FUNGSTER

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1230/002/001
  • Authorization date:
  • 20-06-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1230/002/001

CaseNo:2051538

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

TransferredfromPA0969/010/001.

PIERREFABREDERMATOLOGIE

45PlaceAbel-Gance,92100BoulogneCedex,France

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Fungster250mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/06/2008until10/04/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fungster250mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains281.25mgterbinafinehydrochlorideequivalentto250mgterbinafine.

(Forafulllistofexcipientsseesection6.1)

3PHARMACEUTICALFORM

Tablet

White,oralmostwhite,round,biconvextabletswithabreaklineononesideand250engravedontheother.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofTerbinafinesensitivefungalinfectionssuchasTineacorporis,TineacrurisandTineapedis

(causedbyDematophytesseeSection5.1)isconsideredappropriateduetothesite,severityorextentoftheinfection.

Thetreatmentofonychomycosis(terbinafine-sensitivefungalinfectionofthenails)causedbydermatophytes.

N.B.OrallyadministeredterbinafinetabletsarenoteffectiveagainstPityriasisversicolor.Considerationshouldbe

giventoofficialguidanceontheappropriateuseofantifungalagents.

4.2Posologyandmethodofadministration

Routeofadministration:

Oraluse

Thedurationoftreatmentisdependentontheindicationandthedegreeofseverityoftheinfection.

Adults:

250mgoncedaily.

Skininfections

ThelikelydurationsoftreatmentforTineapedis,TineacorporisandTineacrurisare2–4weeks.

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

Completedisappearanceofthesymptomsoftheinfectionmaynotoccuruntilseveralweeksaftermycologicalcure.

Onychomycosis

Inmostpatientsthedurationofsuccessfultreatmentis6-12weeks.

Fingernailonychomycosis:Inmostcases6weeks'treatmentissufficientinfingernailonychomycosis.

Toenailonychomycosis:Inmostcases12weeks'treatmentissufficientintoenailonychomycosisalthoughafew

patientsmayrequiretreatmentupto6months.Poornailoutgrowthduringthefirstweeksoftreatmentmayenable

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 2

Completeresolutionofthesignsandsymptomsofinfectionmaynotoccuruntilseveralweeksaftermycologicalcure

andisonlyseenseveralmonthsafterstoppingtreatment,whichisthetimeforgrowthofahealthynail.

Childrenandadolescens(lessthan18yearsofage)

ThereisnoexperiencewithoralTerbinafineinchildrenanditsusecannotthereforeberecommended.

Useinrenalimpairment

Patientswithimpairedrenalfunction(creatinineclearancelessthan50ml/minuteorserumcreatinineofmorethan300

micromol/l)shouldreceivehalfthenormaldose.

Useinhepaticimpairment

Patientswithpre-existingliverdiseaseshouldreceivehalfthenormaldose.

Useintheelderly:

Thereisnoevidencetosuggestthatelderlypatientsrequiredifferentdosages.

4.3Contraindications

Knownhypersensitivitytoterbinafineoranyoftheexcipients.

Severerenalimpairment

Severehepaticimpairment

4.4Specialwarningsandprecautionsforuse

BeforeprescribingTerbinafinetablets,pre-existingliverdiseaseshouldbeassessed.Hepatotoxicitymayoccurin

patientswithandwithoutpre-existingliverdisease.

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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 3

DrugsthatinhibitCYP2D6,CYP1A2andCYP3A4e.g.ketoconazole,cimetidine,quinidine,erythromycinand

grapefruitmightleadtoincreasedlevelsofpropafenonehydrochloride.Whenpropafenonehydrochlorideis

administeredwithinhibitorsoftheseenzymes,thepatientsshouldbecloselymonitoredandthedoseadjusted

accordingly.

Invivoandinvitrostudieshaveshown,thatterbinafineinhibitstheCYP2D6-mediatedmetabolism.Forthisreason,it

isimportanttomonitorpatientswhoaretreatedsimultaneouslywithdrugsthataremainlymetabolisedbythisenzyme,

suchastricyclicantidepressants,-blockers,antiarrhythmicsclass1C,selectiveserotoninre-uptakeinhibitorsand

monoamineoxidaseinhibitorstypeBiftheco-medicationhasanarrowtherapeuticindex.

Otherinvitroandclinicalstudiessuggestthatterbinafineshowsnegligiblepotentialtoinhibitorinducetheclearance

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

triazolam,oralcontraceptives).Therehasbeensomecasesreportedofmenstrualdisturbancessuchasbreakthrough

bleedingandirregularcycleinpatientstakingTerbinafineconcomitantlywithoralcontraceptives.

4.6Pregnancyandlactation

Foetaltoxicityandfertilitystudiesinanimalssuggestnoundersirableeffects.

Pregnancy

Thereisnoadequatedatafromtheuseofterbinafineinpregnantwomen,thereforeterbinafineshouldnotbe

administeredduringpregnancyunlessclearlynecessary.

Lactation:

Terbinafineisexcretedinbreastmilkandthereforemothersshouldnotreceiveterbinafinewhilstbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Terbinafinehasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

a)Adverseeffectsaregenerallymildtomoderateinseverityandtransient.

Frequency

PrimarySystem

OrganClass

(MedDRA9.1)

Common

1/100,

<

1/10 Uncommon

1/1,000,

<

1/100 Rare

1/10,000,

<

1/1,000 Veryrare

<

1/10,000

Bloodand

lymphatic

system

disorders Agranulocytosis

Neutropenia

Thrombocytopenia

Immunesystem

disorders Anaphylactic

reaction

Serumsickness

likereaction

(LLT) Manifestationor

aggravationof

cutaneousor

systemiclupus

erythematosus

(LLT)

Metabolismand

nutrition

disorders Lossof

appetite

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 4

*see4.4.Specialwarnings

Musculo-skeletaldisordersincludingarthralgiaandmyalgiahavebeenreported.Thesemayoccuraspartofa

hypersensitivityreactioninassociationwithallergicskinreactions.

Seriousskinreactions:Stevens-Johnsonsyndrome,toxicepidermalnecrolysis,photosensitivity

Manifestationoraggravationofcutaneousorsystemiclupuserythematosus.

Somecasesofmenstrualdisturbance(breakthroughbleedingandirregularcycle)havebeenreportedinpatientstaking

Psychiatric

disorders Anxiety

Depression

Nervoussystem

disorders Headache Ageusia

Dysgeusia Dizziness

Hypoaesthesia

Paraesthesia

Gastrointestinal

disorders Abdominal

distension

Abdominal

pain

Diarrhoea

Dyspepsia

Nausea

Hepatobiliary

disorders Cholestasis*

Hepatic

function

abnormal*

Hepatitis*

Jaundice* severehepatic

failure

Skinand

subcutaneous

tissuedisorders Rash

Urticaria Angioneurotic

oedema Photosensitivity

reaction

Exacerbationof

psoriasis(LLT)*

Stevens-Johnson

syndrome

Toxicepidermal

necrolysis

Hairloss(LLT)

Musculoskeletal

andconnective

tissuedisorders Arthralgia

Myalgia

Reproductive

systemand

breastdisorders Menstruation

irregular

Break-through

bleeding(LLT)

General

disordersand

administration

siteconditions Fatigue

Malaise

Investigations Hepatic

enzyme

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 5

4.9Overdose

Afewcasesofoverdose(upto5g)havebeenreported,givingrisetoheadache,nausea,abdominalpainanddizziness.

Recommendedtreatmentforoverdoseconsistsofeliminatingtheactivesubstance,primarilybytheadministrationof

activatedcharcoal,andgivingsymptomaticsupportivetherapy,ifrequired.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Dermatologicals,antifungalsforsystemicuse

ATCcode:D01BA02

Terbinafineisanallylaminewhichhasabroadspectrumofantifungalactivity.Atlowconcentrationsterbinafineisfung

againstdermatophytes,moulds

andcertaindimorphicfungi.Theactivityversusyeastsisfungicidalorfungistaticdependingonthespecies.

Terbinafineinterferesselectivelywithfungalsterolbiosynthesisatanearlystagethroughinhibitionoftheenzyme

squaleneepoxidase.Thisleadstoadeficiencyinergosterolandtoanintracellularaccumulationofsqualeneinthe

fungalcellmembrane.Boththedeficiencyinergosterolandtheaccumulationofsqualeneareresponsibleforfungal

celldeath.

Whengivenorally,theactivesubstanceconcentratesinskin,hairandnailsatlevelsassociatedwithfungicidal

activity.Measurableconcentrationsoftheactivesubstancearestillevident15–20daysaftercessationoftreatment.

Terbinafineisusedforthetreatmentoffungalinfectionsoftheskinandnails,whichiscausedbyTrichophyton(e.g.T.

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

followingtableoutlinestherangeofminimuminhibitoryconcentrations(MIC)againstthedermatophytes.

TerbinafineexhibitspoorefficacyagainstmanyyeastsoftheCandidaspecies.

Terbinafinetabletsincontrasttolocallyadministeredterbinafinetreatment,has

noeffectinthetreatmentofPityriasis(Tinea)versicolor.

5.2Pharmacokineticproperties

Asingleoraldoseof250mgterbinafineresultsinmeanplasmaconcentrationsof0.97 µ

g/mlwithin1-2hoursafter

administration.Theabsorptionhalf-lifeis0.8hoursandthedistributionhalf-lifeis4.6hours.

Terbinafinebindsstronglytoplasmaproteins(99%).Terbinafinerapidlydiffusesthroughtheskinandconcentratesin

thelipohilicstratumcorneum.Terbinafineisalsosecretedinthesebumthusachievinghighconcentrationsinhair

follicles,hairandpartsoftheskinrichinsebaceousglands.Thereisalsoevidencethatterbinafineisdistributedinto

Organism MICrange

(µg/ml)

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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 6

TerbinafineisrapidlymetabolisedbytheCYP-isoenzymes,mainlybyCYP2C9,CYP1A2,CYP3A4,CYP2C8and

CYP2C19.Biotransformationresultsinmetaboliteswithnoantifungalactivity,whichareexcretedpredominantlyin

theurine.

Theeliminationhalf-lifeisabout17hours.

Thereisnoevidenceofaccumulationintheplasma.

Noage-dependentchangesinpharmacokineticshavebeenobservedbuttheeliminationratemaybereducedinpatients

withrenalorhepaticimpairment,resultinginhigherbloodlevelsofterbinafine.

Inpatientswithpre-existingmildtoseverehepaticimpairment,singledosepharmacokineticstudieshaveshownthat

theclearanceofTerbinafinecanbereducedby50%.

Thebioavailabilityofterbinafineisonlyslightlyaffectedbyfood,andthereforeadoseadjustmentisnotnecessary.

5.3Preclinicalsafetydata

TheapproximateLD50valueofterbinafineisover4g/kginbothmiceandrats.

Inlongtermstudies(upto1year)inratsanddogsnomarkedtoxiceffectswereseenuptooraldosesofabout100mg/k

aday.Athighoraldoses,theliverandpossiblyalsothekidneyswereidentifiedaspotentialtargetorgan.

Inatwo-yearoralcarcinogenicitystudyinmice,noneoplasticorotherabnormalfindingsattributabletotreatmentwere

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

increasedincidenceoflivertumourswasobservedinmalesatthehighestlevelof69mg/kg/day,atwhichsystemic

exposurewassimilartoclinicalexposure.Themechanismoftumourdevelopmenthasnotbeenestablished.Theclinic

relevanceisunknown.Thechanges,whichmightbeassociatedwithperoxisomeproliferation,havebeenshowntobe

species-specificsincetheywerenotseeninthecarcinogenicitystudyinmice,dogsormonkeys.

Duringhigh-dosesstudiesinmonkeys,refractileirregularitieswereobservedintheretinaatthehigherdoses(non-toxic

effectlevel50mg/kg).Theseirregularitieswereassociatedwiththepresenceofterbinafinemetaboliteinoculartissue

anddisappearedafterdiscontinuationoftheactivesubstance.Theywerenotassociatedwithhistologicalchanges.

Standardbatteryofinvitroandinvivogenotoxicitytestsrevealednoevidenceofmutagenicorclastogenicpotential

Noadverseeffectsonfertilityorotherreproductionparameterswerefoundinstudiesinratsorrabbits.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulosemicrocrystalline

Hypromellose

Sodiumstarchglycolate

Silicacolloidalanhydrous

Magnesiumstearate

6.2Incompatibilities

Noneknown

6.3ShelfLife

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 7

6.4Specialprecautionsforstorage

Storeinoriginalcontainer.

6.5Natureandcontentsofcontainer

ThefoldedcartonofFungster250mgtabletcontains8,14,28,42,and98tablets.(Notallpacksizeswillbe

marketed.)Theblisterismadeofaluminium/PVC.

6.6Specialprecautionsfordisposal

None

7MARKETINGAUTHORISATIONHOLDER

PIERREFABREDERMATOLOGIE

45,PlaceAbelGance

92100Boulogne

FRANCE

8MARKETINGAUTHORISATIONNUMBER

PA1230/2/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:April11th2008

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/06/2008 CRN 2051538 page number: 8