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:
  • PPA1562/025/001
  • Authorization date:
  • 08-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Casodex50mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilmcoatedtabletcontains50mgbicalutamide

Excipient:containslactosemonohydrate.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet

ProductimportedfromItaly

Round,white,biconvextabletintagliatedwith"Cdx50"ononefaceandalogoonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedprostatecancerincombinationwithLHRHanaloguetherapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmalesincludingtheelderly:Onetablet(50mg)onceaday.TreatmentwithCasodexshouldbestartedatthesame

timeastreatmentwithanLHRHanalogueorsurgicalcastration.

Children:Casodexiscontraindicatedinchildren.

RenalImpairment:Nodosageadjustmentisnecessaryforpatientswithrenalimpairment.

HepaticImpairment:Nodosageadjustmentisnecessaryforpatientswithmildhepaticimpairment.Increased

accumulationmayoccurinpatientswithmoderatetoseverehepaticimpairment(seesection4.4,Specialwarningsand

precautionsforuse).

4.3Contraindications

Casodexiscontra-indicatedinfemalesandchildren(seesection4.6).

Casodexmustnotbegiventoanypatientwhohasshownahypersensitivityreactiontotheactivesubstanceortoanyof

theexcipientsofthisproduct.

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4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialist.

Casodexisextensivelymetabolisedintheliver.Datasuggeststhatitseliminationmaybeslowerinsubjectswith

severehepaticimpairmentandthiscouldleadtoincreasedaccumulationofCasodex.Therefore,Casodexshouldbe

usedwithcautioninpatientswithmoderatetoseverehepaticimpairment.

Periodicliverfunctiontestingshouldbeconsideredduetothepossibilityofhepaticchanges.Themajorityofchanges

areexpectedtooccurwithinthefirst6monthsofCasodextherapy.

SeverehepaticchangesandhepaticfailurehavebeenobservedrarelywithCasodex,andfataloutcomeshavebeen

reported(seesection4.8).Casodextherapyshouldbediscontinuedifchangesaresevere.

AreductioninglucosetolerancehasbeenobservedinmalesreceivingLHRHagonists.Thismaymanifestasdiabetes

orlossofglycaemiccontrolinthosewithpre-existingdiabetes.Considerationshouldthereforebegiventomonitoring

bloodglucoseinpatientsreceivingCasodexincombinationwithLHRHagonists.

BicalutamidehasbeenshowntoinhibitcytochromeP450(CYP3A4),assuchcautionshouldbeexercisedwhen

coadministeredwithdrugsmetabolisedpredominantlybyCYP3A4(seesections4.3and4.5).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ThereisnoevidenceofanypharmacodynamicorpharmacokineticinteractionsbetweenCasodexandLHRH

analogues.

InvitrostudieshaveshownthatR-bicalutamideisaninhibitorofCYP3A4,withlesserinhibitoryeffectsonCYP2C9,

2C19and2D6activity.

AlthoughclinicalstudiesusingantipyrineasamarkerofcytochromeP450(CYP)activityshowednoevidenceofa

druginteractionpotentialwithCasodex,meanmidazolamexposure(AUC)wasincreasedbyupto80%,after

CoadministrationofCasodexfor28days.Fordrugswithanarrowtherapeuticindexsuchanincreasecouldbeof

relevance.Assuch,concomitantuseofterfenadine,astemizoleandcisaprideiscontraindicated(seesection4.3)and

cautionshouldbeexercisedwiththeco-administrationofCasodexwithcompoundssuchasciclosporinandcalcium

channelblockers.Dosagereductionmayberequiredforthesedrugsparticularlyifthereisevidenceofenhancedor

adversedrugeffect.Forciclosporin,itisrecommendedthatplasmaconcentrationsandclinicalconditionareclosely

monitoredfollowinginitiationorcessationofCasodextherapy.

CautionshouldbeexercisedwhenprescribingCasodexwithotherdrugswhichmayinhibitdrugoxidatione.g.

cimetidineandketoconazole.Intheory,thiscouldresultinincreasedplasmaconcentrationsofbicalutamidewhich

theoreticallycouldleadtoanincreaseinsideeffects.

InvitrostudieshaveshownthatCasodexcandisplacethecoumarinanticoagulant,warfarin,fromitsproteinbinding

sites.ItisthereforerecommendedthatifCasodexisstartedinpatientswhoarealreadyreceivingcoumarin

anticoagulants,prothrombintimeshouldbecloselymonitored.

4.6Fertility,pregnancyandlactation

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4.7Effectsonabilitytodriveandusemachines

Casodexisunlikelytoimpairtheabilityofpatientstodriveoroperatemachinery.However,itshouldbenotedthat

occasionallysomnolencemayoccur.Anyaffectedpatientsshouldexercisecaution.

4.8Undesirableeffects

Inthissection,undesirableeffectsaredefinedasfollows:Verycommon(1/10);common(1/100to<1/10);

uncommon(1/1,000to1/100);rare(1/10,000to1/1,000);veryrare(1/10,000);notknown(cannotbeestimated

fromtheavailabledata).

Table1 FrequencyofAdverseReactions

SystemOrganClass Frequency Event

Bloodandlymphaticsystem

disorders Verycommon Anaemia

Immunesystemdisorders Uncommon Hypersensitivity,

angioedemaurticaria

Metabolismandnutrition

disorders Common Decreasedappetite

Psychiatricdisorders Common Decreasedlibido

Depression

Nervoussystemdisorders Verycommon Dizziness

Common Somnolence

Cardiacdisorders Common Myocardialinfarction(fatal

outcomeshavebeenreported)

Cardiacfailure 4

Vasculardisorders Verycommon Hotflush

Respiratory,thoracicand

mediastinaldisorders Uncommon Interstitiallungdisease.Fatal

outcomeshavebeenreported.

Gastrointestinaldisorders Verycommon Abdominalpain

Constipation

Nausea

Common Dyspepsia

Flatulence

Hepato-biliarydisorders Common Hepatotoxicityjaundice,

hypertransaminasaemia 1

Rare Hepaticfailure 2

.Fatal

outcomeshavebeenreported.

Skinandsubcutaneoustissue

disorders Common Alopecia

Hirsuitism/hairre-growth

Dryskin

Pruritis

Rash

Renalandurinarydisorders Verycommon Haematuria

Reproductivesystemand

breastdisorders Verycommon Gynaecomastiaandbreast

tenderness 3

Common Erectiledysfunction

Generaldisordersand

administrationsiteconditions Verycommon Asthenia

Oedema

Common Chestpain

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Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinuedtherapyor

followingcessationoftherapy.

HepaticfailurehasoccurredrarelyinpatientstreatedwithCasodex,butacausalrelationshiphasnotbeen

establishedwithcertainty.Periodicliverfunctiontestingshouldbeconsidered(seealsosection4.4).

Maybereducedbyconcomitantcastration.

Observedinapharmaco-epidemiologystudyoftheLHRHagonistsandanti-androgensusedinthetreatmentof

prostatecancer.TheriskappearstobeincreasedwhenCasodex50mgwasusedincombinationwithLHRH

agonistsbutnoincreaseinriskwasevidentwhenCasodex150mgwasusedasamonotherapytotreatprostate

cancer.

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.

Casodexisaracematewithitsantiandrogenicactivitybeingalmostexclusivelyinthe(R)-enantiomer.

5.2Pharmacokineticproperties

Casodexiswellabsorbedfollowingoraladministration.Thereisnoevidenceofanyclinicallyrelevanteffectoffood

onbioavailability.

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

about1week.

OndailyadministrationofCasodex,the(R)-enantiomeraccumulatesabout10foldinplasmaasaconsequenceofits

longhalf-life.

Steadystateplasmaconcentrationsofthe(R)-enantiomerofapproximately9microgram/mlareobservedduringdaily

administrationof50mgdosesofCasodex.Atsteadystatethepredominantlyactive(R)-enantiomeraccountsfor99%of

thetotalcirculatingenantiomers.

Thepharmacokineticsofthe(R)-enantiomerareunaffectedbyage,renalimpairmentormildtomoderatehepatic

impairment.Thereisevidencethatforsubjectswithseverehepaticimpairment,the(R)-enantiomerismoreslowly

eliminatedfromplasma.

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

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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

Core:

LactoseMonohydrate

SodiumStarchGlycolate(TypeA)

Povidone

MagnesiumStearate

Filmcoating:

Hypromellose

Macrogol300

TitaniumDioxide(171)

6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelflifeexpirydateforthisproductshallbethedateshownontheblisterandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

Cardboardoutercontainingblisterstrips.

Packsize28.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

LTTPharmaLimited

Unit18,OxleasowRoad

EastMoonMoat

Redditch

WorcestershireB980RE

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1562/25/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8thofOctober2010

10DATEOFREVISIONOFTHETEXT

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