CEFUROXIME SODIUM

Main information

  • Trade name:
  • CEFUROXIME SODIUM
  • Dosage:
  • 750 Milligram
  • Pharmaceutical form:
  • Pdr for Soln for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0372/007/002
  • Authorization date:
  • 25-08-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cefuroxime750mgpowderforsolution/suspensionforinjection.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1vialcontains750mgofcefuroximeas789mgofcefuroximesodium.

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Powderforsolutionforinjection.

Whitetoalmostwhitepowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cefuroximeisindicatedintheparenteraltreatmentofthefollowinginfectionscausedbysensitivepathogens

respiratorytractinfections:e.g.acuteandchronicbronchitis,bacterialpneumonia

infectionsoftheear,noseandthroat,

urinarytractinfections

infectionsofskinandsofttissue

boneandjointinfections

obstetricandgynaecologicalinfections

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

RouteofAdministration:

Byintramuscularinjection,intravenousinjectionorinfusion.

UsualdosageforAdultsandtheElderly:

Mostinfectionswillrespondtocefuroxime750mgthreetimesaday.Formoresevereinfections,thedosemaybe

increasedto1.5gthreetimesadaybyintravenousinjection.

Theintramuscularmethodofadministrationisreservedtoexceptionalclinicalsituationsandshouldundergoa

risk-benefitassessment.

Specialadviceforintramuscularinjectionhastoberegarded(seesection6.6,Specialprecautionsfordisposalofa

usedmedicinalproductorwastederivedfromsuchmedicinalproductandotherhandlingoftheproduct).

Ifnecessary,thefrequencyofadministrationofcefuroximecanbeincreasedtofourtimesadayuptototaldailydoses

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Infants,toddlersandChildren:

Thedailydosagerangeis30to100mg/kg/daygivenasthreeorfourdivideddoses.Mostinfectionswillrespondtoa

doseof60mg/kg/day.

Neonates(seesection5.2,PharmacokineticProperties).

Thedailydosagerangeis30to100mg/kg/daygivenastwoorthreedivideddoses.Inthefirstweeksoflifetheserum

half-lifeofcefuroximecanbethreetofivetimesthatinadults.

Forimpairedrenalfunction:

Itisnotnecessarytoreducethedoseifcreatinineclearanceismorethan20ml/min.Therecommendedmaintenance

dosesinimpairedrenalfunctionareasfollows:

Specialprecautionsarerequiredifcreatinineclearanceis<10ml/minuteunderappropriateexpertsupervision.

Patientsundergoinghaemodialysiswillrequireafurther750mgdoseofcefuroximeattheendofeachdialysis

treatment.Asuitabledosageforpatientsoncontinuousperitonealdialysisisusually750mgtwicedaily.

Adosageof750mgtwicedailyisrecommendedforpatientsinrenalfailureoncontinuousarteriovenous

haemodialysisorhighfluxhaemofiltrationinintensivetherapyunits.

Cefuroximeisusuallyeffectiveasasingletherapyinthetreatmentoftheaboveinfections.

4.3Contraindications

HypersensitivitytoCefuroximeortoanyothercephalosporinantibiotics.

Previousimmediateand/orseverehypersensitivityreactiontopenicillinoranybeta-lactamdrug.

4.4Specialwarningsandprecautionsforuse

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontoapenicillinortoanyothertypeof

beta-lactamdrug.

Ifafteradministrationofcefuroximesodiumsensitivityreactionsoccur,theuseshouldbediscontinuedimmediately

andanappropriatetreatmentshouldbeestablished.

Specialcareshouldbetakeninpatientswithhepaticdysfunction.

Aswithotherbroadspectrumantibiotics,prolongeduseofCefuroximesodiummayresultintheovergrowthofnon-

susceptibleorganisms(e.g.,candida,enterococciandclostridiumdificile,whichmayrequireinterruptionoftreatment.

Inpatientswhodevelopseverediarrhoeaduringorafteruseofcefuroximesodium,theriskoflifethreateningpseudo-

membranouscolitisshouldbetakenintoaccount.Theuseofcefuroximesodiumshouldbediscontinuedandthe

appropriatetreatmentestablished.Theuseofpreparationsinhibitingtheintestinalperistalticiscontra-indicated(See

Creatinine

clearance(ml/min) Recommended

dosage of

cefuroxime(mg) Frequency of

dosage(hours)

>20 normaldosage

10-20 750 12

<10 750 24

CAPDpatients 750 12

Patients

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Longtermuseofcefuroximesodiummayleadtoanexcessofpathogensresistanttocefuroximesodium.Itisofhigh

importancethatthepatientiscarefullychecked.Ifasuper-infectionoccursduringtreatment,appropriatemeasures

shouldbetaken(Seesection4.8,Undesirableeffects).

Eithertheglucoseoxidaseorthehexokinasemethodsarerecommendedtodeterminethebloodandplasmaglucose

levelsinpatientsreceivingCefuroximesodium.Cefuroximedoesnotinterfereinthealkalinepicrateassayfor

creatinine(Seesection4.5,Interactionwithothermedicinalproductsandotherformsofinteractions).

Cefuroximeisexcretedviathekidneys.Thereforeadosageadjustmentisrequiredinpatientswithimpairedrenal

function(seesection4.2,Posologyandmethodofadministration).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingconcurrenttreatmentwith

potentdiureticssuchasfurosemide,aminoglycosidesandamphotericinasconcomitantuseincreasestheriskof

nephrotoxicity.

Concomitanttherapywithprobenecidcanreducetherenalexcretionofcephalosporins.Plasmaconcentrationsare

enhancedifprobenecidisgivenconcomitantly.

Sincebacteriostaticdrugsmayinterferewiththebactericidalactionofcephalosporins,itisadvisabletoavoid

givingtetracyclines,macrolides,orchloramphenicolinconjunctionwithcefuroxime.

Urinesugartestsusingreductionmethodsmayshowfalsepositivereactions,thereforeenzymaticmethodsshouldbe

used(seesection4.4,Specialwarningsandprecautionsforuse).

Duringintravenousadministrationadmixturewithothermedicationsinsolutionshouldbeavoided.

SodiumbicarbonateisnotrecommendedforthedilutionofCefuroxime.

TheuseofcefuroximesodiummaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(Seesection4.8,Undesirableeffects).

4.6Pregnancyandlactation

Useinpregnancy

Therearenotsufficientdataontheuseofcefuroximesodiumduringpregnancytoassessitspossibleharmfulness.So

far,animaltestshavenotyieldedevidenceofharmfulness.Cefuroximecrossestheplacenta.Cefuroximesodium

shouldnotbeusedduringpregnancyunlessconsideredessentialbythephysician.

Useduringlactation

Cefuroximeisexcretedtoasmalldegreeinhumanmilk;breastfeedingshouldbeavoidedinwomenusingcefuroxime

sodium.

4.7Effectsonabilitytodriveandusemachines

Cefuroximemaysometimesbeassociatedwithsideeffects,suchasdizziness,thatmayimpairtheabilitytodrivea

vehicle,tooperatemachineryortoworksafely(Seesection4.8,Undesirableeffects).

4.8Undesirableeffects

Common((>1/100,<1/10)

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

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

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Infectionsandinfestations:

Rare

Pseudomembranouscolitis

Aswithotherantibioticsprolongedusemayleadtosecondarysuperinfectionscausedbyinsusceptibleorganisms,e.g.

Candida,EnterococciandClostridiumdifficile.

Bloodandthelymphaticsystemdisorders

Insomepatientsdecreasedhaemoglobinconcentration,eosinophilia,leucopenia,neutropeniaandthrombocytopenia

mightoccur.

Veryrare

Haemolyticanemia

Immunesystemdisorders:

Rare

Serumsickness

Veryrare

Anaphylaxis

Nervoussystemdisorders

Uncommon

Headache,dizziness

Veryrare

Vertigo,restlessness,nervousness,confusion

Earandlabyrinthdisorders:

Mildtomoderatehearinglosshasbeenreportedinsomechildrentreatedformeningitiswithcefuroxime.

Gastrointestinaldisorders:

Common

Gastrointestinaldisturbancessuchasdiarrhoea,nauseaandvomitinghavebeenreported..

Hepato-biliarydisorders:

Uncommon

Transientincreasesofhepaticenzymelevels(AST,ALTandLDH)andserumbilirubinhavebeenreported.

Veryrare

Jaundice.

Skinandsubcutaneoustissuedisorders:

Common

Skinrashes,urticaria,pruritus.

Rare

Erythemamultiforme,Stevens-Johnsonsyndromeandtoxicepidermalnecrolysis

Renalandurinarydisorders

Common

Increasedlevelsofcreatinineandureainserumhavebeenreportedcommonly,especiallyinpatientswithimpaired

renalfunction.

Uncommon

Acuteinterstitialnephritis.

Nephrotoxicityhasbeenreported.Acuterenaltubularnecrosishasfollowedexcessivedosageandhasalsobeen

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Generaldisordersandadministrationsiteconditions:

Rare

Drugfever

Common

Transientpainandindurationmaybecommonlyexperiencedatthesiteofintramuscularinjection.Thisismorelikely

tooccurwithhigherdoses.Thrombophlebitisandpainmaycommonlyfollowintravenousinjection.However,thisis

unlikelytobeacausefordiscontinuationoftreatment.Afterrapidintravenousadministrationofcefuroximeheat

sensationsornauseamayoccur.Dizzinessandheadachehavebeenreportedinpatientswhoreceivedcefuroxime.

Investigations

TheuseofcefuroximemaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththeperformanceof

crossmatchingtestswithblood.

4.9Overdose

Overdosageofcephalosporinscancausecerebralirritationleadingtoconvulsions.Serumlevelsofcefuroximecanbe

reducedbyhaemodialysisorperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Generalproperties:

ATCclassification

Pharmacotherapeuticgroup:cephalosporinsandrelatedsubstances

ATC-Code:J01DA06

Modeofaction

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

cefuroximedespiteapparentinvitrosusceptibility.

StrainsofEnterobacteriaceae,inparticularKlebsiellaspp.andEscherichiacolithatproduceESBLs(extended

spectrum-lactamase)maybeclinicallyresistanttotherapywithcephalosporinsdespiteapparentinvitrosusceptibility

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Breakpoints:

ThefollowingMICbreakpointsseparatingsusceptiblefromintermediatelysusceptibleorganismandintermediately

susceptiblefromresistantorganismsareused.

Table1:Susceptibilitybreakpoints.

NCCLS:NationalCommitteeforClinicalLaboratoryStandards,

DIN:DeutschesInstitutfürNormung,

BSAC:BritishSocietyforAntimicrobialChemotherapy,

BacterialBreakpoints Organism

NCCLSBreakpoints

≤8mg/L

I:16 R: ≥32mg/L Enterobacteriaceae

≤4mg/L

≥16mg/L Enterococcus

≤4mg/L

≥16mg/L Haemophilusinfluenzae

≤1mg/L

≥4mg/L

Neisseriagonorrhoeae

≤0.5mg/LI:1

≥2mg/L

Streptococcuspneumoniae

DINBreakpoints

≤4mg/L

≥16mg/L Allbacterialisolates

BSACBreakpoints

≤1mg/L

I:2-16 R: ≥32mg/L Acinetobacterspp.and

Enterobacteriaceae

≤1mg/L

≥2mg/L Streptococcuspneumoniae,Moraxella

catarrhalis,Neisseriagonorrhoeae,

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Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationis

desirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhenthelocal

prevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsisquestionable.

5.2Pharmacokineticproperties

Absorption

Cefuroximeispoorlyabsorbedfromthegastro-intestinaltractandisgivenbyintramuscularorintravenousinjectionor

infusionasthesodiumsalt.Peakplasmaconcentrationof27µgpermlhavebeenachievedabout45minutesafteran

intramusculardoseof750mgwithmeasurableamountspresent8hoursafteradose.

Distribution

Cefuroximeiswidelydistributedinthebodyincludingpleuralfluid,sputum,bone,synovialfluid,andaqueous

humour,butonlyachievestherapeuticconcentrationsintheCSFwhenthemeningesareinflamed.About50%of

cefuroximeinthecirculationisboundtoplasmaproteins.Itdiffusesacrosstheplacentaandhasbeendetectedinbreast

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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Metabolism

Cefuroximeisnotmetabolized.

Elimination

Mostofthedoseofcefuroximeisexcretedunchanged.About50%isexcretedbyglomerularfiltrationandabout50%

throughrenaltubularsecretionwithin24hours,withthemajoritybeingeliminatedwithin6hours;highconcentrations

areachievedintheurine.Smallamountsofcefuroximeareexcretedinbile.

Probenecidcompeteswithcefuroximeforrenaltubularsecretionresultinginhigherandmoreprolongedplasma

concentrationsofcefuroxime.Theplasmahalf-lifeisabout70minutesaftereitherintramuscular,orintravenous

injectionandisprolongedinpatientswithrenalimpairmentandinneonates.

5.3Preclinicalsafetydata

Cefuroximesodiumhasaveryloworderoftoxicityasdemonstratedbyacutetoxicitystudies.Investigationsofchronic

toxicityinseveralanimalspecies(rat,dogandmonkey)yieldednoindicationsofdrugrelatedtoxicologicaleffects.

Themostprominenttreatment-relatedeffectwastissuedamageattheinjectionsites.

Acefuroximeesterdidnotshowclinicallyrelevanteffectswhentestedinvitroandinvivoforgenotoxicpotential

Preclinicalnephrotoxicitystudiesshowedtheproductcancauserenaldamageinsomespecieswhenadministeredin

veryhighdoses.Itsnephrotoxicityincreaseswhenadministeredincombinationwithglycerolandfurosemide.

Nolong-terminvestigationsfordeterminationoftumorigenicpotentialwereperformed.

Investigationsinrabbitsandmicedidnotdemonstratereproductivetoxicityorteratogenic-effects.Cefuroximehas

beenshowntopasstheplacenta.

Gamma-glutamyltranspeptidaseactivityinraturineisinhibitedbyvariouscephalosporins,however,thelevelof

inhibitionislesswithcefuroxime.Thismayhavesignificanceintheinterferenceinclinicallaboratorytestsinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

None.

6.2Incompatibilities

Cefuroximeshouldnotbemixedinthesyringewithaminoglycosideantibiotics.

Mixingofcefuroximewithsodiumbicarbonatesolutionssignificantlyaffectsthecolourofthesolution.Therefore,this

solutionisnotrecommendedforthedilutionofcefuroxime.Ifrequired,thecefuroximesolutioninwaterforinjections

canbeintroducedintothetubingofthegivingsetinpatientsreceivingsodiumbicarbonatesolutionbyinfusion.

6.3ShelfLife

3years.

Reconstitutedsolution:Chemicalandphysicalstabilityhasbeendemonstratedfor2hoursat25°Candfor24hoursat

2°C–8°C.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.

Ifnotusedimmediately,in-usestoragetimesandconditionsaretheresponsibilityoftheuserandwouldnormallybe

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6.4Specialprecautionsforstorage

Keepthecontainersinoutercartoninordertoprotectfromlight..

Reconstitutedsolution:Theproductshouldbeusedimmediately.Keepthevialsinoutercartoninordertoprotectfrom

light.

6.5Natureandcontentsofcontainer

250mgand750mgpowderforsolution/suspensionforinjection:

15mlvialsofclearglasstypeIII(Ph.Eur.)closedwithrubberstopperandflip-offborderedcaps.

Packsizes:1,5,10,25,50,100vials.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Compatibilitywithintravenoussolutions

Cefuroximeremainsstablefor2hoursatroomtemperatureand24hat2°C–8°C,ifdissolvedin:

waterforinjections

0.9%sodiumchloridesolution

5%glucosesolution

Instructionsforreconstitution

Cefuroxime250and750mg,powderforsolution/suspensionforinjection,asintramuscularadministration:Add1ml

ofwaterforinjectionsor1.0%lidocain,solutionrespectivelytoCefuroxime250mg,powderforsolution/suspension

forinjectionand3mltoCefuroxime750mg,powderforsolution/suspensionforinjection.Shakegentlytoproduce

anhomogenoussuspension.Cefuroxime1500mg,powderforsolutionforinjection,shouldnotbeadministered

intramuscularly.

Cefuroxime250,750and1500mg,powderforsolution/suspensionforinjection,asintravenousinjection:Dissolve

Cefuroxime250mg,powderforsolution/suspensionforinjectiong,inatleast2mlofwaterforinjections,0.9%

sodiumchloridesolutionor5%glucosesolutionCefuroxime750mg,powderforsolution/suspensionforinjection,in

atleast6mlandCefuroxime1500mg,powderforsolutionforinjectionin15ml.

Shakegentlytoproduceaclearsolution.

Thecontentsandconcentrationsofcefuroximeassolution/suspensionareshowninthetablebelow

Note:Antibioticsshouldnotbeaddedtoroutineinfusionfluids.Mostinfusionfluidsaregivenover6to8hoursand

thisisimpracticalforantibiotictherapy.Cefuroximeshouldbegivenovershortperiods(30minutes).

Whenreconstitutedforintramuscularorintravenousinjection,thewhitetoalmostwhitepowdergivesacolourlessto

mgcefuroxime

pervial additionof

mlsolvent volumemlof

finalsolution/

suspension Concentration

mg/ml

1500

1500 2

16.5

51.5 114

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Asforallparenteralmedicinalproducts,inspectthereconstitutedsolution/suspensionvisuallyforparticulatematter

anddiscolorationpriortoadministration.Thereconstitutedsolutionisclear.Forsingleuseonly.Anyremaining

solutionshouldbediscarded.

7MARKETINGAUTHORISATIONHOLDER

SandozLtd

WoolmerWay

Bordon

Hants

GU359QE

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0372/007/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:25August2006

10DATEOFREVISIONOFTHETEXT

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