FAMLOV

Main information

  • Trade name:
  • FAMLOV Film Coated Tablet 125 Milligram
  • Dosage:
  • 125 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FAMLOV Film Coated Tablet 125 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1130/013/001
  • Authorization date:
  • 17-10-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Famlov125mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains125mgoffamciclovir.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedTablet.

White,round,coatedtabletwith‘FC’over“125”ononesideand‘>’ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Varicellazostervirus(VZV)infections–herpeszoster

-Famciclovirisindicatedfor

-thetreatmentofherpeszosterandophthalmiczosterinimmunocompetentadults(seesection4.4)

-thetreatmentofherpeszosterinimmunocompromisedadults(seesection4.4)

Herpessimplexvirus(HSV)infections–genitalherpes

Famciclovirisindicatedfor

-thetreatmentoffirstandrecurrentepisodesofgenitalherpesinimmunocompetentadults

-thetreatmentofrecurrentepisodesofgenitalherpesinimmunocompromisedadults

-thesuppressionofrecurrentgenitalherpesinimmunocompetentandimmunocompromisedadults

ClinicalstudieshavenotbeenconductedinHSV-infectedpatientsimmunocompromisedforothercausesthanHIV-

infection(seesection5.1).

4.2Posologyandmethodofadministration

Herpeszosterinimmunocompetentadults

500mgthreetimesdailyforsevendays.

Treatmentshouldbeinitiatedassoonaspossibleafteradiagnosisofherpeszoster.

Herpeszosterinimmunocompromisedadults

500mgthreetimesdailyfortendays.

Treatmentshouldbeinitiatedassoonaspossibleafteradiagnosisofherpeszoster.

Genitalherpesinimmunocompetentadults

Firstepisodeofgenitalherpes:250mgthreetimesdailyforfivedays.Initiationoftreatmentisrecommendedassoon

aspossibleafteradiagnosisoffirstepisodeofgenitalherpes.

Episodictreatmentofrecurrentgenitalherpes:125mgtwicedailyforfivedays.Initiationoftreatmentisrecommended

assoonaspossibleafteronsetofprodromalsymptoms(e.g.tingling,itching,burning,pain)orlesions.

Recurrentgenitalherpesinimmunocompromisedadults

Episodictreatmentofrecurrentgenitalherpes:500mgtwicedailyforsevendays.Initiationoftreatmentis

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Suppressionofrecurrentgenitalherpesinimmunocompetentadults

250mgtwicedaily.Suppressivetherapyshouldbediscontinuedafteramaximumof12monthsofcontinuousantiviral

therapytoreassessrecurrencefrequencyandseverity.Theminimumperiodofreassessmentshouldincludetwo

recurrences.Patientswhocontinuetohavesignificantdiseasemayrestartsuppressivetherapy.

Suppressionofrecurrentgenitalherpesinimmunocompromisedadults

500mgtwicedaily.

Patientswithrenalimpairment

Becausereducedclearanceofpenciclovirisrelatedtoreducedrenalfunction,asmeasuredbycreatinineclearance,

specialattentionshouldbegiventodosesinpatientswithimpairedrenalfunction.Doserecommendationsforadult

patientswithrenalimpairmentareprovidedinTable1.

Table1Doserecommendationsforadultpatientswithrenalimpairment

Indicationandnominaldose

regimen Creatinineclearance

[ml/min] Adjusteddoseregimen

Herpeszosterin

immunocompetentadults

500mgthreetimesdailyfor7days 60

40to59

20to39

<20

Haemodialysispatients 500mgthreetimesdailyfor7

days

500mgtwicedailyfor7days

500mgoncedailyfor7days

250mgoncedailyfor7days

250mgfollowingeachdialysis

during7days

Herpeszosterin

immunocompromisedadults

500mgthreetimesdailyfor

10days 60

40to59

20to39

<20

Haemodialysispatients 500mgthreetimesdailyfor10

days

500mgtwicedailyfor10days

500mgoncedailyfor10days

250mgoncedailyfor10days

250mgfollowingeachdialysis

during10days

Genitalherpesin

immunocompetentadults–firstepisode

ofgenitalherpes

250mgthreetimesdailyfor5days 40

20to39

<20

Haemodialysispatients 250mgthreetimesdailyfor5

days

250mgtwicedailyfor5days

250mgoncedailyfor5days

250mgfollowingeachdialysis

during5days

Genitalherpesin

immunocompetentadults–

episodictreatmentofrecurrentgenital

herpes

125mgtwicedailyfor5days 20

<20

Haemodialysispatients 125mgtwicedailyfor5days

125mgoncedailyfor5days

125mgfollowingeachdialysis

during5days

Genitalherpesin

immunocompromisedadults-

episodictreatmentofrecurrentgenital

herpes

500mgtwicedailyfor7days 40

20to39

<20

Haemodialysispatients 500mgtwicedailyfor7days

500mgoncedailyfor7days

250mgoncedailyfor7days

250mgfollowingeachdialysis

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Patientswithrenalimpairmentonhaemodialysis

Since4hhaemodialysisresultedinupto75%reductioninplasmapenciclovirconcentrations,famciclovirshouldbe

administeredimmediatelyfollowingdialysis.Therecommendeddoseregimensforhaemodialysispatientsareincluded

inTable1.

Patientswithhepaticimpairment

Nodoseadjustmentisrequiredinpatientswithmildormoderatehepaticimpairment.Nodataareavailableforpatients

withseverehepaticimpairment(seesections4.4and5.2).

Elderlypatients(65years)

Dosemodificationisnotrequiredunlessrenalfunctionisimpaired.

Paediatricpopulation

Thesafetyandefficacyoffamciclovirinchildrenandadolescentsagedlessthan18yearshavenotbeenestablished.

Currentlyavailabledataaredescribedinsections5.1and5.2

Blackpatients

Aplacebo-controlledstudyinimmunocompetentblackpatientswithrecurrentgenitalherpesshowednodifferencein

efficacybetweenpatientsreceivingfamciclovir1000mgtwicedailyforonedayandplacebo.Therewereno

unexpectedornewsafetyfindinginthistrialinBlackpatients.

Thislackofefficacyintheone-daytreatmentregimencannotbeextrapolatedtothefive-daytreatmentregimenfor

recurrentgenitalherpes(125mgtwicedailyforfivedays)orotherindicationsinBlackpatients.

Methodofadministration

Famciclovircanbetakenwithoutregardtomeals(seesection5.2).

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Hypersensitivitytopenciclovir

4.4Specialwarningsandprecautionsforuse

Useinpatientswithrenalimpairment

Inpatientswithimpairedrenalfunctiondoseadjustmentisnecessary(seesections4.2and4.9).

Useinpatientswithhepaticimpairment

Famciclovirhasnotbeenstudiedinpatientswithseverehepaticimpairment.Conversionoffamciclovirtoitsactive

metabolitepenciclovirmaybeimpairedinthesepatientsresultinginlowerpenciclovirplasmaconcentrations,andthus

Suppressionofrecurrentgenitalherpesin

immunocompetentadults

250mgtwicedaily 40

20to39

<20

Haemodialysispatients 250mgtwicedaily

125mgtwicedaily

125mgoncedaily

125mgfollowingeachdialysis

Suppressionofrecurrentgenitalherpesin

immunocompromisedadults

500mgtwicedaily 40

20to39

<20

Haemodialysispatients 500mgtwicedaily

500mgoncedaily

250mgoncedaily

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Useforzostertreatment

Clinicalresponseshouldbecloselymonitored,particularlyinimmunocompromisedpatients.

Considerationshouldbegiventointravenousantiviraltherapywhenresponsetooraltherapyisconsideredinsufficient.

Patientswithcomplicatedherpeszoster,i.e.thosewithvisceralinvolvement,disseminatedzoster,motorneuropathies,

encephalitisandcerebrovascularcomplicationsshouldbetreatedwithintravenousantiviraltherapy.

Moreover,immunocompromisedpatientswithophthalmiczosterorthosewithahighriskfordiseasedisseminationand

visceralorganinvolvementshouldbetreatedwithintravenousantiviraltherapy.

Transmissionofgenitalherpes

Patientsshouldbeadvisedtoavoidintercoursewhensymptomsarepresenteveniftreatmentwithanantiviralhasbeen

initiated.Duringsuppressivetreatmentwithantiviralagents,thefrequencyofviralsheddingissignificantlyreduced.

However,transmissionisstillpossible.Therefore,inadditiontotherapywithfamciclovir,itisrecommendedthat

patientsusesafersexpractices.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Effectsofothermedicinalproductsonfamciclovir

Noclinicallysignificantinteractionshavebeenidentified.

Concurrentuseofprobebecidmayresultinincreasedplasmaconcentrationsofpenciclovir,theactivemetaboliteof

famciclovir,bycompetingforelimination.

Therefore,patientsreceivingfamcicloviratadoseof500mgthreetimesdailyco-administeredwithprobenecid,should

bemonitoredfortoxicity.Ifpatientsexperienceseveredizziness,somnolence,confusionorothercentralnervous

systemdisturbances,adosereductionoffamciclovirto250mgthreetimesdailymaybeconsidered.

Famciclovirneedsaldehydeoxidasetobeconvertedintopenciclovir,itsactivemetabolite.Raloxifenhasbeenshown

tobeapotentinhibitorofthisenzymeinvitro.Co-administrationofraloxifenecouldaffecttheformationof

penciclovirandthustheefficacyoffamciclovir.Whenraloxifenisco-administeredwithfamciclovirtheclinical

efficacyoftheantiviraltherapyshouldbemonitored.

4.6Fertility,pregnancyandlactation

Pregnancy

Thereisalimitedamountofdata(lessthan300pregnancyoutcomes)fromtheuseoffamciclovirinpregnantwomen.

Basedontheselimitedamountsofinformation,thecumulativeanalysisofbothprospectiveandretrospective

pregnancycasesdidnotprovideevidenceindicatingthattheproductcausesanyspecificfoetaldefectorcongenital

anomaly.Animalstudieshavenotshownanyembryotoxicorteratogeniceffectswithfamciclovirorpenciclovir(the

activemetaboliteoffamciclovir).Famciclovirshouldonlybeusedduringpregnancywhenthepotentialbenefitsof

treatmentoutweighthepotentialrisks.

Lactation

Itisunknownwhetherfamciclovirisexcretedinhumanbreastmilk.Animalstudieshaveshownexcretionof

penciclovirinbreastmilk.Ifthewoman’sconditionmandatestreatmentwithfamciclovir,discontinuationofbreast-

feedingmaybeconsidered.

Fertility

Clinicaldatadonotindicateanimpactoffamciclovironmalefertilityfollowinglong-termtreatmentatanoraldoseof

250mgtwicedaily(seesection5.3).

4.7Effectsonabilitytodriveandusemachines

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However,patientswhoexperiencedizziness,somnolence,confusionorothercentralnervoussystemdisturbanceswhile

takingFamciclovirTabletsshouldrefrainfromdrivingoroperatingmachinery.

4.8Undesirableeffects

Headacheandnauseahavebeenreportedinclinicalstudies.Theseweregenerallymildormoderateinnatureand

occurredatasimilarincidenceinpatientsreceivingplacebotreatment.Allotheradversereactionswereaddedduring

postmarketing.

Atotalof1,587patientshavereceivedfamcicloviratrecommendeddosesinplacebo-(n=657)andactive-(n=930)

controlledstudies.Theseclinicalstudieswereretrospectivelyreviewedtoobtainafrequencycategoryforalladverse

reactionsmentionedbelow.Foradversereactionswhichhaveneverbeenobservedinthesestudies,theupperlimitof

the95%confidenceintervalisnotexpectedtobehigherthan3/X(basedonthe“ruleofthree”),withXrepresenting

thetotalsamplesize(n=1,587).

Adversereactions(Table2)arerankedunderheadingsoffrequency,usingthefollowingconvention: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)

Table2Adversereactions

Bloodandlymphaticsystemdisorders

Rare: Thrombocytopenia.

Psychiatricdisorders

Uncommon: Confusion.

Rare: Hallucinations.

Nervoussystemdisorders

Verycommon: Headache.

Common: Dizziness,somnolence.

Gastrointestinaldisorders

Common: Nausea,vomiting.

Hepatobiliarydisorders

Common: Abnormalliverfunctiontests.

Rare: Cholestaticjaundice.

Skinandsubcutaneoustissuedisorders

Common: Rash,pruritus.

Uncommon: Urticaria,seriousskinreactions*(e.g.erythemamultiforme,Stevens- JohnsonSyndrome,ToxicEpidermal

Necrolysis),angioedema,

(e.g.faceoedema,eyelidoedema,periorbitaloedema,pharyngealoedema).

*Neverreportedinclinicaltrials;categoryisbasedonthe“ruleofthree”

Overall,adversereactionsreportedfromclinicalstudieswithimmunocompromisedpatientsweresimilartothose

reportedintheimmunocompetentpopulation.Nausea,vomitingandabnormalliverfunctiontestswerereportedmore

frequently,especiallyathigherdoses.

4.9Overdose

Overdoseexperiencewithfamciclovirislimited.Intheeventofanoverdosesupportiveandsymptomatictherapy

shouldbegivenasappropriate.Acuterenalfailurehasbeenreportedrarelyinpatientswithunderlyingrenaldisease

wherethefamciclovirdosehasnotbeenappropriatelyreducedforthelevelofrenalfunction.Penciclovirisdialysable;

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Nucleosidesandnucleotidesexcludingreversetranscriptaseinhibitors

ATCcode:J05AB09

Mechanismofaction

Famcicloviristheoralprodrugofpenciclovir.Famciclovirisrapidlyconvertedinvivointopenciclovir,whichhasin

vitroactivityagainstherpessimplexviruses(HSVtypes1and2),varicellazostervirus,Epstein-Barrvirusand

cytomegalovirus.

Theantiviraleffectoforallyadministeredfamciclovirhasbeendemonstratedinseveralanimalmodels:thiseffectis

duetoinvivoconversiontopenciclovir.Invirus-infectedcellstheviralthymidinekinase(TK)phosphorylates

penciclovirtoamonophosphateformthat,inturn,isconvertedtopenciclovirtriphosphatebycellularkinases.This

triphosphatepersistsininfectedcellsinexcessof12hoursandinhibitsviralDNAchainelongationbycompetitive

inhibitionwithdeoxyguanosinetriphosphateforincorporationintothegrowingviralDNA,thushaltingvirus

replicationofviralDNA.Inuninfectedcellstreatedwithpenciclovir,concentrationsofpenciclovir-triphosphateare

onlybarelydetectable.Hencetheprobabilityoftoxicitytomammalianhostcellsislowanduninfectedcellsare

unlikelytobeaffectedbytherapeuticconcentrationsofpenciclovir.

Resistance

Likeaciclovir,themostcommonformofresistanceencounteredamongHSVstrainsisadeficiencyintheproduction

ofthethymidinekinase(TK)enzyme.SuchTKdeficientstrainswouldgenerallybeexpectedtobecross-resistantto

bothpenciclovirandaciclovir.

Resultsfrom11worldwideclinicalstudiesinvolvingpenciclovir(topicalorintravenousformulations)orfamciclovirin

immunocompetentorimmunocompromisedpatients,includingstudiesofupto12monthstreatmentwithfamciclovir,

haveshownasmalloverallfrequencyofpenciclovirresistantisolates:0.2%(2/913)inimmunocompetentpatientsand

2.1%(6/288)inimmunocompromisedpatients.Theresistantisolatesweremostlyfoundatthestartoftreatmentorina

placebogroup,withresistanceoccurringonoraftertreatmentwithfamciclovirorpenciclovironlyintwo

immunocompromisedpatients.

Clinicalefficacy

Inplacebo-controlledandactive-controlledstudiesbothinimmunocompetentandimmunocompromisedpatientswith

uncomplicatedherpeszoster,famciclovirwaseffectiveintheresolutionoflesions.Inanactive-controlledclinical

study,famciclovirwasshowntobeeffectiveinthetreatmentofophthalmiczosterinimmunocompetentpatients.

Efficacyoffamciclovirinimmunocompetentpatientswithfirstepisodeofgenitalherpeswasshowninthreeactive-

controlledstudies.Twoplacebo-controlledstudiesinimmunocompetentpatientsandone-activecontrolledstudyin

HIV-infectedpatientswithrecurrentgenitalherpesshowedthatfamciclovirwaseffective.

Twoplacebo-controlled12-monthstudiesinimmunocompetentpatientswithrecurrentgenitalherpesshowedthat

famciclovir-treatedpatientshadasignificantreductionofrecurrencesascomparedtoplacebo-treatedpatients.Placebo-

controlledanduncontrolledstudiesofupto16weeksdurationshowedthatfamciclovirwaseffectiveinthesuppression

ofrecurrentgenitalherpesinHIV-infectedpatients;theplacebo-controlledstudyshowedthatfamciclovirsignificantly

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Paediatricpopulation

Famciclovirexperimentaloralgranuleswereevaluatedin169paediatricpatients1monthto12yearsofage.One

hundredofthesepatientswere1to12yearsofageandweretreatedwithfamcicloviroralgranules(dosesranged

from150mgto500mg)eithertwice(47patientswithherpessimplexvirusinfections)orthreetimes(53patientswith

chickenpox)dailyfor7days.Theremaining69patients(18patients1to12months,51patients1to12years)

participatedinsingle-dosepharmacokineticandsafetystudiesusingfamcicloviroralgranules(dosesrangedfrom25

mgto500mg).Famciclovirweight-baseddoseswereselectedtoprovidepenciclovirsystemicexposuressimilartothe

penciclovirsystemic

exposuresobservedinadultsafteradministrationof500mgfamciclovir.Oneofthesestudiescomprisedacontrol

group;thereforeaconclusionontheefficacyoftheinvestigatedregimensisnotpossible.Thesafetyprofilewassimilar

tothatseeninadults.However,systemicdrugexposureininfants<6monthsofagewaslow,thusprecludingany

assessmentoffamciclovir’ssafetyinthisagegroup.

5.2Pharmacokineticproperties

Generalcharacteristics

Absorption

Famcicloviristheoralprodrugoftheantivirallyactivecompoundpenciclovir.Followingoraladministration,

famciclovirisrapidlyandextensivelyabsorbedandconvertedtopenciclovir.

Bioavailabilityofpenciclovirafteroraladministrationoffamciclovirwas77%.Meanpeakplasmaconcentrationof

penciclovir,followinga125mg,250mg,500mgand750mgoraldoseoffamciclovir,was0.8microgram/ml,1.6

micrograms/ml,3.3micrograms/mland5.1micrograms/ml,respectively,andoccurredatamediantimeof45minutes

post-dose.

Plasmaconcentration-timecurvesofpencicloviraresimilarfollowingsingleandrepeat(t.i.d.and

b.i.d.)dosing,indicatingthatthereisnoaccumulationofpenciclovironrepeateddosingwithfamciclovir.

Theextentofsystemicavailability(AUC)ofpenciclovirfromoralfamciclovirisunaffectedbyfood.

Distribution

Penciclovirandits6-deoxyprecursorarepoorly(<20%)boundtoplasmaproteins.

Metabolismandelimination

Famcicloviriseliminatedprincipallyaspenciclovirandits6-deoxyprecursor,whichareexcretedinurine.No

unchangedfamciclovirhasbeendetectedinurine.Tubularsecretioncontributestotherenaleliminationofpenciclovir.

Theterminalplasmahalf-lifeofpenciclovirafterbothsingleandrepeatdosingwithfamciclovirwasapproximately2

hours.

EvidencefrompreclinicalstudieshasshownnopotentialforinductionofcytochromeP450enzymesandinhibitionof

CYP3A4.

Characteristicsinspecialpopulations

Patientswithherpeszosterinfection

Uncomplicatedherpeszosterinfectiondoesnotsignificantlyalterthepharmacokineticsofpenciclovirmeasuredafter

theoraladministrationoffamciclovir.Theterminalplasmahalf-lifeofpenciclovirinpatientswithherpeszosterwas

2.8hand2.7h,respectively,aftersingleandrepeateddosingoffamciclovir.

Subjectswithrenalimpairment

Theapparentplasmaclearance,renalclearance,andplasmaeliminationrateconstantofpenciclovirdecreasedlinearly

withreductionsinrenalfunction,bothaftersingleandrepeateddosing.Doseadjustmentisnecessaryinpatientswith

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Subjectswithhepaticimpairment

Mildandmoderatehepaticimpairmenthadnoeffectontheextentofsystemicavailabilityofpenciclovirfollowingoral

administrationoffamciclovir.Nodoseadjustmentisrecommendedforpatientswithmildandmoderatehepatic

impairment(seesections4.2and4.4).Thepharmacokineticsofpenciclovirhavenotbeenevaluatedinpatientswith

severehepaticimpairment.Conversionoffamciclovirtotheactivemetabolitepenciclovirmaybeimpairedinthese

patientsresultinginlowerpenciclovirplasmaconcentrations,andthuspossiblyadecreaseofefficacyoffamciclovir.

Elderlypatients(65years)

Basedoncross-studycomparisons,themeanpenciclovirAUCwasabout30%higherandpenciclovirrenalclearance

about20%lowerafteroraladministrationoffamciclovirinelderlyvolunteers(65-79years)comparedtoyounger

volunteers.Partlythisdifferencemaybeduetodifferencesinrenalfunctionbetweenthetwoagegroups.Nodose

adjustmentbasedonageisrecommendedunlessrenalfunctionisimpaired(seesection4.2).

Paediatricpopulation

Repeatedoraldosingoffamciclovir(250or500mgthreetimesdaily)topaediatricpatients

(6-11years)infectedwithhepatitisBdidnothaveanotableeffectonthepharmacokineticsofpenciclovircomparedto

singledosedata.Therewasnoaccumulationofpenciclovir.Inchildren(1-12years)withherpessimplexvirus

infectionorchickenpoxgivensingleoraldosesoffamciclovir(seesection5.1),theapparentclearanceofpenciclovir

increasedwithbodyweightinanonlinearmanner.Theplasmaeliminationhalf-lifeofpenciclovirtendedtodecrease

withdecreasingage,fromanaverageof1.6hoursinthepatientsaged6-12yearsto1.2hoursinpatientsaged1-<2

years.

Gender

Smalldifferenceinrenalclearanceofpenciclovirbetweenfemalesandmaleshavebeenreportedandwereattributedto

genderdifferencesinrenalfunction.Nodoseadjustmentbasedongenderisrecommended

5.3Preclinicalsafetydata

Generaltoxicity

Studiesonsafetypharmacologyandrepeateddosetoxicityrevealnospecialhazardforhumans.

Genotoxicity

Famciclovirwasnotfoundtobegenotoxicinacomprehensivebatteryofinvivoandinvitrotestsdesignedtodetect

genemutation,chromosomaldamageandrepairabledamagetoDNA.Penciclovir,incommonwithothersubstancesof

thisclass,hasbeenshowntocausechromosomaldamage,butdidnotinducegenemutationinbacterialormammalian

cellsystems,norwasthereevidenceofincreasedDNArepairinvitro.

Carcinogenicity

Athighdosesinfemalerats,therewasanincreasedincidenceofmammaryadenocarcinoma,atumourcommonly

observedinthestrainofratsusedinthecarcinogenicitystudy.Therewasnoeffectontheincidenceofneoplasiain

maleratsorinmiceofeithersex.

Reproductivetoxicity

Impairedfertility(includinghistopathologicalchangesinthetestis,alteredspermmorphology,reducedsperm

concentrationandmotility,andreducedfertility)wasobservedinmaleratsgiven500mg/kg/day.Furthermore,

degenerativechangesofthetesticularepitheliumwerenotedinthegeneraltoxicitystudies.Thisfindingwasreversible

andhasalsobeenobservedwithothersubstancesofthisclass.Animalstudiesdidnotindicateanynegativeeffecton

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Sodiumstarchglycollate(TypeA)

Microcrystallinecellulose

Hydroxypropylcellulose

Magnesiumstearate

Tabletcoat

Polyvinylalcohol

Titaniumdioxide(E-171)

Macrogol3350

Talc

6.2Incompatibilities

Notapplicable.

6.3Shelflife

30months

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

PVC/PVDC/aluminiumfoilblisterscontaining10,30and56film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

ArrowGenericsLimited

Unit2

EastmanWay

Stevenage

Hertfordshire

SG14SZ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1130/13/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17 th

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10DATEOFREVISIONOFTHETEXT

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