystemorganclassassociatedwithEstopausetreatmentarepresented

inthetablebelow.

Organgroup Common>1/100 Uncommon>1/1000,

<1/100 Rare>1/10,000;

<1/1,000

Gastrointestinal Nausea,abdominalpain Dyspepsia,vomiting,

flatulence,gallbladder

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Breastcancer

TheriskofbreastcancerincreaseswiththenumberofyearsofHRTusage.TheMillionWomenStudyshowedthat,

comparedtonever-users,useofoestrogen-progestagencombinedHRTisassociatedwithahigherriskofbreastcancer

(RR=2.00,95%CI:1.88-2-12)thatuseofoestrogenalone(RR=1.30,95%CI:1.21-1.40).

ForwomennotusingHRTabout32inevery1000areexpectedtohavebreastcancerdiagnosedbetweentheagesof50

and65years.AmongthosewithwithcurrentorrecentuseofHRT,thenumberofadditionalcasesfromthisstudyis

shownintable1.ThenumberofadditionalcasesofbreastcancerduetoHRTisbroadlysimilarforwomenwhostart

HRTirrespectiveofageatstartofuse(betweenagesof45-65).

Endometrialcancer

Inwomenwithanintactuterus,theriskofendometrialhyperplasiaandendometrialcancerincreaseswithincreasing

durationofuseofunopposedoestrogen.Accordingtodatafromepidemiologicalstudies,thetestestimateoftheriskof

endometrialcanceristhatforwomen

notusingHRT;about5inevery1000areexpectedtohaveendometrialcancerdiagnosedbetweentheagesof50and

65.AmongthosewithcurrentorrecentHRT,thenumberofadditionalcasesisshownintable1Addinga

progesteronetooestrogen-onlytherapygreatlyreduces,butmaynoteliminate,thisincreasedrisk.

Table1:Bestestimateofabsoluterisk(numberofcasesexpectedin1000womenfromageof50-65)ofbreastand

endometrialcancerinwomennottakingHRTandnumberofadditionalcases(+95%CIsforbreastcancer)inwomen

takingHRTbyregimenanddurationofintake

Otheradversereactionshavebeenreportedinassociationwithoestrogen/progesteronetreatment:

Oestrogen-dependantneoplasm’sbenignandmalignant,e.g.endometrialcancer

Skin Chloasma Alopecia,

hirsutism,rash,

itching

Headache Dizziness,migraine

Urogenital Uterinebleeding,increase

insizeofuterinefibroids Vaginalcandidiasis,

changesinvaginal

secretion

Cardiovascular Increaseinbloodpressure Venous

thromboemolism

Miscellaneous Weightincrease/decrease,

oedema,breast

tenderness,breast

enlargement,changesin

moodincludinganxiety

anddepressivemood,

changesinlibido. Legcramps,cholestasis

Exposure Breast Endometrium

NoHRT 32

Oestrogenonly

5years

10years Additionalcases

+2(0-3)

+5(3-7) Additionalcases

Oestrogen+Progestagen

5years

10years Additionalcases

+6(5-7)

+19(18-20) Additionalcases

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amonghormonereplacementtherapyusersthanamongnon-users.Forfurtherinformation,seesection4.3

Contraindicationsand4.4Specialwarningsandprecautionsforuse

Myocardialinfarctionandstroke

Gallbladderdisease

Skinandsubcutaneousdisorders:chloasma,erythemamultiforme,erythemanodosum,vascularpurpura

Probabledementia

4.9Overdose

Oestrogenoverdosemaycausenausea,headacheanduterinebleeding.Numerousreportsonhighdosesofoestrogen-

containingoralcontraceptivesingestedbyyoungchildrenindicatethatseriousharmfuleffectsdonotoccur.Treatment

ofoestrogenoverdoseissymptomatic.Highdosesofmedoxyprogestroneacetate(MPA)usedforcancertreatment

havenotresultedinseriousundesirableeffects.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Progestogensandoestrogens

ATCCode:G03fA12

Theactiveformofoestradiol(sythetic17-oestradiol)ischemicallyandbiologicallyidenticaltoendogenoushuman

oestradiol.Itsubstitutesforthelossofoestrogenproductioninmenopausalwomenandalleviatesmenopausal

symptoms.

Oestrogenpreventsbonelossfollowingmenopauseorovariectomy.

Medroxyprogesteroneacetateisaderivativeofthenaturalprogesterone,17-alpha-hydroxy-6-methylprogesterone.

Medroxyprogesteroneacetatebindstoprogestin-specificreceptorsandactsontheendometriumtoconvertthestatusof

theendometriumfromproliferativetosecretory.

Asoestrogenpromotesthegrowthoftheendometrium,unopposedoestrogensincreasetheriskofendometrial

hyperplasiaandcancer.Theadditionofmedroxyprogesteroneacetategreatlyreducestheoestrogen-inducedriskof

endometrialhyperplasiainnon-hysterectomisedwomen.

Reliefofoestrogendeficiencysymptomsandbleedingpatterns.

Reliefofmenopausalsymptomswasachievedduringthefirstweeksoftreatment.Bleedingand/orspottingappeared

in31%ofthewomenreceiving1mgoestradiolvalerateand51%ofwomenreceiving2mgoestradiolvalerateduring

thefirstthreemonthsoftreatmentandin9%ofthewomenreceiving1mgoestrogenvalerateandin20%ofwomen

receiving2mgoestradiolvalerateafter10-12monthsoftreatment.

Amenorrhoeawasseenin91%ofwomenreceiving1mgoestradiolvalerateandin80%ofwomenreceiving2mg

oestradiolvalerateafter10-12monthstreatment.

Preventionofosteoporosis

Oestrogendeficiencyofmenopauseisassociatedwithanincreasingboneturnoveranddeclineofthebonemass.The

effectofoestrogensonbonemineraldensity(BMD)isdosedependant.Protectionappearstobeeffectiveforaslong

astreatmentiscontinued.AfterdiscontinuationofHRT,bonemassislostaratesimilartothatinuntreatedwomen.

EvidencefortheWHItrialandmeta-analysedtrialsshowsthatcurrentuseofHRT,aloneorincombinationwitha

progesterone-giventopredominantlyhealthywomen-reducestheriskofhip,vertebral,andotherosteoporotic

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evidenceforthislimited.

Informationonserumlipid

Nobenefithasbeendemonstratedinprimaryandsecondarycoronaryheartdisease.Theclinicalrelevanceoflipid

changesisunknownandtherelevanceforthesafetyofEstopausethereforehighlyquestionable.

5.2Pharmacokineticproperties

Followingoraladministration,oestradiolisabsorbedfromthegastrointestinaltractandrapidlyhydrolysedtooestradiol

byesterases.Inpostmenopausalwomenaged50-59yearsthemaximumconcentrationofoestradiolinserum(C

wasreachedwithin4hoursaftermultipledosingof1mgor2mgoestradiolvalerate.After1mgdoseC

wasabout

166pmol/l,troughconecentration(C

)about101pmol/landaverageconcentration(C

average )about123pmol.For

2mgdoseCmaxwas308pmol/l,C

171pmol/landC

average 228pmol.Comparableoestradiolconcentrations

wereobservedinwomenover65years.

Afteroraladministration,progesteroneisabsorbedfromthegastrointestinaltract,butisrapidlymetabolisedbysmall

intestineandliver.Aftermultipledosingof2.5mgor5mgmedoxyprogesteroneacetatetowomenaged50-65years,

maximumconcentrationinserumwasreachedinlessthan2hours.After2.5mgdoseC

wasabout0.37ng/ml,c

minabout0.05ng/mlandcaverageabouto.11ng/ml.After5mgdoseC

wasabout0.64ng/ml,cminabout

0.12ng/mlandC

average about0.21ng/ml.Comparablemedroxyprogesteroneacetateconcentrationswereobservedin

womenover65years.

Medroxyprogestroneacetateisover90%boundtoplasmaproteins,mainlytoalbumin.Theeliminationhalf-lifeof

oralmedroxyprogesteroneacetateisapproximately24hours.Medroxyprogesteroneacetateisextensivelymetabolised

byhepatichydroxylationandconjugationandexcretedintheurineandthebile.Metabolismispoorlydocumentedand

thepharmacologicalactivityofthemetabolitesisnotknown.

5.3Preclinicalsafetydata

Animalstudieswithoestradiolandmedroxyprogesteronehaveshownexpectedestrogeniceffects.Bothcompounds

inducedadverseeffectsinreproductivetoxicitystudies.Chiefly,estradiolshowedembryotoxiceffectsandinduced

feminizationofmalefetuses.Medroxyprogesteroneacetateshowedembryotoxiceffectsandinducedanti-androgenic

effectsinmalefetuses.Therelevanceofthesedataforhumanexposureisunknown(seesection4.6).

Concerningotherpreclinicaleffects,thetoxicityprofilesofestradiolandmedroxyprogesteroneacetatearewellknown

andrevealnoparticularhumanhealthrisksbeyondthosealreadydiscussedinothersectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Eachwhitetabletcontains:

Lactosemonohydrate

Crospovidone(typeA)

PovidoneK25

Talc

Magnesiumstearate

OpadryWhiteY-1-7000

hypromellose

macrogol400

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Eachpale-bluetabletcontains:

Lactosemonohydrate

Crospovidone(typeA)

PovidoneK25

Talc

Magnesiumstearate

OpadryWhiteY-1-7000

hypromellose

macrogol400

titaniumdioxide(E171)

Indigocarminelake(E132)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

C.Storeintheoriginalpackage.

Keepcontainerintheoutercarton.

6.5Natureandcontentsofcontainer

Calendarpackconsistingof16round,white,biconvex,film-coatedtabletsand12round,pale-blue,biconvex,film-

coatedtabletswithinaPVC/aluminumfoilblisterpack.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ResourceMedical(UK)Ltd.

2CarltonAvenue

Batley

WestYorkshire

WF177AQ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1201/001/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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Dateoflastrenewal: 14June2004

10DATEOFREVISIONOFTHETEXT

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