FINTEX

Main information

  • Trade name:
  • FINTEX Film Coated Tablet 5 Milligram
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FINTEX Film Coated Tablet 5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0915/016/001
  • Authorization date:
  • 26-09-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fintex5mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains5mgoftheactiveingredientFinasteride.

Alsocontains90.962mgofLactoseMonohydrate.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedTablet.

Blue,7mm,roundbiconvex,film-coatedtabletsmarked“F5”ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

'Fintex'isindicatedforthetreatmentandcontrolofbenignprostatichyperplasia(BPH)andforthepreventionof

urologiceventsto:

−reducetheriskofacuteurinaryretention

−reducetheriskofsurgeryincludingtransurethralresectionoftheprostate(TURP)andprostatectomy.

'Fintex'causesregressionoftheenlargedprostate,improvesurinaryflowandimprovesthesymptomsassociatedwith

BPH.

Patientswithanenlargedprostatearetheappropriatecandidatesfortherapywith'Fintex'.

4.2Posologyandmethodofadministration

Therecommendeddosageisone5mgtabletdaily,withorwithoutfood.

Althoughearlyimprovementinsymptomsmaybeseen,treatmentforatleastsixmonthsmaybenecessarytoassess

whetherabeneficialresponsehasbeenachieved.Theriskofacuteurinaryretentionisreducedwithinfourmonthsof

treatment.

Useinrenalinsufficiency

Noadjustmentindosageisrequiredinpatientswithvaryingdegreesofrenalinsufficiency(creatinineclearancesas

lowas9ml/min),aspharmacokineticstudiesdidnotindicateanychangeinthedispositionoffinasteride.

Useintheelderly

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4.3Contraindications

'Fintex'isnotindicatedforuseinwomenorchildren.'Fintex'iscontra-indicatedinthefollowing:hypersensitivityto

anycomponentofthisproduct;pregnancy-womenwhentheyareormaypotentiallybepregnant(see4.6'Pregnancy

andlactation',Exposuretofinasteride-risktomalefoetus).

4.4Specialwarningsandprecautionsforuse

General:Patientswithlargeresidualurinevolumeand/orseverelydiminishedurinaryflowshouldbecarefully

monitoredforobstructiveuropathy.

Effectsonprostate-specificantigen(PSA)andprostatecancerdetection:Noclinicalbenefithasyetbeendemonstrated

inpatientswithprostatecancertreatedwith'Fintex'.PatientswithBPHandelevatedPSAweremonitoredincontrolled

clinicalstudieswithserialPSAsandprostatebiopsies.IntheseBPHstudies,'Fintex'didnotappeartoaltertherateof

prostatecancerdetectionandtheoverallincidenceofprostatecancerwasnotsignificantlydifferentinpatientstreated

with'Fintex'orplacebo.Digitalrectalexamination,aswellasotherevaluationsforprostatecancer,shouldbe

performedonpatientswithBPHpriortoinitiatingtherapywith'Fintex'andperiodicallythereafter.SerumPSAisalso

usedforprostatecancerdetection.Generally,abaselinePSA>10ng/ml(Hybritech)promptsfurtherevaluationand

considerationofbiopsy;forPSAlevelsbetween4and10ng/ml,furtherevaluationisadvisable.Thereisconsiderable

overlapinPSAlevelsamongmenwithandwithoutprostatecancer.Therefore,inmenwithBPH,PSAvalueswithin

thenormalreferencerangedonotruleoutprostatecancerregardlessoftreatmentwith'Fintex'.AbaselinePSA<4

ng/mldoesnotexcludeprostatecancer.

'Fintex'causesadecreaseinserumPSAconcentrationsbyapproximately50%inpatientswithBPHeveninthe

presenceofprostatecancer.ThisdecreaseinserumPSAlevelsinpatientswithBPHtreatedwith'Fintex'shouldbe

consideredwhenevaluatingPSAdataanddoesnotruleoutconcomitantprostatecancer.Thisdecreaseispredictable

overtheentirerangeofPSAvalues,althoughitmayvaryinindividualpatients.AnalysisofPSAdatafromover3,000

patientsinthefour-year,double-blind,placebo-controlled'Fintex'Long-termEfficacyandSafetyStudy(PLESS)

confirmedthatintypicalpatientstreatedwith'Fintex'forsixmonthsormore,PSAvaluesshouldbedoubledfor

comparisonwithnormalrangesinuntreatedmen.ThisadjustmentpreservesthesensitivityandspecificityofthePSA

assayandmaintainsitsabilitytodetectprostatecancer.

AnysustainedincreaseinPSAlevelsofpatientstreatedwithfinasterideshouldbecarefullyevaluated,including

considerationofnon-compliancetotherapywith'Fintex'.

PercentfreePSA(freetototalPSAratio)isnotsignificantlydecreasedby'Fintex'andremainsconstantevenunderthe

influenceof'Fintex'.WhenpercentfreePSAisusedasanaidinthedetectionofprostatecancer,noadjustmentis

necessary.

Patientswithrarehereditaryproblemsofgalactoseintolerance,thelapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noclinicallyimportantdruginteractionshavebeenidentified.'Fintex'doesnotappeartosignificantlyaffectthe

cytochromeP450-linkeddrugmetabolisingenzymesystem.Compoundswhichhavebeentestedinmaninclude

propranolol,digoxin,glibenclamide,warfarin,theophylline,andantipyrineandnoclinicallymeaningfulinteractions

werefound.

Otherconcomitanttherapy:Althoughspecificinteractionstudieswerenotperformedinclinicalstudies,'Fintex'was

usedconcomitantlywithACEinhibitors,alpha-blockers,beta-blockers,calcium-channelblockers,cardiacnitrates,

diuretics,H2antagonists,HMG-CoAreductaseinhibitors,non-steroidalanti-inflammatorydrugs(NSAIDs)including

aspirinandparacetamol,quinolonesandbenzodiazepineswithoutevidenceofclinicallysignificantadverse

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4.6Fertility,pregnancyandlactation

Pregnancy:'Fintex'iscontra-indicatedinwomenwhentheyareormaypotentiallybepregnant(see4.3'Contra-

indications').

BecauseoftheabilityofTypeII5-reductaseinhibitorstoinhibitconversionoftestosteronetodihydrotestosterone,

thesedrugs,includingfinasteride,maycauseabnormalitiesoftheexternalgenitaliaofamalefoetuswhenadministered

toapregnantwoman.

Inanimaldevelopmentalstudies,dose-dependentdevelopmentofhypospadiaswasobservedinthemaleoffspringof

pregnantratsgivenfinasterideatdosesrangingfrom100µg/kg/dayto100mg/kg/day,atanincidenceof3.6%to

100%.Additionally,pregnantratsproducedmaleoffspringwithdecreasedprostaticandseminalvesicularweights,

delayedpreputialseparation,transientnippledevelopmentanddecreasedanogenitaldistance,whengivenfinasterideat

dosesbelowtherecommendedhumandose.Thecriticalperiodduringwhichtheseeffectscanbeinducedhasbeen

definedinratsasdays16-17ofgestation.

ThechangesdescribedaboveareexpectedpharmacologicaleffectsofTypeII5-reductaseinhibitors.Manyofthe

changes,suchashypospadias,observedinmaleratsexposedinuterotofinasteridearesimilartothosereportedinmale

infantswithageneticdeficiencyofTypeII5 -reductase.Itisforthesereasonsthat'Fintex'iscontraindicatedin

womenwhentheyareormaypotentiallybepregnant.

Theinuteroeffectsoffinasterideexposureduringtheperiodofembryonicandfoetaldevelopmentwereevaluatedin

therhesusmonkey(gestationdays20-100),aspeciesmorepredictiveofhumandevelopmentthanrats.Intravenous

administrationoffinasteridetopregnantmonkeysatdosesashighas800ng/day(atleast60to120timesthehighest

estimatedexposureofwomentofinasteridefromsemenofmentaking5mg/day)resultedinnoabnormalitiesinmale

foetuses.Inconfirmationoftherelevanceoftherhesusmodelforfoetaldevelopment,oraladministrationofavery

highdoseoffinasteride(2mg/kg/day;20timestherecommendedhumandoseof5mg/dayorapproximately1-2

milliontimesthehighestestimatedexposuretofinasteridefromsemenofmentaking5mg/day)topregnantmonkeys

resultedinexternalgenitalabnormalitiesinmalefoetuses.Nootherabnormalitieswereobservedinmalefoetusesand

nofinasteride-relatedabnormalitieswereobservedinfemalefoetusesatanydose.

Exposuretofinasteride-risktomalefoetus

Womenshouldnothandlecrushedorbrokentabletsof'Fintex'whentheyareormaypotentiallybepregnant,because

ofthepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefoetus(seePregnancy).'Fintex'

tabletsarecoatedandwillpreventcontactwiththeactiveingredientduringnormalhandling,providedthatthetablets

havenotbeenbrokenorcrushed.

Lactation:'Fintex'isnotindicatedforuseinwomen.Itisnotknownwhetherfinasterideisexcretedinhumanmilk.

Smallamountsoffinasteridehavebeenrecoveredfromthesemeninsubjectsreceivingfinasteride5mg/day.Itisnot

knownwhetheramalefoetusmaybeadverselyaffectedifhismotherisexposedtothesemenofapatientbeingtreated

withfinasteride.Whenthepatient’ssexualpartnerisormaypotentiallybepregnant,thepatientisrecommendedto

minimiseexposureofhispartnertosemen.

4.7Effectsonabilitytodriveandusemachines

Nonereported.

4.8Undesirableeffects

'Fintex'iswelltolerated.Incontrolledclinicalstudieswherepatientsreceived5mgoffinasterideoverperiodsofupto

fouryears,thefollowingadversereactionswereconsideredpossibly,probablyordefinitelydrug-relatedandoccurred

withafrequencygreaterthanplaceboandgreaterthanorequalto1%:impotence,decreasedlibido,ejaculation

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Therewasnoevidenceofincreasedadverseexperienceswithincreaseddurationoftreatmentwith'Fintex'andthe

incidenceofnewdrug-relatedsexualadverseexperiencesdecreasedwithdurationoftreatment.

Otherlong-termdata

Ina7yearplacebo-controlledtrialthatenrolled18,882healthymen,ofwhom9060hadprostateneedlebiopsydata

availableforanalysis,prostatecancerwasdetectedin803(18.4%)menreceiving'Fintex'and1147(24.4%)men

receivingplacebo.Agreaternumberofhighgradetumours(Gleasonscore7-10)weredetectedonneedlebiopsyin

patientsinthe'Fintex'group,280(6.4%)vs237(5.1%).Additionalanalysessuggestthattheincreaseintheprevalence

ofhigh-gradeprostatecancerobservedinthe'Fintex'groupmaybeexplainedbyadetectionbiasduetotheeffectof

'Fintex'onprostatevolume.Therelationshipbetweenlong-termuseof'Fintex'andtumourswithGleasonscores7-10is

unknown.

Post-marketingexperience

Thefollowingadditionaladverseexperienceshavebeenreportedinpost-marketingexperience:

−hypersensitivityreactions,includingpruritus,urticariaandswellingofthelipsandface

−testicularpain.

Laboratorytestfindings

SerumPSAconcentrationiscorrelatedwithpatientageandprostaticvolume,andprostaticvolumeiscorrelatedwith

patientage.WhenPSAlaboratorydeterminationsareevaluated,considerationshouldbegiventothefactthatPSA

levelsdecreaseinpatientstreatedwith'Fintex'.Inmostpatients,arapiddecreaseinPSAisseenwithinthefirstmonths

oftherapy,afterwhichtimePSAlevelsstabilisetoanewbaseline.Thepost-treatmentbaselineapproximateshalfof

thepretreatmentvalue.Therefore,intypicalpatientstreatedwith'Fintex'forsixmonthsormore,PSAvaluesshouldbe

doubledforcomparisontonormalrangesinuntreatedmen.Forclinicalinterpretationsee4.4'Specialwarningsand

specialprecautionsforuse',Effectsonprostate-specificantigen(PSA)andprostatecancerdetection.

Nootherdifferencewasobservedinpatientstreatedwithplaceboor'Fintex'instandardlaboratorytests.

4.9Overdose

Nospecifictreatmentofoverdosagewith'Fintex'isrecommended.Patientshavereceivedsingledosesof'Fintex'upto

400mgandmultipledosesof'Fintex'upto80mg/dayforuptothreemonthswithoutanyadverseeffects.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

FinasterideisacompetitiveinhibitorofhumanTypeII5 -reductase,anintracellularenzymewhichmetabolises

testosteroneintothemorepotentandrogen,dihydrotestosterone(DHT).Inbenignprostatichyperplasia(BPH),

enlargementoftheprostateglandisdependentupontheconversionoftestosteronetoDHTwithintheprostate.'Fintex'

ishighlyeffectiveinreducingcirculatingandintraprostaticDHT.Finasteridehasnoaffinityfortheandrogenreceptor.

Theeffectoftherapywith'Fintex'onBPH-relatedurologicevents(surgicalintervention[e.g.transurethalresectionof

theprostateandprostatectomy]oracuteurinaryretentionrequiringcatheterisation)hasbeenassessedoverafour-year

periodin3,016patientswithmoderatetoseveresymptomsofBPHinthe'Fintex'Long-termEfficacyandSafetyStudy

(PLESS).Inthisdouble-blind,randomised,placebo-controlledmulticentrestudy,treatmentwith'Fintex'reducedthe

riskoftotalurologiceventsby51%andwasalsoassociatedwithamarkedandsustainedregressioninprostate

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AdditionalClinicalStudies

Informationfromarecentlycompleted7-yearplacebo-controlledtrialthatenrolled18,882men ≥55yearsofage,with

anormaldigitalrectalexaminationandaPSAof ≤3.0ng/ml,mayberelevantformencurrentlybeingtreatedwith

'Fintex'forBPH.Attheendofthestudy,9060menhadprostateneedlebiopsydataavailableforanalysis.Inthisstudy,

prostatecancerwasdetectedin803(18.4%)menreceiving'Fintex'and1147(24.4%)menreceivingplacebo.'Fintexis

notindicatedtoreducetheriskofdevelopingprostatecancer(see'Undesirableeffects',Otherlongtermdata).

5.2Pharmacokineticproperties

Afteranoraldoseof14C-finasterideinman,39%ofthedosewasexcretedintheurineintheformofmetabolites

(virtuallynounchangeddrugwasexcretedintheurine),and57%oftotaldosewasexcretedinthefaeces.Two

metaboliteshavebeenidentifiedwhichpossessonlyasmallfractionofthe5-reductaseactivityoffinasteride.

Theoralbioavailabilityoffinasterideisapproximately80%,relativetoanintravenousreferencedose,andisunaffected

byfood.Maximumplasmaconcentrationsarereachedapproximatelytwohoursafterdosingandtheabsorptionis

completewithin6-8hours.Proteinbindingisapproximately93%.Plasmaclearanceandthevolumeofdistributionare

approximately165ml/minand76l,respectively.

Intheelderly,theeliminationrateoffinasterideissomewhatdecreased.Half-lifeisprolongedfromameanhalflifeof

approximately6hoursinmenaged18-60yearsto8hoursinmenagedmorethan70years.Thisisofnoclinical

significanceanddoesnotwarrantareductionindosage.

Inpatientswithchronicrenalimpairment,whosecreatinineclearancerangedfrom9to55ml/min,thedispositionofa

singledoseof14C-finasteridewasnotdifferentfromthatinhealthyvolunteers.Proteinbindingalsodidnotdifferin

patientswithrenalimpairment.Aportionofthemetaboliteswhichnormallyisexcretedrenallywasexcretedinthe

faeces.Itthereforeappearsthatfaecalexcretionincreasescommensuratetothedecreaseinurinaryexcretionof

metabolites.Dosageadjustmentinnondialysedpatientswithrenalimpairmentisnotnecessary.

Therearenodataavailableinpatientswithhepaticinsufficiency.

Finasteridehasbeenfoundtocrosstheblood-brainbarrier.Smallamountsoffinasteridehavebeenrecoveredinthe

seminalfluidoftreatedpatients.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofrepeateddosetoxicity,

genotoxicity,andcarcinogenicpotential.Reproductiontoxicologystudiesinmaleratshavedemonstratedreduced

prostateandseminalvesicularweights,reducedsecretionfromaccessorygenitalglandsandreducedfertilityindex

(causedbytheprimarypharmacologicaleffectoffinasteride).Theclinicalrelevanceofthesefindingsisunclear.

Aswithother5-alpha-reductaseinhibitors,femininisationofmaleratfoetuseshasbeenseenwithadministrationof

finasterideinthegestationperiod.Intravenousadministrationoffinasteridetopregnantrhesusmonkeysatdosesupto

800ng/dayduringtheentireperiodofembryonicandfoetaldevelopmentresultedinnoabnormalitiesinmalefoetuses.

Thisdoseisabout60-120timeshigherthantheestimatedamountinsemenofamanwhohavetaken5mgfinasteride,

andtowhichawomancouldbeexposedviasemen.InconfirmationoftherelevanceoftheRhesusmodelforhuman

foetaldevelopment,oraladministrationoffinasteride2mg/kg/day(thesystemicexposure(AUC)ofmonkeyswas

slightlyhigher(3x)thanthatofmenwhohavetaken5mgfinasteride,orapproximately1-2milliontimestheestimated

amountoffinasterideinsemen)topregnantmonkeysresultedinexternalgenitalabnormalitiesinmalefoetuses.No

otherabnormalitieswereobservedinmalefoetusesandnofinasteride-relatedabnormalitieswereobservedinfemale

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

Lactosemonohydrate

Cellulosemicrocrystalline

PregelatinisedMaizeStarch

LauroylMacrogolglycerides

SodiumstarchglycollateTypeA,

Magnesiumstearate

FilmCoat

Hypromellose6cps

Titaniumdioxide

Indigocarmine-lake

Macrogol6000

6.2Incompatibilities

Nonereported.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Nospecialstorageprecautionsnecessary.

6.5Natureandcontentsofcontainer

Blister(al/pvc),Blister(al/al)andHDPEcontainer

PackSizes:Fintextabletsaresuppliedinpacksof10,14,28,30,50,60,90,100film-coatedtablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Womenshouldnothandlecrushedorbroken'Fintex'Tabletswhentheyareormaypotentiallybepregnant(seesection

4.3'Contra-indications'andsection4.6'Pregnancyandlactation').

7MARKETINGAUTHORISATIONHOLDER

HelsinnBirexTherapeuticsLtd

Damastown,

Mulhuddart

Dublin15

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:26 th

September2008

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