BICALINN

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0915/015/001
  • Authorization date:
  • 12-09-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0915/015/001

CaseNo:2070471

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

HelsinnBirexTherapeuticsLtd

Damastown,Mulhuddart,Dublin15,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Bicalinn50mgfilm-coatedtablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom18/12/2009until11/09/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 05/01/2010 CRN 2070471 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Bicalinn50mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains50mgbicalutamide.

Alsocontains60mgoflactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

White,round,biconvexfilm-coatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedprostatecancerincombinationwithLHRHanaloguetherapyorsurgicalcastration.

4.2Posologyandmethodofadministration

Adultmalesincludingtheelderly:Onetablet(50mg)onceaday.TreatmentwithBicalinnshouldbestartedatthe

sametimeastreatmentwithanLHRHanalogueorsurgicalcastration.

Children:Bicalinniscontraindicatedinchildren.

Renalimpairment:Nodosageadjustmentisnecessaryforpatientswithrenalimpairment.

HepaticImpairment:Nodosageadjustmentisnecessaryforpatientswithmildhepaticimpairment.Increased

accumulationmayoccurinpatientswithmoderatetoseverehepaticimpairment(seesection4.4Specialwarningsand

specialprecautionsforuse).

4.3Contraindications

Bicalinniscontraindicatedinfemalesandchildren.

Bicalinnmustnotbegiventoanypatientwhohasshownahypersensitivityreactiontoitsuse.

4.4Specialwarningsandprecautionsforuse

Initiationoftreatmentshouldbeunderthedirectsupervisionofaspecialistandsubsequentlypatientsshouldbekept

underregularsurveillance.Bicalinnisextensivelymetabolisedintheliver.Datasuggeststhatitseliminationmaybe

slowerinsubjectswithseverehepaticimpairmentandthiscouldleadtoincreasedaccumulationofBicalinn.Therefore,

Bicalinnshouldbeusedwithcautioninpatientswithmoderatetoseverehepaticimpairment.

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SeverehepaticchangesandhepaticfailurehavebeenobservedrarelywithBicalinn(seesection4.8Undesirable

effects).Bicalinntherapyshouldbediscontinuedifchangesaresevere.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ThereisnoevidenceofanypharmacodynamicorpharmacokineticinteractionsbetweenBicalinnandLHRH

analogues.

InvitrostudieshaveshownthatR-bicalutamideisaninhibitorofCYP3A4,withlesserinhibitoryeffectsonCYP2C9,

2C19and2D6activity.

AlthoughinvitrostudieshavesuggestedthepotentialforBicalinntoinhibitcytochrome3A4,anumberofclinical

studiesshowthemagnitudeofanyinhibitionisunlikelytobeofclinicalsignificance.

InvitrostudieshaveshownthatBicalinncandisplacethecoumarinanticoagulant,warfarin,fromitsproteinbinding

sites.ItisthereforerecommendedthatifBicalinnisstartedinpatientswhoarealreadyreceivingcoumarin

anticoagulants,prothrombintimeshouldbecloselymonitored.

4.6Pregnancyandlactation

Bicalinniscontraindicatedinfemalesandmustnotbegiventopregnantwomenornursingmothers.

4.7Effectsonabilitytodriveandusemachines

Bicalinnisunlikelytoimpairtheabilityofpatientstodriveoroperatemachinery.

4.8Undesirableeffects

Bicalinn50mgisonlyusedincombinationwithsurgicalormedicalcastration.Thereportedadversedrugprofileof

Bicalinn50mgthereforeincludeseffectsthatmayalsobeseenwithcastrationtherapyalone.Themostcommon

reactionsreportedreflectthepharmacologicalactivity;withthemajority(53%)ofpatientsreportinghotflushesand

lowerproportions(approximately10%)reportinggynaecomastiaorbreasttenderness.

Table1FrequencyofAdverseReactions

Frequency SystemOrganClass Event

Verycommon

≥10%) Reproductive system and breast

disorders Breasttenderness

Gynaecomastia

Generaldisorders Hotflushes

Common

≥1%and<10%) Gastrointestinaldisorders Diarrhoea

Nausea

Hepato-biliarydisorders Hepaticchanges(elevatedlevelsof

transaminases,jaundice) 1

Generaldisorders Asthenia

Pruritus

Uncommon Immunesystemdisorders Hypersensitivityreactions,including

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Hepaticchangesarerarelysevereandwerefrequentlytransient,resolvingorimprovingwithcontinuedtherapy

orfollowingcessationoftherapy(seesection4.4Specialwarningsandspecialprecautionsforuse).Periodic

liverfunctiontestingshouldbeconsidered.

Inaddition,thefollowingadverseexperienceswerereportedinclinicaltrials(aspossibleadversedrugreactionsinthe

opinionofinvestigatingclinicians,withafrequencyof ≥1%)duringtreatmentwithBicalinnplusanLHRHanalogue.

Nocausalrelationshipoftheseexperiencestodrugtreatmenthasbeenmadeandsomeoftheexperiencesreportedare

thosethatcommonlyoccurinelderlypatients:

4.9Overdose

Thereisnohumanexperienceofoverdosage.Thereisnospecificantidote;treatmentshouldbesymptomatic.Dialysis

maynotbehelpful,sinceBicalinnishighlyproteinboundandisnotrecoveredunchangedintheurine.General

supportivecare,includingfrequentmonitoringofvitalsigns,isindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Bicalinnisanon-steroidalantiandrogen,devoidofotherendocrineactivity.Itbindstoandrogenreceptorswithout

activatinggeneexpression,andthusinhibitstheandrogenstimulus.Regressionofprostatictumoursresultsfromthis

inhibition.Clinically,discontinuationofBicalinncanresultinantiandrogenwithdrawalsyndromeinasubsetof

patients.

Bicalinnisaracematewithitsantiandrogenicactivitybeingalmostexclusivelyinthe(R)-enantiomer.

5.2Pharmacokineticproperties

Bicalinniswellabsorbedfollowingoraladministration.Thereisnoevidenceofanyclinicallyrelevanteffectoffood

onbioavailability.

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

about1week.

OndailyadministrationofBicalinn,the(R)-enantiomeraccumulatesabout10-foldinplasmaasaconsequenceofits

≥0.1%and<1%)

Respiratory,thoracicandmediastinal

disorders Interstitiallungdisease

Rare

≥0.01%and<0.1%) Gastrointestinaldisorders Vomiting

Hepato-biliarydisorders Hepaticfailure

SkinandsubcutaneoustissuedisordersDryskin

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

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Steadystateplasmaconcentrationsofthe(R)-enantiomerofapproximately9microgram/mlareobservedduringdaily

administrationof50mgdosesofBicalinn.Atsteadystatethepredominantlyactive(R)-enantiomeraccountsfor99%

ofthetotalcirculatingenantiomers.

Thepharmacokineticsofthe(R)-enantiomerareunaffectedbyage,renalimpairmentormildtomoderatehepatic

impairment.Thereisevidencethatforsubjectswithseverehepaticimpairment,the(R)-enantiomerismoreslowly

eliminatedfromplasma.

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

glucuronidation:itsmetabolitesareeliminatedviathekidneysandbileinapproximatelyequalproportions.

Inaclinicalstudy,themeanconcentrationofR-bicalutamideinsemenofmenreceivingBicalinn150mgwas4.9

microgram/ml.Theamountofbicalutamidepotentiallydeliveredtoafemalepartnerduringintercourseislowand

equatestoapproximately0.3microgram/kg.Thisisbelowthatrequiredtoinducechangesinoffspringoflaboratory

animals.

5.3Preclinicalsafetydata

Bicalinnisapotentantiandrogen.Expectedpharmacologicaleffectsofantiandrogensseeninanimalstudiesincludethe

following:atrophyoftheprostateandseminalvesicles,benignLeydigcelltumours(rats)andadrenalcortical

hypertrophy.Bicalinnisamixedfunctionoxidaseinducerinanimalsandthyroidhypertrophyandadenoma(rat)and

hepatocellularcarcinoma(malemice)areaconsequenceofthis.Enzymeinductionhasnotbeenobservedinman.

Noneofthefindingsinpreclinicaltestingareconsideredtohaverelevancetothetreatmentofadvancedprostatecancer

patients.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Core

LactoseMonohydrate

PovidoneK-30

SodiumStarchGlycollate(TypeA)

MagnesiumStearate

Film-coating:

OpadryWhiteY-1-7000containing:

Hypromellose

Macrogol400

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

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PVC/aluminiumblisterpacksof28tablets.

Availableinpacksizes:10,14,28,50,60,90,100Film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

HelsinnBirexTherapeuticsLimited

Damastown

Mulhuddart

Dublin15

8MARKETINGAUTHORISATIONNUMBER

PA0915/015/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:12 th

September2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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