CYPROTERONE ACETATE/ETHINYLESTRADIOL

Main information

  • Trade name:
  • CYPROTERONE ACETATE/ETHINYLESTRADIOL
  • Dosage:
  • 2mg/35ug %v/v
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CYPROTERONE ACETATE/ETHINYLESTRADIOL
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0405/032/002
  • Authorization date:
  • 10-12-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CyproteroneAcetate/EthinylestradiolTablets2mg/0.035mg

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onecoatedtabletcontains:

Cyproteroneacetate2.000mg

Ethinylestradiol 0.035mg

Forexcipients,see6.1.

3PHARMACEUTICALFORM

CoatedTablet.

Eachtabletisround,beigeincolourwithnomarkings.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CyproteroneAcetate/EthinylestradiolTablets2mg/0.035mgisrecommendedforuseinwomenonlyforthetreatmentof

Severeandrogen-dependentacne,refractorytoprolongedantibiotictherapy,or

Moderatelyseverehirsutism

Inwomenrequiringtreatmentfortheseconditions,cyproteroneacetate/ethinylestradiolalsoprovidescontraception

(seeSection4.4Warningsandprecautionsforuse).

4.2Posologyandmethodofadministration

CypteroneAcetate/Ethinylestradiolinhibitsovulationandtherebypreventsconception.Patientswhoareusing

CyproteroneAcetate/Ethinylestradiolshouldnotthereforeuseanadditionalhormonalcontraceptive,asthiswillexpose

thepatienttoanexcessivedoseofhormonesandisnotnecessaryforeffectivecontraception.

Thefirstperiodoftreatmentisstartedonthefirstdayofthemenstrualcyclethenonetabletdailyfor21days.Each

subsequentcourseisstartedafter7tablet-freedays.

Withdrawalbleedingusuallyoccursby2-4daysafterthelasttablet.Ifthisdoesnotoccur,itmaybenecessaryto

excludepregnancy.

Startingtablets

Noprevioushormonalcontraception(duringtheprecedingmonth):Tabletsshouldbestartedonday1ofthenatural

menstrualcycle(firstdayofbleeding).Tablet-takingmayalsobestartedduringbleedingdays2-5,butinthatcasean

additionalnon-hormonalcontraceptivemethodisrecommendedforthefirstsevendaysofthefirstcycle.

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ofthelastactivetabletoftheoldcombinedoralcontraceptive,andatthelatestfollowingtheusualtablet-freeinterval

oftheoldcombinedoralcontraceptiveorafteraplacebotabletcourse.

Switchfromprogestin-onlycontraceptives(minipills,injections,implants):Theswitchfromminipillscanbemadeat

alltimes(theswitchfromimplantsonthedayofitsremovalandfrominjectionsonthenextscheduleddayof

injection),buttheusershouldbeadvisedtouseanadditionalnon-hormonalcontraceptivemethodforthefirstseven

daysoftablet-taking.

Afterabortionduringthefirsttrimester:Tablet-takingcanbestartedimmediately.Inthiscasenoothercontraceptive

methodisneeded.

Afterchildbirthorabortionduringthesecondtrimester:Breastfeedingmothers:seeparagraph4.6.Theuseofthe

tabletsshouldbestarted21to28daysafterchildbirthorabortionduringthesecondtrimester.Iftablet-takingisstarted

laterthanthis,anadditionalnon-hormonalcontraceptivemethodshouldbeusedforthefirstsevendaysoftablet-

taking.However,ifintercoursehasalreadyoccurred,pregnancyshouldbeexcludedorthewomanshouldwaitforher

firstnaturalperiodbeforestartingthenexttablet.

Missingtablets:Ifthepatientforgetsasingletablet,itshouldbetakenwithin12hoursofthecorrecttimetomaintain

contraceptiveprotection.Withlargererrors,additionalcontraceptionisneeded.Onlythemostrecentdelayedtablet

shouldbetaken,earliermissedtabletsbeingomittedandadditionalcontraception(barriersandspermicides)shouldbe

usedforthenext7dayswhilethenext7tabletsaretaken.Ifpillshavebeenmissedduringthelast7daysofapack,

thereshouldbenobreakbeforethenextpackisstarted.

Vomiting:Ifvomitingoccurstabletsshouldbetakenatregulartimeperiods.Inaddition,asupplementalnon-

hormonalcontraceptivemethodshouldbeusedforthenext7days.

Durationoftreatment

Completeremissionofacneistobeexpectedinnearlyallcaseswithinafewmonths,butinparticularlyseverecases

treatmentforlongermaybenecessarybeforethefullbenefitisseen.Itisrecommendedthattreatmentbewithdrawn3

to4cycesaftertheindicatedcondition(s)has/havecompletelyresolvedandthatCyproteroneAcetate/Ethinylestradiol

isnotcontinuedsolelytoprovideoralcontraception.RepeatcoursesofCyproteroneAcetate/Ethinylestradiolmaybe

giveniftheandrogen-dependentcondition(s)recur.

4.3Contraindications

PregnancyandLactation(see4.4Specialwarningsandspecialprecautionsforuseand5.3Preclinicalsafety

data).

Severedisturbancesofliverfunction,jaundiceorpersistentitchingduringapreviouspregnancy,Dublin-Johnson

syndrome,Rotorsyndrome,previousorexistinglivertumours.

Personalorfamilyhistoryofconfirmed,idiopathicvenousthromboembolism(VTE)(whereafamilyhistoryrefers

toVTEinasiblingorparentatarelativelyearlyage).

Currentvenousthromboticorembolicprocesses.

Existingorpreviousarterialthromboticorembolicprocesses.

Thepresenceofasevereormultipleriskfactor(s)forvenousorarterialthrombosismayalsoconstitutea

contraindication(seesection4.4Specialwarningsandprecautionsforuse).

Sickle-cellanaemia.

Mammaryorendometrialcarcinoma,orahistoryoftheseconditions.

Severediabetesmellituswithvascularchanges.

Abnormalvaginalbleedingofunknowncause.

Disordersoflipidmetabolism

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Deteriorationofotosclerosisduringpregnancy.

Hypersensitivitytocyproteroneacetate,ethinylestradioloranyoftheexcipientsoftheproduct.

Migrainewithfocalneurologicalsystems.

4.4Specialwarningsandprecautionsforuse

Priortotheinitiationorreinstitutionoftreatmentacompletemedicalhistory(includingfamilyhistory)shouldbetaken

andpregnancymustberuledout.Bloodpressureshouldalwaysbemeasured.Otherphysicalexaminationshouldbe

guidedbytheindividual’smedicalhistoryandbythecontraindications(section4.3)andwarnings(section4.4).The

frequencyandnatureofexaminationsshouldbebasedonestablishedpracticeguidelinesandbeadaptedtothe

individualwoman.Thewomanshouldalsobeinstructedtocarefullyreadtheuserleafletandtoadheretotheadvice

given.

Warnings:Likemanyothersteroids,cyproteroneacetate,whengiveninveryhighdosesandforthemajorityofthe

animal’slifespan,hasbeenfoundtocauseanincreaseintheincidenceoftumours,includingcarcinoma,intheliverof

rats.Therelevanceofthisfindingtohumansisunknown.

Inrarecasesbenignandinevenrarercasesmalignantlivertumoursleadinginisolatedcasestolife-threateningintra-

abdominalhaemorrhagehavebeenobservedaftertheuseofhormonalsubstancessuchasthosecontainedin

CyproteroneAcetate/Ethinylestradiol.Ifsevereupperabdominalcomplaints,liverenlargementorsignsonintra-

abdominalhaemorrhageoccur,alivertumourshouldbeincludedinthedifferentialdiagnosis.

PregnancyisanabsolutecontraindicationfortreatmentwithCyproteroneacetate/Ethinylestradiolandmustbe

excludedbeforesuchtreatmentisbegun(seesection4.6Pregnancyandlactationandsection4.3Contraindications).

CyproteroneAcetate/Ethinylestradioliscomposedoftheprogestogencyproteroneacetateandtheoestrogen

ethinylestradiolandisadministeredfor21daysofthemonthlycycle.Itthereforehasasimilarcompositiontothatofa

combinedoralcontraceptive(COC).TheuseofanyCOCor‘CyproteroneAcetate/Ethinylestradiolcarriesan

increasedriskforvenousthromboembolism(VTE),includingdeepvenousthrombosisandpulmonaryembolism,

comparedwithnouse.TheexcessriskofVTEishighestduringthefirstyearawomeneverusesCOC.Thisincreased

riskislessthantheriskofVTEassociatedwithpregnancy,whichisestimatedas60per100,000pregnancies.

Fullrecoveryfromsuchdisordersdoesnotalwaysoccur;VTEisfatalin1-2%ofcases.

EpidemiologicalstudieshaveshownthattheincidenceofVTEinusersoforalcontraceptiveswithlowestrogen

content(<50µgethinylestradiol)isupto40casesper100,0000women-years.Thiscompareswith5-10casesper

100,000women-yearsfornon-users.

Certainfactorsmayincreasetheriskofvenousthrombosise.g.severeobesity(bodymassindex>30kg/m 2

),increasing

age,ageneticpredispositiontoclottingorapersonalorfamilyhistoryofconfirmed,idiopathicVTE(wherefamily

historyreferstoVTEinasiblingorparentatarelativelyearlyage,seeContraindicationssection4.3).Inaddition,the

riskofVTEmaybetemporarilyincreasedbyprolongedimmobilisation,majorsurgery,anysurgerytothelegs,or

majortrauma(see“ReasonsforstoppingCyproteroneacetate/Ethinylestradiolimmediately”).

ThereissomeepidemiologicalevidencethattheincidenceofVTEishigherinusersofCyproterone

acetate/EthinylestradiolwhencomparedtousersofCOCswithlowoestrogencontent(<50µg).

TheusergroupofCyproteroneacetate/Ethinylestradiolastreatmentforsevereacneormoderatelyseverehirsutismis

likelytoincludepatientsthatmayhaveaninherentlyincreasedcardiovascularrisksuchasthatassociatedwith

polycysticovariansyndrome.

EpidemiologicalstudieshavealsoassociatedtheuseofCOCswithanincreasedriskforarterial(myocardialinfarction,

transientischaemicattack)thromboembolism.Certainfactorssuchassmoking,obesity,cardiovasculardisease,

hypertension,diabetesandmigrainemayincreasetheriskofarterialthromboembolism.Theriskofarterialthrombosis

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Anincreasedriskofcervicalcancerinlong-termusersofcombinedoralcontraceptiveshasbeenreportedinsome

studies,buttherecontinuestobecontroversyabouttheextenttowhichthisisattributabletotheconfoundingeffectsof

sexualbehaviourandotherfactors.

Thepossibilitycannotberuledoutthatcertainchronicdiseasesmayoccasionallydeteriorateduringtheuseofthe

product(see‘Precautions’).

Ameta-analysisfrom54epidemiologicalstudiesreportedthatthereisaslightlyincreasedrelativerisk(RR=1.24)of

havingbreastcancerdiagnosedinwomenwhoarecurrentlyusingcombinedoralcontraceptives(COCs).Theexcess

riskgraduallydisappearsduringthecourseofthe10yearsaftercessationofCOCuse.Becausebreastcancerisrarein

womenunder40yearsofage,theexcessnumberofbreastcancerdiagnosesincurrentandrecentCOCusersissmallin

relationtotheoverallriskofbreastcancer.Theobservedpatternofincreasedriskmaybeduetoanearlierdiagnosisof

breastcancerinCOCusers,thebiologicaleffectsofCOCsoracombinationofboth.Thebreastcancersdiagnosedin

ever-userstendtobelessadvancedclinicallythanthecancersdiagnosedinnever-users.

Usewithcautioninwomenwithafamilyhistoryofbreastcancer.Womenonthistherapy,particularlywithfibrocystic

diseaseofthebreast,orwithafamilyhistoryofbreastcancer(firstdegreerelatives)shouldhaveregularbreast

examinations,includingmammography.

ReasonsforstoppingCyproteroneacetate/EthinylestradiolTablets2mg/0.035mgimmediately:

Occurrenceforthefirsttime,orexacerbation,ofmigrainousheadachesorunusuallyfrequentorunusuallysevere

headaches.

Suddendisturbancesofvision,orhearingorotherperceptualdisorders.

Firstsignsofthrombophlebitisorthromboembolicsymptoms(e.g.unusualpainsinorswellingofthelegs(s),stabbing

painsonbreathingorcoughingfornoapparentreason).Feelingofpainandtightnessinthechest.

Sixweeksbeforeanelectivemajoroperation(e.g.abdominal,orthopaedic),anysurgerytothelegs,medicaltreatment

forvaricoseveinsorprolongedimmobilisation,e.g.afteraccidentsorsurgery.Donotrestartuntil2weeksafterfull

ambulation.Incaseofemergencysurgery,thomboticprophylaxisisusuallyindicatede.g.subcutaneousheparin.

Onsetofjaundice,hepatitis,itchingofthewholebody.

Increaseinepilepticseizures.

Significantriseinbloodpressure.

Onsetofseveredepression.

Severeupperabdominalpainorliverenlargement.

Clearworseningofconditionsknowntodeteriorateduringuseofhormonalcontraceptionorduringpregnancy.

Pregnancyisareasonforstoppingimmediatelybecauseithasbeensuggestedbysomeinvestigationsthatoral

contraceptivestakenearlyinpregnancymayslightlyincreasetheriskoffoetalmalformations.Otherinvestigations

havefailedtosupportthesefindings.Thepossibilitythereforecannotbeexcluded,butitiscertainthatifariskexists

atall,itissmall.

Precautions:Itshouldbeborneinmindthattheuseofultravioletlampsforthetreatmentofacne,orprolonged

exposuretosunlight,increasestheriskofthedeteriorationofchloasma.

HerbalpreparationscontainingStJohn’swort(Hypericumperforatum)shouldnotbeusedwhiletakingCyproterone

Acetate/EthinylestradiolTabletsduetotheriskofdecreasedplasmaconcentrationsandreducedclinicaleffectsof

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Interactionwithotherdrugs:Somedrugstakenconcurrentlyacceleratethemetabolismofthehormonesandmay

reducethecontraceptivereliabilityoftheproductandincludebarbiturates,anti-epilepticssuchasprimidone,

phenobarbitone,phenytoinandcarbamazepine,phenylbutazone,rifampicin,ampicillin,griseofulvinandother

antibiotics.Oraltetracyclines,ifusedinconjunctionwiththeproduct,mayhavesuchaneffect,althoughithasnot

beenshown.Whendrugsoftheseclassesarebeingtaken,itis,therefore,advisabletouseadditionalmethodsof

contraception(excludingoralcontraceptivesandotherhormonalmethods)sinceanextremelyhighdegreeofprotection

mustbeprovidedwhentheproductisbeingtaken.Therequirementfororalantidiabeticsorinsulincanchange.MAO

inhibitorsinhibitthemetabolismofoestrogenwhichmaycauseoestrogeninducedside-effects.

TheherbalremedyStJohn’swort(Hypericumperforatum)shouldnotbetakenconcomitantlywiththismedicineas

thiscouldpotentiallyleadtoalossofcontraceptiveeffect.

Breakthroughbleedingandunintendedpregnancieshavebeenreported.Thisisduetoinductionofdrugmetabolising

enzymesbyStJohn’sWort.Theinducingeffectmaypersistforatleast2weeksaftercessationoftreatmentwithSt

John’swort.

Forwomentakingrifampicin,additionalcontraceptiveprecautionsshouldbecontinuedfor4weeksaftertreatment

stops,evenifonlyashortcoursewasadministered.

4.6Pregnancyandlactation

Theproductmustnotbeusedinpregnancyandlactation.

Pregnancyisanabsolutecontra-indicationfortreatmentwiththeproduct,andmustbeexcludedbeforesuchtreatment

isbegun.

Animalstudieshaverevealedthatfeminisationofmalefoetusesmayoccurifcyproteroneacetateisadministered

duringthephaseofembryogenesisatwhichdifferentiationoftheexternalgenitaliaoccurs.Althoughtheresultsof

thesetestsarenotnecessarilyrelevanttoman,thepossibilitymustbeconsideredthatadministrationoftheproductto

womenafterthe45thdayofpregnancycouldcausefeminisationofmalefoetuses.

Smallquantitiesofcyproteroneacetateandethinylestradiolmaybeexcretedinbreastmilk(0.2%and0.02%

respectively).

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

ThereisanincreasedriskofvenousthromboembolismforallwomenwhouseCyproteroneacetate/Ethinylestradiol

(seeSection4.4Specialwarningsandspecialprecautionsforuse).

Side-effectswhichhavebeenseeninconnectionwiththeuseofcombinedoralcontraceptivepillshavealsobeen

experiencedwhentakingCyproteroneAcetate/Ethinylestradioltablets.Around10–30%ofwomencanexpectsome

side-effectsduringthefirstfewcyclesoftreatment.Theseincludetensioninthebreasts,nausea,vomitting,headaches,

changedbodyweightorlibidoanddepressivemoods.Theseinitialside-effectsareoftenmildandusuallydisappear

within2–4monthsoftreatment.

Reductionofmenstrualflowmayoccur.Thisisnotabnormalanditistobeexpectedinsomepatients.

Ifwithdrawalbleedingdoesnotoccur,pregnancymustbeexcludedbyapregnancytestafterasuitableintervalbefore

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Verylight‘spotting’orheavierbreakthroughbleedingmayoccurduringtablet-taking,especiallyinthefirstfew

cycles.Itappearstobegenerallyofnosignificanceexceptwhereitindicateserrorsoftablet-taking,orwherethe

possibilityofinteractionwithotherdrugsexists.However,ifirregularbleedingispersistent,anorganiccauseshould

beconsidered.

Theuseofcombinedoralcontraceptives(COCs)isassociatedwithanincreasedriskforvenous(deepvenous

thrombosis,pulmonaryembolism)andarterial(myocardialinfarction,transientischaemicattack)thromboembolism.

(SeeSection4.4.Specialwarningsandspecialprecautionsforuse).

Transientliverfunctionchangesmayoccur;occasionallytheremayalsoberaisedblood-pressureinwomenwhoare

predisposedtothis.Insomecasestherehasbeenareducedtolerancetocontactlenswear.

Theradio-iodineuptakeshowsthatthyroidfunctionisunchanged.Thereisariseinserumprotein-boundiodine,

similartothatinpregnancyandduringtheadministrationofoestrogens.Thisisduetotheincreasedcapacityofthe

plasmaproteinsforbindingthyroidhormones,ratherthantoanychangeinglandularfunction.Inwomentakingthe

product,thecontentofprotein-boundiodineinbloodserumshould,therefore,notbeusedfortheevaluationofthyroid

function.

Theproductmayaccelerateerythrocytesedimentationintheabsenceofanydisease.Thiseffectisduetochangeinthe

proportionoftheplasmaproteinfractions.Increasesinplasmacopper,ironandalkalinephosphatasehavealsobeen

recorded.

4.9Overdose

Therehavebeennoreportsconcerningoverdosage,but,ongeneralprinciplesfromaknowledgeofthe

pharmacologicalactionsoftheconstituentsoftheproduct,itwouldseemunnecessarytotreat.Therearenospecific

Common

(>1/100) General:Changeinbody-weight,headache,migraine

CNS:Depressivemoods,changeinlibido

Endocrine:Breasttension

Gastrointestinal:Nausea,vomiting

Urogenital:Bleeding,dysmenorrhoea

Lesscommon General:Fluidretention

Circulation:Elevationofbloodpressure

Urogenital:Reductionofmenstrualflow

Rare

(<1/1000) Circulation:Venousthromboembolism(deepvenousthrombosis,

pulmonaryembolism.Arterialthromboembolism(myocardialinfarction,

ischaemicattack).

Endocrine:Decreasedglucosetolerance,elevatedbloodsugar,increased

insulinneed,pancreatitis

Skin:Chloasma,pruritus,alopecia

Liver:Reversibleelevationoftransaminaselevels,hepatitis,intrahepatic

cholestasis,gallstones,benignliveradenoma,focalnodularhyperplasia

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:G03HB AntiandrogenandEstrogens

Cyproteroneandestrogen

CyproteroneAcetatepossessesanti-androgenicandprogestationalactivity.Itblocksandrogen-receptors;italso

reducesandrogensynthesisbyanegativefeedbackeffectonthehypothalamo-pituitary-ovariansystems.Sexhormone-

bindingglobulin(SHBG)levelsareincreasedbytheoestrogencomponentoftheproduct,thusreducingthefree,

circulatingplasmalevelsofandrogens.Unlikesomeotherprogestogens,cyproteroneacetatehasnotendencytoreduce

SHBGlevels.Theoestrogencomponentalsoactsasanoralcontraceptive,withamodeofactionsimilartothosefor

oestrogensingeneral.

Theresultsfromepidemiologicalinvestigationshaveshownthattheuseofhighdosedcombinedoral

contraceptives(50µgethinylestradiol)lowerstheriskofendometrialandovariancancer.However,ithasyetto

beestablishedwhetherthebeneficialeffectsalsoapplytothelowerdoseoralcontraceptives.

5.2Pharmacokineticproperties

CyproteroneAcetate

Afteroraladministrationof2mgCyproteroneAcetatesugar-coatedtablets,CPAiscompletelyabsorbed.Itisrapidly

metabolisedandslowlyexcretedinthefaecesandurine.Itsterminalt½afterasingleoral50mgdosetohealthy

volunteershasbeenreportedtobebetween38h(radioimmunoassay)and39h(totalradioactivity)althoughaterminal

half-lifeinhealthyvolunteersofupto100hourshasalsobeenreported.

CyproteroneAcetateismetabolisedfirstbyhydrolysistofreecyproterone,thenby15-hydroxylationto15-

hydroxycyproterone.Thismetabolitehas10%oftheprogestationalactivityofCyproteroneAcetatebuthassimilar

anti-androgenicactivity.Excretioniseffectedslowlyviathekidneysandfaeces.

Ethinylestradiol

Ethinylestradiolisrapidlyandalmostcompletelyabsorbedfromthegastro-intestinaltract,butistoacertaindegree

subjecttoafirst-pastmetabolismintheintestinewall.Bioavailabilityamountstoapproximately40%.Maximum

plasmaconcentrationsareachieved1-2hoursafteroralapplication.Ethinylestradiolaccumulatesinthebodyfatand

endometrium.Thereported(half-lifet½)variesfrom6to30hours.Incomparisontootheroestrogensitisonly

metabolisedslowlyintheliver.Itisconjugatedwithglucuronicacidandsulphate.Ethinylestradiolissubjecttoa

clearenterohepaticcycle.60%ofexcretioniseffectedviathekidneysand40%viafaeces.

5.3Preclinicalsafetydata

Inlaboratoryanimals,mostoftheeffectsofcyproteroneacetatefollowingrepeatedadministrationarerelatedtothe

anti-androgenicandprogestagenicactionsofthedrug.Inratandmousestudies,cyproteroneacetateproducedan

inductionofliverenzymesandliverhypertrophy.

Thepotentiallysensitisingeffectofethinylestradiolandcyproteroneacetatehasnotbeenstudiedinanimals.

Recognizedfirst-linetestsofgenotoxicitygavenegativeresultswhenconductedwithcyproteroneacetate.However,

furthertestsshowedthatcyproteroneacetatewascapableofproducingadductswithDNA(andanincreaseinDNA

repairactivity)inlivercellsfromratsandmonkeysandalsoinfreshlyisolatedhumanhepatocytes.ThisDNA-adduct

formationoccurredatexposuresthatmightbeexpectedtooccurintherecommendeddoseregimensforcyproterone

acetate.Onein-vivoconsequenceofcyproteroneacetatetreatmentwastheincreasedincidenceoffocal,possiblypre-

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Theclinicalrelevanceofthesefindingsispresentlyuncertain.Clinicalexperiencewithcyproteroneacetatetodate

wouldnotsupportanincreasedincidenceofhepatictumoursinman.

Inlong-termstudiesinmiceandratscyproteroneacetateenhancedtheincidencesoftumoursofthepituitary,liver

and/ormammarygland.Long-termtreatmentwithethinylestradiolcanalsoenhancetheincidencesofcertain

neoplasmsinlaboratoryanimals.Theclinicalrelevancewithrespecttolow-dosetreatmentwithcyproteroneacetate

andethinylestradiolis,however,questionable.

Theuseofthispreparationiscontraindicatedduringpregnancy(forfurtherinformationseeSections4.3and4.4).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

Lactosemonohydrate

Maizestarch

Povidone25000

Talc

Magnesiumstearate

TabletCoat

Sucrose

Povidone700000

Macrogol6000

Calciumcarbonate

Talc

Glycerol

Titaniumdioxide(E171)

Ironoxidepigmentyellow(E172)

Montanglycolwax

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Keepcontainerintheoutercarton.

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

Blisterstrips

Polyvinylchlorideblisterssealedontoaluminiumfoil.

Packsizes

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Generics(UK)Limited,

StationClose,PottersBar,

HertfordshireEN61TL,

UnitedKingdom.

8MARKETINGAUTHORISATIONNUMBER

PA0405/032/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10December1999

Dateoflastrenewal: 09October2001

10DATEOFREVISIONOFTHETEXT

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