CYPROTERONE ACETATE

Main information

  • Trade name:
  • CYPROTERONE ACETATE
  • Dosage:
  • 50 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0405/032/001
  • Authorization date:
  • 24-06-1996
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CyproteroneAcetateTablets50 mg.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

CyproteroneAcetate50 mg.

3PHARMACEUTICALFORM

Tablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forcontroloflibido in severehypersexuality and/orsexualdeviation in theadultmale.

Forthemanagementofpatientswith prostaticcancer(1)to suppress“flare”with initialLHRHanaloguetherapy, (2)in

long-termpalliativetreatmentwhereLHRHanaloguesorsurgery arecontra-indicated, nottolerated, orwhereoral

therapy ispreferred, and (3)in thetreatmentofhotflushesin patientsundertreatmentwith LHRHanaloguesorwho

havehad an orchidectomy.

4.2Posologyandmethodofadminstration

Fororaladministration only.

Controloflibido in severehypersexuality and/orsexualdeviation

Adultsand theelderly:Theusualdoseis1 tablettwicedaily.Thedaily doseshould bedivided and taken afterthe

morning and evening meals.

Children (under18 yearsold):Notrecommended.

Themanagementofpatientswith prostaticcancer

Adultsand theelderly:To suppress“flare”with initialLHRHanaloguetherapy:300mg/day which may bereducedto

200 mg ifthehigherdoseisnottolerated.

In long termpalliativetreatmentwhereLHRHanaloguesorsurgery arecontraindicated, nottolerated, orwhen oral

therapy ispreferred:200–300mg/day.

In thetreatmentofhotflushesin patientsundertreatmentwith LHRHanaloguesorwho havehad an orchidectomy:

50mg starting dosewith upward titration ifnecessary within therange50–150mg/day.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Issued 28/10/2005 CRN 2016169 page number: 1

4.3Contraindications

Cyproteroneacetateiscontraindicated forusein patientswith:liverdisease;malignanttumours(otherthan prostatic

cancer);wasting diseases(becauseoftransientcatabolicaction);ahistory oforexisting thrombosisorembolism;

severediabeteswith vascularchanges;sickle-cellanaemia;severechronicdepression.Cyproteroneacetateshould not

begiven to youthsundertheageof18 orthosewhosebonematuration and testicularmaturation isincomplete.

4.4Special warningsandspecialprecautionsforuse

Directhepatictoxicity, including jaundice, hepatitisand hepaticfailure, which hasbeen fatalin somecases, hasbeen

reported in patientstreated with 200–300mg CyproteroneAcetate.Mostreported casesarein menwith prostatic

cancer.Toxicity isdose-related and develops, usually, severalmonthsaftertreatmenthasbegun.Liverfunction tests

should beperformed pre-treatmentand wheneverany symptomsorsignssuggestiveofhepatotoxicity occur.If

hepatotoxicity isconfirmed CyproteroneAcetateshould normally bewithdrawn, unlessthehepatotoxicity can be

explained by anothercause, e.g. metastaticdisease, in whichcaseCyproteroneAcetateshould becontinued only ifthe

perceived benefitoutweighstherisk.

Recognised first-linetestsofgenotoxicity gavenegativeresultswhen conducted with CyproteroneAcetate.However,

furthertestsshowed thatCyproteroneAcetatewascapableofproducing adductswith DNA(and increasein DNA

repairactivity)in livercellsfromratesand monkeysand also in freshly isolated human hepatocytes.

ThisDNAadductformation occurred atexposuresthatmightbeexpected to occurin therecommended doseregimens

forCyproteroneAcetate.Onein-vivoconsequenceofCyproteroneAcetatetreatmentwastheincreased incidenceof

focal, possibly pre-neoplastic, liverlesionsin which cellularenzymeswerealtered infemalerats.Theclinical

relevanceofthesefindingsispresently uncertain.Clinicalexperienceto datewould notsupportan increased incidence

ofhepatictumoursin man.

Adrenocorticalfunction:during treatmentadrenocorticalfunction should besupervised, sincesuppression hasbeen

observed.

Diabetes:CyproteroneAcetatecan influencecarbohydratemetabolism.Parametersofcarbohydratemetabolismshould

beexamined carefully in alldiabeticsbeforeand regularly during treatment.

ChronicAlcoholism:thechronicabuseofalcoholappearsto reducetheeffectofCyproteroneAcetatein male

hypersexuality buttherelevanceofthisto thetreatmentofprostaticcancerisnotknown.

Haemoglobin:hypochromicanaemiahasbeen found rarely during long termtreatment, and blood countsbeforeand at

regularintervalsduring treatmentareadvisable.

Nitrogen balance:anegativenitrogen balanceisusualatthestartoftreatment, butusually doesnotpersist.

Spermatogenesis:aspermatogramshould berecorded beforestarting treatmentin patientsofprocreativeage, asa

guard againstattribution ofpre-existing infertility to CyproteroneAcetateatalaterstage.

Itshould benoted thatdeclinein spermatogenesisisslowand CyproteroneAcetateshould notberegarded asamale

contraceptive.

Doctorsareadvised thatfully informed consentofthepatientto CyproteroneAcetatetreatmentshould beobtained and

beverified.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Issued 28/10/2005 CRN 2016169 page number: 2

4.6Pregnancyandlactation

Notapplicable.

4.7Effectsonabilitytodriveandusemachines

Markedlassitudeand astheniamay beexperiencedparticularlyduring thefirstfewweeksoftreatment, thisnecessitates

specialcarewhen driving oroperating machinery.

4.8Undesirableeffects

CyproteroneAcetatehasbeen found to causeliverabnormalitiesin animals, including thedevelopmentoftumours.

Disturbancesofliverfunction, someofthemsevere, havebeen reported with high-doseCyproteroneAcetate

treatment.Liverfunction testsshould beperformed regularly during treatment.

In rarecasesbenign and in even rarercasesmalignantlivertumours, leading in isolated casesto life-threatening intra-

abdominalhaemorrhage, havebeen observedaftertheuseofsex steroids, to which classCyproteroneAcetatebelongs.

Ifsevereupperabdominalcomplaints, liverenlargementorsignsofintra-abdominalhaemorrhageoccur, hepatic

tumourshould beconsidered in thedifferentialdiagnosisand, ifnecessary, CyproteroneAcetateshould bewithdrawn.

Inhibition ofspermatogenesis:thespermcountand thevolumeofejaculatearereduced.Infertility isusual, and there

may beazoospermiaaftereightweeks.Thereisusually slightatrophy oftheseminiferoustubules.Follow-up

examinationshaveshown thesechangesto bereversible, spermatogenesisusually reverting to itspreviousstateabout

threeto fivemonthsafterstopping treatmentorin someusersup to20 months.Thatspermatogenesiscan recovereven

aftervery long treatmentisuncertain.Thereisevidencethatabnormalsperms, which mightgiveriseto malformed

embryos, areproduced during treatment.

Thromboembolism:patientswith ahistory ofthrombosismaybeatrisk ofrecurrenceofthediseaseduring

CyproteroneAcetatetherapy.In patientswith ahistory ofthromboembolicprocessesorsuffering fromsickle-cell

anaemiaorseverediabeteswith vascularchanges, therisk:benefitratio mustbeconsidered carefully in each individual

casebeforeCyproteroneAcetateisprescribed.

ChronicDepression:ithasbeen found thatsomepatientswith severechronicdepression deterioratewhilsttaking

CyproteroneAcetatetherapy.

Tiredness:fatigueand lassitudearecommon in thefirstfewweeksoftreatmentbutbecomelessfromthethird month.

Breathlessness:asensation ofshortnessofbreath may occurunderhigh-dosetreatmentwith CyproteroneAcetate,

owing to theknown stimulatory effectofprogesteroneandsyntheticprogestogenson breathing, which isaccompanied

by hypocapniaand compensatory alkalosis, and isnotconsidered to requiretreatment.

Gynaecomastia:somepatientsdevelop transientorperhapsin somecasespermanentenlargementofthemammary

glands.In rarecasesgalactorrhoeaand tenderbenign noduleshavebeen reported.Symptomsmostly subsideafter

discontinuation oftreatmentorreduction ofdosage, butthisshould beweighed againsttherisk tothetumourofusing

inadequatedoses.

Bodyweight:during long-termtreatment, changesin bodyweighthavebeen reported.Both increasesand decreases

havebeen seen.

Otherchangesthathavebeen reported includereduction ofsebumproduction and consequently improvementof

existing acnevulgaris, transientpatchy lossand reducedgrowth ofbody hair, increased growth ofscalp hair, lightening

ofhaircolourand femaletypeofpubichairgrowth.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Issued 28/10/2005 CRN 2016169 page number: 3

4.9Overdose

Therehavebeen no reportsofilleffectsfromoverdosage, which itis, thereforegenerally unnecessary to treat.There

areno specialantidotesand treatmentshould besymptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

CyproteroneAcetateisasyntheticsteroid possessing anti-androgenicand progestationalactivity.

5.2Pharmacokineticproperties

CyproteroneAcetatehasbeen reported asbeing quickly and completely absorbed fromtablets.Afteroral

administration, CyproteroneAcetateplasmalevelspeaked after2.85±0.69 hoursand declined afterwards

biphasically.Terminalhalf-lifewasreported asbeing 3.56±1.25 days.Ithasalong elimination half-liferesulting in

steady stateonly beingreached after9 to 10 dayson oncedaily dosage.

Thereisan activemetabolite, 15-hydroxycyproteroneand thisattainshigherlevelsthan theparent.Ithasthesame

elimination half-lifeand isthereforeprobably formation ratecontrolled.

5.3Preclinical safetydata

MostoftheeffectsofCyproteroneAcetatefollowing repeatdoseadministration to laboratory speciesarerelated to the

anti-androgenicand progestationalactionsofthedrug.High doselevelsofCyproteroneAcetateareembryotoxic

beforeimplantation whereaslowdoseshavedelayed effectson embryonicdevelopment.In ratstudiesthecompound is

an inducerofliverenzymesand in ratcarcinogenicity studiesitwasassociated with increased incidencesof

hepatocellularadenoma.In long-termtestsin mice, CyproteroneAcetatehasbeen associated with increased incidences

ofmammary glandadenocarcinomain females.Theincreased tumourincidencesin miceand ratsmay bedueto a

tumourpromoting action ofthecompound, although recentevidencesuggeststhatitmay also possessdirectgenotoxic

actionsin bothin vitroandin vivotestsystems.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

Maizestarch

Povidone(K29-32)

Colloidalsilicon dioxide

Magnesiumstearate

6.2Incompatibilities

Noneknown.

6.3ShelfLife

Shelf-lifeofpackaged product:2 years.

6.4Special precautionsforstorage

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Issued 28/10/2005 CRN 2016169 page number: 4

6.5Natureandcontentsofcontainer

Blisterstrips

Polyvinylchlorideblisterssealed onto aluminiumfoil.

Pack sizes:56, 84 and 168 tablets.

Tabletcontainers

Polypropylenetabletcontainerswith polyethylenecapsand polyethyleneullagefiller.

Pack sizes:100, 250 and 500 tablets.

6.6Instructionsforuseandhandling

None.

7MARKETINGAUTHORISATIONHOLDER

Generics(UK)Limited

Station Close

PottersBar

HertfordshireEN6 1TL

England

8MARKETINGAUTHORISATIONNUMBER

PA405/32/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 24 th

June1996

Dateoflastrenewal: 24 th

June2001

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Issued 28/10/2005 CRN 2016169 page number: 5