CASODEX 50MG FILM-COATED TABLETS

Main information

  • Trade name:
  • CASODEX 50MG FILM-COATED TABLETS
  • Dosage:
  • 50 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CASODEX 50MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/144/001A
  • Authorization date:
  • 02-07-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Casodex50mgFilm-CoatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains50mgbicalutamide.

Excipients:ContainsLactoseMonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets

ProductimportedfromGreeceandItaly:

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

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedprostatecancerincombinationwithLHRHanaloguetherapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmales:onetablet(50mg)onceaday.

(includingtheelderly)TreatmentwithCasodexshouldbestartedatthesametimeastreatmentwithaLHRHanalogue

orsurgicalcastration.

Children:Casodexiscontra-indicatedinchildren

RenalImpairment:Nodosageadjustmentisnecessaryforpatientswithrenalimpairment

HepaticImpairment:Nodosageadjustmentisnecessaryforpatientswithmildhepaticimpairment.Increased

accumulationmayoccurinpatientswithmoderatetoseverehepaticimpairment(seeunder4.4“Specialwarningsand

specialprecautionsforuse”).

4.3Contraindications

Casodexiscontraindicatedinfemalesandchildren.

Casodexmustnotbegiventoanypatientwhohasshownahypersensitivityreactiontoitsuse.

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4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialist.

Casodexisextensivelymetabolisedintheliver.Datasuggeststhatitseliminationmaybeslowerinsubjectswith

severehepaticimpairmentandthiscouldleadtoincreasedaccumulationofCasodex.Therefore,Casodexshouldbe

usedwithcautioninpatientswithmoderatetoseverehepaticimpairment.

Periodicliverfunctiontestingshouldbeconsideredduetothepossibilityofhepaticchanges.Themajorityofchanges

areexpectedtooccurwithinthefirst6monthsofCasodextherapy.

SeverehepaticchangesandhepaticfailurehavebeenobservedrarelywithCasodex(seesection4.8Undesirable

Effects).'Casodex'therapyshouldbediscontinuedifchangesaresevere.

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,itisrecommendedthatplasmaconcentrationsandclinicalconditionarecloselymonitoredfollowing

initiationorcessationofCasodextherapy.

CautionshouldbeexercisedwhenprescribingCasodexwithotherdrugswhichmayinhibitdrugoxidatione.g.

cimetidineandketoconazole.Intheory,thiscouldresultinincreasedplasmaconcentrationsofbicalutamidewhich

theoreticallycouldleadtoanincreaseinsideeffects.

InvitrostudieshaveshownthatCasodexcandisplacethecoumarinanticoagulant,warfarin,fromitsproteinbinding

sites.ItisthereforerecommendedthatifCasodexisstartedinpatientswhoarealreadyreceivingcoumarin

anticoagulants,prothrombintimeshouldbecloselymonitored.

4.6Fertility,pregnancyandlactation

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4.7Effectsonabilitytodriveandusemachines

Casodexisunlikelytoimpairtheabilityofpatientstodriveoroperatemachinery.

However,itshouldbenotedthatoccasionallysomnolencemayoccur.Anyaffectedpatientsshouldexercisecaution.

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(cannotbe

estimatedfromtheavailabledata).

Table1FrequencyofAdverseReactions

1.Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinuedtherapyor

SystemOrganClass Frequency Event

Bloodandlymphaticsystem

disorders Common Anaemia

Immunesystemdisorders Uncommon Hypersensitivityreactions

(includingangioneuroticoedema

andurticaria)

MetabolismandnutritiondisordersCommon Anorexia

Psychiatricdisorders Common Decreasedlibido

Depression

Nervoussystemdisorders Verycommon Dizziness

Common Somnolence

Vasculardisorders Verycommon Hotflush

Respiratory,thoracicand

mediastinaldisorders Uncommon Interstitiallungdisease

Gastrointestinaldisorders Verycommon Abdominalpain

Constipation

Nausea

Common Dyspepsia

Flatulence

Hepato-biliarydisorders Common Hepaticchanges(including

elevatedlevelsoftransaminases,

jaundice)/hepato-biliary

disorders 1

Rare

Hepaticfailure 2

Skinandsubcutaneoustissue

disorders Common Alopecia,Hirsuitism/hairre-

growth,Dryskin,Pruritis,Rash

Renalandurinarydisorders Verycommon Haematuria

Reproductivesystemandbreast

disorders Verycommon Gynaecomastiaandbreast

tenderness 3

Common Impotence

Generaldisordersand

administrationsiteconditions Verycommon Asthenia,Chestpain,Oedema

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2.HepaticfailurehasoccurredrarelyinpatientstreatedwithCasodex,butacausalrelationshiphasnotbeen

establishedwithcertainty.Periodicliverfunctiontestingshouldbeconsidered(seealsosection4.4).

3.Maybereducedbyconcomitantcastration.

Inaddition,cardiacfailurewasreportedinclinicaltrials(asapossibleadversedrugreactionintheopinionof

investigatingclinicians,withafrequencyof(>1%)duringtreatmentwithCasodexplusanLHRHanalogue.Thereisno

evidenceofacausalrelationshipwithdrugtreatment.

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)-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

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5.3Preclinicalsafetydata

Casodexisapotentantiandrogen.Expectedpharmacologicaleffectsofantiandrogensseeninanimalstudiesincludethe

following:atrophyoftheprostateandseminalvesicles,benignLeydigcelltumours(rats)andadrenalcortical

hypertrophy.Casodexisamixedfunctionoxidaseinducerinanimalsandthyroidhypertrophyandadenoma(rat)and

hepatocellularcarcinoma(malemice)areaconsequenceofthis.Enzymeinductionhasnotbeenobservedinman.

Noneofthefindingsinpreclinicaltestingareconsideredtohaverelevancetothetreatmentofadvancedprostatecancer

patients.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumstarchglycollate(TypeA)

Povidone

Magnesiumstearate

Hypromellose

Macrogol300

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof14tabletscontainedinanouterover-labelledcardboardcarton

Packsize:28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

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8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/144/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisations:02July2004

Dateoflastrenewal:02July2009

10DATEOFREVISIONOFTHETEXT

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