AUGMENTIN

Main information

  • Trade name:
  • AUGMENTIN Film Coated Tablet 250/125 Milligram
  • Dosage:
  • 250/125 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AUGMENTIN Film Coated Tablet 250/125 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/047/001A
  • Authorization date:
  • 14-04-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Augmentin250mg/125mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontainspotassiumclavulanate,equivalentto125mgofclavulanicacidandamoxicillintrihydrate,

equivalentto250mgamoxicillin.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromtheUK:

Whitetooffwhite,ovalshaped,engraved‘AUGMENTIN’ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Augmentinisindicatedforthetreatmentofthefollowinginfectionsinadultsandchildren(seesections4.2,4.4and

5.1).

Acutebacterialsinusitis(adequatelydiagnosed)

Cystitis

Pyelonephritis

Cellulitis

Animalbites

Severedentalabscesswithspreadingcellulitis.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Dosesareexpressedthroughoutintermsofamoxicillin/clavulanicacidcontentexceptwhendosesarestatedinterms

ofanindividualcomponent.

ThedoseofAugmentinthatisselectedtotreatanindividualinfectionshouldtakeintoaccount:

Theexpectedpathogensandtheirlikelysusceptibilitytoantibacterialagents(seesection4.4)

Theseverityandthesiteoftheinfection

Theage,weightandrenalfunctionofthepatientasshownbelow.

TheuseofalternativepresentationsofAugmentin(e.g.thosethatprovidehigherdosesofamoxicillinand/ordifferent

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250mg/125mgfilm-coatedtablets,

Foradultsandchildren 40kg,thisformulationofAugmentinprovidesatotaldailydoseof750mgamoxicillin/375

mgclavulanicacid,whenadministeredasrecommendedbelow.Ifitisconsideredthatahigherdailydoseof

amoxicillinisrequired,itisrecommendedthatanotherpreparationofAugmentinisselectedinordertoavoid

administrationofunnecessarilyhighdailydosesofclavulanicacid(seesections4.4and5.1).

Treatmentshouldnotbeextendedbeyond14dayswithoutreview.

Adultsandchildren 40kg

One250mg/125mgtablettakenthreetimesaday.

Children<40kg

250mg/125mgfilm-coatedtablets

Augmentin250mg/125mgfilm-coatedtabletsarenotrecommendedinchildren<40kg.

Elderly

Nodoseadjustmentisconsiderednecessary.

Renalimpairment

Doseadjustmentsarebasedonthemaximumrecommendedlevelofamoxicillin.

Noadjustmentindoseisrequiredinpatientswithcreatinineclearance(CrCl)greaterthan30ml/min.

Adultsandchildren 40kg

Children<40kg

Inchildren<40kgwithcreatinineclearancelessthan30ml/min,theuseofAugmentinpresentationswithan

amoxicillintoclavulanicacidratioof2:1isnotrecommended,asnodoseadjustmentsareavailable.Insuchpatients,

Augmentinformulationswithanamoxicillintoclavulanicacidratioof4:1arerecommended.

HepaticImpairment:

Dosewithcaution,monitorhepaticfunctionatregularintervals(seesections4.3and4.4).

Methodofadministration

Augmentinisfororaluse.

Administeratthestartofamealtominimisepotentialgastrointestinalintoleranceandoptimiseabsorptionof

CrCl:10-30ml/min 250mg/125mgtwicedaily

CrCl<10ml/min 250mg/125mgoncedaily

Haemodialysis Twodosesof250mg/125mgevery24hours,plustwo

dosesof250mg/125mgduringdialysis,toberepeatedat

theendofdialysis(asserumconcentrationsofboth

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4.3Contraindications

Hypersensitivitytotheactivesubstances,toanyofthepenicillinsortoanyoftheexcipients.

Historyofasevereimmediatehypersensitivityreaction(e.g.anaphylaxis)toanotherbeta-lactamagent(e.g.a

cephalosporin,carbapenemormonobactam).

Historyofjaundice/hepaticimpairmentduetoamoxicillin/clavulanicacid(seesection4.8).

4.4Specialwarningsandprecautionsforuse

Beforeinitiatingtherapywithamoxicillin/clavulanicacid,carefulenquiryshouldbemadeconcerningprevious

hypersensitivityreactionstopenicillins,cephalosporinsorotherbeta-lactamagents.

Seriousandoccasionallyfatalhypersensitivity(anaphylactoid)reactionshavebeenreportedinpatientsonpenicillin

therapy.Thesereactionsaremorelikelytooccurinindividualswithahistoryofpenicillinhypersensitivityandin

atopicindividuals.Ifanallergicreactionoccurs,amoxicillin/clavulanicacidtherapymustbediscontinuedand

appropriatealternativetherapyinstituted.

Inthecasethataninfectionisproventobeduetoanamoxicillin-susceptibleorganisms(s)thenconsiderationshouldbe

giventoswitchingfromamoxicillin/clavulanicacidtoamoxicillininaccordancewithofficialguidance.

ThispresentationofAugmentinisnotsuitableforusewhenthereisahighriskthatthepresumptivepathogenshave

reducedsusceptibilityorresistancetobeta-lactamagentsthatisnotmediatedbybeta-lactamasessusceptibleto

inhibitionbyclavulanicacid(e.g.penicillin-insusceptibleS.pneumoniae).

Convulsionsmayoccurinpatientswithimpairedrenalfunctionorinthosereceivinghighdoses(seesection4.8).

Amoxicillin/clavulanicacidshouldbeavoidedifinfectiousmononucleosisissuspectedsincetheoccurrenceofa

morbilliformrashhasbeenassociatedwiththisconditionfollowingtheuseofamoxicillin.

Concomitantuseofallopurinolduringtreatmentwithamoxicillincanincreasethelikelihoodofallergicskinreactions.

Prolongedusemayoccasionallyresultinovergrowthofnon-susceptibleorganisms.

Theoccurrenceatthetreatmentinitiationofafeverishgeneralisederythemaassociatedwithpustulamaybeasymptom

ofacutegeneralisedexanthemouspustulosis(AGEP)(seeSection4.8).ThisreactionrequiresAugmentin

discontinuationandcontra-indicatesanysubsequentadministrationofamoxicillin.

Amoxicillin/clavulanicacidshouldbeusedwithcautioninpatientswithevidenceofhepaticimpairment(seesections

4.2,4.3and4.8).

Hepaticeventshavebeenreportedpredominantlyinmalesandelderlypatientsandmaybeassociatedwithprolonged

treatment.Theseeventshavebeenveryrarelyreportedinchildren.Inallpopulations,signsandsymptomsusually

occurduringorshortlyaftertreatmentbutinsomecasesmaynotbecomeapparentuntilseveralweeksaftertreatment

hasceased.Theseareusuallyreversible.Hepaticeventsmaybesevereand,inextremelyrarecircumstances,deaths

havebeenreported.Thesehavealmostalwaysoccurredinpatientswithseriousunderlyingdiseaseortaking

concomitantmedicationsknowntohavethepotentialforhepaticeffects(seesection4.8).

Antibiotic-associatedcolitishasbeenreportedwithnearlyallantibacterialagentsandmayrangeinseverityfrommild

tolifethreatening(seesection4.8).Therefore,itisimportanttoconsiderthisdiagnosisinpatientswhopresentwith

diarrhoeaduringorsubsequenttotheadministrationofanyantibiotics.Shouldantibiotic-associatedcolitisoccur,

amoxicillin/clavulanicacidshouldimmediatelybediscontinued,aphysicianbeconsultedandanappropriatetherapy

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Periodicassessmentoforgansystemfunctions,includingrenal,hepaticandhaematopoieticfunctionisadvisableduring

prolongedtherapy.

Prolongationofprothrombintimehasbeenreportedrarelyinpatientsreceivingamoxicillin/clavulanicacid.

Appropriatemonitoringshouldbeundertakenwhenanticoagulantsareprescribedconcomitantly.Adjustmentsinthe

doseoforalanticoagulantsmaybenecessarytomaintainthedesiredlevelofanticoagulation(seesection4.5and4.8).

Inpatientswithrenalimpairment,thedoseshouldbeadjustedaccordingtothedegreeofimpairment(seesection4.2).

Inpatientswithreducedurineoutput,crystalluriahasbeenobservedveryrarely,predominantlywithparenteral

therapy.Duringtheadministrationofhighdosesofamoxicillin,itisadvisabletomaintainadequatefluidintakeand

urinaryoutputinordertoreducethepossibilityofamoxicillincrystalluria.Inpatientswithbladdercatheters,aregular

checkofpatencyshouldbemaintained(seesection4.9).

Duringtreatmentwithamoxicillin,enzymaticglucoseoxidasemethodsshouldbeusedwhenevertestingforthe

presenceofglucoseinurinebecausefalsepositiveresultsmayoccurwithnon-enzymaticmethods.

ThepresenceofclavulanicacidinAugmentinmaycauseanon-specificbindingofIgGandalbuminbyredcell

membranesleadingtoafalsepositiveCoombstest.

TherehavebeenreportsofpositivetestresultsusingtheBio-RadLaboratoriesPlateliaAspergillusEIAtestinpatients

receivingamoxicillin/clavulanicacidwhoweresubsequentlyfoundtobefreeofAspergillusinfection.Cross-reactions

withnon-AspergilluspolysaccharidesandpolyfuranoseswithBio-RadLaboratoriesPlateliaAspergillusEIAtesthave

beenreported.Therefore,positivetestresultsinpatientsreceivingamoxicillin/clavulanicacidshouldbeinterpreted

cautiouslyandconfirmedbyotherdiagnosticmethods.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Oralanticoagulants

Oralanticoagulantsandpenicillinantibioticshavebeenwidelyusedinpracticewithoutreportsofinteraction.

However,intheliteraturetherearecasesofincreasedinternationalnormalisedratioinpatientsmaintainedon

acenocoumarolorwarfarinandprescribedacourseofamoxicillin.Ifco-administrationisnecessary,theprothrombin

timeorinternationalnormalisedratioshouldbecarefullymonitoredwiththeadditionorwithdrawalofamoxicillin.

Moreover,adjustmentsinthedoseoforalanticoagulantsmaybenecessary(seesection4.4and4.8).

Methotrexate

Penicillinsmayreducetheexcretionofmethotrexatecausingapotentialincreaseintoxicity.

Probenecid

Concomitantuseofprobenecidisnotrecommended.Probeneciddecreasestherenaltubularsecretionofamoxicillin.

Concomitantuseofprobenecidmayresultinincreasedandprolongedbloodlevelsofamoxicillinbutnotofclavulanic

acid.

4.6Fertility,pregnancyandlactation

Pregnancy

Animalstudiesdonotindicatedirectorindirectharmfuleffectswithrespecttopregnancy,embryonal/foetal

development,parturitionorpostnataldevelopment(seesection5.3).Limiteddataontheuseofamoxicillin/clavulanic

acidduringpregnancyinhumansdonotindicateanincreasedriskofcongenitalmalformations.Inasinglestudyin

womenwithpreterm,prematureruptureofthefoetalmembraneitwasreportedthatprophylactictreatmentwith

amoxicillin/clavulanicacidmaybeassociatedwithanincreasedriskofnecrotisingenterocolitisinneonates.Use

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Lactation

Bothsubstancesareexcretedintobreastmilk(nothingisknownoftheeffectsofclavulanicacidonthebreast-fed

infant).Consequently,diarrhoeaandfungusinfectionofthemucousmembranesarepossibleinthebreast-fedinfant,so

thatbreast-feedingmighthavetobediscontinued.Thepossibilityofsensitisationshouldbetakenintoaccount.

Amoxicillin/clavulanicacidshouldonlybeusedduringbreast-feedingafterbenefit/riskassessmentbythephysicianin

charge.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,undesirableeffects

mayoccur(e.g.allergicreactions,dizziness,convulsions),whichmayinfluencetheabilitytodriveandusemachines

(seesection4.8).

4.8Undesirableeffects

Themostcommonlyreportedadversedrugreactions(ADRs)arediarrhoea,nauseaandvomiting.

TheADRsderivedfromclinicalstudiesandpost-marketingsurveillancewithAugmentin,sortedbyMedDRASystem

OrganClassarelistedbelow.

Thefollowingterminologieshavebeenusedinordertoclassifytheoccurrenceofundesirableeffects.

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)

Notknown(cannotbeestimatedfromtheavailabledata)

Infectionsandinfestations

Mucocutaneouscandidosis Common

Overgrowthofnon-susceptibleorganisms Notknown

BloodandLymphaticsystemdisorders

Reversibleleucopenia(includingnetropenia) Rare

Thrombocytopenia Rare

Reversibleagranulocytosis Notknown

Haemolyticanaemia NotKnown

Prolongationofbleedingtimeand

prothrombintime 1 NotKnown

Immunesystemdisorders 10

Angioneuroticoedema Notknown

Anaphylaxis Notknown

Serumsickness-likesyndrome Notknown

Hypersensitivityvasculitis Notknown

Nervoussystemdisorders

Dizziness Uncommon

Headache Uncommon

Reversiblehyperactivity Notknown

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.Seesection4.4

.Seesection4.4.

.Nauseaismoreoftenassociatedwithhigheroraldoses.Ifgastrointestinalreactionsareevident,theymaybereduced

bytakingamoxicillin/clavulanicacidatthestartofameal.

.Includingpseudomembranouscolitisandhaemorrhagiccolitis(seesection4.4)

.AmoderateriseinASTand/orALThasbeennotedinpatientstreatedwithbeta-lactamclassantibiotics,butthe

significanceofthesefindingsisunknown.

.Theseeventshavebeennotedwithotherpenicillinsandcephalosporins(seesection4.4).

.Ifanyhypersensitivitydermatitisreactionoccurs,treatmentshouldbediscontinued(seesection4.4).

.Seesection4.9

.Seesection4.4

0.Seesections4.3and4.4

4.9Overdose

Symptomsandsignsofoverdose

Gastrointestinalsymptomsanddisturbanceofthefluidandelectrolytebalancesmaybeevident.Amoxicillin

crystalluria,insomecasesleadingtorenalfailure,hasbeenobserved(seesection4.4).

Convulsionsmayoccurinpatientswithimpairedrenalfunctionorinthosereceivinghighdoses.

Amoxicillinhasbeenreportedtoprecipitateinbladdercatheters,predominantlyafterintravenousadministrationof

Convulsions 2

Gastrointestinaldisorders

Diarrhoea Verycommon

Nausea 3 Common

Vomiting Common

Indigestion Uncommon

Antibiotic-associatedcolitis 4 Notknown

Hepatobiliarydisorders

RisesinASTand/orALT 5 Uncommon

Hepatitis 6 Notknown

Cholestaticjaundice 6 Notknown

Skinandsubcutaneoustissuedisorders 7

Skinrash Uncommon

Pruritus Uncommon

Urticaria Uncommon

Erythemamultiforme Rare

Stevens-Johnsonsyndrome Notknown

Toxicepidermalnecrolysis Notknown

Bullousexfoliative-dermatitis Notknown

Acutegeneralisedexanthemouspustulosis

(AGEP) 9 Notknown

Renalandurinarydisorders

Interstitialnephritis Notknown

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Treatmentofintoxication

Gastrointestinalsymptomsmaybetreatedsymptomatically,withattentiontothewater/electrolytebalance.

Amoxicillin/clavulanicacidcanberemovedfromthecirculationbyhaemodialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Combinationsofpenicillins,incl.beta-lactamaseinhibitors;ATCcode:J01CR02.

Modeofaction

Amoxicillinisasemisyntheticpenicillin(beta-lactamantibiotic)thatinhibitsoneormoreenzymes(oftenreferredtoas

penicillin-bindingproteins,PBPs)inthebiosyntheticpathwayofbacterialpeptidoglycan,whichisanintegralstructural

componentofthebacterialcellwall.Inhibitionofpeptidoglycansynthesisleadstoweakeningofthecellwall,whichis

usuallyfollowedbycelllysisanddeath.

Amoxicillinissusceptibletodegradationbybeta-lactamasesproducedbyresistantbacteriaandthereforethespectrum

ofactivityofamoxicillinalonedoesnotincludeorganismswhichproducetheseenzymes.

Clavulanicacidisabeta-lactamstructurallyrelatedtopenicillins.Itinactivatessomebeta-lactamaseenzymesthereby

preventinginactivationofamoxicillin.Clavulanicacidalonedoesnotexertaclinicallyusefulantibacterialeffect.

PK/PDrelationship

Thetimeabovetheminimuminhibitoryconcentration(T>MIC)isconsideredtobethemajordeterminantofefficacy

foramoxicillin.

Mechanismsofresistance

Thetwomainmechanismsofresistancetoamoxicillin/clavulanicacidare:Inactivationbythosebacterialbeta-

lactamasesthatarenotthemselvesinhibitedbyclavulanicacid,includingclassB,CandD.

AlterationofPBPs,whichreducetheaffinityoftheantibacterialagentforthetarget.

Impermeabilityofbacteriaoreffluxpumpmechanismsmaycauseorcontributetobacterialresistance,particularlyin

Gram-negativebacteria.

Breakpoints

MICbreakpointsforamoxicillin/clavulanicacidarethoseoftheEuropeanCommitteeonAntimicrobialSusceptibility

Testing(EUCAST).

Organism SusceptibilityBreakpoints(g/ml)

Susceptible Intermediate Resistant

Haemophilusinfluenzae1 1 - >1

Moraxellacatarrhalis1

Staphylococcusaureus2 1

>1

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Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspecies,andlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

Coagulase-negative

staphylococci2 0.25 >0.25

Enterococcus1 4 8 >8

StreptococcusA,B,C,G5 0.25 - >0.25

Streptococcuspneumoniae3 0.5 1-2 >2

Enterobacteriaceae1,4 - - >8

Gram-negativeAnaerobes1 4 8 >8

Gram-positiveAnaerobes1 4 8 >8

Non-speciesrelated

breakpoints1 2 4-8 >8

1ThereportedvaluesareforAmoxicillinconcentrations.Forsusceptibilitytesting

purposes,theconcentrationofClavulanicacidisfixedat2mg/l.

2ThereportedvaluesareOxacillinconcentrations.

3BreakpointvaluesinthetablearebasedonAmpicillinbreakpoints.

4TheresistantbreakpointofR>8mg/lensuresthatallisolateswithresistance

mechanismsarereportedresistant.

5BreakpointvaluesinthetablearebasedonBenzylpenicillinbreakpoints.

Commonlysusceptiblespecies

AerobicGram-positivemicro-organisms

Enterococcusfaecalis

Staphylococcusaureus(methicillin-susceptible)£

Streptococcusagalactiae

Streptococcuspneumoniae1

Streptococcuspyogenesandotherbeta-hemolyticstreptococci

Streptococcusviridansgroup

AerobicGram-negativemicro-organisms

Capnocytophagaspp.

Eikenellacorrodens

Haemophilusinfluenzae2

Moraxellacatarrhalis

Pasteurellamultocida

Anaerobicmicro-organisms

Bacteroidesfragilis

Fusobacteriumnucleatum

Prevotellaspp.

Speciesforwhichacquiredresistancemaybeaproblem

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5.2Pharmacokineticproperties

Absorption

Amoxicillinandclavulanicacid,arefullydissociatedinaqueoussolutionatphysiologicalpH.Bothcomponentsare

rapidlyandwellabsorbedbytheoralrouteofadministration.Absorptionofamoxicillin/clavulanicacidisoptimised

whentakenatthestartofameal.Followingoraladministration,amoxicillinandclavulanicacidareapproximately

70%bioavailable.Theplasmaprofilesofbothcomponentsaresimilarandthetimetopeakplasmaconcentration

(Tmax)ineachcaseisapproximatelyonehour.

Thepharmacokineticresultsforastudy,inwhichamoxicillin/clavulanicacid(250mg/125mgtabletsthreetimesdaily)

Enterococcusfaecium$

AerobicGram-negativemicro-organisms

Escherichiacoli

Klebsiellaoxytoca

Klebsiellapneumoniae

Proteusmirabilis

Proteusvulgaris

Inherentlyresistantorganisms

AerobicGram-negativemicro-organisms

Acinetobactersp.

Citrobacterfreundii

Enterobactersp.

Morganellamorganii

Providenciaspp.

Pseudomonassp.

Serratiasp.

Stenotrophomonasmaltophilia

$Naturalintermediatesusceptibilityintheabsenceofacquiredmechanismofresistance.

£Allmethicillin-resistantstaphylococciareresistanttoamoxicillin/clavulanicacid

1Streptococcuspneumoniaethatisfullysusceptibletopenicillinmaybetreatedwiththis

presentationofamoxicillin/clavulanicacid.Organismsthatshowanydegreeofreduced

susceptibilitytopenicillinshouldnotbetreatedwiththispresentation(seesections4.2and

4.4).

2StrainswithdecreasedsusceptibilityhavebeenreportedinsomecountriesintheEUwith

afrequencyhigherthan10%.

Mean(±SD)pharmacokineticparameters

Activesubstance

administered Dose Cmax Tmax AUC(0-

24h) T1/2

(mg) ((µg/ml) (h) ((µg.h/ml) (h)

Amoxicillin

AMX/CA

250mg/125mg 250 3.3

±1.12 1.5

(1.0-2.0 26.7±4.56 1.36

±0.56

Clavulanicacid

AMX/CA

250mg/125mg 125 1.5

0.70 1.2

(1.0-2.0) 12.6

3.25 1.01

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Amoxicillinandclavulanicacidserumconcentrationsachievedwithamoxicillin/clavulanicacidaresimilartothose

producedbytheoraladministrationofequivalentdosesofamoxicillinorclavulanicacidalone.

Distribution

About25%oftotalplasmaclavulanicacidand18%oftotalplasmaamoxicillinisboundtoprotein.Theapparent

volumeofdistributionisaround0.3-0.4l/kgforamoxicillinandaround0.2l/kgforclavulanicacid.

Followingintravenousadministration,bothamoxicillinandclavulanicacidhavebeenfoundingallbladder,abdominal

tissue,skin,fat,muscletissues,synovialandperitonealfluids,bileandpus.Amoxicillindoesnotadequatelydistribute

intothecerebrospinalfluid.

Fromanimalstudiesthereisnoevidenceforsignificanttissueretentionofdrug-derivedmaterialforeithercomponent.

Amoxicillin,likemostpenicillins,canbedetectedinbreastmilk.Tracequantitiesofclavulanicacidcanalsobe

detectedinbreastmilk(seesection4.6).

Bothamoxicillinandclavulanicacidhavebeenshowntocrosstheplacentalbarrier(seesection4.6).

Biotransformation

Amoxicillinispartlyexcretedintheurineastheinactivepenicilloicacidinquantitiesequivalenttoupto10to25%of

theinitialdose.Clavulanicacidisextensivelymetabolizedinmanandeliminatedinurineandfaecesandascarbon

dioxideinexpiredair.

Elimination

Themajorrouteofeliminationforamoxicillinisviathekidney,whereasforclavulanicaciditisbybothrenalandnon-

renalmechanisms.

Amoxicillin/clavulanicacidhasameaneliminationhalf-lifeofapproximatelyonehourandameantotalclearanceof

approximately25l/hinhealthysubjects.Approximately60to70%oftheamoxicillinandapproximately40to65%of

theclavulanicacidareexcretedunchangedinurineduringthefirst6hafteradministrationofsingleAugmentin250

mg/125mgor500mg/125mgtablets.Variousstudieshavefoundtheurinaryexcretiontobe50-85%foramoxicillin

andbetween27-60%forclavulanicacidovera24hourperiod.Inthecaseofclavulanicacid,thelargestamountof

drugisexcretedduringthefirst2hoursafteradministration.

Concomitantuseofprobeneciddelaysamoxicillinexcretionbutdoesnotdelayrenalexcretionofclavulanicacid(see

section4.5).

Theeliminationhalf-lifeofamoxicillinissimilarforchildrenagedaround3monthsto2yearsandolderchildrenand

adults.Forveryyoungchildren(includingpretermnewborns)inthefirstweekoflifetheintervalofadministration

shouldnotexceedtwicedailyadministrationduetoimmaturityoftherenalpathwayofelimination.Becauseelderly

patientsaremorelikelytohavedecreasedrenalfunction,careshouldbetakenindoseselection,anditmaybeusefulto

monitorrenalfunction.

Gender

Followingoraladministrationofamoxicillin/clavulanicacidtohealthymalesandfemalesubjects,genderhasno

AMX–amoxicillin,CA–clavulanicacid

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Renalimpairment

Thetotalserumclearanceofamoxicillin/clavulanicaciddecreasesproportionatelywithdecreasingrenalfunction.The

reductionindrugclearanceismorepronouncedforamoxicillinthanforclavulanicacid,asahigherproportionof

amoxicillinisexcretedviatherenalroute.Dosesinrenalimpairmentmustthereforepreventundueaccumulationof

amoxicillinwhilemaintainingadequatelevelsofclavulanicacid(seesection4.2).

Hepaticimpairment

Hepaticallyimpairedpatientsshouldbedosedwithcautionandhepaticfunctionmonitoredatregularintervals

5.3Preclinicalsafetydata

Nonclinicaldatarevealnospecialhazardforhumansbasedonstudiesofsafetypharmacology,genotoxicityand

toxicitytoreproduction.

Repeatdosetoxicitystudiesperformedindogswithamoxicillin/clavulanicaciddemonstrategastricirritancyand

vomiting,anddiscolouredtongue.

Carcinogenicitystudieshavenotbeenconductedwithamoxicillin/clavulanicacidoritscomponents.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Magnesiumstearate

Sodiumstarchglycolate,TypeA

Colloidalanhydroussilica,

Microcrystallinecellulose,

Filmcoat

Titaniumdioxide(E171),

Hypromellose

Macrogol,

Dimeticone.

6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelflifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25 0

Bottles–Keepcontainertightlyclosed.Theencloseddesiccantsshouldnotberemoved.Storeintheoriginalpackage.

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6.5Natureandcontentsofcontainer

Amberglassbottlesof100tablets.

AluminiumPVC/PVdCblisterinanaluminiumpouchwithdessicant,containing21tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/047/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:14April2000

Dateoflastrenewal:14April2010

10DATEOFREVISIONOFTHETEXT

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