CEFUROXIME TEVA

Main information

  • Trade name:
  • CEFUROXIME TEVA
  • Dosage:
  • 500 Base Milligrams
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CEFUROXIME TEVA
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/082/003
  • Authorization date:
  • 12-02-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CefuroximeTeva500mgFilmCoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each500mgfilm-coatedtabletcontains500mgcefuroxime(ascefuroximeaxetil)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

CefuroximeTeva500mgfilm-coatedtablets:lightbluecolouredfilm-coatedtabletsengravedwith“500”ononeside

and“P126”ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CefuroximeTevaisindicatedforthetreatmentofthefollowingmildtomoderatelysevereinfectionscausedbymicro-

organismssusceptibletocefuroxime:

upperrespiratorytractinfections:acuteotitismedia,sinusitis,tonsillitisandpharyngitis

acutebacterialbronchitis,acuteexacerbationsofchronicbronchitis

loweruncomplicatedurinarytractinfections:cystitis

skinandsofttissueinfections:furunculosis,pyodermaandimpetigo

treatmentofearlystageLymedisease(stadiumI)andsubsequentpreventionoflatecomplicationsinadultsand

childrenabove12yearsofage.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

CefuroximeTevatabletsarecoatedtomasktheirtaste:theyshouldnotbechewed.

Theusualdurationoftherapyis7days(rangingfrom5to10days).Fortreatmentofpharyngotonsillitiscausedby

Streptococcuspyogenesatherapydurationofatleast10daysisindicated.ThedurationoftreatmentofearlyLyme

diseaseshouldbe20days.InordertoachieveoptimumabsorptionCefuroximeTevatabletsshouldbetakenshortly

aftermeals.

Thedosagedependsontheseverityoftheinfection.Forsevereinfectionsparenteralformsofcefuroximeare

recommended.WhereappropriateCefuroximeTevaiseffectivewhenusedfollowinginitialparenteralcefuroxime

sodiuminthetreatmentofpneumoniaandacuteexacerbationsofchronicbronchitis.Thedosemayneedtoberevised

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Dosageschedulefortablets:

Childrenunder5yearsofage:

CefuroximeTevatabletsarenotsuitableforuseinchildrenundertheageof5.Forpatientsinthisagegroupitis

advisedtouseanoralsuspension.Thereisnoexperienceinchildrenunder3monthsofage.

Dosageregimeninrenalimpairment,indialysispatientsandelderly:

Nospecialprecautionsarenecessaryinpatientswithrenalimpairment,orinelderlypatientsifthedailydosagedoes

notexceed1gram.Inpatientswithrenalimpairmentandcreatinineclearancebelow20ml/minCefuroximeTeva

tabletsshouldbedosedcarefully.Patientsundergoinghaemodialysiswillrequireasupplementarydoseofcefuroxime

attheendofeachdialysistreatment.

4.3Contraindications

Hypersensitivitytocefuroxime,othercephalosporinsortoanyoftheexcipients.

Previousimmediateand/orseverehypersensitivityreactiontoapenicillinortoanyothertypeofbetalactammedicinal

products.

4.4Specialwarningsandprecautionsforuse

IfafteradministrationofCefuroximeTevasensitivityreactionsoccur,theuseshouldbediscontinuedimmediatelyand

anappropriatetreatmentshouldbeestablished.

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontopenicillinsorotherbeta-lactams.

Aswithotherbroadspectrumantibiotics,prolongeduseofcefuroximeaxetilmayresultintheovergrowthofnon-

susceptibleorganisms(e.g.candida,enterococciandclostridiumdifficile),whichmayrequireinterruptionoftreatment.

InpatientswhodevelopseverediarrhoeaduringorafteruseofCefuroximeTeva,theriskoflifethreatening

pseudomembranouscolitisshouldbetakenintoaccount.TheuseofCefuroximeTevashouldbediscontinuedandthe

appropriatetreatmentestablished.Theuseofpreparationsinhibitingtheintestinalperistaltismiscontra-indicated(see

section4.8).

A20-daytreatmentofLymediseasemaycausethefrequencyofdevelopingdiarrhoeatoincrease.

Adultsandchildrenover12yearsofage Dosage

Upperrespiratorytractinfections 250(–500)mgtwicedaily

Lowerrespiratorytractinfections 500mgtwicedaily

Loweruncomplicatedurinarytractinfections 125–250mgtwicedaily

Skinandsofttissueinfections 250–500mgtwicedaily

EarlyLymedisease 500mgtwicedailyduring20days

Childrenfrom5to12yearsofage

Above-mentionedindications,ifrelevantforthisgroup

ofchildren 125–250mgtwicedaily

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Itisofhighimportancethatthepatientiscarefullychecked.

Ifasuperinfectionoccursduringtreatment,appropriatemeasuresshouldbetaken(seesection4.8).

TheuseofCefuroximeTevaisnotrecommendedinpatientswithsevereintestinaltractdisordersaccompaniedby

vomitinganddiarrhoea,sinceinthesesituationsasufficientabsorptioncannotbeguaranteed.Administrationofa

parenteralformulationofcefuroximeshouldbeconsidered.

TheJarisch-HerxheimerreactionhasbeenreportedfollowingcefuroximeaxetiltreatmentofLymedisease.The

reactionresultsdirectlyfromthebactericidalactivityofcefuroximeaxetilonthespirochaeteBorreliaburgdorferi.

Patientsshouldbeinformedofthiscommonandusuallyself-limitingreactionbeingaconsequenceofantibiotic

treatmentofLymedisease.

SimultaneoususeofmedicinesenhancingthepHofthestomachisnotrecommended(seesection4.5).

Thereisnoclinicalexperiencewiththeuseofcefuroximeaxetilinchildrenundertheageof3months.Withrespectto

thetreatmentofearlyLymediseasethereisonlyclinicalexperiencewithchildrenfromtheageof12andwithadults.

Eithertheglucoseoxidaseorthehexokinasemethodsarerecommendedtodeterminethebloodandplasmaglucose

levelsinpatientsreceivingCefuroximeTeva.Cefuroximedoesnotinterfereinthealkalinepicrateassayforcreatinine

(seesection4.5).

Pleaserefertosection4.5forinformationontheuseofcefuroximeaxetilincombinationwithoralcontraceptives.

Duringthetreatmentwithcefuroximesodium,somechildrenhaveexperiencedslighttomoderatehearingloss.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SimultaneoususeofmedicinesenhancingthepHofthestomachdecreasesthebioavailabilityofCefuroximeTeva.Itis

recommendedtoavoidthiscombination(seesection4.4).

Sincebacteriostaticdrugsmayinterferewiththebactericidalactionofcephalosporins,itisadvisabletoavoidgiving

tetracyclines,macrolides,orchloramphenicolinconjunctionwithCefuroximeTeva.

Theconcomitantadministrationofprobenecidcanproducehigherandsustainedconcentrationsofcefuroximeinthe

serumandinthebile.

Cefuroximemayinterferewiththedeterminationofglucoseinurinewithcoppercontainingreagentia(Benedict-or

Fehling-solution,Clinitest).ForthedeterminationofbloodandplasmasugarlevelsinpatientsreceivingCefuroxime

Teva,theglucose-oxidase-orhexokinasemethodisrecommended(seesection4.4).

TheuseofCefuroximeTevamaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(seesection4.8).

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingpotentdiuretics,

aminoglycosides,oramphotericinasthesecombinationsincreasetheriskofnephrotoxicity.

Thereliabilityofthecontraceptiveeffectoforalcontraceptivesisindoubtwhenusingcefuroximeaxetilatthesame

time.Forthisreason,othernon-hormonalcontraceptivemeansshouldbeusedinadditiontooralcontraceptivesduring

treatmentwithCefuroximeTeva.

Pleaserefertosection4.4forinformationonotherinteractions.

4.6Fertility,pregnancyandlactation

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Therearenotsufficientdataontheuseofcefuroximeaxetilduringpregnancytoassessitspossibleharmfulness.

Animalstudiesdonotshowanyharmfuleffectsonembryonalandfetaldevelopment(seesection5.3).

Cefuroximecrossestheplacenta.CefuroximeTevashouldnotbeusedduringpregnancyunlessconsideredessentialby

thephysician.

Lactation

Cefuroximeisexcretedtoasmalldegreeinhumanmilk;breastfeedingshouldbeavoidedinwomenusingCefuroxime

Teva.

4.7Effectsonabilitytodriveandusemachines

Therearenostudiesoftheeffectofcefuroximeaxetilontheabilitytodriveandtohandlemachines.However,any

effectsarenottobeexpected.

4.8Undesirableeffects

Common(1/100to<1/10)

Uncommon(1/1,000to<1/100)

Rare(1/10,000to<1/1,000)

Veryrare(<1/10,000)

Infectionsandinfestations

Rare

Pseudomembranouscolitis

Aswithotherantibioticsprolongedusemayleadtosecondarysuperinfectionscausedbyinsusceptibleorganisms,e.g.

Candida,EnterococciandClostridiumdifficile(seesection4.4)

Bloodandthelymphaticsystemdisorders

Rare

Decreasedhaemoglobinconcentration,eosinophilia,leucopenia,neutropeniaandthrombocytopenia

Veryrare

Haemolyticanaemia

Immunesystemdisorders

Common

Jarisch-HerxheimerreactionfollowingcefuroximeaxetiltreatmentofLymedisease(seesection4.4)

Rare

Serumsickness

Veryrare

Anaphylaxis

Nervoussystemdisorders

Uncommon

Headache,dizziness

Veryrare

Restlessness,nervousness,confusion

Gastrointestinaldisorders

Common

Diarrhoea,nauseaandvomiting.Thefrequencyofdiarrhoeaisrelatedtotheadministereddoseandmayrangeupto

10%withtablets.Theincidenceisevenhigher(approx.13%)afterprolongedtreatmentofearlyLymediseasefor20

days

Hepato-biliarydisorders

Rare

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Veryrare

Jaundice

Skinandsubcutaneoustissuedisorders

Common

Skinrashes,urticaria,pruritus

Veryrare

Erythemamultiforme,Stevens-Johnsonsyndromeandtoxicepidermalnecrolysis

Renalandurinarydisorders

Common

Increasedlevelsofcreatinineandureainserum,especiallyinpatientswithimpairedrenalfunction

Uncommon

Acuteinterstitialnephritis

Generaldisordersandadministrationsiteconditions

Rare

Drugfever

Investigations

TheuseofCefuroximeTevamaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(see4.5.Interactions).

4.9Overdose

Overdoseofcephalosporinsmaycausecerebralirritancyleadingtoconvulsions.Incaseofoverdosecefuroximeserum

levelscanbereducedbyhaemodialysisandperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:second-generationcephalosporins

ATC-Code:J01DC02

Modeofaction

Cefuroximeaxetilowesitsinvivobactericidalactivitytotheparentcompoundcefuroxime.Allcephalosporins(-

lactamantibiotics)inhibitcellwallproductionandareselectiveinhibitorsofpeptidoglycansynthesis.Theinitialstepin

drugactionconsistsofbindingofthedrugtocellreceptors,calledPenicillin-BindingProteins.Aftera-lactam

antibiotichasboundtothesereceptors,thetranspeptidationreactionisinhibitedandpeptidoglycansynthesisis

blocked.Bacteriallysisistheendresult.

PK/PDrelationship

Forcephalosporins,themostimportantpharmacokinetic-pharmacodynamicindexcorrelatingwithinvivoefficacyhas

beenshowntobethedurationthattheunbounddrugconcentrationremainsabovetheminimuminhibitory

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

Mechanismofresistance

Bacterialresistancetocefuroximemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbybeta-lactamases.Cefuroximemaybeefficientlyhydrolysedbycertainoftheextended-spectrum

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

derepressedincertainaerobicgram-negativebacterialspecies

reducedaffinityofpenicillin-bindingproteinsforcefuroxime

outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbindingproteinsingram-

negativeorganisms

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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.

AccordingtotheEUCAST2006v1.1thefollowingbreakpointshavebeendefinedforcefuroximeaxetil:

Foruncomplicatedurinarytractinfectionsonly.

Susceptibilityofstaphylococcitocephalosporinsisinferredfromthemethicillinsusceptibility

ThesusceptibilityofstreptococcusgroupsA,B,CandGcanbeinferredfromtheirsusceptibilitytobenzylpenicillin

Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

BACTERIASPECIES MICbreakpoints

S /R>(mg/L)

Enterobacteriaceae

8.0/8.0 1

Haemophilusinfluenzae 0.12/1.0

Moraxellacatarrhalis 0.12/2.0

Staphylococcusspp Note 2

Strept-coccusA,B,C,G Note 3

Streptococcuspneumoniae 0.25/0.5

Commonlysusceptiblespecies

Aerobes,Grampositive:

Staphylococcusaureus(methicillin-susceptible)

Coagulase-negativestaphylococci(methicillin

susceptible)

Streptococcusagalactiae

Streptococcuspyogenes

Aerobes,Gramnegative:

Haemophilusinfluenzae

Moraxellacatarrhalis

Proteusmirabilis

Anaerobes:

Peptococcusspecies

Peptostreptococcusspecies

Otherorganisms:

Borreliaburgdorferi

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5.2Pharmacokineticproperties

Absorption:Afteroraladministrationcefuroximeaxetilisabsorbedfromthegastrointestinaltractandrapidly

hydrolysedintheintestinalmucosaandbloodcausingthereleaseoftheactivecompoundcefuroximeintothe

circulation.Optimumabsorptionoccurswhencefuroximaxetilistakenshortlyafterameal(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-liferangesbetween60and90minutesandisprolongedinpatientswithrenalimpairmentandin

neonates.

Dialysiscausesthedecreaseofcefuroximeserumlevels.

5.3Preclinicalsafetydata

Cefuroximesodiumhasaveryloworderoftoxicityasdemonstratedbyacutetoxicitystudies.Investigationsofchronic

toxicityinseveralanimalspecies(rat,dogandmonkey)yieldednoindicationsofdrugrelatedtoxicologicaleffects.

Themostprominenttreatment-relatedeffectwastissuedamageattheinjectionsites.

Preclinicalnephrotoxicitystudiesshowedtheproductcancauserenaldamageinsomespecieswhenadministeredin

veryhighdoses.Itsnephrotoxicityincreaseswhenadministeredincombinationwithglycerolandfurosemide.

Acefuroximeesterdidnotshowclinicallyrelevanteffectswhentestedinvitroandinvivoforgenotoxicpotential.

Acinetobacterspecies

Citrobacterspecies

Enterobacterspecies

Escherichiacoli

Klebsiellaspecies

Providenciarettgeri

Streptococcuspneumoniae

Inherentlyresistantorganisms

Bacteroidesfragilis

Clostridiumdifficile

Enterococcusspp

Listeriamonocytogenes

Morganellamorganii

Proteusvulgaris

Pseudomonasaeruginosa

Serratiaspecies

Others:

Legionellaspp.

Clamydophiliapneumoniae

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Investigationsinrabbitsandmicedidnotdemonstratereproductivetoxicityorteratogenic-effects.Cefuroximehas

beenshowntopasstheplacenta.

Gamma-glutamyltranspeptidaseactivityinraturineisinhibitedbyvariouscephalosporins,however,thelevelof

inhibitionislesswithcefuroxime.Thismayhavesignificanceintheinterferenceinclinicallaboratorytestsinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Core:

Pregelatinizedstarch

Croscarmellosesodium

Sodiumlaurilsulfate

Microcrystallinecellulose

Colloidalanhydroussilica

Hydrogenatedvegetableoil(TypeI)

Coat:

Hypromellose(E464)

Titaniumdioxide(E171)

Propyleneglycol(E1520)

BrilliantBlueFCFaluminiumlake(E133)

IndigoCarmineAluminiumLake(E132)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

PVC/PCTFEAluminiumblisterpackaging

Packsizes:500mg:6,8,10,12,14,16,20,24tablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

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8MARKETINGAUTHORISATIONNUMBER

PA749/82/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12thFebruary2010

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