FEMSEVEN SEQUI

Main information

  • Trade name:
  • FEMSEVEN SEQUI
  • Pharmaceutical form:
  • Transdermal Patch
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FEMSEVEN SEQUI
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0654/010/001
  • Authorization date:
  • 20-04-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0654/010/001

CaseNo:2075955

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

MerckSeronoLimited

BedfontCross,StanwellRoad,Feltham,Middlesex,TW148NX,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

FemSevenSequi50micrograms/10micrograms/24hours,transdermalpatch

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/04/2010until26/09/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FemSevenSequi50micrograms/10micrograms/24hours,transdermalpatch

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Phase1:

Eachpatchcontains1.5mgofestradiolhemihydrateinapatchsizeof15cm 2

,releasing50microgramsofestradiol

per24hours.

Phase2:

Eachpatchcontains1.5mgofestradiolhemihydrateand1.5mgoflevonorgestrelinapatchsizeof15cm 2

,releasing

50microgramsofestradioland10microgramsoflevonorgestrelper24hours.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Transdermalpatch

Octagonal,transparent,flexible,rounded-edgetransdermalmatrixpatchlocatedonanoversizedremovableprotective

liner.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hormonereplacementtherapy(HRT)foroestrogendeficiencysymptomsinpost-menopausalwomen.

Experienceoftreatingwomenolderthan65yearsislimited.

4.2Posologyandmethodofadministration

Fortransdermaluse.

ApplyFemSevenSequionceaweek,i.e.replaceeachpatchevery7days.FemSevenSequiisacontinuoussequential

hormonereplacementtherapy(HRT)withoutatreatment-offphase:asonepatchisremoved,thenextisapplied

immediately.

EachtreatmentcyclewithFemSevenSequiconsistsofthesuccessiveapplicationoftwotransdermalpatches

containingestradiol(phase1)andthentwotransdermalpatchescontainingestradiolandlevonorgestrel(phase2).

Accordingly,thefollowingtreatmentcycleshouldbeobserved:

onephase1patchonceaweekforthefirsttwoweeks

thenonephase2patchonceaweekforthefollowingtwoweeks.

InwomenwhoarenottakingHRTorwomenwhoswitchfromacontinuouscombinedHRTproduct,treatmentmaybe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 2

InwomentransferringfromasequentialHRTregimen,treatmentshouldbeginthedayfollowingcompletionofthe

priorregimen.

Forinitiationandcontinuationoftreatmentofpostmenopausalsymptoms,thelowesteffectivedosefortheshortest

duration(seealsosection4.4)shouldbeused.

Methodofadministration

FemSevenSequishouldbeappliedtoclean,dry,healthyskin(whichisneitherirritatednorgrazed),freefromany

cream,lotionorotheroilyproduct.

FemSevenSequishouldbeappliedtoanareaofskinwithoutmajorskinfolds,e.g.thebuttocksorhips,andnotsubject

tochafingbyclothing(avoidthewaistandalsoavoidwearingtightclothingthatcouldloosenthetransdermalpatch).

FemSevenSequimustnotbeappliedeitheronornearthebreasts.Itisadvisabletoavoidapplyingthepatchtothe

samesitetwice.Atleastoneweekshouldbeallowedtoelapsebetweenapplicationstothesamesite.

Afteropeningthesachet,peeloffone-halfoftheprotectivefoil,beingcarefulnottotouchtheadhesivepartofthe

transdermalpatchwiththefingers.Applydirectlytotheskin.Nowpeelofftheotherhalfoftheprotectivefoiland

pressthepatchonfirmlywiththepalmofthehandforatleast30seconds,concentratingontheedges.Thepressure

andthewarmthofthehandareessentialtoensuremaximaladhesivestrengthofthepatch.

Itispossibletotakeashowerorhaveabathwithoutremovingthetransdermalpatch.

Shouldapatchdetachprematurely,before7days(duetovigorousphysicalactivity,excessivesweating,abnormal

chafingofclothing),itshouldberemovedandanewpatchofthesamephaseapplied.Toaidcomplianceitis

recommendedthepatientthencontinuestochangethepatchontheusualdayandaccordingtotheinitialtreatment

cycle.Thisadvicealsoappliesifapatientforgetstochangethepatchonschedule.Forgettingapatchmayincreasethe

likelihoodofbreak-throughbleedingorspotting.

Onceapplied,thetransdermalpatchshouldnotbeexposedtosunlight.

Removalofthetransdermalpatchshouldbecarriedoutslowlytoavoidirritatingtheskin.Intheeventofsomeofthe

adhesiveremainingontheskin,thiscanusuallyberemovedbygentlyrubbingwithacreamoranoilylotion.

Afteruse,foldFemSevenSequiintwo(withtheadhesivesurfacetotheinside)anddisposeofitwithnormal

householdsolidwaste.

4.3Contraindications

Known,pastorsuspectedbreastcancer;

Knownorsuspectedoestrogen-dependentmalignanttumours(e.g.endometrialcancer);

Undiagnosedgenitalbleeding;

Untreatedendometrialhyperplasia;

Previousidiopathicorcurrentvenousthromboembolism(deepvenousthrombosis,pulmonaryembolism);

Activeorrecentarterialthromboembolicdisease(e.g.angina,myocardialinfarction);

Acuteliverdiseaseorahistoryofliverdiseaseaslongasliverfunctiontestshavefailedtoreturntonormal;

Knownhypersensitivitytotheactivesubstancesortoanyoftheexcipients;

Porphyria.

4.4Specialwarningsandprecautionsforuse

Forthetreatmentofpostmenopausalsymptoms,HRTshouldonlybeinitiatedforsymptomsthatadverselyaffect

qualityoflife.Inallcases,acarefulappraisaloftherisksandbenefitsshouldbeundertakenatleastannuallyandHRT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 3

Medicalexamination/follow-up

BeforeinitiatingorreinstitutingHRT,acompletepersonalandfamilymedicalhistoryshouldbetaken.Physical

(includingpelvicandbreast)examinationshouldbeguidedbythisandbythecontraindicationsandwarningsforuse.

Duringtreatment,periodiccheck-upsarerecommendedofafrequencyandnatureadaptedtotheindividualwoman.

Womenshouldbeadvisedwhatchangesintheirbreastsshouldbereportedtotheirdoctorornurse(see“Breast

cancer”below).Investigations,includingmammography,shouldbecarriedoutinaccordancewithcurrentlyaccepted

screeningpractices,modifiedaccordingtotheclinicalneedsoftheindividual.

Conditionswhichneedsupervision

Ifanyofthefollowingconditionsarepresent,haveoccurredpreviouslyand/orhavebeenaggravatedduringpregnancy

orprevioushormonetreatment,thepatientshouldbecloselysupervised.Itshouldbetakenintoaccountthatthese

conditionsmayrecurorbeaggravatedduringtreatmentwithFemSevenSequi,inparticular:

Leiomyoma(uterinefibroids)orendometriosis

Ahistoryof,orriskfactorsfor,thromboembolicdisorders(seebelow)

Riskfactorsforoestrogendependenttumours,e.g.1 st

degreeheredityforbreastcancer

Hypertension

Liverdisorders(e.g.liveradenoma)

Diabetesmellituswithorwithoutvascularinvolvement

Cholelithiasis

Migraineor(severe)headache

Systemiclupuserythematosus

Ahistoryofendometrialhyperplasia(seebelow)

Epilepsy

Asthma

Otosclerosis.

Reasonsforimmediatewithdrawaloftherapy:

Therapyshouldbediscontinuedifacontra-indicationisdiscoveredandinthefollowingsituations:

Jaundiceordeteriorationinliverfunction

Significantincreaseinbloodpressure

Newonsetofmigraine-typeheadache

Pregnancy.

Endometrialhyperplasia

Theriskofendometrialhyperplasiaandcarcinomaisincreasedwhenoestrogensareadministeredalonefor

prolongedperiods(seesection4.8).Theadditionofaprogestagenforatleast12dayspercycleinnon-

hysterectomisedwomengreatlyreducesthisrisk.

Break-throughbleedingandspottingmayoccurduringthefirstmonthsoftreatment.Ifbreak-throughbleeding

orspottingappearsaftersometimeontherapy,orcontinuesaftertreatmenthasbeendiscontinued,thereason

shouldbeinvestigated,whichmayincludeendometrialbiopsytoexcludeendometrialmalignancy.

Breastcancer

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

includingtheMillionWomenStudy(MWS),havereportedanincreasedriskofbreastcancerinwomentaking

oestrogens,oestrogen-progestagencombinationsortiboloneforHRTforseveralyears(seesection4.8).ForallHRT,

anexcessriskbecomesapparentwithinafewyearsofuseandincreaseswithdurationofintakebutreturnstobaseline

withinafew(atmostfive)yearsafterstoppingtreatment.

IntheMWS,therelativeriskofbreastcancerwithconjugatedequineoestrogens(CEE)orestradiol(E2)wasgreater

whenaprogestagenwasadded,eithersequentiallyorcontinuously,andregardlessoftypeofprogestagen.Therewas

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 4

IntheWHIstudy,thecontinuouscombinedconjugatedequineoestrogenandmedroxyprogesteroneacetate(CEE+

MPA)productusedwasassociatedwithbreastcancersthatwereslightlylargerinsizeandmorefrequentlyhadlocal

lymphnodemetastasescomparedtoplacebo.

HRT,especiallyoestrogen-progestagencombinedtreatment,increasesthedensityofmammographicimageswhich

mayadverselyaffecttheradiologicaldetectionofbreastcancer.

Venousthromboembolism

HRTisassociatedwithahigherrelativeriskofdevelopingvenousthromboembolism(VTE),i.e.deepvein

thrombosisorpulmonaryembolism.Onerandomisedcontrolledtrialandepidemiologicalstudiesfoundatwo-to

threefoldhigherriskforuserscomparedwithnon-users.Fornon-usersitisestimatedthatthenumberofcasesof

VTEthatwilloccurovera5yearperiodisabout3per1000womenaged50-59yearsand8per1000women

agedbetween60-69years.ItisestimatedthatinhealthywomenwhouseHRTfor5yearsthenumberof

additionalcasesofVTEovera5yearperiodwillbebetween2and6(bestestimate=4)per1000womenaged

50-59yearsandbetween5and15(bestestimate=9)per1000womenaged60-69years.Theoccurrenceofsuch

aneventismorelikelyinthefirstyearofHRTthanlater.

GenerallyrecognizedriskfactorsforVTEincludeapersonalhistoryorfamilyhistory,severeobesity(BMI>30

kg/m 2

)andsystemiclupuserythematosus(SLE).Thereisnoconsensusaboutthepossibleroleofvaricoseveins

inVTE.

PatientswithahistoryofVTEorknownthrombophilicstateshaveanincreasedriskofVTE.HRTmayaddto

thisrisk.Personalorstrongfamilyhistoryofthromboembolismorrecurrentspontaneousabortionshouldbe

investigatedinordertoexcludeathrombophilicpredisposition.Untilathoroughevaluationofthrombophilic

factorshasbeenmadeoranticoagulanttreatmentinitiated,useofHRTinsuchpatientsshouldbeviewedas

contra-indicated.Thosewomenalreadyonanticoagulanttreatmentrequirecarefulconsiderationofthebenefit-

riskofuseofHRT.

TheriskofVTEmaybetemporarilyincreasedwithprolongedimmobilisation,majortraumaormajorsurgery.

Asinallpostoperativepatients,scrupulousattentionshouldbegiventoprophylacticmeasurestopreventVTE

followingsurgery.Whereprolongedimmobilisationisliabletofollowelectivesurgery,particularlyabdominalor

orthopaedicsurgerytothelowerlimbs,considerationshouldbegiventotemporarilystoppingHRTfourtosix

weeksearlier,ifpossible.Treatmentshouldnotberestarteduntilthewomaniscompletelymobilised.

IfVTEdevelopsafterinitiatingtherapy,thedrugshouldbediscontinued.

Patientsshouldbetoldtocontacttheirdoctorsimmediatelywhentheyareawareofapotentialthromboembolic

symptom(e.g.painfulswellingofaleg,suddenpaininthechest,dyspnea).

Coronaryarterydisease(CAD)

Thereisnoevidencefromrandomisedcontrolledtrialsofcardiovascularbenefitwithcontinuouscombinedconjugated

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

Estrogen/progestinReplacementStudy)showedapossibleincreasedriskofcardiovascularmorbidityinthefirstyear

ofuseandnooverallbenefit.ForotherHRTproductsthereareonlylimiteddatafromrandomisedcontrolledtrials

examiningeffectsincardiovascularmorbidityormortality.Therefore,itisuncertainwhetherthesefindingsalso

extendtootherHRTproducts.

Stroke

Onelargerandomisedclinicaltrial(WHI-trial)found,asasecondaryoutcome,anincreasedriskofischaemicstrokein

healthywomenduringtreatmentwithcontinuouscombinedconjugatedoestrogensandMPA.Forwomenwhodonot

useHRT,itisestimatedthatthenumberofcasesofstrokethatwilloccurovera5yearperiodisabout3per1000

womenaged50-59yearsand11per1000womenaged60-69years.Itisestimatedthatforwomenwhouseconjugated

oestrogensandMPAfor5years,thenumberofadditionalcaseswillbebetween0and3(bestestimate=1)per1000

usersaged50-59yearsandbetween1and9(bestestimate=4)per1000usersaged60-69years.Itisunknown

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 5

Ovariancancer

Long-term(atleast5-10years)useofoestrogen-onlyHRTproductsinhysterectomisedwomenhasbeenassociated

withanincreasedriskofovariancancerinsomeepidemiologicalstudies.Itisuncertainwhetherlong-termuseof

combinedHRTconfersadifferentriskthanoestrogen-onlyproducts.

Otherconditions

Oestrogensmaycausefluidretention,andthereforepatientswithcardiacorrenaldysfunctionshouldbecarefully

observed.Patientswithterminalrenalinsufficiencyshouldbecloselyobserved,sinceitisexpectedthatthelevelof

circulatingactiveingredientsinFemSevenSequitransdermalpatchisincreased.

Womenwithpre-existinghypertriglyceridemiashouldbefollowedcloselyduringoestrogenreplacementorhormone

replacementtherapy,sincerarecasesoflargeincreasesofplasmatriglyceridesleadingtopancreatitishavebeen

reportedwithoestrogentherapyinthiscondition.

Oestrogensincreasethyroidbindingglobulin(TBG),leadingtoincreasedcirculatingtotalthyroidhormone,as

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

immunoassay).T3resinuptakeisdecreased,reflectingtheelevatedTBG.FreeT4andfreeT3concentrationsare

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

bindingglobulin(SHBG)leadingtoincreasedcirculatingcorticosteroidsandsexsteroids,respectively.Freeor

biologicalactivehormoneconcentrationsareunchanged.Otherplasmaproteinsmaybeincreased

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

Thereisnoconclusiveevidenceforimprovementofcognitivefunction.ThereissomeevidencefromtheWHItrialof

increasedriskofprobabledementiainwomenwhostartusingcontinuouscombinedCEEandMPAaftertheageof65.

Itisunknownwhetherthefindingsapplytoyoungerpost-menopausalwomenorotherHRTproducts.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Themetabolismofoestrogensandprogestagensmaybeincreasedbyconcomitantuseofsubstancesknowntoinduce

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

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

Ritonavirandnelfinavir,althoughknownasstronginhibitors,bycontrastexhibitinducingpropertieswhenused

concomitantlywithsteroidhormones.

HerbalpreparationscontainingStJohn'swort(HypericumPerforatum)mayinducethemetabolismofoestrogensand

progestagens.

Attransdermaladministration,thefirst-passeffectintheliverisavoidedand,thus,transdermallyappliedoestrogens

andprogestagensmightbelessaffectedthanoralhormonesbyenzymeinducers.

Clinically,anincreasedmetabolismofoestrogensandprogestagensmayleadtodecreasedeffectandchangesinthe

uterinebleedingprofile.

4.6Pregnancyandlactation

Pregnancy:

FemSevenSequiisnotindicatedduringpregnancy.IfpregnancyoccursduringmedicationwithFemSevenSequi,

treatmentshouldbewithdrawnimmediately.

Clinically,dataonalargenumberofexposedpregnanciesindicatenoadverseeffectsoflevonorgestrelonthefoetus.

Theresultsofmostepidemiologicalstudiestodaterelevanttoinadvertentfoetalexposuretocombinationsof

oestrogensandprogestagensindicatenoteratogenicorfoetotoxiceffects.

Lactation:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 6

4.7Effectsonabilitytodriveandusemachines

Noeffectsonabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

Themostfrequentlyreportedundesirableeffects(>10%)inclinicaltrialsduringtreatmentwithFemSevenSequiwere

applicationsitereactions.Theyusuallydisappeared2–3daysafterpatchremoval.

Otherpotentialsystemicundesirableeffectsarethosecommonlyobservedwithoestrogenandprogestintreatments.

Breastcancer

Accordingtoevidencefromalargenumberofepidemiologicalstudiesandonerandomisedplacebo-controlledtrial,the

Women’sHealthInitiative(WHI),theoverallriskofbreastcancerincreaseswithincreasingdurationofHRTusein

currentorrecentHRTusers.

Foroestrogen-onlyHRT,estimatesofrelativerisk(RR)fromareanalysisoforiginaldatafrom51epidemiological

studies(inwhich>80%ofHRTusewasoestrogen-onlyHRT)andfromtheepidemiologicalMillionWomenStudy

(MWS)aresimilarat1.35(95%CI:1.21–1.49)and1.30(95%CI:1.21–1.40),respectively.

ForoestrogenplusprogestagencombinedHRT,severalepidemiologicalstudieshavereportedanoverallhigherrisk

forbreastcancerthanwithoestrogensalone.

TheMWSreportedthat,comparedtoneverusers,theuseofvarioustypesofoestrogen-progestagencombinedHRT

wasassociatedwithahigherriskofbreastcancer(RR=2.00,95%CI:1.88–2.12)thanusewithoestrogensalone(RR

=1.30,95%CI:1.21–1.40)oruseoftibolone(RR=1.45,95%CI:1.25–1.68).

TheWHItrialreportedariskestimateof1.24(95%CI:1.01–1.54)after5.6yearsofuseofoestrogen-progestagen

combinedHRT(CEE+MPA)inalluserscomparedwithplacebo.

TheabsoluteriskscalculatedfromtheMWSandtheWHItrialarepresentedbelow:

TheMWShasestimated,fromtheknownaverageincidenceofbreastcancerindevelopedcountriesthat:

ForwomennotusingHRT,about32inevery1000areexpectedtohavebreastcancerdiagnosedbetweenthe

agesof50and64years.

For1000currentorrecentusersofHRT,thenumberofadditionalcasesduringthecorrespondingperiodwillbe:

Forusersofoestrogens-onlyreplacementtherapy

between0and3(bestestimate=1.5)for5years’use

between3and7(bestestimate=5)for10years’use.

ForusersofoestrogenplusprogestagencombinedHRT,

between5and7(bestestimate=6)for5years’use

Organsystem CommonADRs

>1/100,<1/10 UncommonADRs

>1/1000,<1/100 RareADRs

>1/10.000,<1/1000

Bodyasawhole Headache,

Mastodynia Fluid

retention/oedema/weight

increase/loss,fatigue,

dizziness,legcramps,

migraine

Gastrointestinal Nausea,

Vomiting Bloating,abdominalcramps Cholelithiasis,cholestatic

jaundice

Cardio-vascular Hypertension

Reproductive Breakthrough

bleeding,spotting Dysmenorrhoea,

endometrial

hyperplasia,

benignbreasttumours Increaseinsizeofuterine

fibrosis

Psychiatric Increase/

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 7

TheWHItrialestimatedthatafter5.6yearsoffollow-upofwomenbetweentheagesof50and79years,anadditional

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

womenyears.

Accordingtocalculationsfromthetrialdata,itisestimatedthat:

For1000womenintheplacebogroup,

about16casesofinvasivebreastcancerwouldbediagnosedin5years.

For1000womenwhousedoestrogen+progestagencombinedHRT(CEE+MPA),thenumberofadditional

caseswouldbe

between0and9(bestestimate=4)for5years’use.

ThenumberofadditionalcasesofbreastcancerinwomenwhouseHRTisbroadlysimilarforwomenwhostartHRT

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

Endometrialcancer

Inwomenwithanintactuterus,theriskofendometrialhyperplasiaandendometrialcancerincreaseswithincreasing

durationofuseofunopposedoestrogens.Accordingtodatafromepidemiologicalstudies,thebestestimateoftherisk

isthatforwomennotusingHRT,about5inevery1000areexpectedtohaveendometrialcancerdiagnosedbetween

theagesof50and65.Dependingonthedurationoftreatmentandoestrogendose,thereportedincreaseinendometrial

cancerriskamongunopposedoestrogenusersvariesfrom2-to12-foldgreatercomparedwithnon-users.Addinga

progestagentooestrogen-onlytherapygreatlyreducesthisincreasedrisk.

Otheradversereactionshavebeenreportedinassociationwithoestrogen/progestagentreatment:

Oestrogen-dependentneoplasmsbenignandmalignant:e.g.endometrialcancer.

Venousthromboembolism,i.e.deeplegorpelvicvenousthrombosisandpulmonaryembolism,ismore

frequentamonghormonereplacementtherapyusersthanamongnon-users.Forfurtherinformationseesections

4.3Contraindicationsand4.4Specialwarningsandprecautionsforuse.

Myocardialinfarctionandstroke.

Gallbladderdisease.

Skinandsubcutaneousdisorders:chloasma,erythemamultiforme,erythemanodosum,vascularpurpura.

Probabledementia(seesection4.4).

4.9Overdose

Themodeofadministrationmakessignificantoverdoseunlikely.Signsofanoverdosearegenerallybreasttenderness,

swellingoftheabdomen/pelvis,anxiety,irritability,nauseaandvomiting.Removalofthetransdermalpatchesisall

thatisrequiredshoulditoccur.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

Progestogensandoestrogensforsequentialadministration

ATCcode:G03FB09

Transdermalroute.

Estradiol:theactiveingredient,synthetic17-estradiolischemicallyandbiologicallyidenticaltoendogenoushuman

estradiol.Itsubstitutesforthelossofoestrogenproductioninpostmenopausalwomen,andalleviatesmenopausal

symptoms.

Levonorgestrel:asoestrogenspromotethegrowthoftheendometrium,unopposedoestrogensincreasetheriskof

endometrialhyperplasiaandcancer.Theadditionoflevonorgestrel,asyntheticprogestin,greatlyreducesthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 8

UndertreatmentwithFemSevenSequi,reliefofmenopausalsymptomswasachievedduringthefirstweeksof

treatment.

Attheendofoneyeartreatment,82.7%ofwomenwithbleedingreportedregularwithdrawalbleeding.Thedayof

onsetwasratherconstant1-2daysbeforetheendofthecyclewithameandurationof4-5days.Thepercentageof

womenwithbreakthroughbleedingand/orspottingwas17.3%.Duringthe13cyclesoftherapy,19.4%ofwomen

treatedpresentedwithamenorrhoea.

5.2Pharmacokineticproperties

Withtransdermaladministrationthereisnohepaticfirst-passeffectasobservedwithoraladministration;estradiol

reachesthebloodstreaminunchangedformandinphysiologicalamounts.Therapeuticestradiolconcentrationsare

comparabletothoseobservedinthefollicularphase.

Afterapplicationofthetransdermalsystemcontainingestradiolalone(phase1),therapeuticconcentrationsofestradiol

areachievedwithin4hours;theseconcentrationsaremaintainedthroughouttheentireapplicationperiodofthe

transdermalpatch(7days).Whenestradiolisadministeredsimultaneouslywithlevonorgestrel(phase2),the

pharmacokineticsofestradiolareunalteredbylevonorgestrel.

Peakplasmaconcentrationsofestradiol(C

)rangefrom58to71pg/ml,averageplasmaconcentration(C

)is

between29to33pg/mlandtroughplasmaconcentration(C

)isabout21pg/mlduringbothtreatmentphases.After

removalofthetransdermalpatch,estradiolconcentrationsreturntotheirbaselinevalueswithin12to24hours.

Afterapplicationofthetransdermalsystemcontainingestradiolandlevonorgestrelatadoseof10µg/day(phase2),

themaximumplasmaconcentrationoflevonorgestrel(C

)rangefrom156to189pg/mlandisreachedwithin63to

91hours(t

).Theaverageplasmaconcentrationoflevonorgestrel(C

)duringa7-dayperiodisbetween121and

156pg/mlandthetroughplasmaconcentration(C

)levelsare118pg/ml.Thehalf-lifeoflevonorgestrelafter

transdermalapplicationisapproximately28hours(minimum:16hours,maximum:42hours).

Afterpercutaneousabsorption,levonorgestrelisboundtoplasmaproteins,i.e.albumin(50%),andSHBG(47.5%).

AffinitytoSHBGishigherthanforothercommonlyusedprogestogens.

5.3Preclinicalsafetydata

Animalstudieswithestradiolandlevonorgestrelhaveshownexpectedestrogenicandgestageniceffects.

Therearenopreclinicaldataofrelevancetotheprescriberthatareadditionaltothosealreadyincludedinother

sectionsoftheSPC(seenotablysection4.6).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

6.2Incompatibilities

Notapplicable. Backinglayer Transparentpolyethyleneterephthalate(PET)foil

Adhesivematrix: Styrene-isoprene-styreneblockcopolymer,glycerineestersof

completelyhydrogenatedresins

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 9

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

Eachphase1orphase2transdermalpatchiscontainedinanindividualsachet(Paper/PE/aluminium/ethylene

copolymer).Eachcartoncontains4or12sachetsconsistingof2xphase1patchesand2xphase2patchesor6x

phase1patchesand6xphase2patches.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

See4.2Posologyandmethodofadministration.

7MARKETINGAUTHORISATIONHOLDER

MerckSeronoLtd

BedfontCross

StanwellRoad

Feltham

Middlesex

TW148NX

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA654/10/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:20April2001

Dateoflastrenewal:27September2005

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/04/2010 CRN 2075955 page number: 10