FEMATAB

Main information

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

Documents

Localization

  • Available in:
  • FEMATAB Film Coated Tablet 1 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0108/018/002
  • Authorization date:
  • 16-04-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fematab1mgFilm-coatedtablet

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontainsEstradiolHemihydrateequivalentto1mgestradiolpertablet.

Excipients-ContainsLactoseMonohydrate119.1mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

White,round,biconvex,film-coatedtabletwithinscription'379'ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hormonereplacementtherapy(HRT)forestrogendeficiencysymptomsinmenopausalwomen.

Preventionofosteoporosisinpostmenopausalwomenathighriskoffuturefractureswhoareintolerantof,or

contraindicatedfor,othermedicinalproductsapprovedforthepreventionofosteoporosis.

(Seealsosection4.4).

Theexperienceoftreatingwomenolderthan65yearsislimited.

4.2Posologyandmethodofadministration

FematabisanestrogenonlycontinuousHRTforwomenwithorwithoutauterus.Inwomenwithauterus,a

progestagensuchasDydrogesterone10mg,shouldbeaddedtoFematabfor12-14dayseachmonthtoreducetherisk

totheendometrium.Unlessthereisapreviousdiagnosisofendometriosis,itisnotrecommendedtoaddaprogestagen

inhysterectomisedwomen.

Ingeneral,treatmentshouldstartwithFematab1mg.Dependingontheclinicalresponse,thedosagecanafterwardsbe

adjustedtoindividualneed.Ifthecomplaintslinkedtoestrogendeficiencyarenotamelioratedthedosagecanbe

increasedbyusingFematab2mg.

Thedosageisonetabletperday.Fematabshouldbetakencontinuouslywithoutabreakbetweenpacks.

Fematabcanbetakenwithorwithoutfood.

StartingFematab

Inwomenwhoarenottakinghormonereplacementtherapy,haveestablishedamenorrhoea,arehysterectomised,or

womenwhoswitchfromacontinuouscombinedhormonereplacementtherapy,treatmentmaybestartedonany

convenientday.InwomentransferringfromacyclicorcontinuoussequentialHRTregimen,treatmentshouldbeginthe

dayfollowingcompletionofthepriorregimen.

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Ifadosehasbeenforgotten,itshouldbetakenassoonaspossible.Whenmorethan12hourshaveelapsed,itis

recommendedtocontinuewiththenextdosewithouttakingtheforgottentablet.Thelikelihoodofbreakthrough

bleedingorspottingmaybeincreased.

Forinitiationandcontinuationoftreatmentofpostmenopausalsymptoms,thelowesteffectivedosefortheshortest

duration(seealsosection4.4)shouldbeused.

4.3Contraindications

Non-hysterectomizedwomenwithoutopposingprogestogen

Known,pastorsuspectedbreastcancer.

Knownorsuspectedestrogen-dependentmalignanttumours(e.g.endometrialcancer).

Undiagnosedgenitalbleeding.

Untreatedendometrialhyperplasia.

Previousidiopathicorcurrentvenousthromboembolism(deepveinthrombosis,pulmonaryembolism).

Activeorrecentarterialthromboembolicdisease(e.g.angina,myocardialinfarction,cerebralvascularaccident);

Acuteliverdisease,orahistoryofliverdiseaseaslongasliverfunctiontestshavefailedtoreturntonormal.

Knownhypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Porphyria.

4.4Specialwarningsandprecautionsforuse

Forthetreatmentofpostmenopausalsymptoms,HRTshouldonlybeinitiatedforsymptomsthatadverselyaffect

qualityoflife.Inallcases,acarefulappraisaloftherisksandbenefitsshouldbeundertakenatleastannuallyandHRT

shouldonlybecontinuedaslongasthebenefitoutweighstherisk.

Medicalexamination/followup

BeforeinitiatingorreinstitutingHRT,acompletepersonalandfamilymedicalhistoryshouldbetaken.Physical(including

pelvicandbreast)examinationshouldbeguidedbythisandbythecontraindicationsandwarningsforuse.During

treatment,periodiccheck-upsarerecommendedofafrequencyandnatureadaptedtotheindividualwoman.Women

shouldbeadvisedwhatchangesintheirbreastsshouldbereportedtotheirdoctorornurse(see”breastcancer”below).

Investigations,includingmammography,shouldbecarriedoutinaccordancewithcurrentlyacceptedscreeningpractices,

modifiedtotheclinicalneedsoftheindividual.

Conditionswhichneedsupervision

Ifanyofthefollowingconditionsarepresent,haveoccurredpreviously,and/orhavebeenaggravatedduringpregnancyor

previoushormonetreatment,thepatientshouldbecloselysupervised.Itshouldbetakenintoaccountthattheseconditions

mayrecurorbeaggravatedduringtreatmentwithFematab,inparticular:

Leiomyoma(uterinefibroids)orendometriosis.

Ahistoryof,orriskfactorsfor,thromboembolicdisorders(seebelow).

Riskfactorsforestrogen-dependenttumours,e.g.1 st

degreeheredityforbreastcancer.

Hypertension.

Liverdisorders(e.g.liveradenoma).

Diabetesmellituswithorwithoutvascularinvolvement.

Cholelithiasis.

Migraineor(severe)headache.

Systemiclupuserythematosus.

Ahistoryofendometrialhyperplasia(seebelow).

Epilepsy.

Asthma.

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Reasonsforimmediatewithdrawaloftherapy:

Therapyshouldbediscontinuedincaseswhereacontra-indicationisdiscoveredandinthefollowingsituations:

Jaundiceordeteriorationinliverfunction.

Significantincreaseinbloodpressure.

Newonsetofmigraine-typeheadache.

Pregnancy.

Endometrialhyperplasia

Theriskofendometrialhyperplasiaandcarcinomaisincreasedwhenestrogensareadministeredaloneforprolonged

periods(seesection4.8).Theadditionofaprogestagenforatleast12daysofthecycleinnon-hysterectomisedwomen

greatlyreducesthisrisk.

Fororaldosesofestradiol>2mgandpatches>50µg/daytheendometrialsafetyofaddedprogesteronehasnotbeen

studied.

Break-throughbleedingandspottingmayoccurduringthefirstfewmonthsoftreatment.Ifbreak-throughbleedingor

spottingappearsaftersometimeontherapy,orcontinuesaftertreatmenthasbeendiscontinued,thereasonshouldbe

investigated,whichmayincludeendometrialbiopsytoexcludeendometrialmalignancy.

Unopposedestrogenstimulationmayleadtopremalignantormalignanttransformationintheresidualfociof

endometriosis.Therefore,theadditionofprogestagenstoestrogenreplacementtherapyshouldbeconsideredinwomen

whohaveundergonehysterectomybecauseofendometriosis,iftheyareknowntohaveresidualendometriosis.

BreastCancer

Arandomisedplacebo-controlledtrial,theWomen’sHealthInitiativestudy(WHI)andepidemiologicalstudies,including

theMillionWomenStudy(MWS),havereportedanincreasedriskofbreastcancerinwomentakingestrogens,estrogen-

progestagencombinationsortiboloneforHRTforseveralyears(seeSection4.8).

ForallHRT,anexcessriskbecomesapparentwithinafewyearsofuseandincreaseswithdurationofintakebut

returnstobaselinewithinafew(atmostfive)yearsafterstoppingtreatment.

IntheMWS,therelativeriskofbreastcancerwithconjugatedequineestrogens(CEE)orestradiol(E2)wasgreater

whenaprogestagenwasadded,eithersequentiallyorcontinuously,andregardlessoftypeofprogestagen.Therewas

noevidenceofadifferenceinriskbetweenthedifferentroutesofadministration.

IntheWHIstudy,thecontinuouscombinedconjugatedequineestrogenandmedroxyprogesteroneacetate(CEE+

MPA)productusedwasassociatedwithbreastcancersthatwereslightlylargerinsizeandmorefrequentlyhadlocal

lymphnodemetastasescomparedtoplacebo.

HRT,especiallyestrogen-progestagencombinedtreatment,increasesthedensityofmammographicimageswhichmay

adverselyaffecttheradiologicaldetectionofbreastcancer.

Venousthromboembolism

HRTisassociatedwithahigherrelativeriskofdevelopingvenousthromboembolism(VTE),i.e.deepveinthrombosisor

pulmonaryembolism.Onerandomisedcontrolledtrialandepidemiologicalstudiesfoundatwo-tothreefoldhigherriskfor

userscomparedwithnon-users.Fornon-users,itisestimatedthatthenumberofcasesofVTEthatwilloccurovera5year

periodisabout3per1000womenaged50-59yearsand8per1000womenagedbetween60-69years.Itisestimatedthat

inhealthywomenwhouseHRTfor5years,thenumberofadditionalcasesofVTEovera5yearperiodwillbebetween2

and6(bestestimate=4)per1000womenaged50-59yearsandbetween5and15(bestestimate=9)per1000womenaged

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GenerallyrecognisedriskfactorsforVTEincludeapersonalorfamilyhistoryandsevereobesity(BMI >

kg/m 2

)andsystemiclupuserythematosus(SLE).Thereisnoconsensusaboutthepossibleroleofvaricose

veinsinVTE.

PatientswithahistoryofVTEorknownthrombophilicstateshaveanincreasedriskofVTE.HRTmayadd

tothisrisk.Personalorstrongfamilyhistoryofthromboembolismorrecurrentspontaneousabortionshouldbe

investigatedinordertoexcludeathrombophilicpredisposition.Untilathoroughevaluationofthrombophilic

factorshasbeenmadeoranticoagulanttreatmentinitiated,useofHRTinsuchpatientsshouldbeviewedas

contraindicated.Thosewomenalreadyonanticoagulanttreatmentrequirecarefulconsiderationofthebenefit-

riskofuseofHRT.

TheriskofVTEmaybetemporarilyincreasedwithprolongedimmobilisation,majortraumaormajor

surgery.Asinallpostoperativepatients,scrupulousattentionshouldbegiventoprophylacticmeasuresto

preventVTEfollowingsurgery.Whereprolongedimmobilisationisliabletofollowelectivesurgery,

particularlyabdominalororthopaedicsurgerytothelowerlimbs,considerationshouldbegiventotemporarily

stoppingHRT4to6weeksearlier,ifpossible.Treatmentshouldnotberestarteduntilthewomanis

completelymobilised.

IfVTEdevelopsafterinitiatingtherapy,thedrugshouldbediscontinued.Patientsshouldbetoldtocontact

theirdoctorsimmediatelywhentheyareawareofapotentialthromboembolicsymptom(e.g.painfulswelling

ofaleg,suddenpaininthechest,dyspnea).

Coronaryarterydisease(CAD)

Thereisnoevidencefromrandomisedcontrolledtrialsofcardiovascularbenefitwithcontinuouscombinedconjugated

estrogensandmedroxyprogesteroneacetate(MPA).Twolargeclinicaltrials(WHIandHERSi.e.Heartand

Estrogen/progestinReplacementStudy)showedapossibleincreasedriskofcardiovascularmorbidityinthefirstyearof

useandnooverallbenefit.ForotherHRTproductsthereareonlylimiteddatafromrandomisedcontrolledtrialsexamining

effectsincardiovascularmorbidityormortality.Therefore,itisuncertainwhetherthesefindingsalsoextendtootherHRT

products.

Stroke

Onelargerandomisedclinicaltrial(WHI-trial)found,asasecondaryoutcome,anincreasedriskofischaemicstrokein

healthywomenduringtreatmentwithcontinuouscombinedconjugatedestrogensandMPA.Forwomenwhodonotuse

HRT,itisestimatedthatthenumberofcasesofstrokethatwilloccurovera5yearperiodisabout3per1000womenaged

50-59and11per1000womenaged60-69years.ItisestimatedthatforwomenwhouseconjugatedestrogensandMPA

for5years,thenumberofadditionalcaseswillbebetween0and3(bestestimate=1)per1000usersaged50-59yearsand

between1and9(bestestimate=4)per1000usersaged60-69years.Itisunknownwhethertheincreasedriskalsoextends

tootherHRTproducts.

Ovariancancer

Long-term(atleast5to10years)useofestrogen-onlyHRTproductsinhysterectomisedwomenhasbeenassociatedwith

anincreasedriskofovariancancerinsomeepidemiologicalstudies.Itisuncertainwhetherlongtermuseofcombined

HRTconfersadifferentriskthanestrogen-onlyproducts.

Otherconditions

Estrogensmaycausefluidretention,andthereforepatientswithcardiacorrenaldysfunctionshouldbe

carefullyobserved.Patientswithterminalrenalinsufficiencyshouldbecloselyobserved,sinceitisexpected

thatthelevelofcirculatingactiveingredientsinFematabisincreased.

Womenwithpre-existinghypertriglyceridemiashouldbefollowedcloselyduringestrogenreplacementor

hormonereplacementtherapy,sincerarecasesoflargeincreasesofplasmatriglyceridesleadingtopancreatitis

havebeenreportedwithestrogentherapyinthiscondition.

Estrogensincreasethyroidbindingglobulin(TBG),leadingtoincreasedcirculatingtotalthyroidhormone,as

measuredbyprotein-boundiodine(PBI),T4levels(bycolumnorbyradio-immunoassay)orT3levels(by

radio-immunoassay).T3resinuptakeisdecreased,reflectingtheelevatedTBG.FreeT4andfreeT3

concentrationsareunaltered.Otherbindingproteinsmaybeelevatedinserum,i.e.corticoid-bindingglobulin

(CBG),sexhormone-bindingglobulin(SHBG),leadingtoincreasedcirculatingcorticosteroidsandsex

steroids,respectively.Freeorbiologicallyactivehormoneconcentrationsareunchanged.Otherplasma

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Thereisnoconclusiveevidenceforimprovementofcognitivefunction.Thereissomeevidencefromthe

WHItrialofincreasedriskofprobabledementiainwomenwhostartusingcontinuouscombinedCEEand

MPAaftertheageof65.Itisunknownwhetherthefindingsapplytoyoungerpost-menopausalwomenor

otherHRTproducts.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-

galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Themetabolismofestrogensmaybeincreasedbyconcomitantuseofsubstancesknowntoinducedrug-

metabolisingenzymes,specificallycytochromeP450enzymes,suchasanticonvulsants(eg.phenobarbital,

phenytoin,carbamezapine)andanti-infectives(e.g.rifampicin,rifabutin,nevirapine,efavirenz).

Ritonavirandnelfinavir,althoughknownasstronginhibitors,bycontrastexhibitinducingpropertieswhenused

concomitantlywithsteroidhormones.

HerbalpreparationscontainingStJohn’sWort(Hypericumperforatum)mayinducethemetabolismof

estrogensandprogestagens.

Clinicallyanincreasedmetabolismofestrogensandprogestagensmayleadtodecreasedeffectandchangesin

theuterinebleedingprofile.

4.6Fertility,pregnancyandlactation

Pregnancy

Fematabisnotindicatedduringpregnancy.IfpregnancyoccursduringmedicationwithFematab,treatmentshouldbe

withdrawnimmediately.

Theresultsofmostepidemiologicalstudiestodaterelevanttoinadvertentfoetalexposuretoestrogensindicateno

teratogenicorfoetotoxiceffects.

Lactation:

Fematabisnotindicatedduringlactation.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

Undesirableeffectsreportedinclinicaltrialsandinpostmarketingexperiencearethefollowing:

MedDRAsystem

organclass Common

>1/100,<1/10 Uncommon

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

>1/10,000,<1/1,000 Veryrare<1/10,000

incl.isolatedreports

Infectionsand

infestations Cystitis-like

syndrome,Vaginal

candidiasis

Neoplasmsbenign,

malignantand

unspecified Increaseinsizeof

leiomyoma

Immunesystem

disorders Hypersensitivity

reactions

Bloodandthe

lymphaticsystem

disorders Haemolytic

anaemia

Psychiatric

disorders Depression,

Changeinlibido,

Nervousness

Nervoussystem

disorders Headache,

Migraine Dizziness Chorea

Eyedisorders Intoleranceto

contactlenses,

Steepeningof

cornealcurvature

Cardiacdisorders Myocardial

infarction

Vasculardisorders Hypertension,

Peripheralvascular

disease,

Varicosevein,

Venous

thromboembolism Stroke

Gastrointestinal

disorders Nausea,Abdominal

pain,Flatulence Dyspepsia Vomiting

Hepatobiliary

disorders Gallbladderdisease Alterationsinliver

function,sometimes

withAstheniaor

Malaise,Jaundice

andAbdominalpain

Skinand

subcutaneoustissue

disorders Allergicskin

reactions,Rash,

Urticaria,Pruritus Chloasmaor

melasma,which

maypersistwhen

drugis

discontinued,

Erythema

multiforme,

Erythemanodosum,

Vascularpurpura,

Angioedema

Musculoskeletal

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Changesincarbohydratemetabolismhavebeenreported

BreastCancer

Accordingtoevidencefromalargenumberofepidemiologicalstudiesandonerandomisedplacebo-controlledtrial,the

Women’sHealthInitiative(WHI),theoverallriskofbreastcancerincreaseswithincreasingdurationofHRTusein

currentorrecentHRTusers.

Forestrogen-onlyHRT,estimatesofrelativerisk(RR)fromareanalysisoforiginaldatafrom51epidemiological

studies(inwhich>80%ofHRTusewasestrogen-onlyHRT)andfromtheepidemiologicalMillionWomenStudy

(MWS)aresimilarat1.35(95%CI1.21–1.49)and1.30(95%CI1.21–1.40),respectively.

ForestrogenplusprogestagencombinedHRT,severalepidemiologicalstudieshavereportedanoverallhigherriskfor

breastcancerthanwithestrogensalone.

TheMWSreportedthat,comparedtoneverusers,theuseofvarioustypesofestrogen-progestagencombinedHRTwas

associatedwithahigherriskofbreastcancer(RR=2.00,95%CI:1.88–2.12)thanuseofestrogensalone(RR=1.30,

95%CI:1.21–1.40)oruseoftibolone(RR=1.45;95%CI1.25-1.68).

TheWHItrialreportedariskestimateof1.24(95%CI1.01–1.54)after5.6yearsofuseofestrogen-progestagen

combinedHRT(CEE+MPA)inalluserscomparedwithplacebo.

TheabsoluteriskscalculatedfromtheMWSandtheWHItrialsarepresentedbelow:

TheMWShasestimated,fromtheknownaverageincidenceofbreastcancerindevelopedcountries,that:

ForwomennotusingHRT,about32inevery1000areexpectedtohavebreastcancerdiagnosedbetweenthe

agesof50and64years.

For1000currentorrecentusersofHRT,thenumberofadditionalcasesduringthecorrespondingperiodwill

Forusersofestrogen-onlyreplacementtherapy:

Between0and3(bestestimate=1.5)for5years’use.

Between3and7(bestestimate=5)for10years’use.

ForusersofestrogenplusprogestagencombinedHRT:

Between5and7(bestestimate=6)for5years’use.

Between18and20(bestestimate=19)for10years’use.

TheWHItrialestimatedthatafter5.6yearsoffollow-upofwomenbetweentheagesof50and79years,anadditional

8casesofinvasivebreastcancerwouldbeduetoestrogen-progestagencombinedHRT(CEE+MPA)per10,000

womenyears.

tissuedisorders

Reproductive

systemandbreast

disorders Breast

pain/tenderness,

Breakthrough

bleedingand

spotting,

Pelvicpain Changeincervical

erosion,Changein

cervicalsecretion,

Dysmenorrhoea,

Menorrhagia,

Metrorrhagia Breastenlargement,

Premenstrual-like

symptoms

Congenitaland

familial/genetic

disorders Aggravationof

porphyria

Generaldisorders

andadministration

sitereactions Asthenia Peripheraloedema

Investigations Increase/decreasein

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For1000womenintheplacebogroup:

About16casesofinvasivebreastcancerwouldbediagnosedin5years.

For1000womenwhousedestrogen+progestagencombinedHRT(CEE+MPA),thenumberofadditional

caseswouldbe:

between0and9(bestestimate=4)for5years’use.

ThenumberofadditionalcasesofbreastcancerinwomenwhouseHRTisbroadlysimilarforwomenwhostartHRT

irrespectiveofageatstartofuse(betweentheagesof45-65)(seesection4.4).’

Endometrialcancer

Inwomenwithanintactuterus,theriskofendometrialhyperplasiaandendometrialcancerincreaseswithincreasing

durationofuseofunopposedestrogens.Accordingtodatafromepidemiologicalstudies,thebestestimateoftheriskis

thatforwomennotusingHRT,about5inevery1000areexpectedtohaveendometrialcancerdiagnosedbetweenthe

agesof50and65.Dependingonthedurationoftreatmentandestrogendose,thereportedincreaseinendometrial

cancerriskamongunopposedestrogenusersvariesfrom2-to12-foldgreatercomparedwithnon-users.Addinga

progestagentoestrogen-onlytherapygreatlyreducesthisincreasedrisk.

Otheradversereactionshavebeenreportedinassociationwithestrogen/progestagentreatment:

Estrogen-dependentneoplasmsbenignandmalignant,e.g.endometrialcancer.

Venousthromboembolism,i.e.deeplegorpelvicvenousthrombosisandpulmonaryembolism,ismore

frequentamonghormonereplacementtherapyusersthanamongnon-users.Forfurtherinformation,seesection

4.3Contraindicationsand4.4Specialwarningsandprecautionsforuse.

Probabledementia(seesection4.4).

4.9Overdose

Bothestradiolanddydrogesteronearesubstanceswithlowtoxicity.Theoretically,symptomssuchasnausea,vomiting,

sleepinessanddizzinesscouldoccurincasesofoverdosing.Itisunlikelythatanyspecificorsymptomatictreatment

willbenecessary.Aforementionedinformationisapplicableforoverdosingbychildrenalso.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Naturalandsemisyntheticestrogens,plain.ATCcode:G03CA03

Estradiol

Theactiveingredient,synthetic17-beta-estradiolischemicallyandbiologicallyidenticaltoendogenoushuman

estradiol.Itsubstitutesforthelossofestrogenproductioninmenopausalwomen,andalleviatesmenopausalsymptoms.

Estrogenspreventbonelossfollowingmenopauseorovariectomy.

Combinedtherapywithprogestagensisalsorecommendedinhysterectomisedwomenwithahistoryofendometriosis

ascancerdevelopmentinextra-uterineendometrioticimplantsinwomenonestrogen-onlytherapyhasbeenreported

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Clinicaltrialinformation

Reliefofestrogen-deficiencysymptomsandbleedingpatterns

Reliefofmenopausalsymptomswasachievedduringthefirstfewweeksoftreatment.

RegularwithdrawalbleedinginwomentreatedwithFematab1mgdailyfor28daysandDydrogesterone10mg

dailyforthelast12-14daysofa28daycycle,occurredinapproximately75-80%ofwomenwithamean

durationof5days.Withdrawalbleedingusuallystartedonthedayofthelastpilloftheprogestagenphase.

Break-throughbleedingand/orspottingoccurredinapproximately10%ofthewomen;amenorrhoeaoccurredin

10-25%ofthewomenpercycleduringthefirstyearoftreatment.

InwomentreatedwithFematab2mgdailyfor28daysandDydrogesterone10mgdailyforthelast12-14days

ofa28daycycle,approximately90%ofwomenhadregularwithdrawalbleeding.Thestartdayanddurationof

bleeding,andthenumberofwomenwithintermittentbleedingwasthesameaswithFematab1mg,

amenorrhoea(nobleedingorspotting)occurredin5-15%ofthewomenpercycleduringthefirstyearof

treatment.

Preventionofosteoporosis

Estrogendeficiencyatmenopauseisassociatedwithanincreasingboneturnoveranddeclineinbonemass.The

effectofestrogensonthebonemineraldensityisdose-dependent.Protectionappearstobeeffectiveforaslong

astreatmentiscontinued.AfterdiscontinuationofHRT,bonemassislostataratesimilartothatinuntreated

women.

EvidencefromtheWHItrialandmeta-analysedtrialsshowsthatcurrentuseofHRT,aloneorincombination

withaprogestagen–giventopredominantlyhealthywomen–reducestheriskofhip,vertebral,andother

osteoporoticfractures.HRTmayalsopreventfracturesinwomenwithlowbonedensityand/orestablished

osteoporosis,buttheevidenceforthatislimited.

AftertwoyearsoftreatmentwithFematab1mg,theincreaseinlumbarspinebonemineraldensity(BMD)was

5.2%±3.7%(mean±SD).ThepercentageofwomenwhomaintainedorgainedBMDinlumbarzoneduring

treatmentwas95%.ForFematab2mgtheincreaseinlumbarspineBMDwas6.6%±3.8%(mean±SD),and

thepercentageofwomenwithnochangeoranincreaseinlumbarspineBMDwas95%.

FematabalsohadaneffectonhipBMD.Theincreaseaftertwoyearsoftreatmentwith1mgestradiolwas2.7%

±4.2%(mean±SD)atfemoralneck,3.5%+/-5.0%(mean±SD)attrochanterand2.7%±6.7%(mean±SD)

atWardstriangle,aftertwoyearsoftreatmentwith2mgestradiolthesefigureswhererespectively,2.6%±

5.0%;4.6%±5.0%and4.1%±7.4%.ThepercentageofwomenwhomaintainedorgainedBMDinthe3hip

areasaftertreatmentwith1mgestradiolwas67-78%and71-88%aftertreatmentwith2mgestradiol.

5.2Pharmacokineticproperties

Orallyadministeredestradiol,comprisingparticleswhosesizehasbeenreducedtolessthan5micrometres,isquickly

andefficientlyabsorbedfromthegastrointestinaltract.Theprimaryunconjugatedandconjugatedmetabolitesareestrone

andestronesulphate.Thesemetabolitescancontributetotheestrogeneffect,bothdirectlyandafterconversiontoestradiol.

Estrogensareexcretedinthebileandreabsorbedfromtheintestine.Duringthisenterohepaticcycletheestrogensare

brokendown.Estrogensareexcretedintheurineasbiologicallyinactiveglucuronideandsulphatecompounds(90to

95%),orinthefaeces(5to10%),mostlyunconjugated.Estrogensaresecretedinthemilkofnursingmothers.The

average is28pg/ml,theC

is20pg/mlandtheC

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5.3Preclinicalsafetydata

Supra-physiologicallyhighdoses(prolongedoverdoses)ofestradiolhavebeenassociatedwiththeinductionof

tumoursinestrogen-dependenttargetorgansforallrodentspeciestested.Thechangesobservedwithdydrogesteronein

animaltoxicitystudiesarecharacteristicforprogesterone-likecompounds.In-vitroandin-vivodatagavenoindicationsof

mutageniceffectsofdydrogesterone.Inlong-termstudies,dosesadministeredtoratsandmiceweresufficienttoproduce

hormone-mediatedchanges,butdidnotprovidetumorogenicpotential.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Hypromellose

Maizestarch

Colloidalanhydroussilica

Magnesiumstearate

PurifiedWater

Opadrycoatingcontaining:

Macrogol400

Titaniumdioxide(E171)

Hypromellose

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Thetabletsarepackedinblisterstripsof28.TheblisterstripsaremadeofPVCfilmwithcoveringAluminiumfoil.

Eachcartoncontains28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AbbottHealthcareProductsLtd

MansbridgeRoad

WestEnd

Southampton

SO183JD

Irish Medicines Board

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Date Printed 15/09/2011 CRN 2105452 page number: 10

8MARKETINGAUTHORISATIONNUMBER

PA108/18/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:16April1999

Dateoflastrenewal:16April2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 15/09/2011 CRN 2105452 page number: 11