CEFUROXIME CEFT LIMITED

Main information

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

Documents

Localization

  • Available in:
  • CEFUROXIME CEFT LIMITED
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1524/004/002
  • Authorization date:
  • 30-09-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CefuroximeCeftLimited250mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains300.72mgcefuroximeaxetilequivalentto250mgcefuroxime.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Whitetooff-white,capsuleshapedtabletswith‘A33’debossedononesideandplainontheotherside.Thesizeis16.0

mmX6.5mm

4CLINICALPARTICULARS

4.1TherapeuticIndications

CefuroximeCeftLimitedisindicatedforthetreatmentofthefollowingmildtomoderatelysevereinfectionscausedby

micro-organismssusceptibletocefuroxime:

upperrespiratorytractinfections:acuteotitismedia,sinusitis,tonsillitisandpharyngitis

acutebacterialbronchitis,acuteexacerbationsofchronicbronchitis

loweruncomplicatedurinarytractinfections:cystitis

skinandsofttissueinfections:furunculosis,pyodermaandimpetigo

treatmentofearlystageLymedisease(stadiumI)andsubsequentpreventionoflatecomplicationsinadultsand

childrenabove12yearsofage.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Routeofadministration:oral

Thismedicinalproductisavailableinthreestrengths:

125mg,250mgand500mg

Theusualdurationoftherapyis7days(rangingfrom5to10days).Fortreatmentofpharyngotonsillitiscausedby

Streptococcuspyogenesatherapydurationofatleast10daysisindicated.ThedurationoftreatmentofearlyLyme

diseaseshouldbe20days.InordertoachieveoptimumabsorptioncefuroximeCeftLimitedtabletsshouldbetaken

shortlyaftermeals.

Thedosagedependsontheseverityoftheinfection.Forsevereinfectionsparenteralformsofcefuroximeare

recommended.Whereappropriatecefuroximeiseffectivewhenusedfollowinginitialparenteralcefuroximesodiumin

thetreatmentofpneumoniaandacuteexacerbationsofchronicbronchitis.Thedosemayneedtoberevisedwhen

switchingfromparenteraltooraltreatment

Dosageschedulefortablets:

Adultsandchildrenover12yearsofage Dosage

Upperrespiratorytractinfections 250(-500)mgtwicedaily

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*CefuroximeCeftLimitedtabletscanbesuitableforuseinchildrenabovetheageof5thatcanswallowwholetablets.

Thechild’stoleranceofthetasteandtablet’ssizeshouldbeascertainedbytheclinicianandparent.Thetabletsshould

notbecrushed.

Childrenunder5yearsofage:

CefuroximeCeftLimitedtabletsarenotsuitableforuseinchildrenundertheageof5.Forpatientsinthisagegroupit

isadvisedtouseanoralsuspension.Thereisnoexperienceinchildrenunder3monthsofage.

Dosageregimeninrenalimpairment,indialysispatientsandelderly:

Nospecialprecautionsarenecessaryinpatientswithrenalimpairmentorinelderlypatientsifthedailydosagedoesnot

exceed1gram.Inpatientswithsevererenalimpairment(creatinineclearance<20ml/min)thedosageshouldbe

reducedtooncedailyinordertocompensatefortheslowerelimination.

Patientsundergoinghaemodialysiswillrequireasupplementarydoseofcefuroximeattheendofeachdialysis

treatment.

4.3Contraindications

Hypersensitivitytocefuroximeortoanyoftheexcipients.

Hypersensitivitytoanyothercephalosporinantibacterialagent.

Severehypersensitivity(eganaphylacticreaction,severeskinreaction)toanyothertypeofbetalactamantibacterial

agent(e.g.penicillinsorcarbapenems).

4.4Specialwarningsandprecautionsforuse

BeforetherapywithCefuroximeaxetilisinstituted,carefulinquiryshouldbemadetodeterminewhetherthepatient

hashadprevioushypersensitivityreactionstocefuroxime,cephalosporins,penicillins,orotherdrugs.Thisproduct

shouldbegivenwithcautiontopenicillin-sensitivepatients(forcontraindicationsduetoknownhypersensitivity

reactionsseesection4.3).

Antibioticsshouldbeadministeredwithcautiontoanypatientwhohasdemonstratedsomeformofallergy,particularly

todrugs.IfanallergicreactiontoCefuroximeaxetiloccurs,discontinuethedrug.

Serioushypersensitivityreactionsmayrequireepinephrineandotheremergencymeasures.

Cefuroximeaxetilshouldnotbeprescribedintheabsenceofaprovenorstronglysuspectedbacterialinfection.

Antibiotic-associateddiarrhoea,colitisandpseudomembranouscolitislinkedtoClostridiumDifficilecanallbe

reportedwiththeuseofcefuroximeaxetil.Thesediagnosesshouldbeconsideredinanypatientwhodevelops

diarrhoeaduringorshortlyaftertreatment.A20-daytreatmentofLymediseasemaycausethefrequencyofdeveloping

diarrhoeatoincrease.CefuroximeCeftshouldbediscontinuedifsevereand/orbloodydiarrhoeaoccursduring

treatmentandappropriatetherapyinstituted.Anti-peristalticsarecontraindicated.

Loweruncomplicatedurinarytractinfections 125–250mgtwicedaily

Skinandsofttissueinfections 250–500mgtwicedaily

EarlyLymedisease 500mgtwicedailyduring20days

Childrenfrom5to12yearsofage*

Above-mentionedindications,ifrelevantforthisgroupofchildren 125–250mgtwicedaily

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(e.g.perianal,oralorvaginalcandidiasis;pseudomembranouscolitis;superinfection.Inthesecases,specific

treatmentshouldbeinitiated.

Duringlong-treatment(>7days)withhigh-dosecefuroxime,bloodcountsandliver/kidneyfunctionmustbe

monitored.

Regularrenalfunctionmonitoringisalsoindicated,ifaminoglycosidesorpotentdiureticssuchasfurosemideare

administeredconcomitantly.Ifcefuroximealonewasgiven,neithernephrotoxicitynorototoxicitywasobserved.

CefuroximeCeftshouldbeadministeredwithcautioninpatientswithrenalinsufficiency,andadjustthedailydosein

termsofcreatinineclearance(seesection4.2)

Theuseofcefuroximeisnotrecommendedinpatientswithsevereintestinaltractdisordersaccompaniedbyvomiting

anddiarrhoea,sinceinthesesituationsasufficientabsorptioncannotbeguaranteed.

Administrationofaparenteralformulationofcefuroximeshouldbeconsidered.

TheJarisch-HerxheimerreactionhasbeenreportedfollowingcefuroximeaxetiltreatmentofLymedisease.The

reactionresultsdirectlyfromthebactericidalactivityofcefuroximeaxetilonthespirochaeteBorreliaburgdorferi.

Patientsshouldbeinformedofthiscommonandusuallyself-limitedreactionbeingaconsequenceofantibiotic

treatmentofLymedisease.

ConcomitantadministrationofmedicinalproductsthatelevategastricpHlevels(e.g.antiaciddrugs)mayimpair

absorption,independentlyfromingestion.

Thereisnoclinicalexperiencewiththeuseofcefuroximeaxetilinchildrenundertheageof3months.Withrespectto

thetreatmentofearlyLymediseasethereisonlyclinicalexperiencewithchildrenfromtheageof12andwithadults.

Eithertheglucoseoxidaseorthehexokinasemethodsarerecommendedtodeterminethebloodandplasmaglucose

levelsinpatientsreceivingcefuroxime.Cefuroximedoesnotinterfereinthealkalinepicrateassayforcreatinine(see

section4.5).

Pleaserefertosection4.5forinformationontheuseofcefuroximeaxetilincombinationwithoralcontraceptives.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SimultaneoususeofmedicinesenhancingthepHofthestomachdecreasesthebioavailabilityofcefuroxime.Itis

recommendedtoavoidthiscombination(seesection4.4).

Sincebacteriostaticdrugsmayinterferewiththebactericidalactionofcephalosporins,itisadvisabletoavoidgiving

tetracyclines,macrolides,orchloramphenicolinconjunctionwithcefuroxime.

Theconcomitantadministrationofprobenicidcanproducehigherandsustainedconcentrationsofcefuroximeinthe

serumandinthebile.

Cefuroximemayinterferewiththedeterminationofglucoseinurinewithcoppercontainingreagentia(Benedict-or

Fehling-solution,Clinitest).Forthedeterminationofbloodandplasmasugarlevelsinpatientsreceivingcefuroxime,

theglucose-oxidase-orhexokinasemethodisrecommended(seesection4.4).

TheuseofcefuroximemaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththeperformance

ofcrossmatchingtestswithblood(seesection4.8).

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingpotentdiuretics,

aminoglycosides,oramphotericinasthesecombinationsincreasestheriskofnephrotoxicity.

Thereliabilityofthecontraceptiveeffectoforalcontraceptivesisindoubtwhenusingcefuroximeaxetilatthesame

time.Forthisreason,othernon-hormonalcontraceptivemeansshouldbeusedinadditiontooralcontraceptivesduring

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Pleaserefertosection4.4forinformationonotherinteractions.

4.6Fertility,pregnancyandlactation

Pregnancy

Dataonalimitednumberofexposedpregnanciesindicatenoadverseeffectsofcefuroximeonthepregnancyoronthe

healthofthefetus/newbornchild.Todatenootherrelevantepidemiologicaldataareavailable.Animalstudiesdonot

showanyharmfuleffectsonembryonalandfetaldevelopment(seesection5.3.).Cefuroximereachestheembryo/fetus

viatheplacenta.Duetothelimitedclinicalexperiencecefuroximeshouldonlybeusedduringpregnancyaftercareful

risk/benefit,especiallyduringthefirsttrimester.

Lactation

Smallamountsofthedrugareexcretedinbreastmilk.Cefuroximeshouldonlybeusedduringperiodsofbreastfeeding

ifthebenefitsoutweighthepossiblerisk.Diarrhoeaandfungusinfectionsofthemucousmembranesinthebreast-fed

infantcannotbeexcluded,sothatnursingmighthavetobediscontinued.Thepossibilityofsensitisationshouldbe

borneinmind.

Fertility:

Reproductivestudiesrevealednoimpairmentoffertilityinanimals(seesection5.3).

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.Sincethismedicinalproduct

maycausedizziness,patientsshouldbewarnedtobecautiouswhendrivingavehicleoroperatingmachinery.

4.8Undesirableeffects

Withineachfrequencyclass,undesirableeffectsarespecifiedinorderofdecreasingseverity.

Thefrequencyisdefinedusingthefollowingconventions:

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

Rare:Pseudomembranouscolitis

Aswithotherantibioticsprolongedusemayleadtosecondarysuperinfectionscausedbyinsusceptibleorganisms,e.g.

Candida,EnterococciandClostridiumdifficile(seesection4.4).

Bloodandthelymphaticsystemdisorders

Common:eosinophilia

Uncommon:thrombocytopenia,lecocytopeniaand/orneutrocytopenia(sometimessevere)

Veryrare:Haemolyticanaemia

Immunesystemdisorders

Common:Jarisch-HerxheimerreactionfollowingcefuroximeaxetiltreatmentofLymedisease(seesection4.4)

Uncommon:rash

Rare:urticaria,pruritus

Veryrare:fever,serumsickness,anaphylaxis

Nervoussystemdisorders

Uncommon:Headache,dizziness

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Gastrointestinaldisorders

Common:Diarrhoea,nauseaandvomiting.Thefrequencyofdiarrhoeaisrelatedtotheadministereddoseandmay

rangeupto10%withtablets.Theincidenceisevenhigher

(approx.13%)afterprolongedtreatmentofearlyLymediseasefor20days.

Hepato-biliarydisorders

Rare:temporaryincreasesofliverenzymes(AST,ALTandLDH)

Veryrare:hepatitis,obstructivejaundice.

Skinandsubcutaneoustissuedisorders

Common:Skinrashes,urticaria,pruritus.

Veryrare:Erythemamultiforme,Stevens-Johnsonsyndromeandtoxicepidermalnecrolysis

Renalandurinarydisorders

Common:Increasedlevelsofcreatinineandureainserum,especiallyinpatientswithimpairedrenalfunction.

Uncommon:Acuteinterstitialnephritis

Generaldisordersandadministrationsiteconditions

Rare:Drugfever

Investigations

Dependingonthemethod,false-positiveorfalse-negativeresultsmaybeobservedinglucosetestingofthebloodor

urine.Thiscanbepreventedbyusingenzymaticmethods.Duringcephalosporintreatment,resultsofCoombs-testing

maybefalse-positive.ThealkalinePikradassay(Jaffémethod)shouldbeusedforcreatinineassessment.

4.9Overdose

Limitedinformationisavailableontheacutetoxicityofcefuroximeaxetilinhumans.Overdosageofcephalosporins

cancauseCNSirritationleadingtoseizures.Ifacuteoverdosageofcefuroximeoccurs,hemodialysisand/orperitoneal

dialysiscanbeusedtoenhanceeliminationofthedrugfromthebody.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Otherbeta-lactamantibacterials,second-generationcephalosporin

ATCcode:J01DC02

Modeofaction

Cefuroximeaxetilowesitsinvivobactericidalactivitytotheparentcompoundcefuroxime.

Allcephalosporins(-lactamantibiotics)inhibitcellwallproductionandareselectiveinhibitorsofpeptidoglycan

synthesis.Theinitialstepindrugactionconsistsofbindingofthedrugtocellreceptors,calledPenicillin-Binding

Proteins.Aftera -lactamantibiotichasboundtothesereceptors,thetranspeptidationreactionisinhibitedand

peptidoglycansynthesisisblocked.Bacteriallysisistheendresult.

PK/PDrelationship

Forcephalosporins,themostimportantpharmacokinetic-pharmacodynamicindexcorrelatingwithinvivoefficacyhas

beenshowntobethedurationthattheunbounddrugconcentrationremainsabovetheminimuminhibitory

concentration(MIC)asapercentageofthedosinginterval(%T>MIC).

Mechanismofresistance

Bacterialresistancetocefuroximemaybeduetooneormoreofthefollowingmechanisms:

-hydrolysisbybeta-lactamases.Cefuroximemaybeefficientlyhydrolysedbycertainoftheextended-spectrumbeta-

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certainaerobicgramnegativebacterialspecies

-reducedaffinityofpenicillin-bindingproteinsforcefuroxime

-outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbindingproteinsingram-negative

organisms

-drugeffluxpumps

Methicillin-resistantstaphylococci(MRS)areresistanttoallcurrentlyavailable -lactamantibioticsincluding

cefuroxime.

Penicillin-resistantStreptococcuspneumoniaearecross-resistanttocephalosporinssuchascefuroximethrough

alterationofpenicillinbindingproteins.

Beta-lactamasenegative,ampicillinresistant(BLNAR)strainsofH.influenzaeshouldbeconsideredresistantto

cefuroximedespiteapparentinvitrosusceptibility.

StrainsofEnterobacteriaceae,inparticularKlebsiellaspp.andEscherichiacolithatproduceESBLs(extended

spectrum-lactamase)maybeclinicallyresistanttotherapywithcephalosporinsdespiteapparentinvitrosusceptibility

andshouldbeconsideredasresistant.

Breakpoints:

AccordingtotheEUCAST2009-05-25(v2.0)thefollowingbreakpointshavebeendefinedforcefuroximeaxetil:

Foruncomplicatedurinarytractinfectionsonly.

Susceptibilityofstaphylococcitocephalosporinsisinferredfromthemethicillinsusceptibility.

ThesusceptibilityofstreptococcusgroupsA,B,CandGcanbeinferredfromthesusceptibilitytobenzylpenicillin.

Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

BACTERIALSPECIES MICbreakpoints

S/R>(mg/L)

Enterobacteriaceae 8.0/8.0 1

Haemophilusinfluenzae 0.12/1.0

Moraxellacatarrhalis 0.12/2.0

Staphylococcusspp.

Note 2

StreptococcusA,B,C,G

Note 3

Streptococcuspneumoniae 0.25/0.5

Commonlysusceptiblespecies

Aerobes,Grampositive:

Staphylococcusaureus(methicillin-susceptible)

Coagulase-negativestaphylococci(methicillinsusceptible)

Streptococcusagalactiae

Streptococcuspneumoniae

Streptococcuspyogenes

Aerobes,Gramnegative:

Haemophilusinfluenzae

Moraxellacatarrhalis

Proteusmirabilis

Anaerobes,

Peptococcusspecies

Peptostreptococcusspecies

Otherorganisms:

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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.Probenecidcompeteswithcefuroximeforrenaltubularsecretion

resultinginhigherandmoreprolongedplasmaconcentrationsofcefuroxime.

Theplasmahalf-liferangesbetween60and90minutesandisprolongedinpatientswithrenalimpairmentandin

neonates.

Dialysiscausesthedecreaseofcefuroximeserumlevels.

5.3Preclinicalsafetydata

Cefuroximesodiumhasaveryloworderoftoxicityasdemonstratedbyacutetoxicitystudies.

Investigationsofchronictoxicityinseveralanimalspecies(rat,dogandmonkey)yieldednoindicationsofdrugrelated

toxicologicaleffects.Themostprominenttreatment-relatedeffectwastissuedamageattheinjectionsites.

Preclinicalnephrotoxicitystudiesshowedtheproductcancauserenaldamageinsomespecieswhenadministeredin

Speciesforwhichresistancemaybeaproblem

Acinetobacterspecies

Citrobacterspecies

Enterobacterspecies

Escherichiacoli

Klebsiellaspecies

Providenciarettgeri

Streptococcuspneumoniae

Inherantlyresistantorganisms

Bacteroidesfragilis

Clostridiumdifficile

Enterococcusspp

Listeriamonocytogenes

Morganellamorganii

Proteusvulgaris

Pseudomonasaeruginosa

Serratiaspecies

Others:

Legionellaspp.

Clamydophiliapneumoniae

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Acefuroximeesterdidnotshowclinicallyrelevanteffectswhentestedinvitroandinvivoforgenotoxicpotential.

Nolong-terminvestigationsfordeterminationoftumorigenicpotentialwereperformed.

Investigationsinrabbitsandmicedidnotdemonstratereproductivetoxicityorteratogeniceffects.

Cefuroximehasbeenshowntopasstheplacenta.

Gamma-glutamyltranspeptidaseactivityinraturineisinhibitedbyvariouscephalosporins,however,thelevelof

inhibitionislesswithcefuroxime.Thismayhavesignificanceintheinterferenceinclinicallaboratorytestsinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose(E460)

Croscarmellosesodium

Sodiumlaurilsulfate

Cottonseedoil,hydrogenated

Colloidalanhydroussilica

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialtemperaturestorageconditions.

Storeintheoriginalpackageinordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Polyamide/Aluminium/PVC/Aluminiumblister

Packsizes:6.8,10,12,14,16,20,24,50,100or500tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

CeftLimited,

65DelamereRoad,

Hayes,

Middlesex,

UB40NN,

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:30thSeptember2011

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