CLAVAMEL

Main information

  • Trade name:
  • CLAVAMEL Tablets 500/ 125 Base Milligrams
  • Dosage:
  • 500/ 125 Base Milligrams
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLAVAMEL Tablets 500/125 Base Milligrams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/103/005
  • Authorization date:
  • 19-10-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0126/103/005

CaseNo:2076341

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ClonmelHealthcareLimited

WaterfordRoad,Clonmel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

ClavamelForte500/125mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom16/04/2010until12/06/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ClavamelForte500/125mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontains500mgamoxicillin(asamoxicillintrihydrate)and125mgclavulanicacid(aspotassium

clavulanate).

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet.

Yellowishwhitetolightyellowoblongtabletswithanembossment“625”ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofbacterialinfectionsinducedbyGram-negativeandGram-positiveamoxicillinresistantmicro-organisms

whenresistanceiscausedbybeta-lactamases,whicharesensitivetothecombinationofamoxicillinandclavulanicacid

(seesection5.1,Pharmacodynamicproperties).

Amoxicillin/Clavulanicacid500/125tabletsaresuitableforthetreatmentofthefollowingindications:

Upperrespiratorytractinfections(e.g.acuteotitismedia;acutesinusitis).

Lowerrespiratorytractinfections,especiallysevereacuteexacerbationsofchronicbronchitis;andcommunity

acquiredpneumonia.

Infectionsofkidneys(e.g.pyelonephritis)andlowerurogenitaltract(e.g.cystitis).

Infectionsofskinandsofttissue.

Publiclyavailableinformationonthepreventionoflocalresistanceandguidelinesfortheuseofantibioticsshouldbe

consultedbeforeprescribingAmoxicillin/Clavulanicacid500/125.

4.2Posologyandmethodofadministration

ThedosageofAmoxicillin/Clavulanicaciddependsontheage,weightandrenalfunctionoftheparticularpatient,on

theseverityandthesiteoftheinfectionandonthesuspectedordemonstratedcausativeagents.

Principally,thepatient’sweightisthedecisivefactorfordosage,evenifthisisnotinaccordwiththegivenagein

individualcases.

Durationofadministration

Asarule,Amoxicillin/Clavulanicacid500/125isadministeredforafurther3or4daysafterimprovementofthe

clinicalsymptoms.Therapyforatleast10daysisindicatedinthetreatmentofinfectionswithbetahaemolytic

streptococciinordertopreventlatecomplications(e.g.rheumaticfever,glomerulonephritis).

However,Amoxicillin/Clavulanicacid500/125shouldnotbeusedformorethan14dayswithoutassessingtheliver

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Posology

Adults,adolescentsandchildrenover40kgbodyweight

Theusualdoseis500/125mg3timesaday.Thesingledoseshouldbetakenatregulartimesthroughouttheday;

ideallyat8hourlyintervals.Thisdosagemaybedoubledinsevere,chronicandrelapsinginfections.

Elderlypatients

Doseasforadults.

Patientswithimpairedrenalfunction

Inpatientswithrenalinsufficiency,theexcretionofclavulanicacidandamoxicillinbythekidneysisdelayed.

Dependingontheseverityoftherenalinsufficiency,thetotaldailydosageofAmoxicillin/Clavulanicacid(expressed

asamoxicillin)shouldnotexceedtheamountsgiveninthetablebelow.Thedosagerecommendationsforpaediatric

patientsarebasedontheoreticalconsiderationsandonpharmacokineticdata.

Patientswithimpairedliverfunction

Amoxicillin/clavulanicacidshouldbeadministeredwithcaretopatientswithliverimpairment.Liverfunctionshould

bemonitoredatregularintervals.Thereare,asyet,insufficientdataonwhichtobaseadosagerecommendation.

Methodofadministration

Inordertopreventpossiblegastro-intestinalundesirableeffects,Amoxicillin/clavulanicacid500/125shouldbetaken

atthestartofameal.

Tabletsshouldbetakenwithwater,withorwithoutchewing.

Theseparatedosesshouldbetakenwithregularintervalsduringtheday.Incasethedrugistakenthreetimesdaily,a

doseintervalof8hoursisrecommended.

4.3Contraindications

Hypersensitivitytoamoxicillin,clavulanicacidortoanyoftheexcipients.

Hypersensitivitytoanyother-lactamantibioticsuchaspenicillinsandcephalosporins.

Aprevioushistoryofamoxicillin/clavulanicacid-associatedjaundiceorhepaticdysfunction.

Patientswithinfectiousmononucleosis(glandularfever)andpatientswithlymphaticleukaemiahaveahigher

riskofexanthema.Amoxicillin/clavulanicacidmustnotbeadministeredinthesediseasesforconcomitantly

occurringbacterialinfections.

4.4Specialwarningsandprecautionsforuse

Seriousandoccasionallyfatalcasesofhypersensitivity(anaphylacticreactions)haveoccurredinpatientsonpenicillin

treatment.Thesereactionsaremorecommoninpatientswithahistoryofhypersensitivity.Treatmentwith

Amoxicillin/Clavulanicacid500/125mustbestoppedimmediatelyandreplacedbyanothersuitabletherapy.Treatment

ofthesymptomsofananaphylacticreactionmaybenecessary,suchasimmediateadministrationofepinephrine,

intravenoussteroidsandthetreatmentofrespiratoryinsufficiency.

Amoxicillin/Clavulanicacid500/125shouldbeusedwithcareinpatientswithknownsevereallergiesorasthmasince

theyaremorelikelytorespondwithallergicreactions.

Glomularfiltrationspeed Adults Children

10-30ml/min 500mg2xdaily 15mg/kg2xdaily

<10ml/min 500mgperday 15mg/kg/day

Haemodialysis 500mgperdayand500

mgduringandafterthe

dialysis 15mg/kg/dayand15

mg/kgduringandafter

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Asisthecaseforotherbroad-spectrumantibiotics,superinfectionsmayoccur,particularlyinpatientswithchronic

diseasesand/ordysfunctioningimmuneresponses.Mucocutanecandidainfectionshavebeenobserved.If

superinfectionsoccur,theproductshouldbediscontinuedand/oranappropriatetherapyinitiated.

Patientswithseveregastrointestinaldisturbanceswithvomitingand/ordiarrhoeashouldnotbetreatedwith

Amoxicillin/Clavulanicacid500/125sinceadequateabsorptioncannotbeguaranteed.Diarrhoeamaydecreasethe

absorptionofotherdrugsandhaveanegativeinfluenceontheireffects.

Intheeventofsevereandpersistentdiarrhoea,thepossibilityofpseudomembraneouscolitismustbeconsideredandif

notrefuted,therapyshouldbediscontinuedandappropriatemeasurestaken.Thenecessarymeasuresshouldalsobe

takenifhaemorrhagiccolitisoccurs.Theuseofantiperistalticsiscontraindicatedinsuchcases.

Administrationofamoxicillin/clavulanicacidtopatientswithadisturbedliverfunctionshouldbeapproachedwith

care.Liverfunctionshouldbemonitoredonaregularbasis.

Inpatientswithrenalinsufficiency,thedoseneedstobeadjusteddependingonseverity.Thisisnecessaryinpatients

withaglomerularfiltrationrate ≤30ml/min.

Intheeventoflong-termtreatment,regularchecksofrenalandhepaticfunctionandhaematologicalstudiesare

indicated.

Amoxicillin/clavulanicacidshouldbeusedwithcareinpatientsonanti-coagulationtherapy,sincerareprolongationof

theprothrombintimehasbeenobserved.

Thepresenceofhighurinaryconcentrationsofamoxicillincancauseprecipitationofamoxicillininurinarycatheters;

therefore,thecathetershouldbecheckedatregularintervals.

Forceddiuresiswillleadtoanincreasedeliminationofamoxicillinresultingindecreasedserumconcentrations.

Treatmentwithamoxicillin/clavulanicacidduringpregnancycanbeassociatedwithanincreasedriskofnecrotising

enterocolitisinneonates(Seesection4.6,Pregnancyandlactation).

Incaseofconvulsion,treatmentwithamoxicillin/clavulanicacidshouldbediscontinued.

Thismedicinalproductcontainspotassium,lessthan1mmolpertablet,i.e.essentially“potassium-free”.

Thismedicinalproductcontainslessthan1mmolsodiumpertablet,i.e.essentially“sodium-free”.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Otherantibioticsorchemotherapeutics

Amoxicillin/clavulanicacidshouldnotbecombinedwithbacteriostatics/chemotherapeutics/antibiotics(suchas

tetracyclines,macrolides,sulphonamidesorchloramphenicol)sinceantagonisticeffectshavebeenobservedinvitro.

Disulfiram

Amoxicillin/clavulanicacidshouldnotbeusedconcomitantlywithdisulfiram.

Probenecid,phenylbutazone,oxyphenbutazone

Concomitantadministrationofprobenecid,phenylbutazoneoroxyphenbutazone(andtoalesserextentacetylsalicylic

acid,indomethacinandsulpinpyrazone)leadstoanincreaseinandprolongationofserumandbileamoxicillin

concentrationsowingtoinhibitionofrenalexcretion.However,thisdoesnotaffecttheexcretionofclavulanicacid.

Allopurinol

Concomitantadministrationofallopurinolduringtherapywithamoxicillin/clavulanicacidmaypromotetheoccurrence

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Sulfasalazine

Aminopenicillinmayreducetheplasmaconcentrationofsulfasalazine.

Methotrexate

Interactionbetweenamoxicillinandmethotrexateleadingtomethotrexatetoxicityhasbeenreported.Serum

methotrexatelevelsshouldbecloselymonitoredinpatientswhoreceiveconcomitantamoxicillin.Amoxicillin

decreasestherenalclearanceofmethotrexate,probablybycompetitionatthecommontubularsecretionsystem.

Digoxin

Anincreaseinabsorptionofdigoxinispossibleinconcurrentadministrationwithamoxicillin/clavulanicacid.

Anticoagulants

Atendencytobleedcanbeincreasedbytoconcomitantadministrationofamoxicillin/clavulanicacidand

anticoagulantsofthecoumarinclass(seesection4.4,Specialwarningsandprecautionsforuse).

Hormonalcontraceptives

Inrarecases,amoxicillincanadverselyaffecttheefficacyofhormonalcontraceptives.Supplementarynon-hormonal

contraceptivemeasuresshouldbetaken.

Influenceonresultsofdiagnosticlaboratorytests

Non-enzymaticmethodsfordeterminingurinarysugarcanyieldfalsepositiveresults.Likewise,theurobilinogentest

canbeaffected.

Inpregnantwomentreatedwithampicillinatransientdecreaseofestriolandconjugatesintheurinehasbeenobserved.

Thiseffectispossiblewithamoxicillin/clavulanicacid.

4.6Pregnancyandlactation

Followingadministrationofamoxicillin/clavulanicacidtopregnantwomen,nodetrimentaleffectsinthefoetusor

neonatewereobserved.However,asinglestudyinwomenwithprematureruptureoftheamnionreportedthat

prophylactictreatmentwithamoxicillin/clavulanicacidcanbeassociatedwithanincreasedriskofnecrotising

enterocolitisinneonates.Asaprecautionarymeasure,Amoxicillin/Clavulanicacid500/125shouldonlybeusedduring

pregnancyafterbenefit/riskassessmentbythephysicianincharge.Amoxicillin/Clavulanicacid500/125shouldbe

avoidedduringthefirsttrimesterofpregnancy.

Bothsubstancesreachtheembryo/foetusviatheplacentaandareexcretedinmaternalmilk.Nothingisknownabout

theeffectsofclavulanicacidonthebreast-fedinfant.Therefore,diarrhoeaandfungusinfectionofthemucous

membranescouldoccurinthebreast-fedinfant,sothatnursingmighthavetobediscontinued.Thepossibilityof

sensitisationshouldbeborneinmind.

4.7Effectsonabilitytodriveandusemachines

Amoxicillin/clavulanicacidhasaminorormoderateinfluenceontheabilitytodriveandusemachines.

Amoxicillin/clavulanicacidmaysometimesbeassociatedwithadversereactionssuchasmentalconfusion,rarely

dizzinessandevenlessoften,convulsionsthatmayimpairtheabilitytodriveavehicle,tooperatemachinesand/orto

worksafely(Seesection4.8,Undesirableeffects).

4.8Undesirableeffects

Infectionsandinfestations

Uncommon( ≥1/1000,<1/100):ProlongedandrepeateduseofAmoxicillin/Clavulanicacidcanresultin

superinfectionsandcolonisationswithresistantmicro-organisms,includingyeasts.

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Bloodandlymphaticsystemdisorders

Rare( ≥1/10000,<1/1000):Thrombocytosis,haemolyticanaemia.

Veryrare(<1/10000):Changesofthebloodcountinformofleucopenia,granulocytopenia,thrombocytopenia,

pancytopenia,anaemiaormyelosuppressionandprolongationofthebleedingaswellastheprothrombintimehave

beenobserved.Thesemanifestationsarereversibleafterdiscontinuationoftherapy.

Immunesystemdisorders

Common( ≥1/100,<1/10):Cutaneousreactionsarepossiblewhicharemanifestedasexanthemasandpruritus.The

typicalmeasles-likeexanthemaoccurssome(5to11)daysaftercommencingtherapy.

Animmediateurticarialreactionislikelytoindicatepenicillinallergyandtherapyshouldbewithheldandappropriate

medicalmeasuresinstituted.Medicaladviceshouldbesoughtregardingthefutureuseofbeta-lactamantibiotics.

Theincidenceofexanthemaishigherinpatientswithinfectiousmononucleosisandpatientswithlymphaticleukaemia.

Animmediateurticarialreactionmostlyindicatesatruepenicillinallergyandcompelsonetodiscontinuetherapyand

anyulteriortherapywithbeta-lactamantibiotics.

Exanthemascanalsooccur,particularlyintheregionofthemouth.Drynessofmouthanddisturbancesofthesenseof

tastearepossible.

Rare( ≥1/10000,<1/1000):Bullousorexfoliativecutaneousreactions(e.g.erythemamultiformeexsudativum,

Steven-Johnsonsyndrome,toxicepidermalnecrolysis)andanaphylacticshockhavebeenreportedinrarecases.

Severeallergicreactions,resultingfromsensitisationtothe6-amino-penicillanicgroup,havebeenobserved,e.g.in

formofdrugfever,eosinophilia,angioneuroticoedema(Quincke’soedema),laryngealoedema,serumsickness,

haemolyticanaemia,allergicvasculitisorinterstitialnephritis.

Anantigenassociationcanexistbetweenfungiandpenicillinsothatpatientswithmycosesreactionssimilartothose

observedafterrenewedcontactcannotbeexcludedevenafterthefirstadministrationofpenicillin.

Nervoussystemdisorders

Rare( ≥1/10000,<1/1000):Dizziness,headache,convulsions(incasesofdisturbedrenalfunctionorincaseswith

highdoses).

Veryrare(<1/10000):Hyperactivity,anxiety,sleeplessness,mentalconfusion,aggressionandconvulsionshavebeen

reported.

Vasculardisorders

Rare( ≥1/10000,<1/1000):Vasculitis.

Gastrointestinaldisorders

Common( ≥1/100,<1/10):Gastrointestinaldisturbancesinformofstomachache,nausea(morefrequentlyathigher

doses),vomiting,meteorism,softstoolsordiarrhoeacanoccurafterintakeofAmoxicillin/Clavulanic.Theseare

mostlymildandfrequentlyregressduringorshortlyfollowingdiscontinuationoftherapy.Tolerabilitycanbeimproved

takingofAmoxicillin/Clavulanicacidatmealtimes.

Pseudomembraneouscolitisshouldbeborneinmindifseverepersistentdiarrhoeaoccursduringtreatmentorduring

thefirstfewweeksaftertreatment(inmostcasescausedbyClostridiumdifficile).

Uncommon( ≥1/1000,<1/100):Dyspepsia

Rare( ≥1/10000,<1/1000):Intestinalcandidiasis,haemorrhagiccolitisandsuperficialtoothdiscoloration.

Hepatobiliarydisorders

Common( ≥1/100,<1/10):Moderateincreaseinliverenzymeconcentrations.

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Thesymptoms/signsofadisturbanceofhepaticfunctioncanappearduringorshortlyaftertherapywith

Amoxicillin/Clavulanicacidbutinsomecasesmaynotbeobserveduntilseveralweeksafterdiscontinuationof

therapy.Suchdisturbancesofhepaticfunctionoccurmainlyinmalesorolderpatients(60yearsandolder)andcanbe

severe.Thesereactionshavebeenveryrarely(<1/10000)reportedinchildren.Theriskofhepaticreactionsishigher

whentreatmentislongerthan14days.Asaruletheyarereversible.However,lethaloutcomeshavebeenreportedin

extremelyrarecases(<1/10000)butwerealmostalwaysassociatedwithsevereprimarydiseasesorconcomitant

administrationofotherdrugs.

Renalandurinarydisorders

Uncommon( ≥1/1000,<1/100):Vaginalitching,sorenessanddischargemayoccur.

Rare( ≥1/10000,<1/1000):Interstitialnephritis.

4.9Overdose

Symptomsofintoxication

Thesymptomsofoverdoselargelycorrespondtotheprofileofundesirableeffects(Seesection4.8,Undesirable

effects).Overdosemayleadtogastro-intestinalsymptomssuchasnausea,vomitinganddiarrhoeawithpossible

disturbanceofthefluidandelectrolytebalance.Convulsionsmayalsooccur.Reducedlevelofconsciousness,muscle

fasciculations,myoclonicjerks,coma,haemolyticreactions,renalfailureandacidosisarepossible.Shockcanoccur

within20to40minutesinexceptionalcircumstances.

Treatmentofintoxication

Thereisnospecificantidotetooverdose.Vomitingshouldbeinducedorgastriclavagecarriedout,followedbythe

administrationofactivecharcoalandanosmoticlaxative(sodiumsulphate).Thefluidandelectrolytebalanceshould

bemaintained.Convulsionscanbetreatedwithdiazepam.Othersymptomsshouldbetreatedsymptomatically.

Haemodialysisshouldbeperformedintheeventofsevererenalinsufficiency.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCclassification:J01CR02.

Pharmacotherapeuticgroup:-lactamantibacterials;combinationsofpenicillinsincluding-lactamaseinhibitor.

Modeofaction

Amoxicillinisabactericidalsemisyntheticaminobenzylpenicillinbelongingtothegroupofbroad-spectrumantibiotic

substances.Itinhibitscross-linkingofstructuresofthecellwallbybindingtotranspeptidase.Theresultinginstability

leadsbywayoflysistodeathofthecell.The-lactamaseinhibitingactionofclavulanicacidextendsthespectrumof

amoxicillintoincludeawiderrangeofmicro-organismsincludingmanyresistanttoother -lactamantibiotics.

ClavulanicacidisanaturalproductofStreptomycesclavuligerusanditsstructureresemblesthatofthepenicillin

nucleus.Itpersehasaweakantibacterialaction.Clavulanicacidisa -lactamcompound,structurallyrelatedto

amoxicillinandotherpenicillins,retainingtheamidebondofthe-lactamgroupoftheparentcompound.Themajor

characteristicofclavulanicacidisitsenzymeinhibitingaction,protectingamoxicillinfromdegradationbythemost

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Breakpoints

TheMICbreakpoints(accordingtoNCCLS)ofanumberofimportantpathogensforamoxicillin/clavulanicacidare

classifiedbelowassusceptible,intermediatelysusceptibleorresistant.

Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformation

onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought

whenlocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsis

questionable.Micro-organismsclassifiedasintermediatelysusceptibleorresistantonthebasisofgenerallyaccepted

breakpoints(seetableabove)orgeneralinformationcanbesusceptibleinclinicalpracticedependingonthelocationof

theinfection.

Thetablebelowonlygivesanindicationonthechancethatmicro-organismswillbesusceptiblefor

amoxicillin/clavulanicacidornot.

Susceptible Intermediately

susceptible Resistant

Enterobacteriacea ≤8/4µg/ml

16/8µg/ml ≥32/16µg/ml

Staphylococcus

species ≤4/2µg/ml ≥8/4µg/ml

Haemophilusspecies ≤4/2µg/ml ≥8/4µg/ml

Streptococcus

pneumonia ≤2/1µg/ml 4/2µg/ml ≥8/4µg/ml

Commonlysusceptiblespecies:

AerobicGram-positivemicro-organisms

Enterococcusfaecalis

<1% Staphylococcusaureus(methicillin-S)*

Staphylococcusepidermidis(methicillin-S)

Streptococcuspyogenes*

AerobicGram-negativemicro-organisms

Haemophilusinfluenzae <1%

Moraxellacatarrhalis* 0%

Proteusmirabilis 2.7-3.6%

Anaerobicmicro-organisms

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*):activityhasbeensatisfactorilydemonstratedinclinicalstudies.

†):highratesofresistancehavebeenobservedinoneoremorecountrieswiththeEU.

Resistance

Resistancetoamoxicillinoccursasaresultoftheproductionofß-lactamasesand/ormodifiedpenicillin-binding

proteins(PBPs).Cross-resistancemayoccur,inparticulartowardsother-lactamantibioticsandmacrolides,andis

dependentonthetypeoftheresistancemechanismofthepathogen.

5.2Pharmacokineticproperties

Amoxicillin

Theabsolutebioavailabilityofamoxicillindependsonthedoseandrangesbetweenapproximately72and94%.Inthe

doserangebetween250mgand750mg,thebioavailability(parameterAUCand/orrecoveryinurine)islinearly

proportionaltothedose.Athigherdosestheextentofabsorptiondecreases.Absorptionisnotaffectedbyfood.Peak

plasmaconcentrationsarepresentabout1to2hoursafteradministrationofamoxicillin.Afterasingleoraldoseof

500/125mgamoxicillin/clavulanicacidthemeantroughplasmaconcentrations(after8h)ofamoxicillinreached0.3

mg/l.

Theapparentdistributionvolumerangesbetweenapproximately0.3and0.4l/kgandbindingtoserumproteinsis

approximately17-20%.Amoxicillindiffusesthroughtheplacentalbarrierandasmallfractionisexcretedintobreast

milk.Amoxicillinislargelyexcretedthroughthekidneys(52+15%ofadoseinunchangedformwithin7hours)anda

smallfractionisexcretedinthebile.Totalclearancerangesbetweenapproximately250and370ml/min.Theserum

half-lifeinsubjectswithintactrenalfunctionisapproximately1hour(0.9–1.2h),inpatientswithcreatinineclearance

rangingbetween10and30ml/minitisabout6hoursandinanuriaitrangesbetween10and15hours.Thesubstanceis

Speciesforwhichacquiredresistancemaybeaproblem:

AerobicGram-positivemicro-organisms

Streptococcuspneumoniae*†

AerobicGram-negativemicro-organisms

Escherichiacoli*

Klebsiellapneumoniae* 0–16.7%

Proteusvulgaris 0–9.1%

Inherentlyresistantorganisms:

AerobicGram-positivemicro-organisms

Staphylococcusaureus(methicillin-R)* upto79%

Staphylococcusepidermidis(methicillin-R)

AerobicGram-negativemicro-organisms

Enterobacteraerogenes

Enterobactercloacae 82%

Morganellamorganii 94.3%

Pseudomonasaeruginosa

Stenotrophomonasmaltophilia

Othermicro-organisms

Chlamydiaspecies

Chamydophilaspecies

Mycoplasmaspecies

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Clavulanicacid

Theabsolutebioavailabilityofclavulanicacidofapproximately60%differsmarkedlyfromindividualtoindividual.

Absorptionisnotaffectedbyintakeoffood.Peakconcentrationsofclavulanicacidarepresentafterapproximately1to

2hours.Afterasingleoraldoseof500/125mgamoxicillin/clavulanicacid,themeantroughplasmaconcentrations

(after8h)ofclavulanicacidreached0.08mg/l.

Theapparentdistributionvolumeisabout0.2l/kgandtheserumproteinbindingrateisapproximately22%.Clavulanic

aciddiffusesthroughtheplacentalbarrier.Nodataareasyetavailableinregardtoexcretionintobreastmilk.The

substanceispartlymetabolised(approximately50-70%)andabout40%iseliminatedthroughthekidneys(18-38%of

thedoseinunchangedform).Thetotalclearanceisapproximately260ml/min.Theserumhalf-lifeinsubjectswith

intactrenalfunctionisapproximately1hour,inpatientswithcreatinineclearancerangingbetween20and70ml/minit

isapproximately2.6hoursandinanuriaitrangesbetween3and4hours.Thesubstanceishaemodialysable.

Pharmacologicallyrelevantinteractionsbetweenamoxicillinandclavulanicacidhavenotbeenobservedsofar.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeatdose

toxicity,genotoxicity,carcinogeneticpotentialandtoxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulose,microcrystalline

Quinolineyellow(E104)

Titaniumdioxide(E171)

Crospovidone

Povidone

Silica,colloidalanhydrous

Stearicacid

Macrogol6000

Hypromellose

Saccharinsodium

Vanillaflavour

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Bottle:3years.

Blister:2years.

6.4Specialprecautionsforstorage

Bottle:Keepthecontainertightlyclosed.

Blister:Donotstoreabove30°C.

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6.5Natureandcontentsofcontainer

10,14,20tabletsinabrownglassbottle(typeIII),withaluminiumscrewcapwithdesiccant(whitegelandmolecular

sieve)or10,12,14,16,20,30,32,50,100or500tabletsinAl/Al-blister.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLtd

WaterfordRoad

Clonmel

Co.Tipperary

8MARKETINGAUTHORISATIONNUMBER

PA0126/103/005

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 19October2001

Dateoflastrenewal: 13June2005

10DATEOFREVISIONOFTHETEXT

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