FINASTERIDE TEVA

Main information

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

Documents

Localization

  • Available in:
  • FINASTERIDE TEVA
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/035/001
  • Authorization date:
  • 29-02-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FinasterideTEVA5mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onefilm-coatedtabletcontains5mgfinasteride.

Excipient:Onefilm-coatedtabletcontains75mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

White,round,biconvex,film-coatedtablet,diameter7mm,embossed“F”and“5”ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Finasterideisindicatedforthetreatmentandcontrolofbenignprostatichyperplasia(BPH)to:

-causeregressionoftheenlargedprostate,improveurinaryflowandimprovethesymptomsassociatedwithBPH

-reducetheincidenceofacuteurinaryretentionandtheneedforsurgeryincludingtransurethralresectionofthe

prostate(TURP)andprostatectomy.

Finasteride5mgtabletsshouldbeadministeredinpatientswithanenlargedprostate(prostatevolumeaboveca.40ml).

4.2Posologyandmethodofadministration

Fororaluseonly.

Therecommendeddosageisone5mgtabletdailywithorwithoutfood.Thetabletshouldbeswallowedwholeand

mustnotbedividedorcrushed(seesection6.6).Eventhoughimprovementcanbeseenwithinashorttime,treatment

foratleast6monthsmaybenecessaryinordertodetermineobjectivelywhetherasatisfactoryresponsetotreatment

hasbeenachieved.

Dosageinhepaticinsufficiency

Therearenodataavailableinpatientswithhepaticinsufficiency(seesection4.4).

Dosageinrenalinsufficiency

Dosageadjustmentsarenotnecessaryinpatientswithvaryingdegreesofrenalinsufficiency(withcreatinineclearance

downtoaslowas9ml/min)asinpharmacokineticstudiesrenalinsufficiencywasnotfoundtoaffecttheeliminationof

finasteride.Finasteridehasnotbeenstudiedinpatientsonhaemodialysis.

Dosageintheelderly

Dosageadjustmentsarenotnecessaryalthoughpharmacokineticstudieshaveshownthattheeliminationrateof

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4.3Contraindications

Finasterideiscontraindicatedinthefollowing:

Hypersensitivitytofinasterideortoanyoftheexcipients.

Pregnancy–Useinwomenwhoareormaypotentiallybepregnant(seesections4.6and6.6).

Finasterideisnotindicatedforuseinwomenorinchildren.

4.4Specialwarningsandprecautionsforuse

General

Toavoidobstructivecomplicationsitisimportantthatpatientswithlargeresidualurinevolumeand/orseverely

diminishedurinaryflowshouldbecarefullymonitored.Thepossibilityofsurgeryshouldbeanoption.

Consultationofanurologistshouldbeconsideredinpatientstreatedwithfinasteride.

Obstructionduetotrilobulargrowthpatternoftheprostateshouldbeexcludedbeforestarting

treatmentwithfinasteride.

Thereisnoexperienceinpatientswithhepaticinsufficiency.Sincefinasterideismetabolizedintheliver(seesection

4.2)cautionisadvisedinpatientswithimpairedhepaticfunctionastheplasmalevelsoffinasteridemaybeincreasedin

suchpatients.

Effectsonprostate-specificantigen(PSA)andprostatecancerdetection

Noclinicalbenefithasyetbeendemonstratedinpatientswithprostatecancertreatedwith

finasteride.PatientswithBPHandelevatedserumprostatespecificantigen(PSA)weremonitoredincontrolledclinical

studieswithserialPSAsandprostatebiopsies.IntheseBPHstudies,finasteridedidnotappeartoaltertherateof

prostatecancerdetection,andtheoverallincidenceofprostatecancerwasnotsignificantlydifferentinpatientstreated

withfinasterideorplacebo.

Digitalrectalexaminationsaswellasotherevaluationsforprostatecancerarerecommendedpriortoinitiatingtherapy

withfinasterideandperiodicallythereafter.SerumPSAisalsousedforprostatecancerdetection.Generallyabaseline

PSA>10ng/ml(Hybritech)promptsfurtherevaluationandconsiderationofbiopsy;forPSAlevelsbetween4and10

ng/ml,furtherevaluationisadvisable.

ThereisconsiderableoverlapinPSAlevelsamongmenwithandwithoutprostatecancer.

Therefore,inmenwithBPH,PSAvalueswithinthenormalreferencerangedonotruleoutprostatecancer,regardless

oftreatmentwithfinasteride.AbaselinePSA<4ng/mldoesnotexcludeprostatecancer.

FinasteridecausesadecreaseinserumPSAconcentrationsbyapproximately50%inpatientswithBPH,eveninthe

presenceofprostatecancer.ThisdecreaseinserumPSAlevelsinpatientswithBPHtreatedwithfinasterideshouldbe

consideredwhenevaluatingPSAdataanddoesnotruleoutconcomitantprostatecancer.Thisdecreaseispredictable

overtheentirerangeofPSAvalues,althoughitmayvaryinindividualpatients.AnalysisofPSAdatafromover3000

patientsinthe4-year,double-blind,placebo-controlledfinasterideLong-TermEfficacyandSafetyStudy(PLESS)

confirmedthatintypicalpatientstreatedwithfinasterideforsixmonthsormore,PSAvaluesshouldbedoubledfor

comparisonwithnormalrangesinuntreatedmen.ThisadjustmentpreservesthesensitivityandspecificityofthePSA

assayandmaintainsitsabilitytodetectprostatecancer.

AnysustainedincreaseinPSAlevelsofpatientstreatedwithfinasterideshouldbecarefully

evaluated,includingconsiderationofnon-compliancetotherapywithfinasteride.

PercentfreePSA(freetototalPSAratio)isnotsignificantlydecreasedbyfinasteride.TheratiooffreetototalPSA

remainsconstantevenundertheinfluenceoffinasteride.WhenpercentfreePSAisusedasanaidinthedetectionof

prostatecancer,noadjustmenttoitsvalueisnecessary.

Drug/laboratorytestinteractions

EffectonlevelsofPSA

SerumPSAconcentrationiscorrelatedwithpatientageandprostaticvolume,andprostaticvolumeiscorrelatedwith

patientage.WhenPSAlaboratorydeterminationsareevaluated,consideration

shouldbegiventothefactthatPSAlevelsdecreaseinpatientstreatedwithfinasteride.Inmostpatients,arapid

decreaseinPSAisseenwithinthefirstmonthsoftherapy,afterwhichtimePSAlevelsstabilizetoanewbaseline.The

post-treatmentbaselineapproximateshalfofthepretreatmentvalue.Therefore,intypicalpatientstreatedwith

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Forclinicalinterpretation,seesection4.4Specialwarningsandprecautionsforuse,EffectsonPSAandprostatecancer

detection.

Breastcancerinmen

Breastcancerhasbeenreportedinmentakingfinasteride5mgduringclinicaltrialsandthepostmarketingperiod.

Physiciansshouldinstructtheirpatientstopromptlyreportanychangesintheirbreasttissuesuchaslumps,pain,

gynaecomastiaornippledischarge.

Paediatricpopulation

Finasterideisnotindicatedforuseinchildren.Safetyandeffectivenessinchildrenhavenotbeenestablished.

Lactose

Thismedicinalproductcontainslactosemonohydrate.Patientswithrarehereditaryproblemsofgalactoseintolerance,

theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nodruginteractionsofclinicalimportancehavebeenidentified.Finasteridedoesnotappeartoaffectsignificantlythe

cytochromeP450-linkeddrugmetabolizingenzymesystem.Compoundswhichhavebeentestedinmanhaveincluded

propranolol,digoxin,glyburide,warfarin,theophyllineandantipyrineandnoclinicallymeaningfulinteractionswere

found.

Otherconcomitanttherapy:

Althoughspecificinteractionstudieswerenotperformedinclinicalstudies,finasteridewasusedconcomitantlywith

ACEinhibitors,alpha-blockers,beta-blockers,calciumchannelblockers,cardiacnitrates,diuretics,H2antagonists,

HMG-CoAreductaseinhibitors,non-steroidalanti-inflammatorydrugs(NSAIDs)includingaspirinandparacetamol,

quinolonesandbenzodiazepineswithoutevidenceofclinicallysignificantadverseinteractions.

4.6Fertility,pregnancyandlactation

Pregnancy

Finasterideiscontraindicatedforuseinwomenwhentheyareormaypotentiallybepregnant(seesection4.3).

Becauseoftheabilityoffinasteridetoinhibitconversionoftestosteronetodihydrotestosterone(DHT)finasteridemay

causeabnormalitiesoftheexternalgenitaliaofamalefetuswhenadministeredtoapregnantwoman.

Exposuretofinasteride–risktomalefetus

Womenshouldnothandlecrushedorbrokenfinasteridetabletswhentheyareormaypotentiallybepregnantbecause

ofthepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefetus.Finasteridetabletshavea

film-coatingwhichpreventscontactwiththeactiveingredientduringnormalhandling,providedthatthetabletshave

notbeenbrokenorcrushed.

Smallamountsoffinasteridehavebeenrecoveredfromthesemeninsubjectsreceivingfinasteride5mg/day.Itisnot

knownwhetheramalefetusmaybeadverselyaffectedifhismotherisexposedtothesemenofapatientbeingtreated

withfinasteride.Whenthepatient’ssexualpartnerisormaypotentiallybepregnant,thepatientisrecommendedto

minimiseexposureofhispartnertosemen.

Breast-feeding

Finasterideisnotindicatedforuseinwomen.

Itisnotknownwhetherfinasterideisexcretedinhumanmilk.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

Themostcommonadversereactionsareimpotenceandreducedlibido.Thesereactionsusuallyoccuratthebeginning

ofthetreatmentandinthemajorityofpatientsareofatransientnatureoncontinuedtreatment.

Theadversereactionsreportedduringclinicaltrialsand/orpost-marketingusearelistedbelow.

Thefrequenciesofadverseeventsarerankedaccordingtothefollowing: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;includingisolated

reports),notknown(cannotbeestimatedfromtheavailabledata).

Inaddition,thefollowinghasbeenreportedinclinicaltrialsandpost-marketinguse:malebreastcancer(seesection

4.4).

Medicaltherapyofprostatesymptoms(MTOPS)

TheMTOPSstudycomparedfinasteride5mg/day(n=768),doxazosin4or8mg/day(n=756),combinationtherapyof

finasteride5mg/dayanddoxazosin4or8mg/day(n=786),andplacebo(n=737).Inthisstudy,thesafetyand

tolerabilityprofileofthecombinationtherapywasgenerallyconsistentwiththeprofilesoftheindividualcomponents.

Theincidenceofejaculationdisorderinpatientsreceivingcombinationtherapywascomparabletothesumof

Immunesystemdisorders

Notknown: Hypersensitivityreactionsincludingswellingoflipsandface

Psychiatricdisorders

Common: Decreasedlibido

Nervoussystemdisorders

Uncommon: Somnolence

Cardiacdisorders

Notknown: Palpitation

Hepatobiliarydisorders

Notknown: Increasedhepaticenzymes

Skinandsubcutaneoustissuedisorders

Uncommon: Rash

Notknown: Pruritus,urticaria

Reproductivesystemandbreastdisorders

Common: Imporence

Uncommon: Ejaculationdisorder,breasttenderness,breastenlargement

Notknown: Testicularpain

Investigations

Common: Decreasedvolumeofejaculate

Systemorganclass Placebo

N=737 Doxazosin

N=756 Finasteride

N=768 Finasteride+Doxazosin

N=786

Patientswithoneor

moreundesirable

effect 46.4 64.9 52.5 73.8

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Otherlong-termdata

Ina7-yearplacebo-controlledtrialthatenrolled18,882healthymen,ofwhom9060hadprostateneedlebiopsydata

availableforanalysis,prostatecancerwasdetectedin803(18.4%)menreceivingfinasterideand1147(24.4%)men

receivingplacebo.Inthefinasteridegroup,280(6.4%)menhadprostatecancerwithGleasonscoresof7-10detected

onneedlebiopsyvs.237(5.1%)menintheplacebogroup.Additionalanalysessuggestthattheincreaseinthe

prevalenceofhigh-gradeprostatecancerobservedinthefinasteridegroupmaybeexplainedbyadetectionbiasdueto

theeffectoffinasterideonprostatevolume.Ofthetotalcasesofprostatecancerdiagnosedinthisstudy,approximately

98%wereclassifiedasintracapsular(clinicalstageT1orT2)atdiagnosis.TheclinicalsignificanceoftheGleason7-10

dataisunknown.

Laboratorytestfindings

WhenPSAlaboratorydeterminationsareevaluated,considerationshouldbegiventothefactthatPSAlevelsare

decreasedinpatientstreatedwithfinasteride(seesection4.4).

4.9Overdose

Patientshavereceivedsingledosesoffinasterideupto400mgandmultipledosesupto80mg/daywithoutadverse

Asthenia 7.1 15.7 5.3 16.8

Cardiacdisorders 10.4 23.1 12.6 22.0

Hypotension

Orthostatic

hypotension 0.7

16.7 1.2

17.8

Nervoussystem

disorders 16.1 28.4 19.7 36.3

Dizziness

Reducedlibido

Somnolence 8.1

17.7

10.0

23.2

11.6

Uro-genitaldisorders 18.6 22.1 29.7 36.8

Ejaculationdisorders

Breastenlargement

Impotency

Othersexual

abnormalities 2.3

12.2

14.4

18.5

14.1

22.6

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Testosterone-5-reductase-inhibitors

ATC-Code:G04CB01

Finasterideisasynthetic4-azasteroid,aspecificcompetitiveinhibitoroftheintracellularenzymeType-II-5-

reductase.Theenzymeconvertstestosteroneintothemorepotentandrogendihydrotestosterone(DHT).Theprostate

glandand,consequently,alsothehyperplasicprostatetissuearedependentontheconversionoftestosteronetoDHT

fortheirnormalfunctionandgrowth.Finasteridehasnoaffinityfortheandrogenreceptor.

ClinicalstudiesshowarapidreductionoftheserumDHTlevelsof70%,whichleadstoareductionofprostatevolume.

After3months,areductionofapprox.20%inthevolumeoftheglandoccurs,andtheshrinkingcontinuesandreaches

approx.27%after3years.Markedreductiontakesplaceintheperiurethralzoneimmediatelysurroundingtheurethra.

Urodynamicmeasurementshavealsoconfirmedasignificantreductionofdetrusorpressureasaresultofthereduced

obstruction.

Significantimprovementsinmaximumurinaryflowrateandsymptomshavebeenobtainedafterafewweeks,

comparedwiththestartoftreatment.Differencesfromplacebohavebeendocumentedat4and7months,respectively.

Allefficacyparametershavebeenmaintainedovera3yearfollow-upperiod.

Effectsoffouryearstreatmentwithfinasterideonincidenceofacuteurineretention,needforsurgery,symptomscore

andprostatevolume:

InclinicalstudiesofpatientswithmoderatetoseveresymptomsofBPH,anenlargedprostateondigitalrectal

examinationandlowresidualurinaryvolumes,finasteridereducedtheincidenceofacuteretentionofurinefrom7/100

to3/100overfouryearsandtheneedforsurgery(TURPorprostatectomy)from10/100to5/100.Thesereductions

wereassociatedwitha2pointimprovementinQUASJI-AUAsymptomscore(range0-34),asustainedregressionin

prostatevolumeofapproximately20%andasustainedincreaseinurinaryflowrate.

5.2Pharmacokineticproperties

Absorption

Thebioavailabilityoffinasterideisapprox.80%.Peakplasmaconcentrationsarereachedapprox.2hoursafterintake,

andabsorptioniscompleteafter6-8hours.

Distribution

Bindingtoplasmaproteinsisapprox.93%.

Clearanceandvolumeofdistributionareapprox.165ml/min(70-279ml/min)and76l(44-96l),respectively.

Accumulationofsmallamountsoffinasterideisseenonrepeatedadministration.Afteradailydoseof5mgthelowest

steady-stateconcentrationoffinasteridehasbeencalculatedtobe8-10ng/ml,whichremainsstableovertime.

Biotransformation:

Finasterideismetabolisedintheliver.FinasteridedoesnotsignificantlyaffectthecytochromeP450enzymesystem.

Twometaboliteswithlow5-reductase-inhibitingeffectshavebeenidentified.

Elimination:

Theplasmahalflifeaverages6hours(4-12hours)(inmen>70years:8hours,range6–15hours).After

administrationofradioactivelylabelledfinasteride,approx.39%(32–46%)ofthedoseisexcretedintheurineinthe

formofmetabolites.Virtuallynounchangedfinasterideisrecoveredintheurine.Approx.57%(51–64%)ofthetotal

doseisexcretedinthefaeces.

Inpatientswithimpairedrenalfunction(creatinineclearanceaslowas9ml/min),nochangesintheeliminationof

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Finasteridehasbeenfoundtocrosstheblood-brainbarrier.Smallamountsoffinasteridehavebeenrecoveredinthe

seminalfluidoftreated.In2studiesofhealthysubjects(n=69)receivingfinasteride5mg/dayfor6-24weeks,

finasterideconcentrationsinsemenrangedfromundetectable(<0.1ng/ml)to10.54ng/ml.Inanearlierstudyusinga

lesssensitiveassay,finasterideconcentrationsinthesemenof16subjectsreceivingfinasteride5mg/dayrangedfrom

undetectable(<1.0ng/ml)to21ng/ml.Thus,basedona5-mlejaculatevolume,theamountoffinasterideinsemenwas

estimatedtobe50-to100-foldlessthanthedoseoffinasteride(5µg)thathadnoeffectoncirculatingDHTlevelsin

men(seealsosection5.3.)

Inpatientswithchronicrenalimpairment,whosecreatinineclearancerangedfrom9-55ml/min,thedispositionofa

singledoseof 14

C-finasteridewasnotdifferentfromthatinhealthyvolunteers.Proteinbindingalsodidnotdifferin

patientswithrenalimpairment.Aportionofthemetaboliteswhichnormallyisexcretedrenallywasexcretedinthe

faeces.Itthereforeappearsthatfaecalexcretionincreasescommensuratetothedecreaseinurinaryexcretionof

metabolites.Dosageadjustmentinnon-dialysedpatientswithrenalimpairmentisnotnecessary.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofrepeateddosetoxicity,

genotoxicity,andcarcinogenicpotential.

Reproductiontoxicologystudiesinmaleratshavedemonstratedreducedprostateandseminalvesicularweights,

reducedsecretionfromaccessorygenitalglandsandreducedfertilityindex(causedbytheprimarypharmacological

effectoffinasteride).Theclinicalrelevanceofthesefindingsisunclear.

Aswithother5-alpha-reductaseinhibitors,femininisationofmaleratfoetuseshasbeenseenwithadministrationof

finasterideinthegestationperiod.Intravenousadministrationoffinasteridetopregnantrhesusmonkeysatdosesas

highas>800ng/dayduringtheentireperiodofembryonicandfoetaldevelopmentresultedinnoabnormalitiesinmale

fetuses.Thisrepresentsatleast750timesthehighestestimatedexposureofpregnantwomentofinasteridefromsemen.

InconfirmationoftherelevanceoftheRhesusmodelforhumanfetaldevelopment,oraladministrationoffinasteride

2mg/kg/day(100timestherecommendedhumandoseorapproximately12milliontimesthehighestestimated

exposuretofinasteridefromsemen)topregnantmonkeysresultedinexternalgenitalabnormalitiesinmalefetuses.No

otherabnormalitieswereobservedinmalefetusesandnofinasteride-relatedabnormalitieswereobservedinfemale

fetusesatanydose.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Cellulosemicrocrystalline

Pregelatinisedstarch(maize)

Sodiumstarchglycolate,typeA

Magnesiumstearate

Sodiumlaurilsulfate

Film-coating:

Hypromellose

Cellulosemicrocrystalline

Macrogolstearate(typeI)

6.2Incompatibilities

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6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

BlisterpacksPVC/PVDC/Aluminium:15,28,30,50,50XI,98,100,100XI

Bottles(HDPE):100

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Womenwhoarepregnantormaybecomepregnantshouldnothandlecrushedorbrokenfinasteridetabletsbecauseof

thepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefoetus(seesection4.6).

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V

Computerweg10

3542DRUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA749/35/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:29thFebruary2008

10DATEOFREVISIONOFTHETEXT

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