AUGMENTIN

Main information

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

Documents

Localization

  • Available in:
  • AUGMENTIN Tablets 250/125 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1463/015/001
  • Authorization date:
  • 17-04-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1463/015/001

CaseNo:2058983

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

IMEDHealthcareLtd.

NewRoad,Buncrana,Co.Donegal,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Augmentin250mg/125mgFilm-coatedtablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom17/04/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Augmentin250mg/125mgFilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontainsamoxicillintrihydrateequivalentto250mgandpotassiumclavulanateequivalentto

125mgofclavulanicacid.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

ProductimportedfromtheUK

Whitetooff-white,ovalshaped,film-coatedtabletengraved'Augmentin'ononesideandplainonthereverseside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

AugmentinisindicatedforshorttermtreatmentofbacterialinfectionsatthefollowingsiteswhenAmoxicillinresistant

beta-lactamaseproducingstrainsaresuspectedasthecause.Inothersituations,Amoxicillinaloneshouldbe

considered.

-UpperRespiratoryTractInfections(includingENT)inparticularsinusitis,otitismedia,recurrenttonsillitis.These

infectionsareoftencausedbyStreptococcuspneumoniae,Haemophilusinfluenzae*,Moraxellacatarrhalis*and

Streptococcuspyogenes.

-LowerRespiratoryTractInfectionsinparticularacuteexacerbationsofchronicbronchitis(especiallyifconsidered

severe),bronchopneumonia.TheseinfectionsareoftencausedbyStreptococcuspneumoniae,Haemophilusinfluenzae*

andMoraxellacatarrhalis*.

-Genito-urinaryTractandAbdominalInfectionsinparticularcystitis(especiallywhenrecurrentorcomplicated-

excludingprostatitis),septicabortion,pelvicorpuerperalsepsisandintra-abdominalsepsis.Theseinfectionsareoften

causedbyEnterobacteriaceae*(mainlyEscherichiacoli*),Staphylococcussaprophyticus,Enterococcusspecies.*

-SkinandSoftTissueInfectionsinparticularcellulitis,animalbitesandseveredentalabscesswithspreadingcellulitis.

TheseinfectionsareoftencausedbyStaphylococcusaureus*,StreptococcuspyogenesandBacteroidesspecies*.

*Somemembersofthesespeciesofbacteriaproducebeta-lactamase,renderingtheminsensitivetoAmoxicillinalone.

AugmentinIntravenousisindicatedwhenparenteraltherapyisrequired.

AugmentinIntravenousisalsoindicatedforProphylaxisagainstwoundinfectionwhichmaybeassociatedwith

surgicalproceduressuchasgastrointestinal,pelvic,headandneck,cardiac,renaljointreplacementandbiliarytract.

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MixedinfectionscausedbyAmoxicillin-susceptibleorganismsinconjunctionwithAugmentin-susceptible

betalactamase-producingorganismsmaybetreatedwithAugmentin.Theseinfectionsshouldnotrequiretheaddition

ofanotherantibioticresistanttobeta-lactamases

4.2Posologyandmethodofadministration

AdultsandChildrenover12yearsofageonly:

Theusualdailydoseis375mgthreetimesdaily.

Thedosagemaybeincreasedto750mgthreetimesdailyinthetreatmentofsevereinfections.

Renalimpairment

Inpatientswithmoderateorsevererenalimpairment,dosagesshouldbeadjustedaccordingtothedegreeof

impairment.

Haemodialysis

DosageadjustmentsarebasedonthemaximumrecommendedlevelofAmoxicillin.

2times250/125mgevery24hoursPLUSonedoseduringdialysis,toberepeatedattheendofdialysis(asserum

concentrationsofbothAmoxicillinandclavulanicacidaredecreased).

Hepaticimpairment

Dosewithcaution,monitorhepaticfunctionatregularintervals.Thereareasyetinsufficientdataonwhichtobasea

dosagerecommendation.

Administration

Oral:Tablets

Tominimisepotentialgastro-intestinalintoleranceadministeratthestartofameal.TheabsorptionofAugmentinis

optimisedwhentakenatthestartofameal.

Durationoftherapyshouldbeappropriatetotheindicationandshouldnotexceed14dayswithoutreview.

4.3Contraindications

Useinpatientswithhypersensitivitytobeta-lactamse.g.penicillinsorcephalosporins.Augmentiniscontra-indicated

Creatinineclearance

ml/min Dosage(mg) Interval

10-30 375–750dependingonseverity

ofinfection 12(b.i.d.)

<10 375–750dependingonseverity

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4.4Specialwarningsandprecautionsforuse

Prolongeduseofananti-infectivemayoccasionallyresultinovergrowthofnon-susceptibleorganisms.

Seriousandoccasionallyfatalhypersensitivity(anaphylactoid)reactionshavebeenreportedinpatientsonpenicillin

therapy.Thesereactionsaremorelikelytooccurinindividualswithahistoryofpenicillinhypersensitivity(see

Contraindications).

Augmentinshouldbeusedwithcautioninpatientswithevidenceofhepaticdysfunctionandwithcareinpatientswith

renaldysfunction.

Eachtabletcontains0.63mmolofpotassium.

PatientswithinfectiousmononucleosisfrequentlydeveloprasheswithAmoxicillintherapy.

Inpatientswithreducedurineoutput,crystalluriahasbeenobservedveryrarely,predominantlywithparenteral

therapy.DuringtheadministrationofhighdosesofAmoxicillin,itisadvisabletomaintainadequatefluidintakeand

urinaryoutputinordertoreducethepossibilityofAmoxicillincrystalluria(seeOverdosage).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Concomitantuseofprobenecidisnotrecommended.Probeneciddecreasestherenaltubularsecretionofamoxicillin.

Concomitantusewithamoxicillin-clavulanatemayresultinincreasedandprolongedbloodlevelsofamoxicillin,but

notofclavulanicacid.

Prolongationofbleedingtimeandprothrombintimehavebeenreportedinsomepatientsreceiving‘Augmentin’.

‘Augmentin’shouldbeusedwithcareinpatientsonanti-coagulationtherapy.

Concomitantuseofallopurinolduringtreatmentwithamoxicillincanincreasethelikelihoodofallergicskinreactions.

Therearenodataontheconcomitantuseofamoxicillin-clavulanateandallopurinol.

Incommonwithotherantibiotics,amoxicillin-clavulanatemayaffectthegutflora,leadingtoloweroestrogen

reabsorptionandreducedefficacyofcombinedoralcontraceptives.

4.6Pregnancyandlactation

Thisproductshouldonlybeusedinpregnancyorlactationifconsideredessentialbythephysician.Animalstudies

haveshownnoevidenceofteratogeniceffectduetodrug,butsafetyofuseinhumanbeingsisnotestablished.Ina

singlestudyinwomenwithpreterm,prematureruptureofthefoetalmembrane(pPROM),itwasreportedthat

prophylactictreatmentwith‘Augmentin’maybeassociatedwithanincreasedriskofnecrotisingenterocolitisin

neonates.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Datafromlargeclinicaltrialswasusedtodeterminethefrequencyofverycommontorareundesirableeffects.The

frequenciesassignedtoallotherundesirableeffects(i.e.,thoseoccurringat<1/10,000)weremainlydeterminedusing

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Thefollowingconventionhasbeenusedfortheclassificationoffrequency:-

verycommon>1/10

common>1/100and<1/10

uncommon>1/1000and<1/100

rare>1/10,000and<1/1000

veryrare<1/10,000.

Infectionsandinfestations

CommonMucocutaneouscandidiasis

Bloodandlymphaticsystemdisorders

RareReversibleleucopenia(includingneutropenia)andthrombocytopenia

VeryrareReversibleagranulocytosisandhaemolyticanaemia.Prolongationofbleedingtimeandprothrombintime

(seeSection4.4Specialwarningsandspecialprecautionsforuse)

Immunesystemdisorders

VeryRareAngioneuroticoedema,anaphylaxis,serumsickness-likesyndrome,hypersensitivityvasculitis

Nervoussystemdisorders

UncommonDizziness,headache

VeryRareReversiblehyperactivityandconvulsions.Convulsionsmayoccurinpatientswithimpairedrenalfunction

orinthosereceivinghighdoses.

Gastrointestinaldisorders

VerycommonDiarrhoea

CommonNausea,vomiting

Nauseaismoreoftenassociatedwithhigheroraldosages.Ifgastrointestinalreactionsareevident,theymaybereduced

bytakingAugmentinatthestartofameal.

UncommonIndigestion

VeryRareAntibiotic-associatedcolitis(includingpseudomembranouscolitisandhaemorrhagiccolitis).

Blackhairytongue

Hepatobiliarydisorders

UncommonAmoderateriseinASTand/orALTandAlkalinePhosphataseshasbeennotedinpatientstreatedwith

beta-lactamclassantibiotics,butthesignificanceofthesefindingsisunknown.

VeryRareHepatitisandcholestaticjaundice.Theseeventshavebeennotedwithotherpenicillinsandcephalosporins.

Hepaticeventshavebeenreportedpredominantlyinmalesandelderlypatientsandmaybeassociatedwithprolonged

treatment.

Signsandsymptomsusuallyoccurduringorshortlyaftertreatmentbutinsomecasesmaynotbecomeapparentuntil

severalweeksaftertreatmenthasceased.Theseareusuallyreversible.Hepaticeventsmaybesevereandinextremely

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Skinandsubcutaneoustissuedisorders

UncommonSkinrash,pruritus,urticaria

RareErythemamultiforme

VeryRareStevens-Johnsonsyndrome,toxicepidermalnecrolysis,bullousexfoliative-dermatitis,acutegeneralized

exanthemouspustulosis(AGEP)

Ifanyhypersensitivitydermatitisreactionoccurs,treatmentshouldbediscontinued.

Renalandurinarydisorders

VeryrareInterstitialnephritis,crystalluria(seeOverdosage)

4.9Overdose

Gastro-intestinalsymptomsanddisturbanceofthefluidandelectrolytebalancesmaybeevident.Theymaybetreated

symptomaticallywithattentiontothefluidandelectrolytebalance.‘Augmentin’mayberemovedfromthecirculation

byhaemodialysis.

Amoxicillincrystalluria,insomecasesleadingtorenalfailure,hasbeenobserved(seeSection4.4Specialwarnings

andspecialprecautionsforuse).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

'Augmentin'isanantibioticagentwithanotablybroadspectrumofactivityagainstthecommonlyoccurringbacterial

pathogensingeneralpracticeandhospital.Thebetalactamaseinhibitoryactionofclavulanateextendsthespectrumof

Amoxicillintoembraceawiderrangeoforganisms,includingmanyresistanttootherbetalactamaseantibiotics.

Resistancetomanyantibioticsiscausedbybacterialenzymeswhichdestroytheantibioticbeforeitcanactonthe

pathogen.Theclavulanatein'Augmentin'anticipatesthisdefencemechanismbyblockingtheß-lactamaseenzymes,

thusrenderingtheorganismssensitivetoAmoxicillin'srapidbactericidaleffectatconcentrationsreadilyattainablein

thebody.

Clavulanatebyitselfhaslittleantibacterialactivity;however,inassociationwithAmoxicillinas'Augmentin',it

producesanantibioticagentofbroadspectrumwithwideapplicationinhospitalandgeneralpractice.

'Augmentin'isbactericidaltoawiderangeoforganismsincluding:

Gram-positive

Aerobes:Enterococcusfaecalis*,Enterococcusfaecium*,Streptococcuspneumoniae,Streptococcuspyogenes,

Streptococcusviridans,Staphylococcusaureus*,Coagulasenegativestaphylococci*(includingStaphylococcus

epidermidis*),Corynebacteriumspecies,Bacillusanthracis*,Listeriamonocytogenes.

Anaerobes:Clostridiumspecies,Peptococcusspecies,Peptostreptococcus.

Gram-negative

Aerobes:Haemophilusinfluenzae*,Moraxellacatarrhalis*(Branhamellacatarrhalis),Escherichiacoli*,Proteus

mirabilis*,Proteusvulgaris*,Klebsiellaspecies*,Salmonellaspecies*,Shigellaspecies*,Bordetellapertussis,

Brucellaspecies,Neisseriagonorrhoeae*,Neisseriameningitidis*,Vibriocholerae,Pasteurellamultocida.

Anaerobes:Bacteroidesspecies*includingB.fragilis

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5.2Pharmacokineticproperties

Thepharmacokineticsofthetwocomponentsof'Augmentin'arecloselymatched.Peakserumlevelsofbothoccur

aboutonehourafteroraladministration.Absorptionof'Augmentin'isoptimisedatthestartofameal.Bothclavulanate

andAmoxicillinhavelowlevelsofserumbinding;about70%remainsfreeintheserum.

Doublingthedosageof'Augmentin'approximatelydoublestheserumlevelsachieved.

Aswithotherpenicillins,themajorrouteofeliminationforAmoxicillinisviathekidney,whereasforclavulanateitis

bybothrenalandnon-renalmechanisms.Approximately60-70%oftheAmoxicillinandapproximately40-65%ofthe

clavulanicacidareexcretedunchangedinurineduringthefirst6hoursafteradminstrationofasingle250/125mgora

single500/125mgtablet.

Amoxicillinisalsopartlyexcretedintheurineastheinactivepenicilloicacidinquantitiesequivalentto10-25%ofthe

initialdose.Clavulanicacidisextensivelymetabolizedinmanto2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-

carboxylicacidand1-amino-4-hydroxy-butan-2-oneandeliminatedinurineandfaecesandascarbondioxidein

expiredair.

5.3Preclinicalsafetydata

Nofurtherinformationofrelevance.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Magnesiumstearate(E572)

Sodiumstarchglycolate

Collodialsilica

Microcrystallinecellulose(E460)

Hypromellose(E464)

Polyetheyleneglycol

Siliconeoil

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Theshelflifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackagingoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25ºC.

Keepthecontainertightlyclosedinordertoprotectfrommoisture

Storeintheoriginalpackageinordertoprotectfromlight

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6.5Natureandcontentsofcontainer

Over-labelledamberbottlewithdesiccantpackagedintoacardboardcarton.

Packsize100tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7ParallelProductAuthorisationHolder

IMEDHealthcareLtd

NewRoad

Buncranna

CountyDonegal

8ParallelProductAuthorisationNumber

PPA1463/15/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17 th

April2009

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