CLAVAMEL 125MG/ 62.5MG PER 5ML JUNIOR POWDER FOR OR

Main information

  • Trade name:
  • CLAVAMEL 125MG/ 62.5MG PER 5ML JUNIOR POWDER FOR OR
  • Dosage:
  • 125/ 62.5 Milligram
  • Pharmaceutical form:
  • Powder for Oral Suspension
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLAVAMEL 125MG/62.5MG PER 5ML JUNIOR POWDER FOR OR
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/103/003
  • Authorization date:
  • 17-09-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0126/103/003

CaseNo:2051983

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ClonmelHealthcareLimited

WaterfordRoad,Clonmel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CLAVAMEL125mg/62.5mgper5mlJuniorPowderforOralSuspension

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/06/2008until16/09/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 27/06/2008 CRN 2051983 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Clavamel125mg/62.5mgper5mlJuniorPowderforOralSuspension

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each5mlofreconstitutedsuspensioncontainsAmoxicillinTrihydrateequivalentto125mgofamoxicillinand

potassiumclavulanateequivalentto62.5mgofclavulaicacid.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Powderfororalsuspension

Clear,glassbottles,containingawhitetooff-whitepowderforreconstitutionwithwater.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Clavamelisindicatedforshorttermtreatmentofbacterialinfectionsatthefollowingsiteswhenamoxicillinresistant

beta-lactamaseproducingstrainsaresuspectedasthecause.Inothersituations,amoxicillinaloneshouldbeconsidered.

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

infectionsareoftencausedbyStreptococcuspneumoniae,Haemophilusinfluenzae*,Moraxellacatarrhalis*and

Streptococcuspyogenes.

-LowerRespiratoryTractInfectionsinparticularacuteexacerbationsofchronicbronchitis(especiallyifconsidered

severe),bronchopneumonia.TheseinfectionsareoftencausedbyStreptococcuspneumoniae,Haemophilus

influenzae*andMoraxellacatarrhalis*.

-Genito-urinaryTractandAbdominalInfectionsinparticularcystitis(especiallywhenrecurrentorcomplicated-

excludingprostatitis),septicabortion,pelvicorpuerperalsepsisandintra-abdominalsepsis.

TheseinfectionsareoftencausedbyEnterobacteriaceae*(mainlyEscherichiacoli*),Staphylococcussaprophyticus,

Enterococcusspecies*.

-SkinandSoftTissueInfectionsinparticularcellulitis,animalbitesandseveredentalabscesswithspreadingcellulitis.

TheseinfectionsareoftencausedbyStaphylococcusaureus*,StreptococcuspyogenesandBacteroidesspecies*.

*Somemembersofthesespeciesofbacteriaproducebeta-lactamase,renderingtheminsensitivetoamoxicillinalone.

-AcomprehensivelistofsensitiveorganismsisprovidedinPharmacodynamicproperties.

Mixedinfectionscausedbyamoxicillin-susceptibleorganismsinconjunctionwithClavamel-susceptiblebeta-

lactamase-producingorganismsmaybetreatedwithClavamel.Theseinfectionsshouldnotrequiretheadditionof

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4.2Posologyandmethodofadministration

Usualdosagesinthetreatmentofinfection:

Children6-12years

Theusualdosageis187mg(5ml)threetimesdaily.

Insevereinfectionsthesedosesmaybedoubled.

Thisformulationisnotrecommendedforchildrenundertheageof6years.

Renalimpairment

Inpatientswithmoderateorsevererenalimpairmentdosagesshouldbeadjustedaccordingtothedegreeofimpairment.

*usingthePaediatricSuspension.

Haemodialysis

Dosageadjustmentsarebasedonthemaximumrecommendedlevelofamoxicillin.

15/3.75mg/kg/daygivenasasingledose.Oneadditionaldoseof15/3.75mg/kgshouldbeadministeredpriorto

haemodialysisandagainafterhaemodialysis.

HepaticImpairment

Dosewithcaution,monitorhepaticfunctionatregularintervals.Thereareasyetinsufficientdataonwhichtobasea

dosagerecommendation.

Administration:

Oral:Suspension.

Tominimisepotentialgastro-intestinalintoleranceadministeratthestartofameal.TheabsorptionofClavamelis

optimisedwhentakenatthestartofameal.

Durationoftherapyshouldbeappropriatetotheindicationandshouldnotexceed14dayswithoutreview.

4.3Contraindications

Useinpatientswithahistoryofhypersensitivitytobeta-lactamse.g.penicillinsandcephalosporins.

Clavameliscontra-indicatedinpatientswithaprevioushistoryofClavamel-associatedjaundice/hepaticdysfunction.

4.4Specialwarningsandprecautionsforuse

Beforeinitiatingtherapywith‘Clavamel’carefulenquiryshouldbemadeconcerningprevioushypersensitivity

reactionstopenicillinsorcephalosporins.Seriousandoccasionallyfatalhypersensitivity(anaphylactoid)reactions

havebeenreportedinpatientsonpenicillintherapy.Thesereactionsaremorelikelytooccurinindividualswitha

historyofpenicillinhypersensitivity(seeContra-indications).

‘Clavamel’shouldbeusedwithcautioninpatientswithevidenceofhepaticdysfunctionandwithcareinpatientswith

renaldysfunctionwhendosageshouldbeadjusted(see4.2).

Creatinineclearance

ml/min Dosage

Interval

10-30 15/3.75*mg/kg

(maximum500/125mgtwicedaily) 12(b.i.d.)

<10 15/3.75*mg/kg

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beenassociatedwiththisconditionfollowingtheuseofamoxicillin.

Prolongeduseofananti-infectiveagentmayresultinsuperinfectionbymicro-organismsincludingcandidaresistantto

thatanti-infective.

ClavamelSuspensioncontains12.5mgaspartameper5mldoseandthereforecareshouldbetakenin

phenylketonuria.Each5mldosecontains12.3mg(0.31mmol)potassium.

Inpatientswithreducedurineoutput,crystalluriahasbeenobservedveryrarely,predominantlywithparenteral

therapy.DuringtheadministrationofhighdosesofAmoxicillin,itisadvisabletomaintainadequatefluidintakeand

urinaryoutputinordertoreducethepossibilityofAmoxicillincrystalluria(seeOverdosage).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Concomitantuseofprobenecidisnotrecommended.Probeneciddecreasestherenaltubularsecretionofamoxicillin.

Concomitantusewithamoxicillin-clavulanatemayresultinincreasedandprolongedbloodlevelsofamoxicillin,but

notofclavulanateacid.

Prolongationofbleedingtimeandprothrombintimehavebeenreportedinsomepatientsreceivingco-amoxiclav.

Augmentin-Duoshouldbeusedwithcareinpatientsonanti-coagulationtherapy.

Concomitantuseofallopurinolduringtreatmentwithamoxicillincanincreasethelikelihoodofallergicskinreactions.

Therearenotdataontheconcomitantuseofamoxicillin-clavulanateandallopurinol.

Incommonwithotherantibiotics,amoxicillin-clavulanatemayaffectthegutflora,leadingtoloweroestrogen

reabsorptionandreducedefficacyofcombinedoralcontraceptives.

4.6Pregnancyandlactation

Useinpregnancy:

Reproductionstudiesinanimals(miceandrats)withorallyandparenterallyadministeredco-amoxiclavhaveshownno

teratogeniceffects.Inasinglestudyinwomenwithpreterm,prematureruptureofthefoetalmembrane(PPROM),it

wasreportedthatprophylactictreatmentwithClavamelmaybeassociatedwithanincreasedriskofnecrotising

enterocolitisinneonates.Aswithallothermedicinesuseshouldbeavoidedinpregnancyunlessconsideredessential

bythephysician.

Useinlactation:

‘Clavamel’maybeadministeredduringtheperiodoflactation.Withtheexceptionoftheriskofsensitisation

associatedwiththeexcretionoftracequantitiesinbreastmilk,therearenoknowndetrimentaleffectsforthebreast-fed

infant.

4.7Effectsonabilitytodriveandusemachines

Adverseeffectsontheabilitytodriveoroperatemachineryhavenotbeenobserved.

4.8Undesirableeffects

Datafromlargeclinicaltrialswasusedtodeterminethefrequencyofverycommontorareundesirableeffects.The

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

post-marketingdataandrefertoareportingrateratherthanatruefrequency.

Thefollowingconventionhasbeenusedfortheclassificationoffrequency:

verycommon>1/10

common>1/100and<1/10

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

veryrare<1/10,000

Infectionsandinfestations

Common Mucocutaneouscandidiasis.

Bloodandlymphaticsystemdisorders

Rare Reversibleleucopenia(includingneutropenia)andthrombocytopenia.

Veryrare Reversibleagranulocytosisandhaemolyticanaemia.Prolongationofbleedingtimeand

prothrombintime(seeSection4.4Specialwarningsandspecialprecautionsforuse).

Immunesystemdisorders

Veryrare Angioneuroticoedema,anaphylaxis,serumsickness-likesyndrome,hypersensitivityvasculitis.

Nervoussystemdisorders

Uncommon Dizziness,headache.

VeryRare Reversiblehyperactivityandconvulsions.Convulsionsmayoccurinpatientswithimpairedrenal

functionorinthosereceivinghighdoses.

Gastrointestinaldisorders

VerycommonDiarrhoea.

Common Nausea,vomiting.

Nauseaisoftenassociatedwithhigheroraldoses.Ifgastrointestinalreactionsareevident,theymaybereduced

bytakingCLAVAMELatthestartofameal.

Uncommon Indigestion.

VeryRare Antibiotic-associatedcolitis(includingpseudomembraneouscolitisandhaemorrhagiccolitis).

Blackhairytongue.

Hepatobiliarydisorders

Uncommon Amoderateriseinaspartateaminotransferase(AST)and/oralanineaminotransferase(ALT)and

AlkalinePhosphateshasbeennotedinpatientstreatedwithbeta-lactamclassantibiotics,butthe

significanceofthesefindingsisunknown.

VeryRare Hepatitisandcholestaticjaundice.Theseeventshavebeennotedwithotherpenicillinsand

cephalosporins.

Hepaticeventshavebeenreportedpredominatelyinmalesandelderlypatientsandmaybeassociatedwithprolonged

treatment.

Signsandsymptomsusuallyoccurduringorshortlyaftertreatmentbutinsomecasesmaynotbecomeapparentuntil

severalweeksaftertreatmenthasceased.Theseareusuallyreversible.Hepaticeventsmaybesevereandinextremely

rarecircumstances,deathshavebeenreported.

Skinandsubcutaneoustissuedisorders

Uncommon Skinrash,pruritis,urticaria.

Rare Erythemamultiforme.

VeryRare Stevens-Johnsonsyndrome,toxicepidermalnecrolysis,bullousexfoliative-dermatitis,acute

generalisedexanthemouspustulosis.(AGEP).

Ifanyhypersensitivitydermatitisreactionoccurs,treatmentshouldbediscontinued.

Renalandurinarydisorders

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4.9Overdose

Gastrointestinalsymptomsanddisturbanceofthefluidandelectrolytebalancesmaybeevident.Theymaybetreated

symptomaticallywithattentiontothefluidandelectrolytebalance.‘Clavamel’mayberemovedfromthecirculationby

haemodialysis.Amoxicillincrystalluria,insomecasesleadingtorenalfailure,hasbeenobserved(seeSection4.4

specialwarningsandspecialprecautionsforuse).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Clavamelisanantibioticagentwithanotablybroadspectrumofactivityagainstthecommonlyoccurringbacterial

pathogensingeneralpracticeandhospital.Thebetalactamaseinhibitoryactionofclavulanateextendsthespectrum

ofamoxicillintoembraceawiderrangeoforganisms,includingmanyresistanttootherbetalacatamaseantibiotics.

Resistancetomanyantibioticsiscausedbybacterialenzymeswhichdestroytheantibioticbeforeitcanactonthe

pathogen.TheclavulanateinClavamelanticipatesthisdefencemechanismbyblockingthebeta-lactamaseenzymes,

thusrenderingtheorganismssensitivetoamoxicillin’srapidbactericidaleffectatconcentrationsreadilyattainablein

thebody.

Clavulanatebyitselfhaslittleantibacterialactivity;however,inassociationwithamoxicillinasClavamel,itproduces

anantibioticagentofbroadspectrumwithwideapplicationinhospitalandgeneralpractice.

Clavamelisbactericidaltoawiderangeoforganismsincluding:

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.

*Somemembersofthesespeciesofbacteriaproducebeta-lactamase,renderingtheminsensitivetoamoxicillinalone.

5.2Pharmacokineticproperties

ThepharmacokineticsofthetwocomponentsofClavamelarecloselymatched.Peakserumlevelsofbothoccurabout

onehourafteroraladministration.AbsorptionofClavamelisoptimisedatthestartofameal.Bothclavulanateand

amoxicillinhavelowlevelsofserumbinding;about70%remainsfreeintheserum.

DoublethedosageofClavamelapproximatelydoublestheserumlevelsachieved.

Aswithotherpenicillins,themajorrouteofeliminationforamoxicillinisviathekidney,whereasforclavulanateitis

bybothrenalandnon-renalmechanisms.Approximately60-70%oftheamoxicillinandapproximately40-65%ofthe

clavulanicacidareexcretedunchangedinurineduringthefirst6hoursafteradministrationofasingle250/125mgora

single500/125mgtablet.

Amoxicillinisalsopartlyexcretedintheurineastheinactivepenicilloicacidinquantitiesequivalentto10-25%ofthe

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

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

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5.3Preclinicalsafetydata

Nofurtherinformationofrelevance.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Xanthangum,E415

Hypromellose,E464

Aspartame

Colloidalanhydroussilica

Colloidalhydratedsilica

Succinicacid

Raspberrydryflavour

Orangedryflavour1

Orangedryflavour2

Goldensyrupdryflavour

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Drypowder:2years.

Reconstitutedsuspension:7days.

6.4Specialprecautionsforstorage

Drypowder: Donotstoreabove25 o

Reconstitutedsuspensionsshouldbekeptinarefrigerator(butnotfrozen)foruptosevendays.

6.5Natureandcontentsofcontainer

GlassbottleswithaluminiumscrewcapsoraROPP(rollonpilferproof),internallylacqueredexternallyenameled

closure,containingaflowed-inPVCliner.Containingpowderforreconstitutionto100ml.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Attimeofdispensingthedrypowdershouldbereconstitutedtoformanoralsuspension.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLtd

WaterfordRoad

Clonmel

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8MARKETINGAUTHORISATIONNUMBER

PA126/103/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17September1999

Dateoflastrenewal:17September2004

10DATEOFREVISIONOFTHETEXT

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