BICALUTAMIDE

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1330/004/001
  • Authorization date:
  • 28-11-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1330/004/001

CaseNo:2058633

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

TransferredfromPA1425/001/001.

GedeonRichterLtd

Gyomroiut19-21,1103Budapest,Hungary

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Bicalutamide50mgFilm-coatedtablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom28/11/2008until20/07/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Bicalutamide50mgFilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontains50mgofbicalutamide.

Excipients:Contains64.4mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whiteoralmostwhite,round,biconvexfilm-coatedtablet,withengravedsign,,L’’ononeside,and,,RG’’ontheother

side.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofadvancedprostatecancerincombinationwithluteinizinghormone-releasinghormone(LHRH)analogue

therapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmalesincludingtheelderly

One50mgtabletonceaday.

Route:oral

Thetabletsshouldbeswallowedwholewithliquid.

TreatmentwithBicalutamideshouldbestartedatleast3daysbeforecommencingtreatmentwithanLHRHanalogue,

oratthesametimeassurgicalcastration.

Childrenandadolescents

Bicalutamideisnotindicatedinchildrenandadolescents.

Renalimpairment

Nodoseadjustmentisnecessaryforpatientswithrenalimpairment.Thereisnoexperiencewiththeuseof

bicalutamideinpatientswithsevererenalimpairment(creatinineclearance<30ml/min)(seesection4.4).

Hepaticimpairment

Nodoseadjustmentisnecessaryforpatientswithmildhepaticimpairment.Themedicinalproductmayaccumulatein

patientswithmoderatetoseverehepaticimpairment(seesection4.4).

4.3Contraindications

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 2

Bicalutamideiscontraindicatedinwomenandchildren.

Co-administrationofterfenadine,astemizoleorcisapridewithbicalutamideiscontra-indicated(seesection4.5).

4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialistandsubsequentlypatientsshouldbekept

underregularsurveillance.

Bicalutamideismetabolisedintheliver.Researchresultssuggestthatbicalutamide’seliminationmaybeslowerin

patientswithseverehepaticimpairmentandthatthiscouldleadtoincreasedaccumulationofbicalutamide.Therefore,

bicalutamideshouldbeusedwithcautioninpatientswithmoderatetoseverehepaticimpairment.

Severehepaticdamageshavebeenrarelyobservedwithbicalutamide(seesection4.8).Bicalutamidetherapyshouldbe

discontinuedifchangesaresevere.

Periodicliverfunctiontestingiswarrantedinordertofindoutaboutpossiblehepaticchanges.Themajorityofchanges

areexpectedtooccurwithinthefirst6monthsofbicalutamidetherapy.

Asthereisnoexperiencewiththeuseofbicalutamideinpatientswithsevererenalimpairment(creatinineclearance<

30ml/min),bicalutamideshouldonlybeusedwithcautioninthesepatients.

Periodicalmonitoringofcardiacfunctionisadvisableinpatientswithheartdisease.

Theproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

NopharmacologicalorpharmacokineticinteractionshavebeendemonstratedbetweenbicalutamideandLHRH

analogues.

InvitrostudieshaveshownthattheR-enantiomerofbicalutamideisaninhibitorofCYP3A4withlesserinhibitory

effectsonCYP2C9,2C19and2D6activity.

Althoughinvitrostudieshaveindicatedthepossibilityofbicalutamideinhibitingcytochrome3A4,anumberof

clinicalstudiesshowthatthescaleofthisinhibitionformostdrugsmetabolisedbycytochromeP450isprobablynot

clinicallysignificant.

Nonetheless,fordrugswithanarrowtherapeuticindexmetabolisedintheliver,theCYP3A4inhibitioncausedby

bicalutamidecouldbeofrelevance.Assuch,concomitantuseofterfenadine,astemizoleandcisaprideiscontra-

indicated.

Cautionshouldbeexercisedwiththeco-administrationofbicalutamidewithcompoundssuchascyclosporinand

calciumchannelblockers.Dosagereductionmayberequiredforthesedrugsparticularlyifthereisevidenceof

enhancedoradversedrugeffect.Forcyclosporin,itisrecommendedthatplasmaconcentrationsandclinicalcondition

arecloselymonitoredfollowinginitiationorcessationofbicalutamidetherapy.

Cautionshouldbeexercisedwhenadministeringbicalutamidetopatientstakingmedicinalproductsthatinhibitthe

oxidationprocessesintheliver,e.g.cimetidineandketoconazole.Thiscouldresultinincreasedplasmaconcentrations

ofbicalutamide,whichtheoreticallycouldleadtoanincreaseinsideeffects.

Invitrostudieshaveshownthatbicalutamidecandisplacethecoumarinanticoagulant,warfarin,fromitsprotein

bindingsite.Itisthereforerecommendedthatprothrombintimeiscloselymonitoredifbicalutamideisstartedin

patientswhoarealreadyreceivingcoumarinanticoagulants.

4.6Pregnancyandlactation

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 3

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,itshouldbenoted

thatoccasionallydizzinessorsomnolencemayoccur(seesection4.8).Anyaffectedpatientsshouldexercisecaution.

4.8Undesirableeffects

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(cannotbeestimatedfromtheavailabledata).

Immunesystemdisorders

Uncommon:Hypersensitivityreactions,includingangio-oedemaandurticaria

Psychiatricdisorders

Uncommon:Depression

Respiratory,thoracicandmediastinaldisorders

Uncommon:Interstitiallungdisease

Gastrointestinaldisorders

Common:Diarrhoea,nausea

Rare:Vomiting

Hepatobiliarydisorders

Common:Hepaticchanges(elevatedlevelsoftransaminases,cholestasisandjaundice) 1

Veryrare:Hepaticfailure 2

Skinandsubcutaneoustissuedisorders

Common:Pruritus

Rare:Dryskin

Renalandurinarydisorders

Uncommon:Haematuria

Reproductivesystemandbreastdisorders

Verycommon:Breasttenderness 3

,gynaecomastia 3

Generaldisordersandadministrationsiteconditions

Verycommon:Hotflushes 3

Common:Asthenia

Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinuedtherapyor

followingcessationoftherapy(seesection4.4).

Hepaticfailurehasoccurredveryrarelyinpatientstreatedwithbicalutamide,butacasualrelationshiphasnotbeen

establishedwithcertainty.Periodicliverfunctiontestingshouldbeconsidered(seealsosection4.4).

Maybereducedbyconcomitantcastration.

Inaddition,thefollowingadverseexperienceswerereportedinclinicaltrialsduringtreatmentwithbicalutamide

with/withoutaLHRHanalogue:

Bloodandlymphaticsystemdisorders

Common:Anaemia

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 4

Metabolismandnutritiondisorders

Common:Diabetesmellitus,weightgain

Uncommon:Anorexia,hyperglycaemia,weightloss

Nervoussystemdisorders

Common:Dizziness,insomnia

Uncommon:Somnolence

Cardiacdisorders

Veryrare:Heartfailure,angina,conductiondefectsincludingPRandQTintervalprolongations,arrhythmiasandnon-

specificECGchanges

Respiratory,thoracicandmediastinaldisorders

Uncommon:Dyspnoea

Gastrointestinaldisorders

Common:Constipation

Uncommon:Drymouth,dyspepsia,flatulence

Skinandsubcutaneoustissuedisorders

Common:Rash,sweating,hirsutism

Uncommon:Alopecia

Renalandurinarydisorders

Uncommon:Nocturia

Reproductivesystemandbreastdisorders

Verycommon:Decreasedlibido,erectiledysfunction,impotence

Generaldisordersandadministrationsiteconditions

Common:Oedema,generalpain,pelvicpain,chills

Uncommon:Abdominalpain,chestpain,headache,painintheback,neckpain

4.9Overdose

Nocaseofoverdosehasbeenreported.Sincebicalutamidebelongstotheanilidecompoundsthereisatheoreticalrisk

ofthedevelopmentofmethaemoglobinaemia.Methaemoglobinaemiahasbeenobservedinanimalsafteranoverdose.

Accordingly,apatientwithanacuteintoxicationcanbecyanotic.Thereisnospecificantidote;treatmentshouldbe

symptomatic.Dialysisisunlikelytobehelpful,sincebicalutamideishighlyproteinboundandisnotrecovered

unchangedintheurine.Generalsupportivecare,includingfrequentmonitoringofvitalsigns,isindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Hormoneantagonistsandrelatedagents,anti-androgens

ATCcode:L02BB03.

Bicalutamideisanon-steroidalantiandrogen,devoidofotherendocrineactivity.Itbindstothewildtypeornormal

androgenreceptorwithoutactivatinggeneexpression,andthusinhibitstheandrogenstimulus.Regressionofprostatic

tumoursresultsfromthisinhibition.Clinically,discontinuationofbicalutamidecanresultinthe‘antiandrogen

withdrawalsyndrome’inasubsetofpatients.

Bicalutamideisaracematewithitsanti-androgenicactivitybeingalmostexclusivelyassociatedwiththe(R)-

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 5

5.2Pharmacokineticproperties

Bicalutamideiswellabsorbedfollowingoraladministration.Thereisnoevidenceofanyclinicallyrelevanteffectof

foodonbioavailability.

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

about1week.

Followingalong-termadministrationofbicalutamide,thepeakconcentrationofthe(R)-enantiomerintheplasmais

about10-fold,ascomparedtothelevelsmeasuredafterasingledoseof50mgofbicalutamide.

Adosingschemeof50mgbicalutamidedailywillresultinasteady-stateconcentrationoftheR-enantiomerof9µg/ml

andasaconsequenceofitslonghalf-life,steadystateisreachedafterapproximately1monthoftherapy.

Thepharmacokineticsofthe(R)-enantiomerareunaffectedbyage,renalimpairmentormildtomoderatehepatic

impairment.Thereisevidencethatthe(R)-enantiomerismoreslowlyeliminatedfromplasmainpatientswithsevere

hepaticimpairment.

Bicalutamideishighlyproteinbound(racemateto96%,(R)-enantiomer99%)andextensivelymetabolised(by

oxidationandglucuronidation).Itsmetabolitesareeliminatedviathekidneysandbileinapproximatelyequal

proportions.

5.3Preclinicalsafetydata

Bicalutamideisapureandpotentandrogenreceptorantagonistinexperimentalanimalsandhumans.Themain

secondarypharmacologicalactionisinductionofCYP450dependentmixedfunctionoxidasesintheliver.Enzyme

inductionhasnotbeenobservedinhumans.Targetorganschangesinanimalsareclearlyrelatedtotheprimaryand

secondarypharmacologicalactionofbicalutamide.Thesecompriseinvolutionofandrogen-dependenttissues;thyroid

follicularadenomas,hepaticandLeydigcellhyperplasiasandneoplasiasorcancer;disturbanceofmaleoffspring

sexualdifferentiation;reversibleimpairmentoffertilityinmales.Genotoxicitystudiesdidnotrevealanymutagenic

potentialofbicalutamide.Alladverseeffectsobservedinanimalstudiesareconsideredtohavenorelevancetothe

treatmentofpatientswithadvancedprostatecancer.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Silica,colloidalanhydrous,

Magnesiumstearate,

PovidoneK-30,

Sodiumstarchglycolate(TypeA),

Lactosemonohydrate.

Film-coating:

OpadryII33G28523White(Triacetin,Macrogol3350,Lactosemonohydrate,Titaniumdioxide(E171),

Hypromellose).

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 6

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

10,14,20,28,30,40,50,56,80,84,90,100,140,200,280film-coatedtabletsinblisterpacks(PVC/PVDC/

aluminiumfoil)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

GedeonRichterPlc

Gyomroiut19-21

1103Budapest

Hungary

8MARKETINGAUTHORISATIONNUMBER

PA1330/4/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21 st

July2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 28/11/2008 CRN 2058633 page number: 7