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:
  • PA1474/002/002
  • Authorization date:
  • 09-10-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1474/002/002

CaseNo:2046797

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

LaboratoriosLeonFarma,S.A.

C/RoadelaVega,15,1-24008Leon,Spain

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/10/2009until08/10/2014.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

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,ifnecessarywithalittleliquidintheordershownon

blisterpack.

Onetabletistobetakendailyfor21consecutivedays.Eachsubsequentpackisstartedafter7-daytablet-freeinterval,

duringwhichtimewithdrawalbleedoccurs.Thisusuallystartsonday2-3afterthelasttabletandmaynothave

finishedbeforethenextpackisstarted.

HowtostartEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTablets

Noprecedinghormonalcontraceptiveuse(inthepastmonth)

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

Changingfromanothercombinedoralcontraceptive(COC)

ThewomanshouldstartEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsontheday

followingtheusualhormonefreeinterval(tablet-freeorplacebotabletinterval)ofherpreviouscombinedoral

contraceptivemethod.Incaseavaginalringortransdermalpatchhasbeenusedthewomanshouldstartusing

Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedtabletspreferablyonthedayofremoval,butat

thelatestwhenthenextapplicationwouldhavebeendue

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

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Thewomanmayswitchanydayfromtheprogestogen-onlypill(fromanimplantortheIUSonthedayofitsremoval,

fromaninjectablewhenthenextinjectionwouldbedue)butshouldinallofthesecasesbeadvisedtoadditionallyuse

abarriermethodforthefirst7daysoftablet-taking.

Followingfirsttrimesterabortion

Thewomanmaystartimmediately.Whendoingso,sheneednottakeadditionalcontraceptivemeasures.

Followingdeliveryorsecond-trimesterabortion

Womanshouldbeadvisedtostaratday21to28afterdeliveryorsecond-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

daysfollowingthelastforgottentablet.

Week3

Theriskofreducedreliabilityisimminentbecauseoftheforthcoming7daytablet-freeinterval.

However,byadjustingthetablet-intakeschedule,reducedcontraceptiveprotectioncanstillbeprevented.Byadhering

toeitherofthefollowingtwooptions,thereisthereforenoneedtouseextracontraceptiveprecaution,providedthatin

the7daysprecedingthefirstmissedtabletthewomanhastakenalltabletscorrectly.Ifthisisnotthecase,sheshould

followthefirstofthesetwooptionsanduseextraprecautionsforthenext7daysaswell.

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeanstakingtwotabletsat

sametime.

Shethencontinuestotakeremainingtabletsatherusualtime.Thenextblisterpackmustbestartedassoonasthe

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Theuserisunliklytohaveawithdrawalbleeduntiltheendoftheactivetabletssectionofthesecondpack,butshemay

experiencespottingorbreakthroughbleedingontablet-takingdays.

Thewomanmayalsobeadvisedtodiscontinuetablet-takingfromthecurrentblisterpack.Sheshouldthen

haveatablet-freeintervalofup7days,includingthedaysshemissedtablets,andsubsequentlycontinuewiththenext

blisterpack.

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.Should

anyoftheconditionsappearforthefirsttimeduringCOCuse,theproductshouldbestoppedimmediately.

Venousthrombosispresentorinhistory(deepvenousthrombosis,pulmonaryembolism)

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

andtransientischaemicattack).

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

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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

motordisturbances

'acuteabdomen’.

TheriskforvenousthromboemboliccomplicationsinCOCusersincreaseswith:

increasingage.

apositivefamilyhistory(venousthromboembolismeverinasiblingorparentatrelativelyearlyage).Ifa

hereditarypredispositionissuspected,thewomanshouldbereferredtoaspecialistforadvicebeforedeciding

aboutanyCOCuse.

prolongedimmobilisation,majorsurgery,anysurgerytothelegs,ormajortrauma.Inthesesituationsitis

advisabletodiscontinuethepill(inthecaseofelectivesurgeryatleastfourweeksinadvance)andnotresume

untiltwoweeksaftercompleteremobilisation.Antithrombotictreatmentshouldbeconsideredifthepillshave

notbeendiscontinuedinadvance.

obesity(bodymassindexover30kg/m²).

thereisnoconsensusaboutthepossibleroleofvaricoseveinsandsuperficialthrombophlebitisintheonsetor

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Theriskofarterialthrombo-emboliccomplicationsorofacerebrovascularaccidentinCOCusersincreaseswith:

increasingage.

smoking(womenover35yearsshouldbestronglyadvisednottosmokeiftheywishtouseanCOC).

dyslipoproteinemia.

hypertension.

migraine.

obesity(bodymassindexover30kg/m²).

valvularheartdisease.

atrialfibrillation.

Thepresenceofoneseriousriskfactorormultipleriskfactorsforvenousorarterialdisease,respectively,canalso

constituteacontraindication.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,

theexcessnumberofbreastcancerdiagnosesincurrentandrecentCOCusersissmallinrelationtotheoverallriskof

breastcancer.Thesestudiesdonotprovideevidenceforcausation.Theobservedpatternofincreasedriskmaybedue

toanearlierdiagnosisofbreastcancerinCOCusers,thebiologicaleffectsofCOCsoracombinationofboth.The

breastcancersdiagnosedinever-userstendtobelessadvancedclinicallythanthecancersdiagnosedinnever-users.

Inrarecases,benignlivertumours,andevenmorerarely,malignantlivertumourshavebeenreportedinusersof

COCs.Inisolatedcases,thesetumourshaveledtolife-threateningintra-abdominalhaemorrhages.Ahepatictumour

shouldbeconsideredinthedifferentialdiagnosiswhensevereupperabdominalpain,liverenlargementorsignsof

intra-abdominalhaemorrhageoccurinwomentakingCOCs.

Otherconditions

Theprogestincomponentinisanaldosteroneantagonistwithpotassiumsparingproperties.Inmostcases,noincrease

ofpotassiumlevelsistobeexpected.Inaclinicalstudy,howeverinsomepatientswithmildormoderaterenal

impairmentandconcomitantuseofpotassium-sparingmedicinalproductsserumpotassiumlevelsslightly,butnot

significantly,increasedduringdrospirenoneintake.Therefore,itisrecommendedtocheckserumpotassiumduringthe

firsttreatmentcycleinpatientspresentingwithrenalinsufficiencyandapretreatmentserumpotassiumintheupper

referencerange,andparticularlyduringconcomitantuseofpotassiumsparingmedicinalproducts.Seealsosection4.5.

Womenwithhypertriglyceridemia,orafamilyhistorythereof,maybeatanincreasedriskofpancreatitiswhenusing

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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-coatedTablets

acompletemedicalhistory(includingfamilyhistory)shouldbetakenandpregnancymustberuledout.Bloodpressure

shouldbemeasuredandaphysicalexaminationshouldbeperformed,guidedbythecontra-indications(seesection4.3)

andwarnings(seesection4.4).Thewomanshouldalsobeinstructedtocarefullyreadtheuserleafletandtoadhereto

theadvicegiven.Thefrequencyandnatureofexaminationsshouldbebasedonestablishedpracticeguidelinesandbe

adaptedtotheindividualwoman.

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

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However,iftheCOChasnotbeentakenaccordingtothesedirectionspriortothefirstmissedwithdrawalbleedorif

twowithdrawalsbleedsaremissed,pregnancymustberuledoutbeforeCOCuseiscontinued.

Theyellowtabletsofthismedicinalproductcontain62mgoflactosepertablet.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionwhoareonalactose-freedietshouldtakethisamountintoconsideration,shouldnottakethismedicine

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Note:Theprescribinginformationofconcomitantmedicationsshouldbeconsultedtoidentifypotentialinteractions.

InfluenceofothermedicinalproductsonEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coated

Tablets

Interactionsbetweenoralcontraceptivesandothermedicinalproductsmayleadtobreakthroughbleeding

and/orcontraceptivefailure.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.

Inwomanonlong-termtreatmentwithhepaticenzyme-inducingdrugs,expertshaverecommendedtoincreasethe

contraceptivesteroiddoses.

Ifahighcontraceptivedosageisnotdesirableorappearstobeunsatisfactoryorunreliable,e.g.inthecaseof

breakthroughbleeding,anothernon-hormonalcontraceptionmethodshouldbeadvised.

ThemainmetabolitesofdrospirenoneinhumanplasmaaregeneratedwithoutinvolvementofthecytochromeP450

system.Inhibitorsofthisenzymesystemarethereforeunlikelytoinfluencethemetabolismofdrospirenone.

InfluenceofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsonother

medicinalproducts

Oralcontraceptivesmayaffectthemetabolismofcertainotheractivesubstances.Accordingly,plasmaandtissue

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

Basedoninvitroinhibitionstudiesandinvivointeractionstudiesinfemalevolunteersusingomeprazole,simvastatin

andmidazolamasmarkersubstrate,aninteractionofdrospirenoneatdosesof3mgwiththemetabolismofotheractive

substancesisunlikely.

Otherinteractions

Inpatientswithoutrenalinsufficiency,theconcomitantuseofdrospirenoneandACE-inhibitorsorNSAIDsdidnot

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Nevertheless,concomitantuseofEthinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletswith

aldosteroneantagonistsorpotassium-sparingdiureticshasnotbeenstudied.Inthiscase,serumpotassiumshouldbe

testedduringthefirsttreatmentcycle.Seealsosection4.4.

Laboratorytests

Theuseofcontraceptivesteroidsmayinfluencetheresultsofcertainlaboratorytests,includingbiochemicalparameters

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

lipid/lipoproteinfractions,parametersofcarbohydratemetabolismandparametersofcoagulationandfibrinolysis.

Changesgenerallyremainwithinthenormallaboratoryrange.Drospirenonecausesanincreaseinplasmareninactivity

andplasmaaldosteroneinducedbyitsmildantimineralocorticoidactivity.

4.6Pregnancyandlactation

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

duringCOCuse.Theseamountsmayaffectthechild.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.Noeffectsonabilitytodrive

andusemachineshavebeenobservedinusersofCOCs.

4.8Undesirableeffects

ThefollowingadversedrugreactionshavebeenreportedduringuseofEthinylestradiol/DrospirenoneLeonFarma

0.03mg/3mgFilm-coatedTablets:

ThetablebelowreportsadversereactionsbyMedDRAsystemorganclasses(MedDRASOCs)..

SystemOrganClass Frequencyofadversereactions

Common Uncommon Rare

≥1/100to<1/10)

≥1/1,000to<1/100)

≥1/10,000to<1/1,000)

Immunesystem

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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

functionreturntonormal.

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

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

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Ethinylestradiol/DrospirenoneLeonFarma0.03mg/3mgFilm-coatedTabletsisacombinedoralcontraceptivewith

ethinylestradiolandtheprogestogendrospirenone.Inatherapeuticdosage,drospirenonealsopossessesantiandrogenic

andmildantimineralocorticoidproperties.Ithasnoestrogenic,glucocorticoidandantiglucocorticoidactivity.This

givesdrospirenoneapharmacologicalprofilecloselyresemblingthenaturalhormoneprogesterone.

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.

Themeanapparentvolumeofdistributionofdrospirenoneis3.7±1.2l/kg.

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-lifeofmetaboliteexcretionwiththeurineandfaecesisabout40h.

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

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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

Ethinylestradiolismetabolizedcompletely(metabolicplasmaclearance5ml/min/kg).

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

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Polysorbate80

Magnesiumstearate

Coating:

Polyvinylalcoholpartialhydrolyzed

Titaniumdioxide(E171)

Macrogol3350

Talc

Yellowironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Blistersofaluminiumpush-throughfoilandPVC/PVDCfilm.

Packsizes:

1x21film-coatedtablets

2x21film-coatedtablets

3x21film-coatedtablets

6x21film-coatedtablets

13x21film-coatedtablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

LaboratoriosLeonFarmaS.A.

C/RoadelaVega15

1-24008Leon

Spain

8MARKETINGAUTHORISATIONNUMBER

PA1474/2/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:9thOctober2009

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