ESTELLE

Main information

  • Trade name:
  • ESTELLE Tablets 75/ 30 Milligram
  • Dosage:
  • 75/ 30 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ESTELLE Tablets 75/30 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/170/002
  • Authorization date:
  • 21-09-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0126/170/002

CaseNo:2077080

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ClonmelHealthcareLimited

WaterfordRoad,Clonmel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Estelle30micrograms/75microgramsCoatedTablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom30/06/2010until20/09/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 30/06/2010 CRN 2077080 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Estelle30micrograms/75microgramsCoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains30microgramsethinylestradioland75microgramsgestodene.

Excipients:

contains38mglactosemonohydrateand20mgsucrose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Coatedtablet.

White,round,biconvexsugarcoatedtablets,bothsidesarewithoutimprinting.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Oralcontraception.

4.2Posologyandmethodofadministration

HowtotakeEstelle:

Thetabletsshouldbetakenintheorderindicatedonthepackage,everydayatapproximatelythesametime.Onetablet

perdayshouldbetakenfor21days.Eachsubsequentpackshouldbestartedaftera7-daytablet-freeintervalduring

whichtimeawithdrawalbleedingwilloccur.Thisbleedingusuallystartsonthe2 nd

or3 rd

dayaftertakingthelast

tablet,andmaynotstopuntilthenextpackisstarted.

HowtostarttakingEstelle:

Ifnoprecedinghormonalcontraceptiveuseinthepastmonth:

Takingofthetabletsshouldbeginonthefirstdayofthewoman’snaturalcycle(i.e.onthefirstdayofthewoman’s

menstrualbleeding).Onemaybegintakingthepillsonday2–5,butinthesecases,itisrecommendedthatabarrier

methodalsobeusedforthefirst7daysonwhichpillsaretakenduringthefirstcycle.

Whenreplacinganothercontraceptivepillofthecombinationtype:

ThewomanshouldstarttakingEstelleonthenextdayaftertakingthelastactivetabletinherpreviouspackageof

contraceptivepills–butnolaterthanthedayaftertheusualtablet-freeorplacebo-tabletperiodofherprevious

contraceptivepill.

Whenchangingfromprogestogen-onlypreparations(progestogen-onlypills,injection,implant,orfromaprogestogen-

releasingintrauterinesystem(IUS)):

Thewomanmaychangefromprogestogen-onlypills(POPs)onanyday.Thefirsttabletshouldbetakenontheday

afteranytabletofthePOPpackage.WhenchangingfromanimplantortheIUS,Estelleshouldbestartedontheday

theimplantisremoved.Whenchangingfrominjections,Estelleshouldbestartedwhenthenextinjectionisduetobe

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Afteranabortioninthefirsttrimester:

Thewomanmaystarttakingthepillsimmediately.Ifshedoesso,nofurthercontraceptivestepsneedbetaken.

Afterdeliveryorabortioninthesecondtrimester:

Forbreastfeedingwomen–seesection4.6.

Thewomanshouldbeadvisedtobegintakingthetabletsonday21–28afterdeliveryinnon-lactatingwomenorafter

abortioninthesecondtrimester.Ifshestartslater,sheshouldbeadvisedtoalsouseabarriermethodduringthefirst7

daysoftakingthepills.Ifshehasalreadyhadintercourse,thepossibilityofpregnancyshouldbeexcludedbeforeshe

beginstakingthepills,orsheshouldwaitforherfirstmenstruation.

Missedtablets:

Missingatabletforlessthan12hoursdoesnotdiminishthecontraceptiveprotection.Thewomanshouldtakethe

tabletassoonassheremembers,andcontinuetakingtherestofthetabletsasusual.

Missingatabletformorethan12hourscandiminishthecontraceptiveprotection.Thetwofollowingrulesmaybe

helpfulindealingwithmissedtablets.

1.Takingofthetabletsshouldneverbediscontinuedforlongerthan7days.

2.Ittakes7daysofuninterruptedingestionofthetabletstoachievesufficientsuppressionofthehypothalamus-

pituitary-ovarianaxis.

Thus,thefollowingadvicecanbegivenindailypractice:

Week1:

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeansthatsheneedstotake2tablets

atthesametime.Fromthenon,sheshouldcontinuetotakethetabletsattheusualtime.Atthesametime,sheshould

useabarriermethod,i.e.acondom,forthenext7days.Ifshehadintercourseduringthepast7days,sheshould

considerthepossibilitythatshemightbepregnant.Themoretabletshavebeenmissed,andthecloserthishappenedto

themonthlytablet-freeperiod,thehighertheriskofpregnancy.

Week2:

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeansthatsheneedstotake2tablets

atthesametime.Fromthenon,sheshouldcontinuetotakethetabletsattheusualtime.Ifthetabletshavebeentaken

correctlyforthe7dayspriortothemissedtablet,itisnotnecessarytotakeanyadditionalcontraceptiveprecautions.If

thisisnotthecase,however,orifmorethan1tablethasbeenmissed,thewomanshoulduseabarriermethod,i.e.a

condomforthenext7days.

Week3:

Theriskofreducedprotectionisimminentbecauseoftheapproachingtablet-freeperiod.Thereducedcontraceptive

protectioncanbeprevented,however,byadjustingtheintakeofthetablets.Byadheringtoeitherofthefollowingtwo

options,itis,therefore,notnecessarytotakeanyadditionalcontraceptiveprecautions,providedthatthetabletshave

beentakencorrectlyforthe7dayspriortothemissedtablet.Ifthisisnotthecase,thewomanshouldbeadvisedto

followthefirstofthetwochoices,andatthesametimeuseabarriermethod,i.e.acondomforthenext7days.

1.Theusershouldtakethelastmissedtabletassoonassheremembersevenifthismeansthatsheneedstotake2

tabletsatthesametime.Fromthenon,sheshouldcontinuetotakethetabletsattheusualtime.Shebeginsthenext

packimmediatelyaftershetookthelasttabletfromthecurrentpackage;thatmeansnopausebetweenpackages.

Theuserwillprobablynotgethermenstruationbeforetheendofthesecondpackage,butshemayexperience

spottingorwithdrawalbleedingonthedayswhenshetakesthetablets.

2.Thewomancanalsobeadvisedtostoptakingtabletsfromthecurrentpackage.Inthatcase,sheshouldhavea

tablet-freeperiodforupto7days,includingthedayswhenshemissedthetablets,andsubsequentlycontinuewith

thenextpack.

Ifthewomanmissedthetablets,andsubsequentlydidnotgethermenstruationinthefirstnormaltablet-freeperiod,

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Whattodoincaseofvomiting/diarrhoea:

Ifvomitingoccurswithin3–4hoursaftertablettaking,absorptionmaynotbecomplete.Inthiscase,theadvice

concerningmissedtablets,describedaboveshouldbefollowed.Unlessdiarrhoeaisextremelysevereitdoesnotaffect

theabsorptionofcombinedoralcontraceptivesandthereforeuseofadditionalcontraceptionisnotnecessary.Ifsevere

diarrhoeacontinuesfor2ormoredays,theproceduresformissedpillsshouldbefollowed.Ifthewomandoesnotwant

tochangeherusualtabletintake,sheshouldtakeanextratablet(s)fromanotherblisterpack.

Howtoadvanceordelaymenstruation:

Todelaymenstruation,thewomanshouldcontinuewithanotherpackofEstellewithoutatablet-freeperiod.

Menstruationcanbedelayedaslongasisdesireduptotheendofthesecondpackage,butnolonger.While

menstruationisbeingdelayed,thewomanmayexperiencewithdrawalbleedingorspotting.RegularintakeofEstelle

shouldberesumedafterthenormaltablet-freeperiodof7days.

Tomovemenstruationtoanotherdayoftheweekthanthewomanisusedtowithhercurrenttabletschedule,shecan

beadvisedtoshortenthenexttablet-freeperiodbyasmanydaysasshewishes.Theshortertheinterval,thehigherthe

riskthatshewillnotgethermenstruationandwillhavebreakthroughbleedingorspottingwhilesheistakingthenext

pack(justaswhenmenstruationisbeingdelayed).

4.3Contraindications

Combinedoralcontraceptives(COCs)mustnotbeusedinthepresenceoftheconditionsmentionedbelow.Ifsucha

conditionshouldoccurforthefirsttimeduringuseofCOCs,theusemustbediscontinuedimmediately:

Venousthromboembolismpresentorinhistory(deepvenousthrombosis,pulmonaryembolism)withorwithout

riskfactors(seesection4.4)

Arterialthromboembolismpresentorinhistory(myocardialinfarction,cerebrovasculardisorder),orprodomal

conditions(anginapectorisandtransientischaemicattack)(seesection4.4)

Hereditaryoracquiredpredispositionforvenousorarterialthrombosis,suchasantithrombindeficiency,proteinC

deficiency,proteinSdeficiency,APC-resistance,antiphospholipidantibodies(anticardiolipin-antibodies,lupus

anticoagulant),hyperhomocysteinemia

Considerableormultipleriskfactorsforarterialthrombosis(seesection4.4)

Severehypertension

Diabetes,complicatedwithmicroormacroangiopathy

Severedyslipoproteinaemia

Knownorsuspectedsex-steroidinfluencedmalignancies(e.g.ofthegenitalorgansorthebreast)

Presenceorhistoryofseverehepaticdisorders,aslongasliverfunctiontestsarenotnormalised

Presenceorhistoryofbenignormalignantlivertumours

Undiagnosedvaginalbleeding

Migrainewithfocalneurologicalsymptoms

Hypersensitivitytotheactivesubstancesortoanyoftheexcipients

4.4Specialwarningsandprecautionsforuse

Assessmentandexaminationpriortostartingcombinedoralcontraceptives:

Beforethestartorresumptionoftreatmentwithcombinedoralcontraceptives,acompletepersonalandfamilymedical

historymustbeobtainedandpregnancyshouldberuledout.Bloodpressureshouldbemeasuredandaphysical

examinationperformedifclinicallyindicated,guidedbythecontraindications(seesection4.3)andwarnings(see

“Warnings”inthissection).Thewomanshouldbeinstructedtocarefullyreadtheuserleafletandadheretotheadvice

given.Thefrequencyandnatureoffurtherperiodicchecksshouldbebasedonestablishedpracticeguidelinesand

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Warnings:

General:

WomenshouldbeadvisedthatCOCsdonotprotectagainstHIV(AIDS)orothersexuallytransmittedinfections(STI).

Ifanyoftheriskfactorsbelowispresentinanyindividualwoman,thebenefitsofcombinedoralcontraceptionmustbe

weighedagainstpossiblerisksineachindividualcaseanddiscussedwiththewomanbeforecombinedoral

contraceptioniscommenced.Intheeventofaggravation,exacerbationorfirstappearanceofanyoftheseconditionsor

riskfactorsthewomanshouldbeadvisedtocontactherphysician.Thephysicianmustthendecide,whethertheuseof

COCsshouldbediscontinued.

1.Circulatorydisorders:

TheuseofanyCOCcarriesanincreasedriskofvenousthromboembolism(VTE)compared

withnouse.TheexcessriskofVTEishighestduringthefirstyearawomaneverusesaCOC.Thisincreasedriskis

lessthantheriskofVTEassociatedwithpregnancy,whichisestimatedas60casesper100,000pregnancies.VTEis

fatalin1–2%ofcases.

Inseveralepidemiologicalstudiesithasbeenfoundthatwomenusingcombinedoralcontraceptiveswith

ethinylestradiol,mostlywithadoseof30mg,andaprogestinsuchasgestodenehaveanincreasedriskofVTE

comparedwiththosewhoareusingcombinedoralcontraceptivescontaininglessthan50 µ gethinylestradiolandthe

progestinlevonorgestrel.

Forcombinedoralcontraceptivescontaining30 µ gofethinylestradiolcombinedwithdesogestrelorgestodene

comparedwiththosecontaininglessthan50 µ gofethinylestradiolandlevonorgestrel,theoverallrelativeriskofVTE

hasbeenestimatedtorangebetween1.5and2.0.TheincidenceofVTEforlevonorgestrelcontainingcombinedoral

contraceptiveswithlessthan50 µ gofethinylestradiolisapproximately20casesper100,000women-yearsofuse.For

Estelletheincidenceisapproximately30–40casesper100,000women-yearsofuse,i.e.additional10–20casesper

100,000women-yearsofuse.Theimpactoftherelativeriskonthenumberofadditionalcaseswouldbethegreatestin

womenduringthefirstyeartheyeveruseacombinedoralcontraceptivewhentheriskforVTEwithallcombinedoral

contraceptivesishighest.

Thrombosisinotherbloodvesselshasveryrarelybeenreported,i.e.hepatic,mesenteric,renalorretinalveinsand

arteries,inusersoforalcontraceptives.Thereisnoconsensus,whethertheoccurrenceofthesecasesisrelatedtouseof

COCs.

Theriskfordevelopmentofvenousthromboembolismincreaseswith:

Increasingage.

Apositivefamilyhistory(e.g.venousthromboembolisminsiblingsorparentsatarelativelyyoungage).Inthe

caseofsuspectedhereditarypredisposition,thewomanshouldbereferredtoaspecialistbeforeshedecidestouse

oralcontraception.

Obesity(bodymassindexabove30kg/m²).

Prolongedimmobilisation,majorsurgery,surgeryonthelegsormajortrauma.Insuchcases,itisrecommended

thattreatmentwithoralcontraceptivesbediscontinued(inthecaseofelectivesurgeryatleast4weekspriortothe

operation)andshouldnotberesumeduntil2weeksaftercompleteremobilisation.

Thereisnoconsensusconcerningthepossibleroleofvaricoseveinsandsuperficialthrombophlebitisinvenous

thromboembolism.

TheuseofCOCsingeneralhasbeenassociatedwithanincreasedriskofacutemyocardialinfarction(AMI)orstroke,

ariskthatisstronglyinfluencedbythepresenceofotherriskfactors(e.g.smoking,highbloodpressure,andage)(see

alsobelow).Theseeventsoccurrarely.

Theriskofarterialthromboemboliceventsincreaseswith:

increasingage;

smoking(withheaviersmokingandincreasingagetheriskfurtherincreases,especiallyinwomenover35yearsof

age);

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obesity(bodymassindexover30kg/m 2

hypertension;

valvularheartdisease;

atrialfibrillation;

apositivefamilyhistory(i.e.arterialthrombosiseverinasiblingorparentatarelativelyearlyage).Ifahereditary

predispositionissuspected,thewomanshouldbereferredtoaspecialistforadvicebeforedecidingaboutany

hormonalcontraceptiveuse.

Symptomsofvenousorarterialthrombosiscaninclude:

unilaterallegpainand/orswelling;

suddenseverepaininthechest,whetherornotitradiatestotheleftarm;

suddenbreathlessness;

suddenonsetofcoughing;

anyunusual,severe,prolongedheadache;

suddenpartialorcompletelossofvision;

diplopia;

slurredspeechoraphasia;

vertigo;

collapsewithorwithoutfocalseizure;

weaknessorverymarkednumbnesssuddenlyaffectingonesideoronepartofthebody;

motordisturbances;

‘acute’abdomen.

Theincreasedriskofvenousthromboembolismduringthepuerperalperiodshouldbetakenintoconsideration.

Othermedicalconditionswhichhavebeenrelatedtocirculatorydisordersincludediabetesmellitus,systemiclupus

erythematosus,haemolyticuraemicsyndrome,chronicinflammatoryboweldisease(Crohn’sdiseaseorcolitis

ulcerosa)andsicklecellanaemia.

Anincreaseinthefrequencyorseverityofmigraine(whichmaybeprodromalforacerebrovascularcondition)during

useoforalcontraceptivesmustleadtoconsiderationofimmediatediscontinuationoforalcontraceptives.

Biochemicalfactorsindicatinghereditaryoracquiredpredispositionforvenousorarterialthrombosis,includeactivated

proteinC(APC)resistance,factorVLeidenmutation,hyperhomocysteinaemia,antithrombinIIIdeficiency,proteinC

deficiency,proteinSdeficiency,antiphospholipidantibodies(anticardiolipinantibodies,lupusanticoagulant).

Whenconsideringrisk/benefit,thephysicianshouldtakeintoaccountthatadequatetreatmentofaconditionmay

reducetheassociatedriskofthrombosisandthattheriskassociatedwithpregnancyishigherthanthatassociatedwith

COCuse.

2.Tumours:

Cervicalcancer:

InsomeepidemiologicalstudiesanincreasedriskofcervicalcancerhasbeenreportedinlongtermusersofCOCs,but

itisstillnotcleartowhichextentthisfindingmaybeinfluencedbyimpactsofsexualbehaviourandotherfactors,such

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Breastcancer:

Ametaanalysisfrom54epidemiologicalstudiesreportedthatthereisaslightlyincreasedrelativerisk(RR=1.24)of

havingbreastcancerdiagnosedinwomenwhoarecurrentlyusingCOCs.Theexcessriskgraduallydisappearsduring

thecourseofthe10yearsaftercessationofCOCuse.Becausebreastcancerisrareinwomenbelow40yearsofage,

theexcessnumberofbreastcancerdiagnosesincurrentandrecentusersofCOCissmallinrelationtotheoverallrisk

ofbreastcancer.

Thesestudiesdonotprovideevidenceforcausation.Theobservedpatternofincreasedriskmaybeduetoanearlier

diagnosisofbreastcancerinCOCusers,thebiologicaleffectsofCOCsoracombinationofboth.Thebreastcancers

diagnosedineveruserstendtobelessadvancedclinicallythanthecancerdiagnosedinneverusers.

Livertumours:

BenignandmalignantlivertumourshavebeenreportedinusersofCOCs.Thesetumourshave,inisolatedcases,lead

tolifethreatening,intra-abdominalhaemorrhage.Alivertumourmustbetakenintoconsiderationasadifferential

diagnosiswhenseverepainoccursintheupperabdomen,ifthereishepatomegaly,oriftherearesignsofintra-

abdominalhaemorrhageinwomentakingCOCs.

3.Otherconditions:

Womenwithhypertriglyceridaemia,orafamilyhistorythereof,maybeatincreasedriskofpancreatitiswhentaking

COCs.

Inthecaseofacuteorchronicimpairmentofliverfunction,theuseofEstelleshouldbestoppeduntilliverfunction

testshavereturnedtonormal.Steroidhormonesmaybepoorlymetabolisedinpatientswithimpairedliverfunction.

EventhoughslightincreasesinbloodpressurehavebeenreportedinmanywomentakingCOCs,clinicallyimportant

increasesinbloodpressurearerare.IfpersistentclinicalhypertensiondevelopsduringCOCuse,intakeshouldbe

discontinuedandthehypertensiontreated.UseofCOCsmayberesumed,ifappropriate,whennormotensivevaluesare

reachedwithantihypertensivetherapy.

Ithasbeenreportedthatthefollowingconditionsmayoccur,orworsenbothduringpregnancyandduringuseof

COCs,buttheevidenceofarelationshipisinconclusive:jaundiceand/orpruritusinconnectionwithcholestasis;

developmentofgallstones;porphyria;systemiclupuserythematosus;haemolyticuraemicsyndrome;Sydenham’s

chorea;herpesgestationis;lossofhearingduetootosclerosis.

COCsmayhaveaninfluenceontheperipheralinsulinresistanceandglucosetolerance.Therefore,diabeticsshouldbe

closelymonitoredduringCOCuse.

Estellecontainslactoseandsucrose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionorwithrarehereditaryproblemsoffructoseintoleranceshouldnottake

thismedicinalproduct.

Worseningofendogenousdepression,ofepilepsy(seesection4.5interactions),ofCrohn’sdiseaseandofulcerative

colitishasbeenreportedduringCOCuse.

Chloasmamayoccur,inparticularinwomenwithamedicalhistoryofchloasmagravidarum.Womenwithatendency

tochloasmashouldavoidexposuretosunlightorultravioletradiationwhiletakingCOCs.

HerbalpreparationscontainingStJohn’swort(Hypericumperforatum)shouldnotbeusedwhiletakingEstelledueto

theriskofdecreasedplasmaconcentrationsandreducedclinicaleffectsofEstelle(seesection4.5).

Reducedefficacy:

Theefficacyoforalcontraceptivesmaybereducedinthecaseofmissedtablets,severediarrhoeaorvomiting(see

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Reducedcyclecontrol:

Withallcombinedoralcontraceptives,irregularbleeding(spottingorbreakthroughbleeding)mayoccur,especially

duringthefirstmonths.Hence,theevaluationofanyirregularbleedingshouldbeconsideredafteraperiodof

adaptationofapproximately3cycles.

IfbleedingirregularitiespersistCOCswithahigherhormonalcontentmayneedtobeconsidered.Ifbleeding

irregularitiesoccurafterpreviouslyregularcycles,thennon-hormonalcausesshouldbeconsidered,andadequate

diagnosticmeasuresareindicatedtoexcludemalignancyorpregnancy.

Occasionallywithdrawalbleedingduringthetablet-freeintervalmaynotoccuratall.Ifthetabletshavebeentaken

accordingtotheinstructionsdescribedinsection4.2,itisunlikelythatthewomanispregnant.However,ifthetablets

havenotbeentakenaccordingtotheinstructions,beforethefirstabsentwithdrawalbleeding,oriftwowithdrawal

bleedingsareoverdue,pregnancyshouldbeexcludedbeforeCOCuseiscontinued.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Druginteractionresultinginelevatedclearanceofsexhormonesmaycausebreakthroughbleedingandcontraceptive

failure.Thishasbeenestablishedwithhydantoins,barbiturates,primidone,carbamazepineandrifampicin;

oxcarbazepine,topiramate,griseofulvin,felbamateandritonavirarealsosuspected.Themechanismofthisinteraction

seemstorestupontheliverenzyme-inducingpropertiesofthesemedicinalproducts.Maximalenzymeinductionis

generallynotvisiblebefore2–3weeksafterthestartofthetreatment,butitmaypersistforatleast4weeksafterthe

endoftreatment.

Contraceptivefailurehasalsobeenreportedwithantibiotics,suchasampicillinandtetracyclins.Themechanismofthis

actionhasnotbeenelucidated.

Womenundergoingshort-termtreatmentwithanyoftheabovementionedgroups,orindividualmedicinalproducts,

shouldtemporarilyuseabarriermethodalongwiththecontraceptivepills;thatmeansduringthetimewhenboththis

medicinalproductandthecontraceptivepillsaretaken,aswellas7daysafterthemedicinalproductisdiscontinued.

Womentreatedwithrifampicinshoulduseabarriermethodalongwiththecontraceptivepillsduringthetimewhen

theyaretreatedwithrifampicinaswellasfor28daysaftertheystoptakingrifampicin.Iftheintakeofanother

concomitantmedicinalproductstretchesbeyondthenumberoftabletsinthecontraceptivepillpack,thewomanshould

startthenextpackwithoutobservingthenormaltablet-freeperiod.

Forlong-termusersofmedicinalproductsthatinduceliverenzymes,useofothercontraceptivemeasuresshouldbe

advised.

PatientsbeingtreatedwithEstelleshouldnotsimultaneouslyuseproducts/alternativemedicinalproductscontaining

Hypericumperforatum(St.John'swort)asthiscanleadtolossofcontraceptiveeffect.Withdrawalbleedingand

undesirablepregnancyhavebeenreported.

Hypericumperforatum(St.John'swort)increases,byenzymeinduction,theamountofenzymesthatmetabolise

medicinalproducts.Theeffectoftheenzymeinductionmaylastforatleast1-2weeksaftertheendoftreatmentwith

Hypericum.

COCeffectsonotherdrugs:oralcontraceptivesmayinterferewiththemetabolismofotherdrugs.Accordingly,plasma

andtissueconcentrationsmayeitherincrease(e.g.ciclosporin)ordecrease(lamotrigine).

Laboratorytests:

Theuseofcontraceptivesteroidscaninfluencetheresultsofcertainlaboratorytests,includingthebiochemical

parametersofliver,thyroid,adrenal,andkidneyfunction;plasmalevelsof(transport)proteins,suchascorticosteroid-

bindingglobulinandlipid/lipoproteinfractions;theparametersofcarbohydratemetabolism,andtheparameterof

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4.6Pregnancyandlactation

Estelleisnotindicatedduringpregnancy.IfpregnancyoccursduringmedicationwithEstelle,thepreparationshouldbe

withdrawnimmediately.

Extensiveepidemiologicalstudieshaverevealedneitheranincreasedriskofbirthdefectsinchildrenborntowomen

whousedCOCspriortopregnancy,norateratogeniceffectwhenCOCsweretakeninadvertentlyduringpregnancy.

Contraceptivesteroidscaninfluencebreastfeeding,astheycanlowertheamountandchangethecompositionofbreast

milk.Smallamountsofcontraceptivesteroidsand/ortheirmetabolitescanbeexcretedinthemilk.Theuseof

contraceptivesteroidsshould,therefore,generallynotbeadvisedtoabreastfeedingmotherbeforeherchildis

completelyweaned.

4.7Effectsonabilitytodriveandusemachines

Estellehasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

ThemostcommonlyreportedADRs(>1/10)areirregularbleeding,nausea,weightincrease,breasttendernessand

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ThefollowingseriousadverseeventshavebeenreportedinwomenusingCOCs,seesections4.3and4.4.

Venousthromboembolism,i.e.deeplegorpelvicvenousthrombosisandpulmonaryembolism

Arterialthromboembolicdisorders

Livertumours

Skinandsubcutaneousdisorders:chloasma

ThefrequencyofdiagnosisofbreastcancerisveryslightlyincreasedamongCOC-users.Asbreastcancerisrarein

womenunder40yearsofagetheexcessnumberissmallinrelationtotheoverallriskofbreastcancer.Causationwith

OrgansystemclassCommon(1/100

to<1/10) Uncommon

(1/1,000to<

1/100) Rare

(1/10,000to<

1,000) Veryrare

(1/10,000)

Nervoussystem

disorders Headache

Nervousness Chorea

Eyedisorders Ocularirritation

whenwearing

contactlenses

Visualdisturbances

Earandlabyrinth

disorders Otosclerosis

Gastrointestinal

disorders Nausea Vomiting Cholelithiasis Pancreatitis

Skinand

Subcutaneoustissue

disorders Acne Chloasma

Metabolismand

nutritiondisorders Hyperlipidaemia

Vasculardisorders Migraine Hypertension Venous

thromboembolism

Arterial

thromboembolic

disorders

Generaldisorders

andadministration

siteconditions Weightincrease

Fluidretention

Immunesystem

disorders Lupus

erythematosus

Reproduction

systemandbreast

disorders Irregularbleeding

Amenorrhoea

Hypomenorrhoea

Breasttenderness Changesinvaginal

secretion

Psychiatric

disorders Changesinlibido

Depression

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4.9Overdose

Noseriousharmfuleffectshavebeenreportedwithoverdoses.Symptomsthatcanariseinconnectionwithanoverdose

are:nausea,vomiting,andvaginalbleeding.Thereisnoantidote,andfurthertreatmentshouldbesymptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:hormonalcontraceptivesforsystemicuse

ATCcode:G03AA10

Thecontraceptiveeffectofcontraceptivepillsrestsontheinteractionofvariousfactors,themostimportantofwhich

areinhibitionofovulationandchangesintheendometrium.Alongwithprotectingagainstpregnancy,COCshave

severalpositivepropertieswhich,nexttothenegativeproperties(see4.8Warnings,Undesirableeffects),canbeuseful

indecidingonthemethodofbirthcontrol.Themenstrualcycleismoreregularandthemenstruationisoftenless

painful,andbleedingisligther.Thelattermayresultinadecreaseintheoccurrenceofirondeficiency.

5.2Pharmacokineticproperties

Gestodene:

Absorption:

Gestodene,whentakenorally,isabsorbedquicklyandcompletely.Followingasingledosethemaximumserum

concentrationof4ng/mlisreachedinapproximatelyonehour.Bioavailabilityisapproximately99%.

Distribution:

Gestodeneisboundtoserumalbuminandtosexhormonebindingglobulin(SHBG).Only1–2%ofthetotalamount

ofgestodeneinserumisfoundasfreesteroid,while50–70%isspecificallyboundtoSHBG.Theethinylestradiol-

inducedincreaseinSHBGinfluencesthedistributionofserumproteins,whichcausesanincreaseoftheSHBG-bound

fraction,andadecreaseofthealbumin-boundfraction.Theapparentdistributionvolumeofgestodeneis0.7l/kg.

Metabolism:

Gestodeneismetabolisedcompletelyviatheknownpathwaysofsteroidmetabolism.Themetabolicclearancerate

fromserumis0.8ml/min/kg.Nointeractionoccurswhengestodeneistakentogetherwithethinylestradiol.

Elimination:

Serumlevelofgestodeneisreducedat2rates.Thelastrateischaracterisedbyahalf-lifeof12–15hours.

Gestodeneisnotexcretedunchanged.Itsmetabolitesareexcretedinurineandinbileataratioof6:4.Thehalf-lifeof

metaboliteexcretionisapproximately1day.

Steady-state:

PharmacokineticsofgestodeneisinfluencedbythelevelsofSHBGinserum,whichincreasetotriplevalueswith

ethinylestradiol.Upondailyintake,thelevelofgestodeneinserumincreasestillapproximatelyfourtimesthesingle

dosevalue,andreachessteady-statewithinthesecondhalfofthetreatmentcycle.

Ethinylestradiol:

Absorption:

Ethinylestradiol,takenorally,isabsorbedquicklyandcompletely.Maximalserumconcentrationofabout80pg/mlis

reachedwithin1–2hours.Completebioavailability,resultingfrompre-systemicconjugationandfirst-pass

metabolism,isapproximately60%.

Distribution:

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Ethinylestradiolispredominantlyboundnon-specificallytoalbumin(approx.98.5),andcausesincreaseinserum

concentrationofSHBG.Theapparentdistributionvolumeisfoundtobeapproximately5l/kg.

Metabolism:

Ethinylestradiolundergoespre-systemicconjugationbothinthemucosaofthesmallintestine,andintheliver.

Ethinylestradiolisprimarilymetabolisedbyaromatichydroxylation,butmanydifferenthydroxylatedandmethylated

metabolitesareformed,andfoundasfreemetabolitesandasglucuronideandsulphateconjugates.Themetabolic

clearancerateisapproximately5ml/min/kg.

Elimination:

Serumlevelofethinylestradiolisreducedat2rates,thelastonewithahalf-lifeof24hours.Unchanged

ethinylestradiolisnotexcreted,butitsmetabolitesareexcretedinurineandinbileataratioof4:6.Thehalf-lifeof

metaboliteexcretionisapproximately1day.

Steady-state:

Steady-stateoccursafter3–4days,andtheserumlevelsofethinylestradiolare30–40%higherthanatsingledose.

5.3Preclinicalsafetydata

Ethinylestradiolandgestodenearenotgenotoxic.Carcinogenicitystudieswithethinylestradiolaloneorincombination

withvariousprogestogensdonotindicateanyparticularcarcinogenichazardtowomenwhenusedasindicatedfor

contraception.Howeveritshouldbenotedthatsexhormonescanadvancethegrowthofcertainhormone-dependent

tissuesandtumours.

Reproductivetoxicitystudiesonfertility,developmentofthefoetusorreproductiveabilitywithethinylestradiolalone

orincombinationwithprogestogensrevealednoundesirableeffectsforhumanswhenusedasrecommended.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Magnesiumstearate

PovidoneK-25

Maizestarch

Lactosemonohydrate

Tabletcoating:

PovidoneK-90

Macrogol6000

Talc

Calciumcarbonate

Sucrose

Waxmontanglycol

6.2Incompatibilities

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6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove30 °

6.5Natureandcontentsofcontainer

Blister:PVC/aluminium.

Packsizes:1x21tablets,3x21tablets,6x21tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLtd

WaterfordRoad

Clonmel

CoTipperary

8MARKETINGAUTHORISATIONNUMBER

PA126/170/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Thedateoffirstauthorisation:21stSeptmeber2007.

10DATEOFREVISIONOFTHETEXT

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