CEFUROXIME

Main information

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

Documents

Localization

  • Available in:
  • CEFUROXIME Tablets 125 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0372/009/001
  • Authorization date:
  • 08-12-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0372/009/001

CaseNo:2052305

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

SandozLtd

37WoolmerWay,Bordon,HantsGU359QE,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cefuroxime125mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom25/08/2008until07/12/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 28/09/2008 CRN 2052305 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cefuroxime125mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains150.36mgcefuroximeaxetilwhichisequivalentto125mgcefuroximepertablet.

Forexcipients:see6.1.

3PHARMACEUTICALFORM

Coatedtablets.

Whitetoslightlyyellowish,biconvex,oblongtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cefuroximeaxetilisindicatedforthetreatmentofmildtomoderatelysevereinfectionscausedbymicro-organisms

susceptibletocefuroxime,suchas:

-upperrespiratorytractinfections:acuteotitismedia,sinusitis,tonsillitisandpharyngitis

-acutebronchitis,acuteexacerbationsofchronicbronchitis

-loweruncomplicatedurinarytractinfections:cystitis

-skinandsofttissueinfections:furunculosis,pyodermaandimpetigo

-uncomplicatedgonorrhoea:urethritisandcervicitis

-treatmentofearlystageLymedisease(stageI)andsubsequentpreventionoflatecomplicationsinadultsandchildren

above12yearsofage.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Cefuroximeaxetiltabletsarecoatedtomasktheirtaste:theyshouldnotbechewed.

Theusualdurationoftherapyis7days(rangingfrom5to10days).Incaseofpharyngotonsillitiscausedby

Streptococcuspyogenesatherapydurationofatleast10daysisindicated.ThedurationoftreatmentofearlyLyme

diseaseshouldbe20days.Inordertoachieveoptimumabsorptioncefuroximeaxetiltabletsshouldbetakenshortly

aftermeals.

Thedosagedependsontheseverityoftheinfection.Forsevereinfectionsparenteralformsofcefuroximeare

recommended.Whereappropriatecefuroximeaxetiliseffectivewhenusedfollowinginitialparenteralcefuroxime

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Dosageschedulefortablets:

Childrenunder5yearsofage:

Cefuroximeaxetiltabletsarenotsuitableforuseinchildrenundertheageof5.Forpatientsinthisagegroupitis

advisedtouseanoralsuspension.Thereisnoexperienceinchildrenunder3monthsofage.

Dosageregimeninrenalimpairment,indialysispatientsandelderly:

Nospecialprecautionsarenecessaryinpatientswithrenalimpairment,orinelderlypatientsifthedailydosagedoes

notexceed1gram.Inpatientswithrenalimpairmentandcreatinineclearancebelow20ml/mincefuroximeaxetil

tabletsshouldbedosedcarefully.Patientsundergoinghaemodialysiswillrequireasupplementarydoseofcefuroxime

attheendofeachdialysistreatment.

4.3Contraindications

Hypersensitivitytocefuroxime,othercephalosporinsortoanyoftheexcipients.

Previousimmediateand/orseverehypersensitivityreactiontoapenicillinortoanyothertypeofbeta-lactamdrug.

4.4Specialwarningsandprecautionsforuse

Ifafteradministrationofcefuroximeaxetilsensitivityreactionsoccur,theuseshouldbediscontinuedimmediatelyand

anappropriatetreatmentshouldbeestablished.

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontopenicillinsorotherbeta-lactams.

Aswithotherbroadspectrumantibiotics,prolongeduseofcefuroximeaxetilmayresultintheovergrowthofnon-

susceptibleorganismse.g.candida,enterococciandclostridiumdiffficile,whichmayrequireinterruptionoftreatment.

Inpatientswhodevelopseverediarrhoeaduringorafteruseofcefuroximeaxetil,theriskoflifethreatening

pseudomembranouscolitisshouldbetakenintoaccount.Theuseofcefuroximeaxetilshouldbediscontinuedandthe

appropriatetreatmentestablished.Theuseofpreparationsinhibitingtheintestinalperistaltismiscontra-indicated(see

4.8undesirableeffects).

A20-daytreatmentofLymediseasemaycausethefrequencyofdevelopingdiarrhoeatoincrease.

Theuseofcefuroximeaxetilisnotrecommendedinpatientswithsevereintestinaltractdisordersaccompaniedby

Adultsandchildrenover12yearsofage Dosage

Upperrespiratorytractinfections 250(–500)mgtwicedaily

Lowerrespiratorytractinfections 500mgtwicedaily

Lower uncomplicated urinary tract

infections 125–250mgtwicedaily

Skinandsofttissueinfections 250–500mgtwicedaily

EarlyLymedisease 500mgtwicedailyduring20days

Uncomplicatedgonorrhoea asingledoseof1000mg,ifdesired1000

mgprobenecidperoscanbeadded.

Childrenfrom5to12yearsofage

Above-mentionedindications,ifrelevantfor

thisgroupofchildren 125–250mgtwicedaily

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Administrationofaparenteralformulationofcefuroximeshouldbeconsidered.

Longtermuseofcefuroximeaxetilmayleadtoanexcessofpathogensresistanttocefuroximeaxetil.Itisofhigh

importancethatthepatientiscarefullychecked.Ifasuperinfectionoccursduringtreatment,appropriatemeasures

shouldbetaken(see4.8adversereactions).

TheJarisch-HerxheimerreactionhasbeenreportedfollowingcefuroximeaxetiltreatmentofLymedisease.The

reactionresultsdirectlyfromthebactericidalactivityofcefuroximeaxetilonthespirochaeteBorreliaburgdorferi.

Patientsshouldbeinformedofthiscommonandusuallyself-limitedreactionbeingaconsequenceofantibiotic

treatmentofLymedisease.

SimultaneoususeofmedicinesenhancingthepHofthestomachisnotrecommended(see4.5.Interactions).

Thereisnoclinicalexperiencewiththeuseofcefuroximeaxetilinchildrenundertheageof3months.Withrespectto

thetreatmentofearlyLymediseasethereisonlyclinicalexperiencewithchildrenfromtheageof12andwithadults.

Specialcareshouldbetakenwithphenylketonuricpatientsbecauseoftheaspartamecontainingcoating.

CefuroximeAxetil125contains0.2mgaspartamepertablet.

Eithertheglucoseoxidaseorthehexokinasemethodsarerecommendedtodeterminethebloodandplasmaglucose

levelsinpatientsreceivingcefuroximeaxetil.Cefuroximedoesnotinterfereinthealkalinepicrateassayforcreatinine

(see4.5Interactions).

Duringthetreatmentwithcefuroximesodium,somechildrenhaveexperiencedslighttomoderatehearingloss.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SimultaneoususeofmedicinesenhancingthepHofthestomachdecreasesthebioavailabilityofcefuroximeaxetil.Itis

recommendedtoavoidthiscombination(see4.4.Specialwarningsandprecautionsforuse).

Sincebacteriostaticdrugsmayinterferewiththebactericidalactionofcephalosporins,itisadvisabletoavoidgiving

tetracyclines,macrolides,orchloramphenicolinconjunctionwithcefuroximeaxetil.

Theconcomitantadministrationofprobenicidecanproducehigherandsustainedconcentrationsofcefuroximeinthe

serumandinthebile.

Cefuroximemayinterferewiththedeterminationofglucoseinurinewithcoppercontainingreagentia(Benedict-or

Fehling-solution,Clinitest).Forthedeterminationofbloodandplasmasugarlevelsinpatientsreceivingcefuroxime

axetil,theglucose-oxidaseorhexokinasemethodisrecommended(see4.4.Specialwarningsandprecautionsforuse).

TheuseofcefuroximeaxetilmaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(see4.8.Undesirableeffects).

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingpotentdiuretics,

aminoglycosides,oramphotericinasthesecombinationsincreasestheriskofnephrotoxicity.

4.6Pregnancyandlactation

Useinpregnancy

Therearenotsufficientdataontheuseofcefuroximeaxetilduringpregnancytoassessitspossibleharmfulness.Sofar,

animaltestshavenotyieldedevidenceofharmfulness.Cefuroximecrossestheplacenta.Cefuroximeaxetilshouldnot

beusedduringpregnancyunlessconsideredessentialbythephysician.

Useduringlactation

Cefuroximeisexcretedtoasmalldegreeinhumanmilk;breastfeedingshouldbeavoidedinwomenusingcefuroxime

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4.7Effectsonabilitytodriveandusemachines

Therearenostudiesoftheeffectofcefuroximeaxetilontheabilitytodriveandtohandlemachines.However,any

effectsarenottobeexpected.

4.8Undesirableeffects

Common(10%orless,butgreaterthan1%)

Uncommon(1%orless,butgreaterthan0.1%)

Rare(0.1%orless,butgreaterthan0.01%)

Veryrare(0.01%orless)

Infectionsandinfestations:

Rare

Pseudomembranouscolitis

Aswithotherantibioticsprolongedusemayleadtosecondarysuperinfectionscausedbyinsusceptibleorganisms,e.g.

Candida,EnterococciandClostridiumdifficile(see4.4Specialwarningsandprecautionsforuse).

Bloodandthelymphaticsystemdisorders

Rare

Decreasedhaemoglobinconcentration,eosinophilia,leucopenia,neutropeniaandthrombocytopenia

Veryrare

Haemolyticanemia

Immunesystemdisorders:

Common

Jarisch-HerxheimerreactionfollowingcefuroximeaxetiltreatmentofLymedisease(see4.4Specialwarningsand

precautionsforuse).

Rare

Serumsickness

Veryrare

Anaphylaxis

Nervoussystemdisorders

Uncommon

Headache,dizziness

Veryrare

Restlessness,nervousness,confusion

Gastrointestinaldisorders:

Common

Diarrhoea,nauseaandvomiting.Thefrequencyofdiarrhoeaisrelatedtotheadministereddoseandmayrateupto10%

withtablets.Theincidenceisevenhigher(approx.13%)atprolongedtreatmentof20daysofearlyLymedisease.

Hepato-biliarydisorders:

Rare

Transientincreasesofhepaticenzymelevels(AST,ALTandLDH)andserumbilirubin.

Veryrare

Jaundice.

Skinandsubcutaneoustissuedisorders:

Common

Skinrashes,urticaria,pruritus.

Veryrare

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Renalandurinarydisorders

Common

Increasedlevelsofcreatinineandureainserum,especiallyinpatientswithimpairedrenalfunction.

Uncommon

Acuteinterstitialnephritis

Generaldisordersandadministrationsiteconditions:

Rare

Drugfever

Investigations

TheuseofcefuroximeaxetilmaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(see4.5.Interactions).

4.9Overdose

Overdosageofcephalosporinsmaycausecerebralirritancyleadingtoconvulsions.Incaseofoverdosagecefuroxime

serumlevelscanbereducedbyhaemodialysisandperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Generalproperties:

ATCclassification

Pharmacotherapeuticgroup:cephalosporinsandrelatedsubstances

ATC-Code:J01DC02

Modeofaction

Cefuroximeaxetilowesitsinvivobactericidalactivitytotheparentcompoundcefuroxime.

Allcephalosporins(-lactamantibiotics)inhibitcellwallproductionandareselectiveinhibitorsofpeptidoglycan

synthesis.Theinitialstepindrugactionconsistsofbindingofthedrugtocellreceptors,calledPenicillin-Binding

Proteins.Aftera-lactamantibiotichasboundtothesereceptors,thetranspeptidationreactionisinhibitedand

peptidoglycansynthesisisblocked.Bacteriallysisistheendresult.

Mechanismofresistance

Bacterialresistancetocefuroximemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbybeta-lactamases.Cefuroximemaybeefficientlyhydrolysedbycertainoftheextended-spectrum

beta-lactamases(ESBLs)andbythechromosomally-encoded(AmpC)enzymethatmaybeinducedorstably

derepressedincertainaerobicgram-negativebacterialspecies

reducedaffinityofpenicillin-bindingproteinsforcefuroxime

outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbindingproteinsingram-

negativeorganisms

drugeffluxpumps

Methicillin-resistantstaphylococci(MRS)areresistanttoallcurrentlyavailable-lactamantibioticsincluding

cefuroxime.

Penicillin-resistantStreptococcuspneumoniaearecross-resistanttocephalosporinssuchascefuroximethrough

alterationofpenicillinbindingproteins.

Beta-lactamasenegative,ampicillinresistant(BLNAR)strainsofH.influenzaeshouldbeconsideredresistantto

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StrainsofEnterobacteriaceae,inparticularKlebsiellaspp.andEscherichiacolithatproduceESBLs(extended

spectrum-lactamase)maybeclinicallyresistanttotherapywithcephalosporinsdespiteapparentinvitrosusceptibility

andshouldbeconsideredasresistant.

Breakpoints:

AccordingtotheNCCLS(NationalCommitteeonClinicalLaboratoryStandards)in2001thefollowingbreakpoints

havebeendefinedforcefuroximeaxetil:

Enterobacteriaceae: 4 µ

g/mlsusceptible, 32 µ

g/mlresistant

Staphylococcusspp.: 4 µ

g/mlsusceptible, 32 µ

g/mlresistant

Haemophilusspp.: 4 µ

g/mlsusceptible; 16 µ

g/mlresistant

Streptococcuspneumoniae: 1 µ

g/mlsusceptible, 4 µ

g/mlresistant

Streptococcusspp.otherthanS.pneumoniae:

Streptococcalisolatessusceptibletopenicillin(MIC

0.12 µ

g/ml)maybeconsideredsusceptibletocefuroxime.

Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

thelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsisquestionable.

Commonlysusceptiblespecies

Aerobes,Grampositive:

Staphylococcusaureus(methicillin-susceptible)

Coagulase-negativestaphylococci(methicillin-

susceptible)

Streptococcusagalactiae

Streptococcuspneumoniae

Streptococcuspyogenes

Aerobes,Gramnegative:

Escherichiacoli

Haemophilusinfluenzae

Klebsiellaspecies

Moraxellacatarrhalis

Neisseriagonorrhoeae

Proteusmirabilis

Proteusrettgeri

Anaerobes

Peptococcusspecies

Peptostreptococcusspecies

Otherorganisms:

Borreliaburgdorferi

Speciesforwhichresistancemaybeaproblem

Acinetobacterspecies

Citrobacterspecies

Enterobacterspecies

Morganellamorganii

Resistant

Bacteroidesfragilis

Clostridiumdifficile

Enterococci

Listeriamonocytogenes

Proteusvulgaris

Pseudomonasspecies

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5.2Pharmacokineticproperties

Absorption:Afteroraladministrationcefuroximeaxetilisabsorbedfromthegastrointestinaltractandrapidly

hydrolysedintheintestinalmucosaandbloodcausingthereleaseoftheactivecompoundcefuroximeintothe

circulation.Optimumabsorptionoccurswhencefuroximeaxetilistakenshortlyafterameal(50-60%).Underthese

circumstancesmaximumserumconcentrationisachievedafter2-3hours.

Distribution:Cefuroximeiswidelydistributedinthebodyincludingpleuralfluid,sputum,bone,synovialfluid,and

aqueoushumour,butonlyachievestherapeuticconcentrationsintheCSFwhenthemeningesareinflamed.About50%

ofcefuroximeinthecirculationisboundtoplasmaproteins.Itdiffusesacrosstheplacentaandhasbeendetectedin

breastmilk.

Metabolism:Cefuroximeisnotmetabolised.

Elimination:Mostofthedoseofcefuroximeisexcretedunchanged.About50%isexcretedbyglomerularfiltrationand

about50%throughrenaltubularsecretionwithin24hours,withthemajoritybeingeliminatedwithin6hours;high

concentrationsareachievedintheurine.Smallamountsofcefuroximeareexcretedinbile.

Probenecidcompeteswithcefuroximeforrenaltubularsecretionresultinginhigherandmoreprolongedplasma

concentrationsofcefuroxime.Theplasmahalf-liferangesbetween60and90minutesandisprolongedinpatientswith

renalimpairmentandinneonates.

Dialysiscausesthedecreaseofcefuroximeserumlevels.

5.3Preclinicalsafetydata

Preclinicaleffectswereobservedindosagesfarabovethemaximalhumandosagewhicharethereforehardlyrelevant

fortheclinicaluseofcefuroximeaxetil.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Core:sodiumlaurylsulphate,copovidone,croscarmellosesodium(E468),magnesiumstearate(E470B),colloidal

anhydroussilica(E551),granulatedmannitol(E421),microcrystallinecellulose(E460),crospovidone(E1202),talc

(E553B).

Coat:mannitol(E421),solublestarch(potato),talc(E553B),titaniumdioxide(E171),aspartame(E951)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Al/Alstrip: 36months

Al/Alblister: 36months

6.4Specialprecautionsforstorage

Al/Alstrip: Storeintheoriginalpackaging

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6.5Natureandcontentsofcontainer

Al/Alstrippackaging

Al/Alblisterpackaging

Packsizes:8,10,12,24tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

SandozLtd

37WoolmerWay

Bordon

Hampshire

GU359QE

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA372/9/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

December2006

10DATEOFREVISIONOFTHETEXT

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