FLUTAPLEX

Main information

  • Trade name:
  • FLUTAPLEX Tablets 250 Milligram
  • Dosage:
  • 250 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLUTAPLEX Tablets 250 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0937/001/001
  • Authorization date:
  • 23-08-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0937/001/001

CaseNo:2016336

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PharmachemieBV

Swensweg5,,P.O.Box552,2003RNHaarlem,Netherlands

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Flutaplex

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/01/2006until22/08/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Flutaplex

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontains250mg flutamide.

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Tablet.

Flutaplex isayellowtabletwith inscription‘Flutamide250’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Flutamidetabletsareindicatedforthetreatmentofadvancedprostaticcarcinomainwhichsuppressionoftestosterone

effectisindicated.

Flutamideisused in thepalliativetreatmentofmetastasized, inoperablecarcinomaoftheprostate, in combination with

an LH-RHagonistorsurgicalcastration.

4.2Posologyandmethodofadminstration

Adults:

Therecommendedadultdose, including theelderly, is250 mg threetimesaday, aftermeals. Thetabletshould be

taken with someliquid (withoutchewing). Itisadvisableto starttheflutamidetreatment(250 mg threetimesaday)

threedaysbeforetheapplication oftheLH-RHagonist, in orderto reducethedevelopmentand seriousnessofthe

‘tumourflarephenomenon’atthestartofthetherapy with an LH-RHagonist.

Children:

Flutamideisnotindicated forusein children.

Thetreatmentduration isdetermined by thephysician in accordancewith thecourseofthedisease. In clinicaltrials,

patientshavebeen treated formorethan 4.5 years.

Dosageadjustmentin renalorliverinsufficiency:

In patientswith impaired liverfunction, long-termtreatmentwith flutamideshould only beadministered aftercareful

assessmentoftheindividualbenefitsand risks.

Flutamideishighly protein bound and willnotberemoved by dialysis.

4.3Contraindications

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 2

4.4Special warningsandprecautionsforuse

Incaseofhepaticdysfunction,thebenefitsoflong-termtreatmentwithflutamideshouldbecarefullyweighedagainst

thepotentialrisks.Beforethestartofthetreatmentandduringtheflutamidetreatmentitselfregularchecksofliver

functionarerequired,especiallyifsignsorsymptomsofhepaticdysfunction(e.g.itching,darkenedurine,persistent

anorexia,jaundice,rightepigastricpainornon-specific"flu-like"symptoms)arepresent.Therapyshouldnotbestarted

orshouldbediscontinuedifthetransaminasesriseabove2or3timesthenormallevelorlaboratorytestsindicateliver

damageorjaundicenotattributabletobiopsyconfirmedhepaticmetastases.Effectsonliverfunctionaregenerally

reversibleafterdiscontinuationofflutamidetreatment.Howevertherehavebeenreportsofdeathfollowingsevere

hepaticinjury associated with theuseofflutamide.

Patientssuffering fromkidney function disordersshould beclosely monitored during theflutamidetreatment.

Inpatientswhohavenotreceivedsurgicalcastration,periodicspermcountdeterminationsmaybeconsideredduring

long-termtreatment.Insuchpatientsflutamideadministrationtendstoelevateplasmatestosteroneandestradiollevels.

Fluidretentionmayoccur,thusthedrugshouldbeusedwithcautionincardiacdisease.Incaseofcyanosis,a

methaemoglobinaemia,possibly caused by overdosage, should besought.

Flutamideisindicated fortheuseinmalepatientsonly.

Thismedicinalproductcontainslactose. Patientswith rarehereditary problemsofgalactoseintolerance, theLapp

lactasedeficiency orglucose-galactosemalabsorption should nottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

An increasein theprothrombintimehasbeen observed when flutamidewasused atthesametimeasthecumarin

derivativewarfarin, and adequatemonitoring oftheprothrombin timeisnecessary.

4.6Pregnancyandlactation

Notapplicable, sincethismedication isnotused in women.

4.7Effectsonabilitytodriveandusemachines

When driving vehiclesoroperating machines, itshould betaken into accountthatundertreatmentwith flutamide

occasionally fatigue, rarely dizzinessand blurred vision havebeen reported.

4.8Undesirableeffects

Thesideeffectsareclassified according to following frequencies:

Very common:>10%

Common:>1%, <10%

Uncommon:>0.1%, <1%

Rare:>0.01%, <0.1%

Very rare, including isolated reports:<0.01%

Monotherapy

Theside-effectsmostfrequentlyobservedduringaflutamidetreatmentaregynaecomastiaandsorebreasts.Theseside

effectsaredosedependent.

Infectionsandinfestations

Rare

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 3

Bloodandlymphaticsystemdisorders

Common

Anaemia, leucopenia, thrombocytopenia, methaemoglobinaemia

Metabolismandnutritiondisorders

Common

Increased appetite

Psychiatricdisorders

Rare

Depression, anxiety, confusion, anorexia

Nervoussystemdisorders

Common

Somnolence, insomnia

Rare

Headache, vertigo

Eyedisorders

Rare

Blurred vision

Cardiacdisorders

Rare

Cardiovasculardisorders

Vasculardisorders

Rare

Hotflushes

Lymphoedemaand ecchymosesaredescribed

Gastrointestinaldisorders

Verycommon

Nausea, vomiting and diarrhoea

Common

Stomatitis, constipation, gastricupset, ulcer-likepain, heartburn

Hepato-biliarydisorders

Common

Hepatitis, jaundice, elevated liverfunction tests.

Generally theliverdisordersarereversibleafterdiscontinuation offlutamide

Rare

Afewcasesofseveretoxichepatitis, hepaticnecrosisand hepaticencephalopathy havebeen reported.

Veryrareincluding isolated reports

Isolated casesoffataloutcomeofhepaticinjury associated with flutamidehavebeenreported.

Skinandsubcutaneoustissuedisorders

Rare

Rashes, pruritus,

Alopeciaand lupus-likesyndromehavebeen observed in anumberofpatients

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 4

Musculoskeletal, connectivetissueandbonedisorders

Musclecrampshavebeen observed

Renalandurinarydisorders

Rare

Elevatedbloodureaandcreatinine(theseverityoftheseeffectsdidnotgenerallynecessitatedosagereductionor

treatmentdiscontinuation)

Green discoloration oftheurine

Reproductivesystemandbreastdisorders

Verycommon

Gynaecomastia, sorebreasts

Uncommon

Galactorrhoea

Rare

Smallnodularchangesofthemammary gland, reduced spermproduction

Atinitiation offlutamidemonotherapy areversibleincreaseofplasmatestosteronelevelmay occur. Reducedlibido has

been reported. In mostpatientswho havebeentreated with flutamide, thelibido and thevirility arepreserved.

Generaldisordersandadministrationsiteconditions

Rare

Fatigue, chestpain, weakness

In addition fluid retention, oedema, thirst, flux and malaisehavebeen reported.

Combination therapy

ThesideeffectsmostfrequentlyobservedinclinicaltrialsoncombinationtherapyofflutamideandLH-RHagonists

werehotflushes,reducedlibido,impotence,diarrhoea,nauseaandvomiting.Gynaecomastia,acommonoccurrence

withflutamidemonotherapywasconsiderablyreducedundercombinationtherapy.Inclinicaltrialstherewasno

significantdifferencein theincidenceofgynaecomastiabetween placebo and flutamide-LH-RHagonisttreatment.

Bloodandlymphaticsystemdisorders

Common

Anaemia, leucopenia, thrombocytopenia

In addition haemolyticanaemia, macrocyticanaemia, methaemoglobinaemiaand thromboemboly havebeen reported

Psychiatricdisorders

Rare

Depression, confusion, anxiety, nervousness,anorexia

Nervoussystemdisorders

Common

Somnolence, insomnia

Rare

Neuromuscularsymptoms

Vasculardisorders

Verycommon

Hotflushes

Rare

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 5

Respiratory, thoracicandmediastinaldisorders

Rare

Pulmonary symptoms(e.g. dyspnoea)

Gastrointestinaldisorders

Verycommon

Diarrhoea, nausea, vomiting

Common

Non-specificgastro-intestinalcomplaints

Hepato-biliarydisorders

Common

Hepatitis, jaundice, elevated liverfunction tests.

Generally theliverdisordersarereversibleafterdiscontinuation offlutamide

Rare

Afewcasesofseveretoxichepatitis, hepaticnecrosisand hepaticencephalopathy havebeen reported.

Veryrareincluding isolated reports

Isolated casesoffataloutcomeofhepaticinjury associated with flutamidehavebeenreported.

Skinandsubcutaneoustissuedisorders

Rare

Rash

Inadditionphotosensitivityreactions(includinglocalisederythema,ulcerations,blisters,epidermalnecrolysis)have

been reported.

Renalandurinarydisorders

Rare

Urogenitaltractsymptoms

Reproductivesystemandbreastdisorders

Verycommon

Impotence, reduced libido

Veryrare, including isolated reports

Gynaecomastia

Generaldisordersandadministrationsiteconditions

Rare

Oedema

Investigations

Laboratoryabnormalitiesincludeelevatedbloodureaand–rarely-elevatedserumcreatinine.Theseverityofthese

effectsdid notgenerally necessitatedosagereduction ortreatmentdiscontinuation.

Twocasesofmammarytumourswereobservedinmenundertreatmentwithflutamide.Inoneofthese,apatientwith

benignprostatichyperplasia,oneofthebreasttumoursthathadbeendetected3-5monthsbeforestartingflutamide

progressed. Following surgery, thiswasdiagnosed asapoorly differentiated ductalcarcinoma.

Theothercasewasapatientwith advanced prostaticcarcinomain whom, in addition to gynaecomastia, atumourmass

wasdetected 2 and 5 monthsafterstarting flutamidemonotherapy. Ninemonthsafterstarting flutamidethismasswas

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 6

4.9Overdose

Sofarnosymptomshavebeenreportedafteranoverdoseofflutamide.Onecaseisknownofapatientwhotook5

gramsofflutamide;therewereno adverseeffectsforthepatient, and no side-effectswereobserved.

Sinceflutamidebelongstotheanilidecompoundsthereisatheoreticalriskofthedevelopmentof

methaemoglobinaemia.Accordingly,apatientwith an acuteintoxication can becyanotic.

Ifapatienthasclinicalsignsofoverdosagevomiting should beinduced spontaneously ifthepatientisalert.General

supportivemeasuresincluding frequentvitalsignsmonitoring and closepatientobservation arewarranted. Sinceavery

high proportion offlutamideisbound to plasmaproteins, itcannotberemoved by dialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Flutamideisanon-steroid, specifically activeanti-androgen. Itisasubstituted anilidecompound. Theprecise

mechanismofflutamideisnotyetknown. Itissuggested thatflutamideand/orthemetabolitesinhibitthebond of

testosteroneand/ordihydrotestosteroneto thereceptor, thuspreventing theandrogensfromhaving theirbiological

effects.

ATC-code:L02BB01

5.2Pharmacokineticproperties

Absorption:

Flutamideisabsorbed quickly and almostcompletely afteroraladministration.

Metabolism:

Flutamideismetabolizedinthelivertoahighextent.Themostimportantmetabolite,whichalsohasstronganti-

androgenicproperties,ishydroxyflutamide.Onehourafteradministrationofflutamidetheratiobetweentheplasma

concentrationsofflutamideand themain metaboliteisabout1:10.

Elimination:

Excretion offlutamidemainly takesplacein theformofmetabolitesin theurine. Within 2 daysabout90%ofthe

administered doseofflutamidehasbeen metabolized andexcreted. Theelimination half-valuetimein plasmais5-6

hours, both forflutamideand itsmain metabolite.

5.3Preclinical safetydata

Inrats,dogsandmonkeys,reductioninthesizeofprostateglandsandseminalvesicleswasobserved,andtherewas

also evidenceofreduction in testessizeand decreased spermatogenesis.

Flutamideshowed no mutageniceffectsin vitro in bacteriaorin vivo mammals. In acarcinogenicity study in rats,

dose-dependentincreaseofmammary adenomasand carcinomaswasestablished from30 mg/kg ofbodyweight

onwards. Thereareno otherpreclinicalfindingsofrelevancebeyond theinformation already providedin othersections

oftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Povidone

Lactosemonohydrate

Potato starch

Sodiumlaurilsulfate

Microcrystallinecellulose(E460)

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 7

Colloidalanhydroussilica(E470B)

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelflifeis5 years.

6.4Special precautionsforstorage

Do notstoreabove25°C.Storein theoriginalpackage.

6.5Natureandcontentsofcontainer

Blister(PVC/A1)of30 tablets.

Blister(PVC/A1)of84 tablets.

Blister(PVC/A1)of90 tablets.

Blister(PVC/A1)of100 tablets.

HospitalUnitDoseblister(PVC/A1)of50 tablets.

PE-bottleof30 tablets.

PE-bottleof90 tablets.

6.6Instructionsforuseandhandling

Notapplicable.

7MARKETINGAUTHORISATIONHOLDER

PharmachemieB.V.

Swensweg 5

POBox 552,

2003 RNHaarlem,

TheNetherlands.

8MARKETINGAUTHORISATIONNUMBER

PA937/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 23 rd

August1999

Dateoflastrenewal: 23 rd

August2004

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/01/2006 CRN 2016336 page number: 8