CASODEX

Main information

  • Trade name:
  • CASODEX Film Coated Tablet 50 Milligram
  • Dosage:
  • 50 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CASODEX Film Coated Tablet 50 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/017/001
  • Authorization date:
  • 16-05-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1447/017/001

CaseNo:2045968

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

G&ALicensingLtd

Ballymurray,Co.Roscommon,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CASODEX50mgFilm-CoatedTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom16/05/2008.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 22/05/2008 CRN 2045968 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Casodex50mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains50mgbicalutamide.

Alsocontains:Lactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets

ProductimportedfromSpain:

Round,white,biconvex,intagliatedwith‘CDX50’ononefaceandalogoonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedprostatecancerincombinationwithLHRHanaloguetherapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmalesincludingtheelderly:Onetablet(50mg)onceaday.TreatmentwithCasodexshouldbestartedatthe

sametimeastreatmentwithanLHRHanalogueorsurgicalcastration.

Children:Casodexiscontraindicatedinchildren.

Renalimpairment:Nodosageadjustmentisnecessaryforpatientswithrenalimpairment.

HepaticImpairment:Nodosageadjustmentisnecessaryforpatientswithmildhepaticimpairment.Increased

accumulationmayoccurinpatientswithmoderatetoseverehepaticimpairment(seesection4.4Specialwarningsand

specialprecautionsforuse).

4.3Contraindications

Casodexiscontraindicatedinfemalesandchildren.

Casodexmustnotbegiventoanypatientwhohasshownahypersensitivityreactiontoitsuse.

4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialistandsubsequentlypatientsshouldbekept

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Casodexisextensivelymetabolisedintheliver.Datasuggeststhatitseliminationmaybeslowerinsubjectswith

severehepaticimpairmentandthiscouldleadtoincreasedaccumulationofCasodex.Therefore,Casodexshouldbe

usedwithcautioninpatientswithmoderatetoseverehepaticimpairment.

Periodicliverfunctiontestingshouldbeconsideredduetothepossibilityofhepaticchanges.

SeverehepaticchangesandhepaticfailurehavebeenobservedrarelywithCasodex(seesection4.8Undesirable

effects).Casodextherapyshouldbediscontinuedifchangesaresevere.

EachtabletofCasodexcontains61mgoflactosemonohydrate.Patientswithrarehereditaryproblemsofgalactose

intolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ThereisnoevidenceofanypharmacodynamicorpharmacokineticinteractionsbetweenCasodexandLHRH

analogues.

InvitrostudieshaveshownthatR-bicalutamideisaninhibitorofCYP3A4,withlesserinhibitoryeffectsonCYP2C9,

2C19and2D6activity.

AlthoughinvitrostudieshavesuggestedthepotentialforCasodextoinhibitcytochrome3A4,anumberofclinical

studiesshowthemagnitudeofanyinhibitionisunlikelytobeofclinicalsignificance.

InvitrostudieshaveshownthatCasodexcandisplacethecoumarinanticoagulant,warfarin,fromitsproteinbinding

sites.ItisthereforerecommendedthatifCasodexisstartedinpatientswhoarealreadyreceivingcoumarin

anticoagulants,prothrombintimeshouldbecloselymonitored.

4.6Pregnancyandlactation

Casodexiscontraindicatedinfemalesandmustnotbegiventopregnantwomenornursingmothers.

4.7Effectsonabilitytodriveandusemachines

Casodexisunlikelytoimpairtheabilityofpatientstodriveoroperatemachinery.

4.8Undesirableeffects

Casodex50mgisonlyusedincombinationwithsurgicalormedicalcastration.Thereportedadversedrugprofileof

Casodex50mgthereforeincludeseffectsthatmayalsobeseenwithcastrationtherapyalone.Themostcommon

reactionsreportedreflectthepharmacologicalactivity;withthemajority(53%)ofpatientsreportinghotflushesand

lowerproportions(approximately10%)reportinggynaecomastiaorbreasttenderness.

Table1FrequencyofAdverseReactions

Frequency SystemOrganClass Event

Verycommon

(10%) Reproductivesystemand

breastdisorders Breasttenderness

Gynaecomastia

Generaldisorders Hotflushes

Common

(1%and<10%) Gastrointestinal

disorders Diarrhoea

Nausea

Hepato-biliary

disorders Hepaticchanges(elevated

levelsoftransaminases,

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1.Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinuedtherapyor

followingcessationoftherapy(seesection4.4Specialwarningsandspecialprecautionsforuse).Periodicliver

functiontestingshouldbeconsidered.

Inaddition,thefollowingadverseexperienceswerereportedinclinicaltrials(aspossibleadversedrugreactionsinthe

opinionofinvestigatingclinicians,withafrequencyof1%)duringtreatmentwithCasodexplusanLHRHanalogue.

Nocausalrelationshipoftheseexperiencestodrugtreatmenthasbeenmadeandsomeoftheexperiencesreportedare

thosethatcommonlyoccurinelderlypatients:

Cardiovascularsystem: heartfailure

Gastrointestinalsystem: anorexia,drymouth,dyspepsia,constipation,flatulence

Centralnervoussystem: dizziness,insomnia,somnolence,decreasedlibido

Respiratorysystem: dyspnoea

Urogenital: impotence,nocturia

Haematological: anaemia

Skinandappendages: alopecia,rash,sweating,hirsutism

Metabolicandnutritional: diabetesmellitus,hyperglycaemia,oedema,weightgain,weightloss

Wholebody: abdominalpain,chestpain,headache,pain,pelvicpain,chills

4.9Overdose

Thereisnohumanexperienceofoverdosage.Thereisnospecificantidote;treatmentshouldbesymptomatic.Dialysis

maynotbehelpful,sinceCasodexishighlyproteinboundandisnotrecoveredunchangedintheurine.General

supportivecare,includingfrequentmonitoringofvitalsigns,isindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Casodexisanon-steroidalantiandrogen,devoidofotherendocrineactivity.Itbindstoandrogenreceptorswithout

activatinggeneexpression,andthusinhibitstheandrogenstimulus.Regressionofprostatictumoursresultsfromthis

inhibition.Clinically,discontinuationofCasodexcanresultinantiandrogenwithdrawalsyndromeinasubsetof

patients.

Generaldisorders Asthenia

Pruritus

Uncommon

(0.1%and<1%) Immunesystem

disorders Hypersensitivityreactions,

includingangioneurotic

oedemaandurticaria

Respiratory,thoracicand

mediastinaldisorders Interstitiallungdisease

Rare

(0.01%and<0.1%) Gastrointestinal

disorders Vomiting

Hepato-biliarydisorders Hepaticfailure

Skinandsubcutaneoustissue

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5.2Pharmacokineticproperties

Casodexiswellabsorbedfollowingoraladministration.Thereisnoevidenceofanyclinicallyrelevanteffectoffood

onbioavailability.

The(S)-enantiomerisrapidlyclearedrelativetothe(R)-enantiomer,thelatterhavingaplasmaeliminationhalf-lifeof

about1week.

OndailyadministrationofCasodex,the(R)-enantiomeraccumulatesabout10-foldinplasmaasaconsequenceofits

longhalf-life.

Steadystateplasmaconcentrationsofthe(R)-enantiomerofapproximately9microgram/mlareobservedduringdaily

administrationof50mgdosesofCasodex.Atsteadystatethepredominantlyactive(R)-enantiomeraccountsfor99%

ofthetotalcirculatingenantiomers.

Thepharmacokineticsofthe(R)-enantiomerareunaffectedbyage,renalimpairmentormildtomoderatehepatic

impairment.Thereisevidencethatforsubjectswithseverehepaticimpairment,the(R)-enantiomerismoreslowly

eliminatedfromplasma.

Casodexishighlyproteinbound(racemate96%,R-bicalutamide99.6%)andextensivelymetabolisedviaoxidationand

glucuronidation:itsmetabolitesareeliminatedviathekidneysandbileinapproximatelyequalproportions.

Inaclinicalstudy,themeanconcentrationofR-bicalutamideinsemenofmenreceivingCasodex150mgwas4.9

microgram/ml.Theamountofbicalutamidepotentiallydeliveredtoafemalepartnerduringintercourseislowand

equatestoapproximately0.3microgram/kg.Thisisbelowthatrequiredtoinducechangesinoffspringoflaboratory

animals.

5.3Preclinicalsafetydata

Casodexisapotentantiandrogen.Expectedpharmacologicaleffectsofantiandrogensseeninanimalstudiesincludethe

following:atrophyoftheprostateandseminalvesicles,benignLeydigcelltumours(rats)andadrenalcortical

hypertrophy.Casodexisamixedfunctionoxidaseinducerinanimalsandthyroidhypertrophyandadenoma(rat)and

hepatocellularcarcinoma(malemice)areaconsequenceofthis.Enzymeinductionhasnotbeenobservedinman.

Noneofthefindingsinpreclinicaltestingareconsideredtohaverelevancetothetreatmentofadvancedprostatecancer

patients.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

Sodiumstarchglycollate

Povidone

Magnesiumstearate

Hypromellose

Macrogol300

Titaniumdioxide(E171)

6.2Incompatibilities

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6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthemarketinthe

countryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof30tabletscontainedinanoverlabelledoutercardboardcarton.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7ParallelProductAuthorisationHolder

G&ALicensingLimited,

Ballymurray,

Co.Roscommon,

Ireland

8ParallelProductAuthorisationNumber

PPA1447/17/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation16thMay2008

Irish Medicines Board

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