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:
  • PPA1500/073/001
  • Authorization date:
  • 12-11-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Casodex50mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains50mgofbicalutamide.

Excipients:Containslactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromItaly:

Round,white,biconvextabletsmarkedwith"Cdx50"ononefaceandalogoonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofadvancedprostatecancerincombinationwith LHRH analoguetherapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmalesincludingtheelderly:Onetablet(50mg)onceaday.TreatmentwithCasodexshouldbestartedatthe

sametimeastreatmentwithan LHRH analogueorsurgicalcastration.

Children:Casodexiscontraindicatedinchildren.

RenalImpairment:Nodosageadjustmentisnecessaryforpatientswithrenalimpairment.

HepaticImpairment:Nodosageadjustmentisnecessaryforpatientswithmildhepaticimpairment.Increased

accumulationmayoccurinpatientswithmoderatetoseverehepaticimpairment(seesection4.4,Specialwarningsand

precautionsforuse).

4.3Contraindications

Casodexiscontra-indicatedinfemalesandchildren(seesection4.6).

Casodexmustnotbegiventoanypatientwhohasshownahypersensitivityreactiontotheactivesubstanceortoanyof

theexcipientsofthisproduct.

Co-administrationofterfenadine,astemizoleorcisapridewithCasodexiscontraindicated(seesection4.5)

4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialist.

Casodexisextensivelymetabolisedintheliver.Datasuggeststhatitseliminationmaybeslowerinsubjectswith

severehepaticimpairmentandthiscouldleadtoincreasedaccumulationofCasodex.Therefore,Casodexshouldbe

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Periodicliverfunctiontestingshouldbeconsideredduetothepossibilityofhepaticchanges.Themajorityofchanges

areexpectedtooccurwithinthefirst6monthsofCasodextherapy.

SeverehepaticchangesandhepaticfailurehavebeenobservedrarelywithCasodex,andfataloutcomeshavebeen

reported(seesection4.8).Casodextherapyshouldbediscontinuedifchangesaresevere.

AreductioninglucosetolerancehasbeenobservedinmalesreceivingLHRHagonists.Thismaymanifestasdiabetes

orlossofglycaemiccontrolinthosewithpre-existingdiabetes.Considerationshouldthereforebegiventomonitoring

bloodglucoseinpatientsreceivingCasodexincombinationwithLHRHagonists.

BicalutamidehasbeenshowntoinhibitcytochromeP450(CYP3A4),assuchcautionshouldbeexercisedwhenco-

administeredwithdrugsmetabolisedpredominantlybyCYP3A4(seesections4.3and4.5).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ThereisnoevidenceofanypharmacodynamicorpharmacokineticinteractionsbetweenCasodexandLHRH

analogues.

InvitrostudieshaveshownthatR-bicalutamideisaninhibitorofCYP3A4,withlesserinhibitoryeffectsonCYP2C9,

2C19and2D6activity.

AlthoughclinicalstudiesusingantipyrineasamarkerofcytochromeP450(CYP)activityshowednoevidenceofa

druginteractionpotentialwithCasodex,meanmidazolamexposure(AUC)wasincreasedbyupto80%,afterco-

administrationofCasodexfor28days.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

Casodexiscontraindicatedinfemalesandmustnotbegiventopregnantwomenornursingmothers.

4.7Effectsonabilitytodriveandusemachines

Casodexisunlikelytoimpairtheabilityofpatientstodriveoroperatemachinery.However,itshouldbenotedthat

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4.8Undesirableeffects

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

uncommon( ≥1/1,000to≤1/100);rare(≥1/10,000to≤1/1,000);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 Uncommon Cardiacfailure 4

Vasculardisorders Verycommon Hotflush

Respiratory,thoracicand

mediastinaldisorders Uncommon Interstitiallungdisease.Fatal

outcomeshavebeen

reported.

Gastrointestinaldisorders Verycommon Abdominalpain

Constipation

Nausea

Common Dyspepsia

Flatulence

Hepato-biliarydisorders Common Hepatotoxicityjaundice,

hypertransaminasaemia 1

Rare

Hepaticfailure 2

.Fatal

outcomeshavebeen

reported.

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

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Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinued

therapyorfollowingcessationoftherapy.

HepaticfailurehasoccurredrarelyinpatientstreatedwithCasodex,butacausalrelationshiphasnotbeen

establishedwithcertainty.Periodicliverfunctiontestingshouldbeconsidered(seealsosection4.4).

Maybereducedbyconcomitantcastration.

Observedinapharmaco-epidemiologystudyoftheLHRHagonistsandanti-androgensusedinthetreatment

ofprostatecancer.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

glucuronidation:itsmetabolitesareeliminatedviathekidneysandbileinapproximatelyequalproportions.

Inaclinicalstudy,themeanconcentrationofR-bicalutamideinsemenofmenreceivingCasodex150mgwas4.9

microgram/ml.Theamountofbicalutamidepotentiallydeliveredtoafemalepartnerduringintercourseislowand

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Thisisbelowthatrequiredtoinducechangesinoffspringoflaboratoryanimals.

5.3Preclinicalsafetydata

Casodexisapotentantiandrogen.Expectedpharmacologicaleffectsofantiandrogensseeninanimalstudiesinclude

thefollowing:-atrophyoftheprostateandseminalvesicles,benignLeydigcelltumours(rats)andadrenalcortical

hypertrophy.Casodexisamixedfunctionoxidaseinducerinanimalsandthyroidhypertrophyandadenoma(rat)and

hepatocellularcarcinoma(malemice)areaconsequenceofthis.Enzymeinductionhasnotbeenobservedinman.

Noneofthefindingsinpreclinicaltestingareconsideredtohaverelevancetothetreatmentofadvancedprostatecancer

patients.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

LactoseMonohydrate

SodiumStarchGlycolate(TypeA)

Povidone

MagnesiumStearate

Hypromellose

Macrogol300

TitaniumDioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30ºC.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Over-labelledcardboardcartoncontainingtwoPVCblister/aluminiumblisters(14tabletsperblister).

Packsize:28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

ProfindWholesaleLtd

Unit625

KilshaneAvenue

NorthwestBusinessPark

Dublin15

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1500/73/1

8MARKETINGAUTHORISATIONNUMBER

PA970/4/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12thNovember2010

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