CERAZETTE

Main information

  • Trade name:
  • CERAZETTE Film Coated Tablet 75 Microgram
  • Dosage:
  • 75 Microgram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CERAZETTE Film Coated Tablet 75 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0061/027/001
  • Authorization date:
  • 14-08-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0061/027/001

CaseNo:2037806

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

Organon(Ireland)Limited

DrynamRoad,Swords,Co.Dublin,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cerazette75microgramfilm-coatedtablet

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom12/12/2007.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cerazette75microgramfilm-coatedtablet

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains75microgramdesogestrel.

Excipientlactose<65mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

Thetabletiswhite,round,biconvexand5mmindiameter.OnonesideitiscodedKVabove2andonthereverseside

Organon*.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Contraception.

4.2Posologyandmethodofadministration

HowtotakeCerazette:

Tabletsmustbetakeneverydayataboutthesametimesothattheintervalbetweentwotabletsalwaysis24hours.The

firsttabletshouldbetakenonthefirstdayofmenstrualbleeding.Thereafteronetableteachdayistobetaken

continuously,withouttakinganynoticeonpossiblebleedings.Anewblisterisstarteddirectlythedayafterthe

previousone.

HowtostartCerazette:

Noprecedinghormonalcontraceptiveuse[inthepastmonth].

Tablettakinghastostartonday1ofthewoman’snaturalcycle(day1isthefirstdayofhermenstrualbleeding).

Startingondays2-5isallowed,butduringthefirstcycleabarriermethodisrecommendedforthefirst7daysoftablet-

taking.

Followingfirst-trimesterabortion:

Afterfirst-trimesterabortionitisrecommendedtostartimmediately.Inthatcasethereisnoneedtouseanadditional

methodofcontraception.

Followingdeliveryorsecond-trimesterabortion:

ContraceptivetreatmentwithCerazetteafterdeliverycanbeinitiatedbeforethemenstruationshavereturned.Ifmore

than21dayshaveelapsedpregnancyoughttoberuledoutandanadditionalmethodofcontraceptionshouldbeused

forthefirstweek.

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HowtostartCerazettewhenchangingfromothercontraceptivemethods:

Changingfromacombinedhormonalcontraceptive(combinedhormonalcontraceptive(COC),vaginalringor

transdermalpatch).

ThewomanshouldstartwithCerazettepreferablyonthedayafterthelastactivetablet(thelasttabletcontainingthe

activesubstances)ofherpreviousCOCoronthedayofremovalofhervaginalringortransdermalpatch.Inthese

cases,theuseofanadditionalcontraceptiveisnotnecessary.NotallcontraceptivemethodsmaybeavailableinallEU

countries.

Thewomenmayalsostartatthelatestonthedayfollowingtheusualtablet-free,patch-free,ring-free,orplacebotablet

intervalofherpreviouscombinedhormonalcontraceptive,butduringthefirst7daysoftablet-takinganaddtional

barriermethodisrecommended.

Changingfromaprogestogen-only-method(minipill,injection,implant,orfromaprogestogen-releasingintrauterine

system[IUS]):

Thewomanmayswitchanydayfromtheminipill(fromanimplantortheIUSonthedayofitsremoval,froman

injectablewhenthenextinjectionwouldbedue.

Managementofmissedtablets:

Contraceptiveprotectionmaybereducedifmorethan36hourshaveelapsedbetweentwotablets.Iftheuserisless

than12hourslateintakinganytablet,themissedtabletshouldbetakenassoonasitisrememberedandthenexttablet

shouldbetakenattheusualtime.Ifsheismorethan12hourslate,sheshoulduseanadditionalmethodof

contraceptionforthenext7days.Iftabletsweremissedinthefirstweekandintercoursetookplaceintheweekbefore

thetabletsweremissed,thepossibilityofapregnancyshouldbeconsidered.

Adviceincaseofgastrointestinaldistubances:

Incaseofseveregastrointestinaldisturbance,absorptionmaynotbecompleteandadditonalcontraceptivemeasures

shouldbetaken.Ifvomittingoccurswithin3-4hoursaftertablettakingabsorbtionmaynotbecomplete.Insuchan

eventtheadviceconcerningmissedtabletsasgiveninsection4.2isapplicable

Treatmentsurveillance

Beforeprescription,athoroughcasehistoryshouldbetakenandathoroughgynaecologicalexaminationis

recommendedtoexcludepregnancy.Bleedingdisturbances,suchasoligomenorrhoeaandamenorrhoeashouldbe

investigatedbeforeprescription.Theintervalbetweencheck-upsdependsonthecircumstancesineachindividualcase.

Iftheprescribedproductmayconceivablyinfluencelatentormanifestdisease(seeSection4.4),thecontrol

examinationsshouldbetimedaccordingly.

DespitethefactthatCerazette ®

istakenregularly,bleedingdisturbancesmayoccur.Ifthebleedingsareveryfrequent

andirregular,anothercontraceptivemethodshouldbeconsidered.Ifthesymptomspersist,anorganiccauseshouldbe

ruledout.

Managementofamenorrhoeaduringtreatmentdependsonwhetherornotthetabletshavebeentakeninaccordance

withtheinstructionsandmayincludeapregnancytest.

Thetreatmentshouldbestoppedifapregnancyoccurs.

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4.3Contraindications

Knownorsuspectedpregnancy.

Activevenousthromboembolicdisorder.

Presenceorhistoryofseverehepaticdiseaseaslongasliverfunctionvalueshavenotreturnedtonormal.

Knownorsuspectedsex-steroidsensitivemalignancies.

Undiagnosedvaginalbleeding.

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Ifanycondition/riskfactorsmentionedbelowispresentthebenefitsofprogestogenuseshouldbeweighedagainstthe

possiblerisksforeachindividualwomananddiscussedwiththewomanbeforeshedecidestostartCerazette.Inthe

eventofaggravation,exacerbation,orfirstappearenceofanyoftheseconditions,thewomanshouldcontacther

physician.ThephysicianshouldthendecideonwhethertheuseofCerazetteshouldbediscontinued.

Theriskforbreastcancerincreasesingeneralwithincreasingage.Duringtheuseofcombinedoralcontraceptives

(COCs)theriskforhavingbreastcancerdiagnosedisslightlyincreased.Thisincreasedriskdisappearsgradually

within10yearsafterdiscontinuationofCOCuseandisnotrelatedtothedurationofuse,buttotheageofthewoman

whenusingtheCOC.Theexpectednumberofcasesdiagnosedper10000womenwhousecombinedCOCs(upto10

yearsafterstopping)relativetoneverusersoverthesameperiodhasbeencalculatedfortherespectiveagegroupsand

ispresentedinthetablebelow.

Theriskinusersofprogestogen-onlycontraceptives(POC),suchasCerazette,ispossiblyofsimilarmagnitudeasthat

associatedwithCOCs.However,forPOCstheevidenceislessconclusive.Comparedtotheriskofgettingbreast

cancereveninlife,theincreasedriskassociatedwithCOCsislow.ThecasesofbreastcancerdiagnosedinCOCusers

tendtobelessadvancedthaninthosewhohavenotusedCOCs.TheincreasedriskinCOCusersmaybeduetoan

earlierdiagnosis,biologicaleffectsofthepilloracombinationofboth.

Sinceabiologicaleffectofprogestogensonlivercancercannotbeexcludedanindividualbenefit/riskassessment

shouldbemadeinwomenwithlivercancer.

Whenacuteorchronicdisturbancesofliverfunctionoccur,thewomanshouldbereferredtoaspecialistfor

examinationandadvice.

EpidemiologicalinvestigationshaveassociatedtheuseofCOCswithanincreasedincidenceofvenous

thromboembolism(VTE,deepvenousthrombosisandpulmonaryembolism).Althoughtheclinicalrelevanceofthis

findingfordesogestrelusedasacontraceptiveintheabsenceofanoestrogeniccomponentisunknown,Cerazette

shouldbediscontinuedintheeventofathrombosis.DiscontinuationofCerazetteshouldalsobeconsideredincaseof

long-termimmobilisationduetosurgeryorillness.Womenwithahistoryofthrombo-embolicdisordersshouldbe

madeawareofthepossibilityofarecurrence.

Althoughprogestogensmayhaveaneffectonperipheralinsulinresistanceandglucosetolerance,thereisnoevidence

foraneedtoalterthetherapeuticregimenindiabeticsusingprogestogen-onlypills.However,diabeticpatientsshould

Agegroup ExpectedcasesCOC-users Expectedcasesnon-users

16-19years 4.5 4

20-24years 17.5 16

25-29years 48.7 44

30-34years 110 100

35-39years 180 160

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IfsustainedhypertensiondevelopsduringtheuseofCerazette,orifasignificantincreaseinbloodpressuredoesnot

adequatelyrespondtoantihypertensivetherapy,thediscontinuationofCerazetteshouldbeconsidered.

TreatmentwithCerazetteleadstodecreasedestradiolserumlevels,toalevelcorrespondingwiththeearlyfollicular

phase.Itisasyetunknownwhetherthedecreasehasanyclinicallyrelevanteffectonbonemineraldensity.

Theprotectionwithtraditionalprogestogen-onlypillsagainstectopicpregnanciesisnotasgoodaswithcombinedoral

contraceptives,whichhasbeenassociatedwiththefrequentoccurrenceofovulationsduringtheuseofprogestogen-

onlypills.DespitethefactthatCerazetteconsistentlyinhibitsovulation,ectopicpregnancyshouldbetakeninto

accountinthedifferentialdiagnosisifthewomangetsamenorrhoeaorabdominalpain.

Chloasmamayoccasionallyoccur,especiallyinwomenwithahistoryofchloasmagravidarum.Womenwitha

tendencytochloasmashouldavoidexposuretothesunorultravioletradiationwhilsttakingCerazette ®

Thefollowingconditionshavebeenreportedbothduringpregnancyandduringsexsteroiduse,butanassociationwith

theuseofprogestogenshasnotbeenestablished:jaundiceand/orpruritusrelatedtocholestasis;gallstoneformation;

porphyria;systemiclupuserythematosus;haemolyticuraemicsyndrome;Sydenham'schorea;herpesgestations;

otosclerosis-relatedhearingloss;(hereditary)angioedema

Cerazettecontainslessthan65mglactoseandthereforeshouldnotbeadministeredtopatientswithrarehereditary

problemsofgalactoseintolerance,theLapplactasedeficiency,orglucose-galactosemalabsorption.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Interactions

Interactionsbetweenhormonalcontraceptivesandothermedicinalproductsmayleadtobreakthroughbleedingand/or

contraceptivefailure.Thefollowinginteractionshavebeenreportedintheliterature(mainlywithcombined

contraceptivesbutoccasionallyalsowithprogestogen-onlycontraceptives).

Hepaticmetabolism:Interactionscanoccurwithmedicinalproductsthatinducemicrosomalenzymes,whichcanresult

inincreasedclearanceofsexhormones(suchas,hydantoins,(e.g.phenytoin),barbiturates(e.g.phenobarbital),

primidone,carbamazepine,rifampicin,andpossiblyalsoforoxcarbazepine,topiramate,rifabutin,felbamate,ritonavir,

nelfinavir,griseofulvinandproductscontainingSt.John'swort(Hypericumperforatum))

Maximalenzymeinductionisnotseenfor2-3weeks,butmaythenbesustainedforatleast4weeksaftercessationof

drugtherapy.

Womenontreatmentwithanyofthesemedicinalproductsshouldtemporarilyuseabarriermethodinadditionto

Cerazette.Withmicrosomalenzyme-inducingdrugs,thebarriermethodshouldbeusedduringthetimeofconcomitant

drugadministrationandfor28daysafterdiscontinuation.Forwomenonlong-termtreatmentwithhepaticenzyme

inducersanon-hormonalmethodofcontraceptionshouldbeconsidered.

Duringthetreatmentwithmedicalcharcoal,theabsorptionofsteroidinthetabletmaybereducedandtherebythe

contraceptiveefficicacy.UnderthesecircumstancestheadviceasgivenformissedpillsinSection4.2isapplicable.

Hormonalcontraceptivesmayinterferewiththemetabolismofotherdrugs.Accordingly,plasmaandtissue

concentrationsmayeitherincrease(e.g.cyclosporin)ordecrease.

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Laboratorytests

DataobtainedwithCOCshavebeenshownthatcontraceptivesteroidsmayinfluencetheresultsofcertainlaboratory

tests,includingbiochemicalparametersofliver,thyroid,adrenalandrenalfunction,serumlevelsof(carrier)proteins,

e.g.corticosteroidbindingglobulinandlipid/lipoproteinfractions,parametersofcarbohydratemetabolismand

parametersofcoagulationandfibrinolysis.Thechangesgenerallyremainwithinnormalrange.Towhatextentthisalso

appliestoprogestogen-onlycontraceptivesisnotknown.

4.6Pregnancyandlactation

Animalstudieshaveshownthatveryhighdosesofprogestagenicsubstancesmaycausemasculinisationoffemale

foetuses.

Extensiveepidemiologicalstudieshaverevealedneitheranincreasedriskofbirthdefectsinchildrenborntowomen

whousedCOCspriortopregnancy,norateratogeniceffectwhenCOCsweretakeninadvertentlyduringearly

pregnancy.Pharmacovigilancedatacollectedwithvariousdesogestrel-containingcombinedCOCsalsodonotindicate

anincreasedrisk.

Cerazette ®

doesnotinfluencetheproductionorthequality(protein,lactose,orfatconcentrations)ofbreastmilk.

However,smallamountsofetonogestrelareexcretedinthebreastmilk.Asaresult,0.01-0.05microgrametonogestrel

perkgbodyweightperdaymaybeingestedbythechild(basedonanestimatedmilkingestionof150ml/kg/day).

Limitedlong-termfollowupdataareavailableonchildren,whosemothersstartedusingCerazetteduringthe4 th

to8 th

weekpost-partum.Theywerebreast-fedfor7monthsandfollowedupto1.5uears(n=32)orto2.5years(n=14)of

age.Evaluationofgrowthandphysicalandpsychomotordevelopmentdidnotindicateanydifferencescomparedwith

nursinginfants,whosemotherusedacopperIUD.BasedontheavailabledataCerazettemaybeusedduringlactation.

Thedevelopmentandgrowthofanursinginfant,whosemotherusesCerazette,shouldhowever,becarefullyobserved.

4.7Effectsonabilitytodriveandusemachines

Cerazettehasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

Themostcommonlyreportedundesirableeffectintheclinicaltrialsisbleedingirregularity.Somekindofbleeding

irregularityhasbeenreportedinupto50%ofwomenusingCerazette ®

.SinceCerazette ®

causesovulationinhibition

closeto100%,incontrasttootherprogestogen-onlypills,irregularbleedingismorecommonthanwithother

progestogen-onlypills.In20-30%ofthewomen,bleedingmaybecomemorefrequent,whereasinanother20%

bleedingmaybecomelessfrequentortotallyabsent.Vaginalbleedingmayalsobeoflongerduration.Afteracoupleof

monthsoftreatment,bleedingstendtobecomelessfrequent.Information,counsellingandableedingdiarycan

improvethewoman’sacceptanceofthebleedingpattern.

ThemostcommonlyreportedothersideeffectsintheclinicaltrialswithCerazette ®

(>2.5%)wereacne,mood

changes,breastpain,nauseaandweightincrease.Thesideeffectsmentionedbelowhavebeenjudgedbythe

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MedDRAversion9.0

BreastdischargemayoccurduringuseofCerazette.Onrareoccasions,ectopicpregnancieshavebeenreported(see

Section4.4).

Inwomenusing(combined)oralcontraceptivesanumberof(serious)undesirableeffectshavebeenreported.These

includevenousthromboembolicdisorders,arterialthromboembolicdisorders,hormone-dependenttumours(e.g.liver

tumours,breastcancer)andchloasmasomeofwhicharediscussedinmoredetailinSection4.4.

4.9Overdose

Therehavebeennoreportsofseriousdeleteriouseffectsfromoverdose.Symptomsthatmayoccurinthiscaseare:

nausea,vomitingand,inyounggirls,slightvaginalbleeding.Therearenoantidotesandfurthertreatmentshouldbe

symptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:hormonalcontraceptivesforsystemicuse,

ATCcode:G03AC09.

Cerazetteisaprogestogen-onlypill,whichcontainstheprogestogendesogestrel.Likeotherprogestogen-onlypills,

Cerazetteisbestsuitedforuseduringbreastfeedingandforwomenwhomaynotordonotwanttouseoestrogens.In

contrasttotraditionalprogestogen-onlypills,thecontraceptiveeffectofCerazetteisachievedprimarilybyinhibitionof

SystemOrganClass

(MedDRA)* Frequencyofadversereactions

Common

≥1/100 Uncommon

<1/100, ≥1/1000 Rare

(<1/1000)

Infectionsandinfestations Vaginalinfection

Psychiatricdisorders Moodaltered,

Libido

decreased

Nervoussystemdisorders Headache

Eyedisorders Contactlens

intolerance

Gastrointestinaldisorders Nausea Vomiting

Skinandsubcutaneoustissue

disorders Acne Alopecia Rash,

Urticaria,

Erythema

nodosum

Reproductivesystemandbreast

disorders Breastpain,

Menstruation

irregular,

Amenorrhoea Dysmenorrhoea

Ovariancyst

Generaldisordersand

administrationsitecondition Fatigue

Investigations Weight

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Whenstudiedfor2cycles,usingadefinitionofovulationasaprogesteronelevelgreaterthan16nmol/Lfor5

consecutivedays,theovulationincidencewasfoundtobe1%(1/103)witha95%confidenceintervalof0.02%-

5.29%intheITTgroup(userandmethodfailures).Ovulationinhibitionwasachievedfromthefirstcycleofuse.In

thisstudy,whenCerazettewasdiscontinuedafter2cycles(56continuousdays)ovulationoccurredonaverageafter17

days(range7-30days).

Inacomparativeefficacytrial(whichallowedamaximumtimeof3hoursformissedpills),theoverallITTPearl–

IndexfoundforCerazettewas0.4(95%confidenceinterval0.09%-1.20%),comparedto1.6(95%confidenceinterval

0.42%-3.96%)for30µglevonorgestrel.

ThePearl-IndexforCerazetteiscomparabletotheonehistoricallyfoundforCOCsinthegeneralCOC-using

population.TreatmentwithCerazetteleadstodecreasedestradiollevels,toalevelcorrespondingtotheearlyfollicular

phase.Noclinicallyrelevanteffectsoncarbohydratemetabolism,lipidmetabolismandhaemostasishavebeen

observed.

5.2Pharmacokineticproperties

BSORPTION

AfteroraldosingofCerazette ®

desogestrel(DSG)israpidlyabsorbedandconvertedintoetonogestrel(ENG).Under

steady-stateconditions,peakserumlevelsarereached1.8hoursaftertablet-intakeandtheabsolutebioavailabilityof

ENGisapproximately70%.

ISTRIBUTION

ENGis95.5-99%boundtoserumproteins,predominantlytoalbuminandtoalesserextenttoSHBG.

ETABOLISM

DSGismetabolisedviahydroxylationanddehydrogenationtotheactivemetaboliteENG.ENGismetabolisedvia

sulphateandglucuronideconjugation.

LIMINATION

ENGiseliminatedwithameanhalf-lifeofapproximately30hours,withnodifferencebetweensingleandmultiple

dosing.Steady-statelevelsinplasmaarereachedafter4-5days.TheserumclearanceafterIVadministrationofENGis

approximately10lperhour.ExcretionofENGanditsmetaboliteseitherasfreesteroidorasconjugates,iswithurine

andfaeces(ratio1.5:1).Inlactatingwomen,ENGisexcretedinbreastmilkwithamilk/serumratioof0.37-0.55.

Basedonthesedataandanestimatedmilkintakeof150ml/kg/day,0.01-0.05microgrametonogestrelmaybe

ingestedbytheinfant.

5.3Preclinicalsafetydata

Toxicologicalstudiesdidnotrevealanyeffectsotherthanthosewhichcanbeexplainedfromthehormonalproperties

ofdesogestrel.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

Silica,Colloidalanhydrous

All-rac--tocopherol

Lactosemonhydrate

Maizestarch

Povidone

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Filmcoating

Hypromellose

Macrogol400

Talc

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

PVC/Aluminumblister.

Eachblistercontains28tablets.Eachcartoncontains1,3or6blisterspackedseparatelyinanalliuminiumlaminated

sachet.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

OrganonIrelandLtd

POBox2857

DrynamRoad

Swords

CoDublin

8MARKETINGAUTHORISATIONNUMBER

PA61/27/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Firstdateofauthorisation:14 th

August1998

Lastdateofrenewal:12 th

December2007

10DATEOFREVISIONOFTHETEXT

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