FLUTAMID STADA

Main information

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

Documents

Localization

  • Available in:
  • FLUTAMID STADA
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0593/016/001
  • Authorization date:
  • 25-06-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FlutamidStada250mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Flutamide250mg

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet

Paleyellowroundtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofadvancedprostaticcarcinomainwhichsuppressionoftestosteroneeffectsisindicated.FlutamidStada

maybeusedasinitialtreatmentincombinationwithLHRHagonistsorasadjunctivetherapyinpatients,already

receivingLHRHagonisttherapy.FlutamidStadamayalsobeusedinsurgicallycastratedpatients.

4.2Posologyandmethodofadminstration

AdultsandElderly:Onetabletthreetimesdaily.Thetabletsshouldbetakenpreferablyaftermeals.

WhenFlutamidStadatabletsareusedasinitialtreatmentwithanLHRHagonist,areductioninseverityoftheflare

reactionmaybeachievediftreatmentwithFlutamidStadaisinitiatedbeforetheLHRHagonist.Consequently,itis

recommendedthattreatmentwithFlutamidStadashouldcommenceatleast3daysbeforetheLHRHagonist.

Inpatientswithimpairedliverfunction,long-termtreatmentwithflutamideshouldonlybeinitiatedaftercareful

assessmentoftheindividualbenefitsandrisks.

FlutamidStadashouldbeadministeredwithcautioninpatientswithimpairedrenalfunction.

4.3Contraindications

FlutamidStadaiscontraindicatedinpatientswhoarehypersensitivetoflutamideoranycomponentoftheproduct.

Forpatientswithsevereliverimpairment(ChildPughC)theuseofflutamideisalsocontraindicated.

4.4Specialwarningsandprecautionsforuse

Inpatientswithpre-existingliverdysfunctionthehazardofflutamide-inducedhepaticinjurymaybeincreased.

Therefore,inthesepatientslong-termtreatmentwithflutamideshouldonlybeinitiatedaftercarefulassessmentofthe

individualbenefitsandrisks.Therehavebeenreportsofelevatedserumtransaminaselevels,cholestaticjaundice,

hepaticnecrosisandhepaticencephalopathyassociatedwithflutamidetreatment.Thehepaticeffectswereusually

reversiblefollowingdiscontinuationofflutamide,althoughtherehavebeenoccasionalreportsoffatalitiesfollowing

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andduringtreatmentespeciallyinpatientsreceivinglong-termtreatmentwithflutamide.

Appropriatelaboratorytestingshouldbedoneatthefirstsymptom/signofliverdysfunction(e.g.pruritus,darkurine,

persistentanorexia,jaundice,rightupperquadranttendernessorunexplained“flu-like”symptoms).Ifthepatienthas

laboratoryevidenceofliverinjuryorjaundice,intheabsenceofbiopsyconfirmedlivermetastases,flutamidetherapy

shouldbediscontinuedordosagereduced.

Flutamideshouldbeadministeredwithcautioninpatientwithimpairedrenalfunction.

Periodicspermcountsshouldbeconsideredinpatientsreceivingchronictreatmentwithflutamidewhohavenot

receivedmedicalorsurgicalcastration.Flutamideadministrationtendstoelevateplasmatestosteroneandoestradiol

levelsinsuchpatients.Thismaybeassociatedwithfluidretentionandthereforecautionshouldbeexercisedintheuse

offlutamideifcardiacdiseaseispresent.

Inpatientsdevelopingaflutamiderefractorystageofprostatecancer,flutamidewithdrawalmayprovideshort-term

(months)therapeuticbenefitinabout30%ofthepatients.Cessationofflutamideforatleast4weeksisneededto

assessflutamidewithdrawalresponseintermsofreducedPSAlevels.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Increasesinprothrombintimehavebeenreportedinpatientstreatedwithwarfarin.Adjustmentofthedosemaybe

necessarywhenusedconcomitantlywithwarfarin.

4.6Pregnancyandlactation

Notrelevantduetotheindication.

4.7Effectsonabilitytodriveandusemachines

Patientshouldbeadvisedthatinitialsedativeeffectsmayinterferewithdrivingandtheoperationofmachinery.

4.8Undesirableeffects

Ithastobenotedthatpublishedfrequenciesofadverseeventsarenotconsistentand/orcomprehensivelyindicatedin

everypublication.

Flutamidemonotherapy

Themostcommonlyreportedadverseeffectsarehotflushes,nausea,diarrhoea,liverdisturbances,andgynecomastia.

Mildgynecomastiawasobservedin57%,moderategynecomastiain36%,andmassivegynecomastiain8%of

patients.Thefollowingadversedrugreactionswerereportedalthoughtheirincidencerateinpartgreatlyvariesamong

differentpublications.

Organsystems Very

common

>1/10 Common

>1/100,<1/10 Uncommon

>1/1,000,

<1/1,000 Rare

>1/10,000,

<1/1,000 Veryrare

<1/10,000

Infectionsand

infestations Urinary

tract

infections

Neoplasms

benignand

malignant Nodular

alterationof

thebreast Malignantmale

breastneoplasms

Bloodandthe

lymphatic

system

disorders Leukopenia,

thrombocytopenia,

haemolyticanemia,

macrocyticanemia, Sulfhemoglobinemia,

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methemoglobinemia

Endocrine

disorders Initially

reversible

increaseof

serum

testosterone

Psychiatric

disorders Anxiety,

depression,

nervousness,

manic-type

syndrome

Nervoussystem

disorders Dizziness,

insomnia,

headache

Eyedisorders Blurredvision

Cardiac

disorders Myocardial

ischemia

Vascular

disorders Thromboembolism Oedema,lymph

oedema,

hypertension

Respiratory,

thoracicand

mediastinal

disorders Chestpain Interstitial

pneumonitis,

hypoxemia

Gastrointestinal

disorders Nausea,

vomiting,

diarrhoea Increasedappetite Anorexia,

constipation,

dyspepsia,

ulcer-likepain

andheartburn,

lymphocytic

colitis Ischemiccolitis(1

case)

Hepato-biliary

disorders Elevatedliver

transaminases Hepatotoxicity Abnormalities

inliverfunction

tests,

cholestatic

hepatitiswith

jaundice Hepaticfailure

Skinand

subcutaneous

tissuedisorders Initially

flushes,

alterationof

thehair

growth

pattern Photosensitivity

erythema,

ulceration,

bullous

eruptions,

papulovesicular

eruptions,

epidermal

necrolysis,

ecchymoses,

herpeszoster,

pruritusand

lupus-like

syndrome

Musuloskeletal,

connective

tissueandbone

disorders Musclecramps,

bonepain Systemiclupus

erythematosus(1

case)

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Theseeffectsarenotnecessarilydrug-relatedandmaybeduetotheunderlyingclinicalcondition.Inmostcasesthe

reactionshavenotbeenofsufficientseveritytonecessitateeitherwithdrawalofflutamideorreductioninthedosage.

Veryrarely,seriousadversereactionsintheformofhepaticinjury(seeSpecialWarningsandPrecautions)have

occurred,inparticularinpatientswithpre-existingliverdysfunction.Hepatotoxicitymayincludeelevatedserum

transaminases,jaundice,hepaticencephalopathy,fulminanthepatitis,cholestatichepatitis,hepaticfailureandhepatic

necrosis.

Combinationtherapy(flutamideplusLHRHagonist)

Incombinationtherapythequalityofadversereactionsislargelycomparabletothatundermonotherapy.Their

frequencymaybecomparabletothatundermonotherapyormaybeatvariance.However,reportsondetailed

incidenceratesundercombinationtherapyarescarce.

Themostcommonlyreportedadverseeffectswerehotflushes(61%),lossoflibido(36%),impotence(33%),nauseaor

vomiting(14%),anddiarrhea(13.6%).However,onlydiarrheaoccurredmorefrequentlyinflutamide-treatedpatients

comparedwiththosetreatedwiththeLHRH-agonistalone.Theincidenceofgynecomastiaobservedwithflutamide

monotherapywasreducedincombinationtherapy.

Thefollowingtablecompilesthoseadversedrugreactionswhichdifferintheirincidenceratesgreatlyfrom

urinary

disorders elevations

ofblood

urea

nitrogen

(BUN)and

elevated

serum

creatinine

levels

without

reportsof

impaired

renal

darkyellow

discolouration

oftheurine case)

Reproductive

systemand

breastdisorders Gynecomastia

breast

tenderness,

sometimes

accompanied

galactorrhoea Decreased

libido,reduced

spermcounts

Congenitaland

familial/genetic

disorders Teratogenicdatais

lackingforhumans.

Animaldataindicate

thatadecreased

survivaltime,

feminizationofmale

fetuses,slight

increaseinminor

skeletal

malformations

General

disorders Insomniaand

tiredness Weakness,

malaise,

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4.9Overdose

Theacutetoxicdoseofflutamideinmanhasnotbeenestablished.Onepatientsurvivedafteringestingmorethan5g

asasingledose.Noadverseeffectswereseen.

Sinceflutamideisananilideithasthetheoreticpotentialofproducingmethaemoglobinaemiawhichmeansthata

patientwithacuteintoxicationmaybecyanotic.

Ifvomitingdoesnotoccurspontaneouslyitshouldbeinduced,providedthatthepatientisalert.Generalsupportive

measuresareappropriate,includingfrequentmonitoringofvitalsignsandcloseobservationsofthepatient.Flutamide

ishighlyproteinboundandwillnotberemovedbydialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Anti-androgens

ATC-code:L02BB01

Flutamideisanonsteroidalsubstance(derivativeofanilide)withantiandrogenproperties.Flutamideactsonthe

cellularlevel.Itexertsitsantiandrogenicactionbyinhibitingandrogen(mainlytestosterone)uptakeand/orby

inhibitingnuclearbindingintargettissues.Bycombinedtreatmentwithanantiandrogensuchasflutamideandan

LHRH-agonistso-calledtotalandrogenblock,lessandrogeneffectinthetumourisobtainedcomparedwiththe

LHRH-agonistusedasmonotherapy.Thisiscausedbyflutamideblockingtheperipheralandrogenreceptorand

therebypreventingandrogenswhichareproducedbothintheadrenalglandandtestistoaffectthetargettissues.

Patientsinanadvancedstagewithsmalltumourburdenwillbenefitmostfromthetreatment.

ConcomitanttreatmentwithanLHRH-agonistalsopreventsaflare-upreactionofthediseasewhichoccursduringthe

firstmonthoftreatmentwiththeLHRH-agonistcausedbyaninitialelevationofthetestosteronelevelswitha

significantincreaseofprostatespecificantigen(PSA).

5.2Pharmacokineticproperties

Thepharmacokineticcharacteristicsofflutamideusedasmonotherapyareincompletelystudied.Peakserum

Organsystems Verycommon

>

1/10 Common

>

1/100, <

1/10 Uncommon

>

1/1,000,

<

1/100 Rare

>

1/10,000,

<

1/1,000 Veryrare

<

1/10,000

Gastrointestinal

disorders lossofappetite,

vomiting/nausea

anddiarrhoea

Skinand

subcutaneous

tissuedisorders flushes,decreased

libido,impotence,

diarrhoea,nausea

andvomiting

Reproductive

systemand

breastdisorders gynecomastia,

lossofsexual

desire,decrease

inpenileerectile

potency,

decreasein

sexual

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metabolised.Onehourafterdosingonly2.5%ofgivendoseconsistsofunchangedflutamide.Themajormetabolitein

plasmaisalphahydroxyflutamidewhichispharmacologicallyactiveandcontributestothepharmacologicaleffecttoa

higherdegreethanthemainsubstance.About30timeshigherplasmaconcentrationoftheactivemetaboliteis

achieved.Theterminalplasmahalf-lifesoftheflutamideandtheactivemetaboliteareabout8hoursand9hours

respectively.Afterrepeateddosethesteady-stateconcentrationofflutamideisobtainedwithinabout4days.Flutamide

ismainlyeliminatedbymetabolismandthemetabolitesareexcretedviaurine.Onlyabout5%isexcretedviathe

faeces.

5.3Preclinicalsafetydata

Theeffectsobservedinoralrepeatdosetoxicologystudiesintherat,dogandmonkeywereasexpectedforapotent

anti-androgenicagent.Reductionsinprostateglandandseminalvesicleweightswereobservedinallspeciesand

reducedtesticularweightswereobservedintheratandmonkey.Histologicalchangescharacteristicofanti-androgenic

activitywereobservedinallspeciesandtherewasevidenceofsuppressionofspermatogenesis.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Maizestarch

Sodiumlaurylsulphate

Lactosemonohydrate

Colloidalanhydroussilica

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage.

6.5Natureandcontentsofcontainer

PVC/Aluminiumfoilblisterstripswith21,50,84,90,100,105or200tabletsineachbox.

Notallpacksizesmaybemarketedinallcountries.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

STADAArzneimittelAG

Stadastrasse2-18

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Germany

8MARKETINGAUTHORISATIONNUMBER

PA593/16/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:25June1999

Dateoflastrenewal:14July2002

10DATEOFREVISIONOFTHETEXT

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