FAMLOV

Main information

  • Trade name:
  • FAMLOV Film Coated Tablet 750 Milligram
  • Dosage:
  • 750 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FAMLOV Film Coated Tablet 750 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1130/013/004
  • Authorization date:
  • 17-10-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Famlov750mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains750mgoffamciclovir.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedTablet.

White,capsule-shaped,coatedtabletwith‘FC750”ononesideand‘>’ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofherpeszoster(shingles)infections.

4.2Posologyandmethodofadministration

Adults:

Herpeszoster(shingles)infections:

One750mgtabletoncedailyforsevendays.

Thetabletsshouldbetakenatapproximatelythesametimeeachday.

Initiationoftreatmentisrecommendedassoonaspossibleaftertheonsetofrash.

Elderly:

Dosagemodificationisnotrequiredunlessrenalfunctionisimpaired.

Childrenandadolescents(lessthan18yearsofage):

Famciclovirisnotrecommendedforuseinchildrenandadolescentsbelow18yearsofageduetoinsufficientdataonsafetyand

efficacy.

Renallyimpaired:

Asreducedrenalfunctionresultsinreducedclearanceofpenciclovir,specialattentionshouldbegiventodosageinpatientswith

impairedrenalfunction(seesection4.9).Thefollowingdosageisrecommendedinrenallyimpairedpatients(fordosesnot

realisable/practicalwiththismedicinalproductotherstrengthsareavailable).

Whenonlyserumcreatinineisavailable,anomogramorthefollowingformula(CockcroftandGault)shouldbeusedtoestimate

Forthetreatmentofherpeszosterinfections:

Creatinineclearance(ml/min/1.73m 2

Dosage

30-59 250mgtwicedaily

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Formulatoestimatecreatinineclearance(ml/min/1.73m 2

[140 ─ageinyears]xweight(kg)xeither88.5(formales)or75.2(forfemales)

72xserumcreatinine(µmol/l)

Renallyimpairedpatientsonhaemodialysis:

Adoseintervalof48hoursisrecommendedforhaemodialysispatientsforperiodsbetweendialysis.Sinceafourhour

haemodialysisresultsina75%reductioninplasmapenciclovirconcentrations,famciclovirshouldbeadministeredimmediately

followingdialysis.

Therecommendeddoseisonestandarddoseforfirstepisodeorrecurrentgenitalherpesinfectionsandforherpeszosterpatients.

HepaticImpairment:

Dosagemodificationisnotrequiredforpatientswithwellcompensatedchronicliverdisease.Thereisnoinformationonpatients

withovertlydecompensatedchronicliverdisease;accordinglynoprecisedoserecommendationscanbemadeforthisgroupof

patients.

Methodofadministration:

Fororaladministration.

Famciclovircanbeadministeredwithorwithoutfood.

Thetabletsshouldbetakenwithasufficientamountofliquid.

Parenteraltreatmentisrecommendedforseverelyillpatients.

4.3Contraindications

Hypersensitivitytofamciclovir,oranyoftheexcipients.

Hypersensitivitytopenciclovir

4.4Specialwarningsandprecautionsforuse

Specialattentionshouldbepaidtopatientswithimpairedrenalfunctionasdosageadjustmentmaybenecessary(seesections4.2

and4.9).Nospecialprecautionsarerequiredforhepaticallyimpairedorelderlypatientswithnormalrenalfunction.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noclinicallysignificantinteractionshavebeenidentified.Probenecidandotherdrugsthataffectrenalphysiologycouldaffect

plasmalevelsofpenciclovir.Accountmustbetakenofthepossibilityofinteractionswithsubstanceseliminatedbyactivetubular

excretionsuchasacetylsalicylicacidandibuprofen.

EvidencefrompreclinicalstudieshasshownnopotentialforinductionofcytochromeP450.InaPhaseIstudy,nointeractions

wereobservedafterco-administrationofzidovudineandfamciclovir.

4.6Pregnancyandlactation

Pregnancy

Thereisnoadequatedatafromtheuseoffamciclovir/penciclovirinpregnantwomen.Studiesinanimalshavenotshown

reproductivetoxicity(seesection5.3).Thepotentialriskforhumansisunknown.Famciclovirshouldnotbeusedduring

pregnancyunlessthepotentialbenefitsoftreatmentforthemotheroutweighanypossibleriskforthechild.

Lactation

Itisunknownwhetherfamciclovir/penciclovirisexcretedinhumanbreastmilk.Animalstudieshaveshownexcretionof

famciclovir/penciclovirinbreastmilk.Famciclovirshouldnotbeusedduringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

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Patientswhoexperiencedizziness,somnolence,confusionorothercentralnervoussystemdisturbanceswhiletakingFamciclovir

Tabletsshouldrefrainfromdrivingoroperatingmachinery.

4.8Undesirableeffects

Thefollowingadverseeffectscanoccurduringtreatmentwithfamciclovir,classifiedinthefollowingcategories

Verycommon( ≥1/10)

Common( ≥

1/100,<1/10)

Uncommon( ≥

1/1000,<1/100)

Rare( ≥

1/10000,<1/1000)

Veryrare(<1/10000).

Bloodandlymphaticsystemdisorders

Veryrare: thrombocytopenia

Psychiatricdisorders

Veryrare: hallucinations

Nervoussystemdisorders

Rare: headache,confusion(predominantlyintheelderly)

Veryrare: dizziness,somnolence(predominantlyintheelderly)

Gastrointestinaldisorders

Rare: nausea,diarrhoea,abdominalpain

Veryrare: vomiting,dyspepsia

Hepato-biliarydisorders

Rare: increasedbilirubinandliverenzymes

Veryrare: jaundice

Skinandsubcutaneoustissuedisorders

Veryrare: seriousskinreactions,suchasStevens-Johnsonsyndrome,toxicepidermalnecrolysisanderythemamultiforme;

pruritus,urticaria

Musculoskeletal,connectivetissueandbonedisorders

Veryrare: myalgia,athralgia

Renalandurinarydisorders

Rare: elevatedserumcalcium,changesincreatinineclearance

Veryrare: asinglereportofhaemolyticuraemicsyndromeathighdosesoffamciclovirhasbeenmadeinanimmuno-

compromisedpatient.

Generaldisordersandadministrationsiteconditions

Rare: fatigue

4.9Overdose

Overdoseexperiencewithfamciclovirislimited.Areportofaccidentalacuteoverdosage(10.5g)wasasymptomatic.Inareport

ofchronicuse(10g/dayfortwoyears),famciclovirwaswelltolerated.Intheeventofanoverdosesupportiveandsymptomatic

therapyshouldbegivenasappropriate.

Acuterenalfailurehasbeenreportedrarelyinpatientswithunderlyingrenaldiseasewherethefamciclovirdosagehasnotbeen

appropriatelyreducedforthelevelofrenalfunction.

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

Nucleosidesandnucleotidesexcl.reversetranscriptaseinhibitors

ATCcode:J05AB09

Famciclovirisaprodrug.Afterabsorption,famciclovirisrapidlyconvertedtopenciclovir,whichhasdemonstrableinvitro

activityagainstherpessimplex(HSV)(types1and2)andvaricellazoster(VZV)viruses.

Theantiviraleffectoforallyadministeredfamciclovirhasbeendemonstratedinseveralanimalmodels,includingvariousstudies

inHSV-infectedmice.Thiseffectisduetoinvivoconversiontopenciclovir.Penciclovirtargetsvirus-infectedcells,whereitis

rapidlyandefficientlyconvertedintothetriphosphatebyviralthymidinekinase(TK).

Penciclovirtriphosphatepersistsininfectedcellsformorethan12hourswhereitinhibitsreplicationofviralDNAandhasahalf-

lifeof9,10and20hoursincellsinfectedwithvaricellazoster,herpessimplexvirustype1andherpessimplexvirustype2

respectively.Inuninfectedcellstreatedwithpenciclovir,concentrationsofpenciclovir-triphosphateareonlybarelydetectable.

Accordingly,uninfectedcellsareunlikelytobeaffectedbytherapeuticconcentrationsofpenciclovir.

ThemostcommonformofresistanceencounteredwithacicloviramongHSVstrainsisadeficiencyintheproductionoftheTK

enzyme.SuchTK-deficientstrainswouldbeexpectedtobecross-resistanttobothpenciclovirandaciclovir.

Resultsfrompenciclovirandfamciclovirclinicaltrials,includingstudiesinwhichpatientsweretreatedwithfamciclovirforupto

fourmonths,haveshownasmalloverallfrequencyofpenciclovir-resistantisolates:0.3%inthe981totalisolatestestedtodate

and0.19%inthe529virusisolatesfromimmunocompromisedpatients.Theresistantisolateswerefoundatthestartoftreatment

orinaplacebogroup,withnoresistanceoccurringduringoraftertreatmentwithfamciclovirorpenciclovir.

Ashasbeenfoundwithallotherantiretroviralagents,itcanbeanticipatedthatresistancewilldevelopinsomepatientsreceiving

long-termtreatment.However,thefrequencyatwhichthisoccurshasnotyetbeenestablished.

Theeffectsoffamciclovirondirectlyvirus-relatedparameterssuchasvirusspreadandskinlesionshavebeendemonstratedin

clinicaltrials.

5.2Pharmacokineticproperties

Followingoraladministration,famciclovirisrapidlyabsorbedandextensivelyconverted,penciclovir.Thebioavailabilityof

penciclovirafteroraladministrationoffamcicloviris77%.

Meanpeakplasmaconcentrationsofpenciclovir,following125mg,250mgand500mgoraldosesoffamciclovir,were0.8

micrograms/ml,1.6micrograms/mland3.3micrograms/ml,respectively,andoccurredatameantimeof45minutespost-dose.

Slightpassageofthemetabolitesacrosstheblood-brainbarrierwasobservedinrats.Penciclovirclearanceisreducedinpatients

withrenalimpairment.Thebioavailabilityofpenciclovirisunaffectedbyhepaticimpairment,butthemeanpeakplasmalevelis

diminished.Ingestionwithfoodleadstolowermeanpeakpenciclovirconcentrations,withouteffectonitsbioavailability.

Plasmaconcentration-timecurvesofpencicloviraresimilarfollowingsingleandrepeat(twoorthreetimesdaily)dosing.The

terminalplasmahalf-lifeofpenciclovirafterbothsingleandrepeatdosingwithfamciclovirisapproximately2hours.Thereisno

accumulationofpenciclovironrepeateddosingwithfamciclovir.Penciclovirandits6-deoxyprecursorarepoorly(<20%)bound

toplasmaproteins.

Famcicloviriseliminatedprincipallyaspenciclovirandits6-deoxyprecursorwhichareexcretedinurineunchanged.No

unchangedfamciclovircanbedetectedinurine.Tubularsecretioncontributestotherenaleliminationofthecompound.

Characteristicsinpatients

Uncomplicatedherpeszosterinfectiondoesnotsignificantlyalterthepharmacokineticparametersofpenciclovirmeasuredafter

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5.3Preclinicalsafetydata

Carcinogenicity

In2-yearstudiesinfemaleratsreceivingthemaximumtolerateddose(600mg/kg/day),anincreasedincidenceofmammary

adenocarcinomawasobserved,acommontumourinthestrainofratsusedinthesestudies.

Noeffectontumourincidencewasfoundwithadose3timeslower(200mg/kg/day),whichcorrespondsto3timestheexposure

achievedinhumansreceivingatherapeuticdose(250mgtwicedaily).

Therewasnoeffectontheincidenceofneoplasiainmaleratsorinmiceofeithersex.

Althoughtherelevanceofthesefindingstohumansisunknown,thesafetymarginisverynarrow.Furthermore,thelong-termuse

offamciclovirisnotrecommended.

Genotoxicity

Famciclovirwasnotfoundtobegenotoxicinacomprehensivebatteryofinvivoandinvitrotests.

Penciclovir,incommonwithothersubstancesofthisclass,hasbeenshowntocausechromosomaldamage,butdidnotinduce

genemutationinbacterialormammaliancellsystems,norwasthereevidenceofincreasedDNArepairinvitro.

Reproductivetoxicity

Famcicloviriswelltoleratedinlaboratoryanimals.Incommonwithothersubstancesofthisclass,degenerativechangesofthe

testicularepitheliumwerenoted.

Inanimalstudies,impairedfertilitywasobservedinmaleratsreceiving500mg/kg.Therewerenosignificanteffectsonfertility

infemaleratsgivenfamciclovir.Famciclovirhasbeenshownnottohaveanysignificanteffectsonspermcount,morphologyor

motilityinman.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Sodiumstarchglycollate(TypeA)

Microcrystallinecellulose

Hydroxypropylcellulose

Magnesiumstearate

Tabletcoat

Polyvinylalcohol

Titaniumdioxide(E-171)

Macrogol3350

Talc

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

30months

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

PVC/PVDC/aluminiumfoilblisterscontaining1and7film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

ArrowGenericsLimited

Unit2

EastmanWay

Stevenage

Hertfordshire

SG14SZ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1130/13/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17 th

October2008

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