FUNGAFINE

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0436/038/001
  • Authorization date:
  • 22-04-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0436/038/001

CaseNo:2084796

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

NortonWaterford

T/AIVAXPharmaceuticalsIreland,Unit301,IDAIndustrialPark,CorkRoad,Waterford,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Fungafine250mgtablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom05/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fungafine250mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains250mgterbinafine,asterbinafinehydrochloride.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

White,round,flat,11mmtablets,scoredonbothsideswithsidescores,marked“T”aboveand“1”belowthescoreon

oneside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

N.B.OrallyadministeredterbinafinetabletsarenoteffectiveagainstPityriasisversicolor.

Theofficiallocalguidelinesshouldbeborneinmind,forexample,nationalrecommendationsrelatingtothecorrect

useandprescriptionofantimicrobialdrugs.

4.2Posologyandmethodofadministration

Routeofadministration:

Oraluse

Thedurationoftreatmentisdependentontheindicationandthedegreeofseverityoftheinfection.

Adults:

250mgoncedaily.

Patientswithimpairedrenalfunction(creatinineclearancelessthan50ml/minuteorserumcreatinineofmorethan300

micromol/l)shouldreceivehalfthenormaldose.

Skininfections

ThelikelydurationsoftreatmentforTineapedis,TineacorporisandTineacrurisare2–4weeks.

ForTineapedis(interdigital,plantar/moccasin-type):recommendedtreatmentperiodsmaybeupto6weeks.

1.TreatmentofTerbinafinesensitivefungalinfectionssuchasTineacorporis,TineacrurisandTineapedis

(causedbyDermatophytesseeSection5.1)isconsideredappropriateduetothesite,severityorextentofthe

infection.

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Onychomycosis

Inmostpatientsthedurationofsuccessfultreatmentis6-12weeks.

Fingernailonychomycosis:Inmostcases6weeks'treatmentissufficientinfingernailonychomycosis.

Toenailonychomycosis:Inmostcases12weeks'treatmentissufficientintoenailonychomycosisalthoughafew

patientsmayrequiretreatmentupto6months.Poornailoutgrowthduringthefirstweeksoftreatmentmayenable

identificationofthosepatientsinwhomlongertherapyisrequired.Completeresolutionofthesignsandsymptomsof

infectionmaynotoccuruntilseveralweeksaftermycologicalcureandisonlyseenseveralmonthsafterstopping

treatment,whichisthetimeforgrowthofahealthynail.

Children

Areviewofsafetyexperiencewithoralterbinafineinchildren,whichincludes314patientsinvolvedinthe

UKLAMISIL®PostMarketingSurveillancestudy,hasshownthattheadverseeventprofileinchildrenis

similartothatseeninadults.Noevidenceofanynew,unusualormoreseverereactionstothoseseeninthe

adultpopulationhasbeennoted.However,asdataisstilllimiteditsuseisnotrecommended.

Useintheelderly

Thereisnoevidencetosuggestthatelderlypatientsrequiredifferentdosages.

4.3Contraindications

HypersensitivitytoTerbinafineortoanyoftheexcipients

Severerenalimpairment

Severehepaticimpairment

4.4Specialwarningsandprecautionsforuse

Rarely,casesofcholestasisandhepatitishavebeenreported,theseusuallyoccurwithintwomonthsofstarting

treatment.Ifapatientpresentswithsignsorsymptomssuggestiveofliverdysfunctionsuchaspruritis,unexplained

persistentnausea,anorexiaortiredness,orjaundice,vomiting,fatigue,abdominalpainordarkurine,orpalestools,

hepaticoriginshouldbeverifiedandTerbinafinetherapyshouldbediscontinued(see4.8Undesirableeffects).

Patientsonterbinafinewhodevelopahighfeverorsorethroatshouldbeexaminedconcerningpossiblehaematological

reactions

Singledosepharmacokineticstudiesinpatientswithpre-existingliverdiseasehaveshownthattheclearanceof

Terbinafinecanbereducedby50%(seesection5.2).TherapeuticuseofTerbinafineinpatientswithchronicoractive

liverdiseasehasnotbeenstudiedinprospectiveclinicaltrials,andthereforecannotberecommended.

Terbinafineshouldbeusedwithcautioninpatientswithpsoriasis,asveryrarecasesofexacerbationofpsoriasishave

beenreported.

TerbinafineisapotentinhibitoroftheisoenzymeCYP2D6,whichshouldbeconsideredifterbinafineiscombinedwith

medicinalproductsmetabolisedbythisisoenzymethataretitratedindividually(seesection4.5).Doseadjustmentsmay

benecessary.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theplasmaclearanceofterbinafinemaybeacceleratedbydrugswhichinducemetabolism(suchasrifampicin)and

maybeinhibitedbydrugswhichinhibitcytochromeP450(suchascimetidine).Whereco-administrationofsuchdrugs

isrequired,itmaybenecessarytoadjustthedoseofTerbinafineaccordingly.

Invitrostudieshaveshown,thatterbinafineinhibitstheCYP2D6-mediatedmetabolism.Forthisreason,itisimportant

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tricyclicantidepressants,-blockers,selectiveserotoninre-uptakeinhibitorsandmonoamineoxidaseinhibitorstypeB

iftheco-medicationhasanarrowtherapeuticindex.

Otherinvitroandclinicalstudiessuggestthatterbinafineshowsnegligiblepotentialtoinhibitorinducetheclearance

ofdrugsthataremetabolisedviaothercytochromeP450enzymes(e.g.ciclosporin,tolbutamine,terfenadine,triazolam,

oralcontraceptives).Therehasbeensomecasesreportedofmenstrualdisturbancessuchasbreakthroughbleedingand

irregularcycleinpatientstakingTerbinafineconcomitantlywithoralcontraceptives.

4.6Pregnancyandlactation

Foetaltoxicityandfertilitystudiesinanimalssuggestnoundesirableeffects.

Pregnancy:

Thereisnoadequatedatafromtheuseofterbinafineinpregnantwomen,therefore,terbinafineshouldnotbe

administeredduringpregnancyunlessclearlynecessary.

Lactation:

Terbinafineisexcretedinbreastmilkandthereforemothersshouldnotreceiveterbinafinetreatmentwhilstbreast-

feeding.

4.7Effectsonabilitytodriveandusemachines

Terbinafinehasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

Gastrointestinaldisorders

Common(>1/100,<1/10))

Dyspepsia,fullness,lossofappetite,nausea,mildabdominalpain,diarrhoea.

Skin-andsubcutaneoustissuedisorders

Common(>1/100,<1/10)

Allergicskinreactions(rash,urticaria).

Rare(>1/10,000,<1/1,000)

Seriousskinreactions(suchasStevens-Johnsonsyndrome,toxicepidermalnecrolysis,photosensitivityand

angioneuroticoedema).IftheskinrashisprogressivethentreatmentwithTerbinafineshouldbediscontinued.

Veryrare(<1/10,000),includingisolatedreports

Exacerbationofpsoriasis,lossofhair.

Nervoussystemdisorders

Common(>1/100,<1/10)

Headache.

Rare(>1/10,000,<1/1,000)

Paraesthesia,hypoaesthesia,dizziness,malaiseandfatigue.

Musculoskeletalandconnectivetissuedisorders

Rare(>1/10,000,<1/1,000)

Arthralgiaandmyalgia.Thesemayoccuraspartofahypersensitivityreactioninassociationwithallergicskin

reactions.

Sensorydisorders

Uncommon(>1/1,000,<1/100)

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usuallyresolvesslowlyondrugdiscontinuation.

Hepatobiliarydisorders

Rare(>1/10,000,<1/1,000)

Serioushepaticdysfunction,includingjaundice,cholestasisliverdecompensationandhepatitis.Ifhepaticdysfunction

develops,treatmentwithTerbinafinetabletsshouldbediscontinued(seealsosection4.4.“Specialwarningsand

precautionsforuse”).

Bloodandlymphaticsystemdisorders

Veryrare(<1/10,000),includingisolatedreports

Haematologicaldisorderssuchasneutropenia,thrombocytopeniaandagranulocytosis.

Psychiatricdisorders

Veryrare(<1/10,000),includingisolatedreports

Psychiatricdisturbancessuchasdepressionandanxiety.

Immunesystemdisorders

Veryrare(<0,01%)

Manifestationoraggravationofcutaneousorsystemiclupuserythematosus

Respiratory

Veryrare(<0.01%)includingisolatedreports

Anaphylacticreactionsandangiooedema

4.9Overdose

Fewcasesofoverdose(upto5g)havebeenreported,givingrisetoheadache,nausea,epigastricpainanddizziness.

Recommendedtreatmentforoverdoseconsistsofeliminatingtheactivesubstance,primarilybytheadministrationof

activatedcharcoal,andgivingsymptomaticsupportivetherapyifrequired.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Dermatologicals;antifungalsforsystemicuse

ATCcode:D01BA02

Terbinafineisanallylaminewhichhasabroadspectrumofantifungalactivity.Atlowconcentrationsterbinafineis

fungicidalagainstdermatophytes,mouldsandcertaindimorphicfungi.Theactivityversusyeastsisfungicidalor

fungistaticdependingonthespecies.

Terbinafineinterferesselectivelywithfungalsterolbiosynthesisatanearlystagethroughinhibitionoftheenzyme

squaleneepoxidase.Thisleadstoadeficiencyinergosterolandtoanintracellularaccumulationofsqualeneinthe

fungalcellmembrane.Boththedeficiencyinergosterolandtheaccumulationofsqualeneareresponsibleforfungal

celldeath.

Whengivenorally,theactivesubstanceconcentratesinskin,hairandnailsatlevelsassociatedwithfungicidalactivity.

Measurableconcentrationsoftheactivesubstancearestillevident15–20daysaftercessationoftreatment.

Terbinafineisusedforthetreatmentoffungalinfectionsoftheskinandnails,whichiscausedbyTrichophyton(e.g.T.

rubrum,T.mentagrophytes,T.verrucosum,T.violaceum),MicrosporumcanisandEpidermophytonfloccosum.The

followingtableoutlinestherangeofminimuminhibitoryconcentrations(MIC)againstthedermatophytes.

Organism MICrange

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TerbinafineexhibitspoorefficacyagainstmanyyeastsoftheCandidaspecies.

Terbinafinetabletsincontrasttolocallyadministeredterbinafinetreatment,hasnoeffectinthetreatmentofPityriasis

(Tinea)versicolor.

5.2Pharmacokineticproperties

Asingleoraldoseof250mgterbinafineresultsinmeanpeakplasmaconcentrationsof0.97mcg/mlwithin2hours

afteradministration.Theabsorptionhalf-lifeis0.8hoursandthedistributionhalf-lifeis4.6hours.Terbinafinebinds

stronglytoplasmaproteins(99%).

Terbinafinerapidlydiffusesthroughtheskinandconcentratesinthelipophilicstratumcorneum.Terbinafineisalso

secretedinsebum,thusachievinghighconcentrationsinhairfollicles,hairandpartsoftheskinrichinsebaceous

glands.Thereisalsoevidencethatterbinafineisdistributedintothenailplatewithinafewweeksaftercommencing

therapy.

TerbinafineisrapidlymetabolisedbytheCYP-isoenzymes,mainlybyCYP2C9,CYP1A2,CYP3A4,CYP2C8and

CYP2C19.Biotransformationresultsinmetaboliteswithnoantifungalactivity,whichareexcretedpredominantlyin

theurine.Theeliminationhalf-lifeis17hours.Thereisnoevidenceofaccumulationintheplasma.

Noage-dependentchangesinpharmacokineticshavebeenobservedbuttheeliminationratemaybereducedinpatients

withrenalorhepaticimpairment,resultinginhigherbloodlevelsofterbinafine.

Inpatientswithpre-existingmildtoseverehepaticimpairment,singledosepharmacokineticstudieshaveshownthat

theclearanceofTerbinafinecanbereducedby50%.

Thebioavailabilityofterbinafineisonlyslightlyaffectedbyfood,andthereforeadoseadjustmentisnotnecessary.

5.3Preclinicalsafetydata

TheapproximateLD

valueofterbinafineisover4g/kginbothmiceandrats.

Inlong-termstudies(upto1year)inratsanddogsnomarkedtoxiceffectswereseenineitherspeciesuptooraldoses

ofabout100mg/kgaday.Athighoraldoses,theliverandpossiblyalsothekidneyswereidentifiedaspotentialtarget

organs.

Inatwo-yearoralcarcinogenicitystudyinmice,noneoplasticorotherabnormalfindingsattributabletotreatmentwere

madeuptodosesof130(males)and156(females)mg/kgaday.Inatwo-yearoralcarcinogenicitystudyinrats,an

increasedincidenceoflivertumourswasobservedinmalesatthehighestdosagelevelof69mg/kg,atwhichsystemic

exposurewassimilartoclinicalexposure.Themechanismoftumourdevelopmenthasnotbeenestablished.The

clinicalrelevanceisunknown.Thechangeswhichmaybeassociatedwithperoxisomeproliferationhavebeenshown

tobespecies-specificsincetheywerenotseeninthecarcinogenicitystudyinmice,dogsormonkeys.

Trichophytonrubrun 0.001–0.15

Trichophytonmentagrophytes 0.0001–0.05

Trichophytonverrucosum 0.001–0.006

Trichophytonviolaceum 0.001–0.1

Microsporumcanis 0.0001–0.1

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effectlevel50mg/kg).Theseirregularitieswereassociatedwiththepresenceofaterbinafinemetaboliteinoculartissue

anddisappearedafterdiscontinuationoftheactivesubstance.Theywerenotassociatedwithhistologicalchanges.

Astandardbatteryofinvitroandinvivogenotoxicitytestsrevealednoevidenceofmutagenicorclastogenicpotential.

Noundesirableeffectsonfertilityorotherreproductionparameterswereobservedinstudiesinratsorrabbits.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Magnesiumstearate

Silica,colloidalanhydrous

Croscarmellosesodium

Hypromellose

Microcrystallinecellulose

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

36months.

6.4Specialprecautionsforstorage

BlisterAlu/PVC:Keeptheblisterintheoutercarton

HDPEcontainers:storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Al/PVC-PVdCblisterandHDPEtabletcontainerwithLDPEcap

PackSizes:14,28tablets.

Notallcontainertypesorpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

NortonWaterfordT/A

IVAXPharmaceuticalsIreland,

Unit301

IDAIndustrialPark,

CorkRoad,

Waterford,

Ireland

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PA436/38/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:22April2005

Dateoflastrenewal:16July2009

10DATEOFREVISIONOFTHETEXT

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