ETHINYLESTRADIOL / DROSPIRENONE LEON FARMA

Main information

  • Trade name:
  • ETHINYLESTRADIOL / DROSPIRENONE LEON FARMA
  • Dosage:
  • 0.03 / 3 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ETHINYLESTRADIOL / DROSPIRENONE LEON FARMA
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/208/002
  • Authorization date:
  • 16-03-2012
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains0.03mgofethinylestradioland3mgofdrospirenone

Excipient:

Lactosemonohydrate62mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Yellow,roundfilm-coatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Oralcontraception

4.2Posologyandmethodofadministration

Routeofadministration:oraluse.

HowtotakeEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

Thetabletsmustbetakeneverydayataboutthesametime,ifnecessarywithalittleliquidintheordershownonblister

pack.

Onetabletistobetakendailyfor21consecutivedays.Eachsubsequentpackisstartedafter7-daytablet-freeinterval,

duringwhichtimewithdrawalbleedoccurs.Thisusuallystartsonday2-3afterthelasttabletandmaynothave

finishedbeforethenextpackisstarted.

HowtotakeEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

Noprecedinghormonalcontraceptiveuse(inthepastmonth)

Tablet-takinghastostartonday1ofthewoman’snaturalcycle(i.e.thefirstdayofhermenstrualbleeding).

Changingfromanothercombinedoralcontraceptive(COC)

ThewomanshouldstartEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsontheday

followingtheusualhormonefreeinterval(tablet-freeorplacebotabletinterval)ofherpreviouscombinedoral

contraceptivemethod.

IncaseavaginalringortransdermalpatchhasbeenusedthewomanshouldstartusingEthinylestradiol/Drospirenone

LeonFarma0.03mg/3mgFilm-coatedtabletspreferablyonthedayofremoval,butatthelatestwhenthenext

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 1

-Changingfromaprogestogen-only-method(progestogen-onlypill,injection,implant)orfromaprogestogen-releasing

intrauterinesystem(IUS)

Thewomanmayswitchanydayfromtheprogestogen-onlypill(fromanimplantortheIUSonthedayofitsremoval,

fromaninjectablewhenthenextinjectionwouldbedue)butshouldinallofthesecasesbeadvisedtoadditionallyuse

abarriermethodforthefirst7daysoftablet-taking.

Followingfirsttrimesterabortion

Thewomanmaystartimmediately.Whendoingso,sheneednottakeadditionalcontraceptivemeasures.

Followingdeliveryorsecond-trimesterabortion

Womanshouldbeadvisedtostartatday21to28afterdeliveryorsecond-trimesterabortion.Whenstartinglater,the

womanshouldbeadvisedtoadditionallyuseabarriermethodforthefirst7days.However,ifintercoursehasalready

occurred,pregnancyshouldbeexcludedbeforetheactualstartofCOCuseorthewomanhastowaitforherfirst

menstrualperiod.

ForbreastfeedingwomenseeSection4.6.

Managementofmissedtablets

Thefollowingadviceonlyreferstomissedactivetablets(rows1-3oftheblister):

Iftheuserislessthan12hourslateintakinganyactivetablet,contraceptiveprotectionisnotreduced.Thewoman

shouldtakethetabletassoonassheremembersandshouldtakefurthertabletsatusualtime.

Ifsheismorethan12hourslateintakinganyactivetablet,contraceptiveprotectionmaybereduced.The

managementofmissedtabletscanbeguidedbythefollowingtwobasicrules:

1.tablet-takingmustneverbediscontinuedforlongerthan7consecutivedays

2.7daysofuninterruptedtablet-takingarerequiredtoattainadequatesuppressionofthehypothalamic-pituitary-

ovarian-axis.

Accordinglythefollowingadvicecanbegivenindailypractice:

Week1

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeanstakingtwotabletsatthesame

time.Shethencontinuestotaketheremainingtabletsatherusualtime.Inaddition,abarriermethodsuchascondom

shouldbeusedforthenext7days.Ifintercoursetookplaceinthepreceding7days,thepossibilityofpregnancy

shouldbeconsidered.Themoretabletsaremissedandtheclosertheyaretotheplacebotabletphase,thehigherthe

riskofapregnancy.

Week2

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeanstakingtwotabletsatthesame

time.Shethencontinuestotaketabletstheremainingtabletsatherusualtime.Providedthatthewomanhastakenher

tabletscorrectlyinthe7daysprecedingthefirstmissedtablet,thereisnoneedtouseextracontraceptiveprecautions.

However,ifshehasmissedmorethan1tablet,thewomanshouldbeadvisedtouseextraprecautionsforthenext7

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 2

Week3

Theriskofreducedreliabilityisimminentbecauseoftheforthcoming7daytablet-freeinterval.

However,byadjustingthetablet-intakeschedule,reducedcontraceptiveprotectioncanstillbeprevented.Byadhering

toeitherofthefollowingtwooptions,thereisthereforenoneedtouseextracontraceptiveprecaution,providedthatin

the7daysprecedingthefirstmissedtabletthewomanhastakenalltabletscorrectly.Ifthisisnotthecase,sheshould

followthefirstofthesetwooptionsanduseextraprecautionsforthenext7daysaswell.

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeanstakingtwo

tabletsatsametime.

Shethencontinuestotakeremainingtabletsatherusualtime.Thenextblisterpackmustbestartedassoonasthe

currentblisterpackisfinishedi.e.nogapshouldbeleftbetweenpacks.

Theuserisunliketohaveawithdrawalbleeduntiltheendoftheactivetabletssectionofthesecondpack,butshemay

experiencespottingorbreakthroughbleedingontablet-takingdays.

Thewomanmayalsobeadvisedtodiscontinuetablet-takingfromthecurrentblisterpack.Sheshould

thenhaveatablet-freeintervalofup7days,includingthedaysshemissedtablets,andsubsequentlycontinuewiththe

nextblisterpack.

Ifthewomanmissedtabletsandsubsequentlyhasnowithdrawalbleedinthefirstnormaltablet–freeintervalthe

possibilityofapregnancyshouldbeconsidered.

Adviceincaseofgastro-intestinaldisturbances

Incaseofseveregastro-intestinaldisturbances(e.g.vomitingorseverediarrhoea),absorptionmaynotbecompleteand

additionalcontraceptivemeasuresshouldbetaken.Ifvomitingoccurswithin3-4hoursaftertablettaking,anewtablet

shouldbetakenassoonaspossible.Thenewtabletshouldbetakenwithin12hoursoftheusualtimeoftablet-taking

ifpossible.

Ifmore12hourselapse,theadviceconcerningmissedtablets,asgiveinsection4.2“Managementofmissedtablets”is

applicable.Ifthewomandoesnotwanttochangehernormaltablet-takingschedule,shehastotaketheextratable(s)

fromanotherblisterpack.

Howtopostponeawithdrawalbleed

TodelayaperiodthewomanshouldcontinuewithanotherblisterpackofEthinylestradiol/DrospirenoneLeonFarma

0.03mg/3mgFilm-coatedTabletswithoutatablet-freeinterval.Theextensioncanbecarriedonforaslongaswished

untiltheendofinthesecondpack.Duringtheextensionthewomanmayexperiencebreakthrough-bleedingor

spotting.RegularintakeofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisthen

resumedaftertheusual7-daystablet–freeinterval.

Toshiftherperiodstoanotherdayoftheweekthanthewomanisusedtowithhercurrentscheme,shecanbeadvised

toshortenherforthcomingtablet-freeintervalbyasmanydaysasshelikes.Theshortertheinterval,thehighertherisk

thatshedoesnothaveawithdrawalbleedandwillexperiencebreakthrough-bleedingandspottingduringsubsequent

pack(justaswhendelayingperiod).

4.3Contraindications

Combinedoralcontraceptives(COC)shouldnotbeusedinthepresenceofanytheconditionslistedbelow.Shouldany

oftheconditionsappearforthefirsttimeduringCOCuse,theproductshouldbestoppedimmediately.

Venousthrombosispresentorinhistory(deepvenousthrombosis,pulmonaryembolism)

Arterialthrombosispresentorinhistory(e.g.myocardialinfarction)orprodomalconditions(e.g.anginapectoris

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 3

Cerebro-vascularaccidentpresentorinhistory

Thepresenceofasevereormultipleriskfactor(s)forarterialthrombosis

Diabetesmellituswithavascularsymptoms

Severehypertension

Severedyslipoproteinemia

Hereditaryoracquiredpredispositionforvenousorarterialthrombosis,suchasAPC-resistance,antithrombin-

III-deficiency,proteinCdeficiency,proteinSdeficiency,hyperhomocysteinemiaandantiphospholipid-

antibodies(anticardiolipin-antibodies,lupusanticoagulant).

Presenceorhistoryofseverehepaticdiseaseaslongasliverfunctionvalueshavenotreturnedtonormal

Severerenalinsufficiencyoracuterenalfailure.

Presenceorhistoryoflivertumours(benignormalignant).

Knownorsuspectedsex-steroidinfluencedmalignancies(e.g.ofthegenitalorgansorthebreasts).

Undiagnosedvaginalbleeding.

Historyofmigrainewithfocalneurologicalsymptoms

HypersensitivitytotheactivesubstancesortoanyoftheexcipientsofEthinylestradiol/DrospirenoneLeon

Farma0.03mg/3mgFilm-coatedTablets.

4.4Specialwarningsandprecautionsforuse

Warnings

Ifanyoftheconditions/riskfactorsmentionedbelowarepresent,thebenefitsofCOCuseshouldbeweighedagainst

thepossiblerisksforeachindividualwomananddiscussedwiththewomanbeforeshedecidestostartusingit.Inthe

eventofaggravation,exacerbationorfirstappearanceofanyoftheseconditionsorriskfactors,thewomanshould

contactherphysician.ThephysicianshouldthendecideonwhetherCOCuseshouldbediscontinued.

CirculatoryDisorders

EpidemiologicalstudieshaveshownthattheincidenceofVTEinusersoforalcontraceptiveswithlowoestrogen

content(<50µgethinylestradiol)(includingEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coated

Tablets)rangesfromabout20to40casesper100,000woman-years,butthisriskestimatevariesaccordingtothe

progestogen.Thiscompareswith5to10casesper100,000woman-yearsfornon-users.

Theuseofanycombinedoralcontraceptivecarriesanincreasedriskofvenousthromboembolism(VTE)compared

withnouse.TheexcessriskofVTEishighestduringthefirstyearawomaneverusesacombinedoralcontraceptive.

TheincidenceofVTEassociatedwithpregnancyisestimatedas60casesper100,000pregnancies.VTEisfatalin1-

2%ofcases.

EpidemiologicalstudieshavealsoassociatedtheuseofcombinedCOCswithanincreasedriskforarterial(myocardial

infarction,transientischaemicattack)thromboembolism.

Extremelyrarely,thrombosishasbeenreportedtooccurinotherbloodvessels,e.g.hepatic,mesenteric,renal,cerebral

orretinalveinsandarteries,incontraceptivepillusers.Thereisnoconsensusastowhethertheoccurrenceofthese

eventsisassociatedwiththeuseofhormonalcontraceptives.

Symptomsofvenousorarterialthrombotic/thromboemboliceventsorofacerebrovascularaccidentcaninclude:

unusualunilaterallegpainand/orswelling

suddenseverepaininthechest,whetherornotitradiatestotheleftarm

suddenbreathlessness

suddenonsetofcoughingwithoutaclearcause

anyunusual,severe,prolongedheadache

suddenpartialorcompletelossofvision

diplopia

slurredspeechoraphasia

vertigo

collapsewithorwithoutfocalseizure

weaknessorverymarkednumbnesssuddenlyaffectingonesideoronepartofthebody

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 4

'acuteabdomen’.

TheriskforvenousthromboemboliccomplicationsinCOCusersincreaseswith:

increasingage.

apositivefamilyhistory(venousthromboembolismeverinasiblingorparentatrelativelyearlyage).Ifa

hereditarypredispositionissuspected,thewomanshouldbereferredtoaspecialistforadvicebeforedeciding

aboutanyCOCuse.

prolongedimmobilisation,majorsurgery,anysurgerytothelegs,ormajortrauma.Inthesesituationsitis

advisabletodiscontinuethepill(inthecaseofelectivesurgeryatleastfourweeksinadvance)andnotresume

untiltwoweeksaftercompleteremobilisation.Antithrombotictreatmentshouldbeconsideredifthepillshave

notbeendiscontinuedinadvance.

obesity(bodymassindexover30kg/m²).

thereisnoconsensusaboutthepossibleroleofvaricoseveinsandsuperficialthrombophlebitisintheonsetor

progressionofvenousthrombosis.

Theriskofarterialthrombo-emboliccomplicationsorofacerebrovascularaccidentinCOCusersincreaseswith:

increasingage.

smoking(womenover35yearsshouldbestronglyadvisednottosmokeiftheywishtouseanCOC).

dyslipoproteinemia.

hypertension.

migraine.

obesity(bodymassindexover30kg/m²).

valvularheartdisease.

atrialfibrillation.

Thepresenceofoneseriousriskfactorormultipleriskfactorsforvenousorarterialdisease,respectively,canalso

constituteacontra-indication.Thepossibilityofanticoagulanttherapyshouldalsobetakenintoaccount.COCusers

shouldbespecificallypointedouttocontacttheirphysicianincaseofpossiblesymptomsofthrombosis.Incaseof

suspectedorconfirmedthrombosis,COCuseshouldbediscontinued.Adequatealternativecontraceptionshouldbe

initiatedbecauseoftheteratogenicityofanticoagulanttherapy(coumarins).

Theincreasedriskofthromboembolisminthepuerperiummustbeconsidered(forinformationon"Pregnancyand

Lactation"seesection4.6).

Othermedicalconditionswhichhavebeenassociatedwithadversevasculareventsincludediabetesmellitus,systemic

lupuserythematosus,haemolyticuremicsyndromeandchronicinflammatoryboweldisease(Crohn'sdiseaseor

ulcerativecolitis)andsicklecelldisease.

AnincreaseinfrequencyorseverityofmigraineduringCOCuse(whichmaybeprodromalofacerebrovascularevent)

maybeareasonforimmediatediscontinuationoftheCOC.

Tumours

Anincreasedriskofcervicalcancerinlong-termusersofCOCshasbeenreportedinsomeepidemiologicalstudies,

buttherecontinuestobecontroversyabouttheextenttowhichthisfindingisattributabletotheconfoundingeffectsof

sexualbehaviourandotherfactorssuchashumanpapillomavirus(HPV).

Ameta-analysisfrom54epidemiologicalstudiesreportedthatthereisaslightlyincreasedrelativerisk(RR=1.24)of

havingbreastcancerdiagnosedinwomenwhoarecurrentlyusingCOCs.Theexcessriskgraduallydisappearsduring

thecourseofthe10yearsaftercessationofCOCuse.

Becausebreastcancerisrareinwomenunder40yearsofage,theexcessnumberofbreastcancerdiagnosesincurrent

andrecentCOCusersissmallinrelationtotheoverallriskofbreastcancer.Thesestudiesdonotprovideevidencefor

causation.TheobservedpatternofincreasedriskmaybeduetoanearlierdiagnosisofbreastcancerinCOCusers,the

biologicaleffectsofCOCsoracombinationofboth.Thebreastcancersdiagnosedinever-userstendtobeless

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 5

Inrarecases,benignlivertumours,andevenmorerarely,malignantlivertumourshavebeenreportedinusersof

COCs.Inisolatedcases,thesetumourshaveledtolife-threateningintra-abdominalhaemorrhages.Ahepatictumour

shouldbeconsideredinthedifferentialdiagnosiswhensevereupperabdominalpain,liverenlargementorsignsof

intra-abdominalhaemorrhageoccurinwomentakingCOCs.

Otherconditions

TheprogestincomponentinEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisan

aldosteroneantagonistwithpotassiumsparingproperties.Inmostcases,noincreaseofpotassiumlevelsistobe

expected.Inaclinicalstudy,howeverinsomepatientswithmildormoderaterenalimpairmentandconcomitantuseof

potassium-sparingmedicinalproductsserumpotassiumlevelsslightly,butnotsignificantly,increasedduring

drospirenoneintake.Therefore,itisrecommendedtocheckserumpotassiumduringthefirsttreatmentcycleinpatients

presentingwithrenalinsufficiencyandapretreatmentserumpotassiumintheupperreferencerange,andparticularly

duringconcomitantuseofpotassiumsparingmedicinalproducts.Seealsosection4.5.

Womenwithhypertriglyceridemia,orafamilyhistorythereof,maybeatanincreasedriskofpancreatitiswhenusing

COCs.

AlthoughsmallincreasesinbloodpressurehavebeenreportedinmanywomentakingCOCs,clinicallyrelevant

increasesarerare.OnlyintheserarecasesanimmediatediscontinuationofCOCuseisjustified.If,duringtheuseofa

COCinpreexistinghypertension,constantlyelevatedbloodpressurevaluesorasignificantincreaseinbloodpressure

donotrespondadequatelytoantihypertensivetreatment,theCOCmustbewithdrawn.Whereconsideredappropriate,

COCusemayberesumedifnormotensivevaluescanbeachievedwithantihypertensivetherapy.

ThefollowingconditionshavebeenreportedtooccurordeterioratewithbothpregnancyandCOCuse,butthe

evidenceofanassociationwithCOCuseisinconclusive:jaundiceand/orpruritusrelatedtocholestasis;gallstones;

porphyria;systemiclupuserythematosus;haemolyticuremicsyndrome;Sydenham'schorea;herpesgestationis;

otosclerosis-relatedhearingloss.

Inwomenwithhereditaryangioedemaexogenousestrogensmayinduceorexacerbatesymptomsofangioedema.

AcuteorchronicdisturbancesofliverfunctionmaynecessitatethediscontinuationofCOCuseuntilmarkersofliver

functionreturntonormal.Recurrenceofcholestaticjaundiceand/orcholestasis-relatedprurituswhichpreviously

occurredduringpregnancyorduringprevioususeofsexsteroidsnecessitatesthediscontinuationofCOCs.

AlthoughCOCsmayhaveaneffectonperipheralinsulinresistanceandglucosetolerance,thereisnoevidencefora

needtoalterthetherapeuticregimenindiabeticsusinglow-doseCOCs(containing<0.05mgethinylestradiol).

However,diabeticwomenshouldbecarefullyobserved,particularlyintheearlystageofCOCuse.

Worseningofendogenousdepression,ofepilepsy,ofCrohn'sdiseaseandofulcerativecolitishasbeenreportedduring

COCuse.

Chloasmamayoccasionallyoccur,especiallyinwomenwithahistoryofchloasmagravidarum.Womenwitha

tendencytochloasmashouldavoidexposuretothesunorultravioletradiationwhilsttakingCOCs.

Yellowtabletsofthismedicinalproductcontain62mglactosepertablet.Patientswithrarehereditaryproblemsof

galactoseintolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Medicalexamination/consultation

PriortotheinitiationorreinstitutionofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsa

completemedicalhistory(includingfamilyhistory)shouldbetakenandpregnancymustberuledout.

Bloodpressureshouldbemeasuredandaphysicalexaminationshouldbeperformed,guidedbythecontra-indications

(seesection4.3)andwarnings(seesection4.4).Thewomanshouldalsobeinstructedtocarefullyreadtheuserleaflet

andtoadheretotheadvicegiven.Thefrequencyandnatureofexaminationsshouldbebasedonestablishedpractice

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 6

WomenshouldbeadvisedthatoralcontraceptivesdonotprotectagainstHIVinfections(AIDS)andothersexually

transmitteddiseases.

Reducedefficacy

TheefficacyofCOCsmaybereducedintheeventofe.g.missedtablets(seesection4.2),gastro-intestinaldisturbances

vomitingorseverediarrhea(seesection4.2)orconcomitantmedication(seesection4.5).

Reducedcyclecontrol

DuringtheuseofanyCOCs,irregularbleeding(spottingorbreakthroughbleeding)mayoccur,especiallyduringthe

firstmonthsofuse.Therefore,theevaluationofanyirregularbleedingisonlymeaningfulafteranadaptationinterval

ofaboutthreecycles.

Ifbleedingirregularitiespersistoroccurafterpreviouslyregularcycles,thennon-hormonalcausesshouldbe

consideredandadequatediagnosticmeasuresareindicatedtoexcludemalignancyorpregnancy.Thesemayinclude

curettage.

Insomewomenwithdrawalbleedingmaynotoccurduringthetablet-freeinterval.IftheCOChasbeentaken

accordingtothedirectionsdescribedinsection4.2,itisunlikelythatthewomanispregnant.However,iftheCOChas

notbeentakenaccordingtothesedirectionspriortothefirstmissedwithdrawalbleedoriftwowithdrawalsbleedsare

missed,pregnancymustberuledoutbeforeCOCuseiscontinued.

Theyellowtabletsofthismedicinalproductcontain62mgoflactosepertablet.Patientswithrarehereditaryproblems

ofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionwhoareonalactose-freediet

shouldtakethisamountintoconsideration.shouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Note:Theprescribinginformationofconcomitantmedicationsshouldbeconsultedtoidentifypotentialinteractions.

InfluenceofothermedicinalproductsEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coated

Tablets

Interactionsbetweenoralcontraceptivesandothermedicinalproductsmayleadtobreakthroughbleedingand/or

contraceptivefailure.Thefollowinginteractionshavebeenreportedintheliterature.

Thishasbeenestablishedwithhydantoins,barbiturates,primidone,carbamazepineandrifampicin;oxcarbazepine,

topiramate,felbamate,ritonavir,griseofulvinandtheherbalremedySt.John'sWort(hypericumperforatum)arealso

suspected.Themechanismofthisinteractionappearstobebasedonthehepaticenzyme-inducingpropertiesofthese

activesubstances.Maximalenzymeinductionisgenerallynotseenfor2-3weeksbutmaythenbesustainedforatleast

4weeksafterthecessationofdrugtherapy.

Contraceptivefailureshavealsobeenreportedwithantibiotics,suchasampicillinandtetracyclines.Themechanismof

thiseffecthasnotbeenelucidated.

Womenonshort-termtreatment(uptooneweek)withanyoftheabove-mentionedclassesofmedicinalproductsor

individualactivesubstancesshouldtemporarilyuseabarriermethodinadditiontotheCOC,i.e.duringthetimeof

concomitantmedicinalproductadministrationandfor7daysaftertheirdiscontinuation.

ForwomenonrifampicinabarriermethodshouldbeusedinadditiontotheCOCduringthetimeofrifampicin

administrationandfor28daysafteritsdiscontinuation.

IfconcomitantmedicinalproductadministrationrunsbeyondtheendofthetabletsintheCOCblisterpack,thenext

COCpackshouldbestartedwithouttheusualtablet-freeinterval.

Inwomenonlong-termtreatmentwithhepaticenzyme-inducingdrugs,expertshaverecommendedtoincreasethe

contraceptivesteroiddoses.

Ifahighcontraceptivedosageisnotdesirableorappearstobeunsatisfactoryorunreliable,e.g.inthecaseof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 7

ThemainmetabolitesofdrospirenoneinhumanplasmaaregeneratedwithoutinvolvementofthecytochromeP450

system.Inhibitorsofthisenzymesystemarethereforeunlikelytoinfluencethemetabolismofdrospirenone.

InfluenceofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsonothermedicinal

products

Oralcontraceptivesmayaffectthemetabolismofcertainotheractivesubstances.Accordingly,plasmaandtissue

concentrationsmayeitherincrease(e.g.cyclosporin)ordecrease(e.g.lamotrigine).

Basedoninvitroinhibitionstudiesandinvivointeractionstudiesinfemalevolunteersusingomeprazole,simvastatin

andmidazolamasmarkersubstrate,aninteractionofdrospirenoneatdosesof3mgwiththemetabolismofotheractive

substancesisunlikely.

Otherinteractions

Inpatientswithoutrenalinsufficiency,theconcomitantuseofdrospirenoneandACE-inhibitorsorNSAIDsdidnot

showasignificanteffectonserumpotassium.Nevertheless,concomitantuseofEthinylestradiol/DrospirenoneLeon

Farma0.03mg/3mgFilm-coatedTabletswithaldosteroneantagonistsorpotassium-sparingdiureticshasnotbeen

studied.Inthiscase,serumpotassiumshouldbetestedduringthefirsttreatmentcycle.Seealsosection4.4.

Laboratorytests

Theuseofcontraceptivesteroidsmayinfluencetheresultsofcertainlaboratorytests,includingbiochemicalparameters

ofliver,thyroid,adrenalandrenalfunction,plasmalevelsof(carrier)proteins,e.g.corticosteroid-bindingglobulinand

lipid/lipoproteinfractions,parametersofcarbohydratemetabolismandparametersofcoagulationandfibrinolysis.

Changesgenerallyremainwithinthenormallaboratoryrange.Drospirenonecausesanincreaseinplasmareninactivity

andplasmaaldosteroneinducedbyitsmildantimineralocorticoidactivity.

4.6Fertility,pregnancyandlactation

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisnotindicatedduringpregnancy.

IfpregnancyoccursduringuseofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets,the

preparationshouldbewithdrawnimmediately.Extensiveepidemiologicalstudieshaverevealedneitheranincreased

riskofbirthdefectsinchildrenborntowomenwhousedCOCspriortopregnancy,norateratogeniceffectwhenCOCs

weretakeninadvertentlyduringpregnancy.NosuchstudiesareconductedwithEthinylestradiol/DrospirenoneLeon

Farma0.03mg/3mgFilm-coatedTablets.

Animalstudieshaveshownundesirableeffectsduringpregnancyandlactation(seesection5.3).Basedontheseanimal

data,undesirableeffectsduetohormonalactionoftheactivecompoundscannotbeexcluded.However,general

experiencewithCOCsduringpregnancydidnotprovideevidenceforanactualundesirableeffectinhumans.

TheavailabledataregardingtheuseofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

duringpregnancyaretoolimitedtopermitconclusionsconcerningnegativeeffectsofEthinylestradiol/Drospirenone

LeonFarma0.03mg/3mgFilm-coatedTabletsonpregnancy,healthofthefoetusorneonate.Todate,norelevant

epidemiologicaldataareavailable.

LactationmaybeinfluencedbyCOCsastheymayreducethequantityandchangethecompositionofbreastmilk.

Therefore,theuseofCOCsshouldgenerallynotberecommendeduntilthebreast-feedingmotherhascompletely

weanedherchild.Smallamountsofthecontraceptivesteroidsand/ortheirmetabolitesmaybeexcretedwiththemilk

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 8

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.Noeffectsonabilitytodrive

andusemachineshavebeenobservedinusersofCOCs.

4.8Undesirableeffects

ThefollowingadversedrugreactionshavebeenreportedduringuseofEthinylestradiol/DrospirenoneLeonFarma

0.03mg/3mgfilm-coatedtablets:

ThetablebelowreportsadversereactionsbyMedDRAsystemorganclasses(MedDRASOCs).

ThefollowingseriousadverseeventshavebeenreportedinwomenusingCOCs,whicharediscussedinsection4.4

Specialwarningsandprecautionsforuse:

Venousthromboembolicdisorders;

Arterialthromboembolicdisorders;

Hypertension;

Livertumours;

OccurrenceordeteriorationofconditionsforwhichassociationwithCOCuseisnotconclusive:Crohn'sdisease,

ulcerativecolitis,epilepsy,migraine,endometriosis,uterinemyoma,porphyria,systemiclupuserythematosus,herpes

gestationis,Sydenham'schorea,haemolyticuremicsyndrome,cholestaticjaundice;

Chloasma;

AcuteorchronicdisturbancesofliverfunctionmaynecessitatethediscontinuationofCOCuseuntilmarkersofliver

SystemOrganClass Frequencyofadversereactions

Common Uncommon Rare

(1/100to<1/10) (1/1,000to<1/100) (1/10,000to<1/1,000)

Immunesystem

disorders Asthma

Endocrinedisorders Menstrualdisorders

Intermenstrualbleeding

Breastpain Breastsecretion

Nervoussystem

disorders Headache

Depressivemood Changesinlibido

Earandlabyrinth

disorders Hypacusis

Vasculardisease Migraine Hipertension

Hypotension Thromboembolism

Gastrointestinal

disorders Nausea Vomiting

Skinandsubcutaneous

tissuedisorders Acne

Eczema

Pruritus

Reproductivesystemand

breastdisorders Leucorrhoea

Vaginalmoniliasis Vaginitis

Generaldisorderand

administrationsite

conditions Fluidretention

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 9

ThefrequencyofdiagnosisofbreastcancerisveryslightlyincreasedamongOCusers.Asbreastcancerisrarein

womenunder40yearsofagetheexcessnumberissmallinrelationtotheoverallriskofbreastcancer.Causationwith

COCuseisunknown.Forfurtherinformation,seesections4.3and4.4.

4.9Overdose

TherehasnotyetbeenanyexperienceofoverdosewithEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mg

Film-coatedTablets.Onthebasisofgeneralexperiencewithcombinedoralcontraceptives,symptomsthatmay

possiblyoccurinthiscaseare:nausea,vomitingand,inyounggirls,slightvaginalbleeding.Therearenoantidotesand

furthertreatmentshouldbesymptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup(ATC):Progestogensandestrogens,fixedcombinationsATCCode:G03AA12

PearlIndex:0.31(upperlimit,97.5%confidenceinterval:0.91)

ThecontraceptiveeffectofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisbasedon

theinteractionofvariousfactors,themostimportantofwhichareseenastheinhibitionofovulationandthechangesin

theendometrium.

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisacombinedoralcontraceptivewith

ethinylestradiolandtheprogestogendrospirenone.Inatherapeuticdosage,drospirenonealsopossessesantiandrogenic

andmildantimineralocorticoidproperties.Ithasnoestrogenic,glucocorticoidandantiglucocorticoidactivity.This

givesdrospirenoneapharmacologicalprofilecloselyresemblingthenaturalhormone

progesterone.

ThereareindicationsfromclinicalstudiesthatthemildantimineralocorticoidpropertiesofEthinylestradiol/

DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsresultinamildantimineralocorticoideffect.

Withtheuseofthehigher-dosedCOCs(50µgethinylestradiol)theriskofendometrialandovariancancerisreduced.

Whetherthisalsoappliestolower-dosedCOCsremainstobeconfirmed.

5.2Pharmacokineticproperties

Drospirenone

Absorption

Orallyadministereddrospirenoneisrapidlyandalmostcompletelyabsorbed.Maximumconcentrationsoftheactive

substanceinserumofabout38ng/mlarereachedatabout1-2haftersingleingestion.Bioavailabilityisbetween76

and85%.

Concomitantingestionoffoodhasnoinfluenceonthebioavailabilityofdrospirenone.

Distribution

Afteroraladministration,serumdrospirenonelevelsdecreasewithaterminalhalf-lifeof31h.

Drospirenoneisboundtoserumalbuminanddoesnotbindtosexhormonebindingglobulin(SHBG)orcorticoid

bindingglobulin(CBG).Only3-5%ofthetotalserumconcentrationsoftheactivesubstancearepresentasfree

steroid.Theethinylestradiol-inducedincreaseinSHBGdoesnotinfluencetheserumproteinbindingofdrospirenone.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 10

Metabolism

Drospirenoneisextensivelymetabolizedafteroraladministration.Themajormetabolitesintheplasmaaretheacid

formofdrospirenone,generatedbyopeningofthelactonering,andthe4,5-dihydro-drospirenone-3-sulfate,bothof

whichareformedwithoutinvolvementoftheP450system.Drospirenoneismetabolizedtoaminorextentby

cytochromeP4503A4andhasdemonstratedacapacitytoinhibitthisenzymeandcytochromeP4501A1,cytochrome

P4502C9andcytochromeP4502C19invitro.

Elimination

Themetabolicclearancerateofdrospirenoneinserumis1.5±0.2ml/min/kg.Drospirenoneisexcretedonlyintrace

amountsinunchangedform.Themetabolitesofdrospirenoneareexcretedwiththefecesandurineatanexcretionratio

ofabout1.2to1.4.Thehalf-lifeofmetaboliteexcretionwiththeurineandfecesisabout40h.

Steady-StateConditions

Duringatreatmentcycle,maximumsteady-stateconcentrationsofdrospirenoneinserumofabout70ng/mlare

reachedafterabout8daysoftreatment.Serumdrospirenonelevelsaccumulatedbyafactorofabout3asa

consequenceoftheratioofterminalhalf-lifeanddosinginterval.

SpecialpatientPopulations

Effectofrenalimpairment

Steady-stateserumdrospirenonelevelsinwomenwithmildrenalimpairment(creatinineclearanceCLcr,50-80

mL/min)werecomparabletothoseofwomenwithnormalrenalfunction.Theserumdrospirenonelevelswereon

average37%higherinwomenwithmoderaterenalimpairment(CLcr,30-50mL/min)comparedtothoseinwomen

withnormalrenalfunction.Drospirenonetreatmentwasalsowelltoleratedbywomenwithmildandmoderaterenal

impairment.Drospirenonetreatmentdidnotshowanyclinicallysignificanteffectonserumpotassiumconcentration.

Effectofhepaticimpairment

Inasingledosestudy,oralclearance(CL/F)wasdecreasedapproximately50%involunteerswithmoderatehepatic

impairmentascomparedtothosewithnormalliverfunction.Theobserveddeclineindrospirenoneclearancein

volunteerswithmoderatehepaticimpairmentdidnottranslateintoanyapparentdifferenceintermsofserumpotassium

concentrations.Eveninthepresenceofdiabetesandconcomitanttreatmentwithspironolactone(twofactorsthatcan

predisposeapatienttohyperkalemia)anincreaseinserumpotassiumconcentrationsabovetheupperlimitofthe

normalrangewasnotobserved.Itcanbeconcludedthatdrospirenoneiswelltoleratedinpatientswithmildor

moderatehepaticimpairment(Child-PughB).

Ethnicgroups

NoclinicallyrelevantdifferencesinthepharmacokineticsofdrospirenoneorethinylestradiolbetweenJapaneseand

Caucasianwomenhavebeenobserved.

Ethinylestradiol

Absorption

Orallyadministeredethinylestradiolisabsorbedrapidlyandcompletely.

Afteradministrationof30µg,peakplasmaconcentrationsof100pg/mLarereached1-2hoursafteringestion.

Ethinylestradiolundergoesanextensivefirst-passeffect,whichdisplaysgreatinter-individualvariation.Theabsolute

bioavailabilityisapprox.45%.

Distribution

Ethinylestradiolhasanapparentvolumeofdistributionof5L/kgandbindingtoplasmaproteinsisapprox.98%.

EthinylestradiolinducesthehepaticsynthesisofSHBG.Duringtreatmentwith30µgethinylestradioltheplasma

concentrationofSHBGincreasesfrom70toabout350nmol/L.

Ethinylestradiolpassesinsmallamountsintobreastmilk(0.02%ofthedose).

Metabolism

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 11

Elimination

Ethinylestradiolisnotexcretedinunchangedformtoanysignificantextent.Themetabolitesofethinylestradiolare

excretedataurinarytobiliaryratioof4:6.Thehalf-lifeofmetaboliteexcretionisabout1day.

Steady-stateconditions

Steady-stateconditionsarereachedduringthesecondhalfofatreatmentcycleandserumlevelsofethinylestradiol

accumulatebyafactorofabout1.4to2.1.

5.3Preclinicalsafetydata

Inlaboratoryanimals,theeffectsofdrospirenoneandethinylestradiolwereconfinedtothoseassociatedwiththe

recognisedpharmacologicalaction.Inparticular,reproductiontoxicitystudiesrevealedembryotoxicandfetotoxic

effectsinanimalswhichareconsideredasspeciesspecific.Atexposurestodrospirenoneexceedingthoseinusersof

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets,effectsonsexualdifferentiationwere

observedinratfetusesbutnotinmonkeys.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Maizestarch

Pregelatinizedstarch(maize)

Crospovidone

Povidone

Polysorbate80

Magnesiumstearate

Coating:

Polyvinylalcoholpartialhydrolyzed

Titaniumdioxide(E171)

Macrogol3350

Talc

Yellowironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Blistersofaluminiumpush-throughfoilandPVC/PVDCfilm.

Packsizes:

1x21film-coatedtablets

2x21film-coatedtablets

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 12

6x21film-coatedtablets

13x21film-coatedtablets

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

RowexLtd

Bantry

Co.Cork

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA711/208/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:9thOctober2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 16/03/2012 CRN 2112880 page number: 13