FINASTERIDE RANBAXY

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0967/015/001
  • Authorization date:
  • 14-12-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FinasterideRanbaxy5mgfilm-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

FinasterideRanbaxyisindicatedforthetreatmentandcontrolofbenignprostatichyperplasia(BPH)to:

causeregressionoftheenlargedprostate,improveurinaryflowandimprovethesymptomsassociatedwithBPH

reducetheincidenceofacuteurinaryretentionandtheneedforsurgeryincludingtransurethralresectionof

theprostate(TURP)andprostatectomy.

FinasterideRanbaxy5mgtabletsshouldonlybeadministeredinpatientswithanenlargedprostate(prostate

volumeaboveca.40ml).

4.2Posologyandmethodofadministration

Fororaluseonly.

Therecommendeddosageisone5mgtabletdailywithorwithoutfood.Thetabletshouldbeswallowedwholeand

mustnotbedividedorcrushed(seesection6.6).Eventhoughimprovementcanbeseenwithinashorttime,treatment

foratleast6monthsmaybenecessaryinordertodetermineobjectivelywhetherasatisfactoryresponsetotreatment

hasbeenachieved.

Dosageinhepaticinsufficiency

Therearenodataavailableinpatientswithhepaticinsufficiency(seesection4.4).

Dosageinrenalinsufficiency

Dosageadjustmentsarenotnecessaryinpatientswithvaryingdegreesofrenalinsufficiency(withcreatinineclearance

downtoaslowas9ml/min)asinpharmacokineticstudiesrenalinsufficiencywasnotfoundtoaffecttheelimination

offinasteride.Finasteridehasnotbeenstudiedinpatientsonhaemodialysis.

Dosageintheelderly

Dosageadjustmentsarenotnecessaryalthoughpharmacokineticstudieshaveshownthattheeliminationrateof

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4.3Contraindications

Hypersensitivitytofinasterideortoanyoftheexcipients.

Contra-indicatedinwomenwhoareormaypotentiallybecomepregnant(seesections4.4,4.6and6.6).

Finasterideisnotindicatedeitherinwomenorinchildren.

4.4Specialwarningsandprecautionsforuse

General:

Patientswithlargeresidualurinevolumeand/orseverelydiminishedurinaryflowshouldbecarefullymonitoredfor

obstructiveuropathy.Consultationofanurologistshouldbeconsideredinpatientstreatedwithfinasteride.

Obstructionduetotrilobulargrowthpatternoftheprostateshouldbeexcludedbeforestartingtreatmentwith

finasteride.

Breastcancerhasbeenreportedinmentakingfinasterideduringclinicaltrialsandinthepost-marketingperiod.

Physiciansshouldinstructtheirpatientstopromptlyreportanychangesintheirbreasttissuesuchaslumps,pain,

gynaecomastiaornippledischarge.

Thereisnoexperienceinpatientswithhepaticinsufficiency.Sincefinasterideismetabolizedintheliver(seesection

4.2)cautionisadvisedinpatientswithimpairedhepaticfunctionastheplasmalevelsoffinasteridemaybeincreasedin

suchpatients

Thismedicinalproductcontainslactosemonohydrate.Patientswithrarehereditaryproblemsofgalactoseintolerance,

theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Effectsonprostate-specificantigen(PSA)andprostatecancerdetection

SerumPSAconcentrationiscorrelatedwithpatientageandprostaticvolume,andprostaticvolumeiscorrelatedwith

patientage.Digitalrectalexamination,and,ifnecessary,determinationofprostate-specific-antigen(PSA)inserum

shouldbecarriedoutonpatientspriortoinitiatingtherapywithfinasterideandperiodicallyduringtreatmenttoruleout

prostatecancer.ThereisconsiderableoverlapinPSAlevelsamongmenwithandwithoutprostatecancer.Therefore,in

menwithBPH,PSAvalueswithinthenormalreferencerangedonotruleoutprostatecancerregardlessoftreatment

withfinasteride.

FinasteridecausesadecreaseinserumPSAconcentrationsbyapproximately50%inpatientswithBPHeveninthe

presenceofprostatecancer.ThisdecreaseinserumPSAlevelsinpatientswithBPHtreatedwithfinasterideshouldbe

consideredwhenevaluatingPSAdataanddoesnotruleoutconcomitantprostatecancer.Thisdecreaseispredictable

overtheentirerangeofPSAvalues,althoughitmayvaryinindividualpatients.Inpatientstreatedwithfinasteridefor

sixmonthsormore,PSAvaluesshouldbedoubledforcomparisonwithnormalrangesinuntreatedmen.This

adjustmentpreservesthesensitivityorspecificityofthePSAassayandmaintainsitsabilitytodetectprostatecancer.

AnysustainedincreaseinPSAlevelsofpatientstreatedwithfinasterideshouldbecarefullyevaluated,including

considerationofnon-compliancetofinasteridetherapy.PercentfreePSA(freetototalPSAratio)isnotsignificantly

decreasedbyfinasterideandremainsconstantevenundertheinfluenceoffinasteride.WhenpercentfreePSAisused

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Long-termdataonfertilityinhumansarelacking,andspecificstudiesinsubfertilemenhavenotbeenconducted.The

malepatientswhowereplanningtofatherachildwereinitiallyexcludedfromclinicaltrials.Although,animalstudies

didnotshowrelevantnegativeeffectsonfertility,spontaneousreportsofinfertilityand/orpoorseminalqualitywere

receivedpost-marketing.Insomeofthesereports,patientshadotherriskfactorsthatmighthavecontributedto

infertility.Normalisationorimprovementofseminalqualityhasbeenreportedafterdiscontinuationoffinasteride.

Womenwhoarepregnantormaybecomepregnantshouldnothandlecrushedorbrokenfinasteridetabletsbecauseof

thepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefetus.Finasteridetabletshavea

filmcoatingwhichpreventscontactwiththeactiveingredientprovidedthatthetabletshavenotbeenbrokenorcrushed

(seesections4.6and6.6).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noclinicallysignificantdruginteractionshavebeenidentified.Finasteridedoesnotappeartoaffectthecytochrome

P450enzymesystem.Thefollowingmedicinalproductshavebeeninvestigatedinmanandnoclinicallysignificant

interactionshavebeenfound:propranolol,digoxin,glibenclamide,warfarin,theophyllineandantipyrine.No

meaningfulinteractionswerefound.

Otherconcomitanttherapy:

Althoughspecificinteractionstudieswerenotperformedinclinicalstudies,finasteridewasusedconcomitantlywith

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

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

quinolonesandbenzodiazepineswithoutevidenceofclinicallysignificantadverseinteractions.

4.6Fertility,pregnancyandlactation

Pregnancy

Pregnancy:Finasterideiscontraindicatedduringpregnancy.

Finasterideisnotindicatedinwomen.

Becauseoftheabilityof5-Reductase-inhibitorstoinhibitconversionoftestosteronetodihydrotestosterone,these

drugs,includingfinasteride,mightcauseabnormalitiesoftheexternalgenitaliaofamalefetuswhenadministeredtoa

pregnantwoman(Seesection5.3).

Exposuretofinasteride-risktomalefetus.

Womenwhoarepregnantormaybecomepregnantshouldnothandlecrushedorbrokenfinasteridetabletsbecauseof

thepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefetus(seesection6.6).

Finasteridetabletshaveafilmcoatingwhichpreventscontactwiththeactiveingredientprovidedthatthetabletshave

notbeenbrokenorcrushed.

Lactation

Finasteride5mgtabletsarenotindicatedforuseinwomen.Itisnotknownwhetherfinasterideisexcretedinbreast

milk.

4.7Effectsonabilitytodriveandusemachines

Thereisnoavailabledataindicatingthatfinasteridewouldhaveaninfluenceontheabilitytodriveortousemachines.

4.8Undesirableeffects

Themostcommonadverseeffectsareimpotenceandreducedlibido.Theseeffectsusuallyoccuratthebeginningofthe

treatmentandinthemajorityofpatientsareofatransientnatureoncontinuedtreatment.

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Frequencyofadversereactionsisdeterminedasfollows:

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);notknown(cannotbeestimatedfromtheavailabledata).

Thefrequencyofadversereactionsreportedduringpost-marketingusecannotbedeterminedastheyarederivedfrom

spontaneousreports.

Immunesystemdisorders

Notknown:Hypersensitivityreactionsincludingpruritus,urticariaandswellingofthefaceandlips

Skinandsubcutaneoustissuedisorders

Common:Skinrash

Rare:Pruritus,Urticaria

Nervoussystemdisorders

RareSomnolence

Psychiatricdisorders:

Uncommon:Decreasedlibido(incidencespresentedasdifferencefromplaceboinclinicalstudiesatmonth12)

Nervoussystemdisorders:

Rare:Somnolence

Cardiacdisorders:

Notknown:Palpitation

Hepatobiliarydisorders

Notknown:Increasedhepaticenzymes

Reproductivesystemandbreastdisorders:

Verycommon:Impotence

Uncommon*:Erectiledysfunction,ejaculationdisorder(includingdecreasedvolumeofejaculate).

VeryRare:Breastsecretion,breastnodules

Notknown:Breasttendernessandenlargement,Testicularpain,infertility**.

**Seesection4.4.

Drug-relatedsexualundesirableeffectsweremorecommoninthefinasteride-treatedmenthantheplacebo-treated

men,withfrequenciesduringthefirst12monthsof3.8%vs2.1%,respectively.Theincidenceoftheseeffects

decreasedto0.6%infinasteride-treatedmenoverthefollowingfouryears.Approximately1%ofmenineach

treatmentgroupdiscontinuedduetodrugrelatedsexualadverseexperiencesinthefirst12months,andtheincidence

declinedthereafter.

Inaddition,thefollowinghavebeenreportedinpostmarketinguse:persistenceoferectiledysfunctionafter

discontinuationoftreatmentwithfinasteride;malebreastcancer(seesection4.4Specialwarningsandprecautionsfor

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Medicaltherapyofprostaticsymptoms(MTOPS)

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

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

tolerabilityprofileofthecombinationtherapywasgenerallyconsistentwiththeprofilesoftheindividualcomponents.

Theincidenceofejaculationdisordereventswithoutregardtodrugrelationshipwere:finasteride8.3%,doxazosin

5.3%,combination15.0%,placebo3.9%.Besidesadversereactionsrelatedto“Nervoussystemdisorders”werealso

observedwithagreaterfrequencyinpatientsreceivingthecombination(seetablebelow).

Laboratorytests:

SerumPSAconcentrationiscorrelatedwithpatientageandprostaticvolume,andprostaticvolumeiscorrelatedwith

patientage.WhenPSAlaboratorydeterminationsareevaluated,considerationshouldbegiventothefactthatPSA

levelsgenerallydecreaseinpatientstreatedwithfinasteride.Inamajorityofthepatients,arapiddecreaseinPSAis

seenwithinthefirstmonthsoftherapy,afterwhichtimePSAlevelsstabilisetoanewbaseline.Thepost-treatment

baselineapproximateshalfofthepre-treatmentvalue.Therefore,intypicalpatientstreatedwithfinasterideforsix

monthsormore,PSAvaluesshouldbedoubledforcomparisontonormalrangesinuntreatedmen.Fordetailsand

clinicalinterpretationseesection4.4(paragraphEffectsonprostate-specificantigen(PSA)andprostatecancer

detection).

Nootherdifferencewasobservedinpatientstreatedwithplaceboorfinasterideinstandardlaboratorytests.

4.9Overdose

Patientshavereceivedsingledosesoffinasterideupto400mgandmultipledosesupto80mg/daywithoutadverse

Systemorganclass Placebo

N=737

N=737 Doxazosin

N=756

N=756 Finasteride

N=768

N=768 Finasteride+

Doxazosin

N=786

N=786

Patientswithoneormore

undesirableeffect 46.4 64.9 52.5 73.8

Generaldisorders 11.7 21.4 11.6 21.5

Asthenia 7.1 15.7 5.3 16.8

Cardiacdisorders 10.4 23.1 12.6 22.0

Hypotension

Orthostatichypotension 0.7

16.7 1.2

17.8

Nervoussystemdisorders 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

Othersexualabnormalities 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:15,28,30,50,98,100

Bottles(HDPEcontainerswithPPchildproofscrewcaps):100

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Womenwhoarepregnantormaybecomepregnantshouldnothandlecrushedorbrokenfinasteridetabletsbecauseof

thepossibilityofabsorptionoffinasterideandthesubsequentpotentialrisktoamalefoetus(seesection4.6).

7MARKETINGAUTHORISATIONHOLDER

Ranbaxy(UK)Ltd

20BaldertonStreet

LondonW1K

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA967/15/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

14thDecember2007

10DATEOFREVISIONOFTHETEXT

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