CEFOTAXIME

Main information

  • Trade name:
  • CEFOTAXIME Pdr for Soln Inj/Inf 2 Grams
  • Dosage:
  • 2 Grams
  • Pharmaceutical form:
  • Pdr for Soln Inj/Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CEFOTAXIME Pdr for Soln Inj/Inf 2 Grams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/012/003
  • Authorization date:
  • 10-11-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cefotaxime2gPowderforSolutionforInjectionorInfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontainscefotaximesodiumequivalentto2gcefotaxime.

3PHARMACEUTICALFORM

Powderforsolutionforinjectionorinfusion.

Whiteorslightlyyellowpowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofthefollowingsevereinfectionswhenknownorthoughtverylikelytobeduetoorganismsthatare

susceptibletocefotaxime(seesection5.1)

Infectionsofthelowerrespiratorytract

Infectionsofthekidneysandotherupperurinarytractinfections

Infectionsoftheskinandsofttissue

Genitalinfectionscausedbygonococci,particularlywhenpenicillinhasfailedorisunsuitable

Intra-abdominalinfections(incl.peritonitis)(cefotaximeshouldbeusedincombinationwithanotherantibiotic

thatcanprovideanaerobiccoverinthetreatmentofintra-abdominalinfections)

Acutemeningitis.

Considerationshouldbegiventoofficiallocalguidanceontheappropriateuseofantibioticswhenusingcefotaxime.

4.2Posologyandmethodofadministration

Cefotaximesodiummaybeadministeredintravenouslybybolusinjectionorinfusionorintramuscularly.

Cefotaxime500mgand1garesuitablefori.v.andi.m.injection.Cefotaxime2gissuitablefori.v.injectionandi.v.

infusion.

Theintramuscularmethodofadministrationisreservedforexceptionalclinicalsituationsandshouldundergoarisk-

benefitassessment.Itisrecommendedthatnomorethan4mlisinjectedunilaterally.Ifthedailydoseexceeds2g

cefotaximeorifcefotaximeisinjectedmorefrequentlythantwiceperday,thei.v.routeisrecommended.

Intramuscularadministrationofcefotaximereconstitutedwithlidocaineshouldnotbeadministratedtochildreninthe

firstyearofage.

Dosagewithindividualanddailyadministration

Dosageandtypeofadministrationdependsontheseverityoftheinfection,thesensitivityofthebacteriumandthe

conditionofthepatient.

Forthedosagesandroutesofadministrationwhicharenotpossiblewiththisstrength,otherstrengthsareavailable.

Thedurationofthetreatmentdependsonthecourseofdisease.Asageneralrulecefotaximeisadministratedfora

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Adultsandadolescents(12to16-18years)ingeneralreceive1gcefotaximeevery12hours.Inseverecases,thedaily

dosecanbeincreasedupto12g.Dailydosesupto6gcanbedividedintoatleasttwoindividualadministrationsat12

hourintervals.Higherdailydosesmustbedividedintoatleast3to4individualadministrationsat8or6-hourintervals,

respectively.

Thefollowingtablemayserveasaguidetodosages:

Infants,toddlers(28daysto23months)andchildren(2to11years)receive50to100mgcefotaximeaccordingto

theseverityoftheinfection(upto150mg)perkilogramofbodyweightperday,in2to4divideddoses(every12-6

hours).Thefollowingtablemayserveasaguidetodosages:

*Inindividualcases-particularlyinlife-threateningsituations-itmaybenecessarytoincreasethedailydoseto200

mgcefotaximeperkilogramofbodyweightwithoutexceedingthemaximumdailydosageof12g.

Pretermnewborninfantsandtermnewborninfants(0-27days)receiveingeneraldosesof50mgcefotaximeper

kilogramofbodyweightperdayin2to4divideddoses(every12-6hours).Incaseoflife-threateningsituationsitmay

benecessarytoincreasethedailydose.Forsevereinfections150mg/kg/dayhasbeengiven.Thefollowingtablemay

Typeofinfection Singledose

cefotaxime Dose

Interval Dailydose

cefotaxime

Typicalinfections,inwhichasensitive

bacteriumisprovenorsuspected 1g 12h 2g

Infections,inwhichvariousbacteriawithhigh

tomediumsensitivityaredemonstratedor

suspected 2g 12h 4g

Unclearbacterialillnesseswhichcannotbe

localisedandwherethepatientiscriticallyill 2-3g 8h

6h 6-9g

8-12g

Typeofinfection Dose

interval Dailydose

cefotaxime

Typicalinfections,inwhich

asensitivebacteriumis

provenorsuspected 6-12h 50mg/kg

Infections,inwhichvarious

bacteriawithhighto

mediumsensitivityare

demonstratedorsuspected 6-12h 100mg/kg

Unclearbacterialillnesses

whichcannotbelocalised

andwherethepatientis

criticallyill 6-8h 150mg/kg*

Typeofinfection Age Dose

interval Dailydose

cefotaxime

Typicalinfectionsdueto

sensitivebacteriaorincases

withhightomedium

sensitivitydemonstratedor

suspected 0-7days

8days–1

month 6-12h 50mg/kg

Unclearbacterialillnesses

whichcannotbelocalised

andwherethepatientis

criticallyill 0-7days

8days–1

month 6-12h 100mg/kg*

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Inindividualcases-particularlyinlife-threateningsituations-itmaybenecessarytoincreasethedailydoseto200mg

cefotaximeperkilogramofbodyweight.Thisdosageshouldnotbeexceededinviewofnotfullymaturedkidney

clearance.

Gonorrhoea

Uncomplicatedgonorrhoea:asingleintramuscularinjectionof0.5to1gramcefotaxime,although1gramis

recommendedaspreferable.Incasesofdisseminatedgonococcalinfection,localofficialguidelinesshouldbefollowed.

Thepossibilityofsyphilisneedstoberuledoutbeforestartingcefotaximetherapy.

Specialdosagerecommendations

Dosageinthecaseofimpairedrenalfunction

Foradultpatientswithacreatinineclearanceof20ml/minuteorless,themaintenancedoseistobereducedtohalfthe

normaldose.

Foradultpatientswithacreatinineclearanceof5ml/minuteorless,afteraninitialloadingdoseof1g,thedailydose

shouldbehalvedwithoutchangeinthefrequencyofdosing,i.e.1g12hourlybecomes0.5g12hourly,1g8hourly

becomes0.5g8hourly,2g8hourlybecomes1g8hourlyetc.Asinallotherpatients,dosagemayrequirefurther

adjustmentaccordingtothecourseoftheinfectionandthegeneralconditionofthepatient.

Haemodialysis

Inpatientsonhaemodialysis,0.5-2gisgivenbyi.v.injectionattheendofeverydialysis.Thisdoseisrepeatedevery

24hours.

Elderlypatients

Nodosageadjustmentsareneededinpatientswithnormalrenalfunction.

Methodofadministration

Seealsosection6.6.Instructionsforuseandhandling.

Intravenoususe

Intravenousinjection

Fori.v.injection,Cefotaxime500mgpowderforsolutionforinjectionisdissolvedinatleast2mlwaterforinjection,

Cefotaxime1gpowderforsolutionforinjectioninatleast4mlandCefotaxime2gpowderforsolutionforinjection

inatleast10mlandsubsequentlyinjecteddirectlyintotheveinover3to5minutesorafterclampingoftheinfusion

tubeintothedistalendofthetube.

Infusion

Shortterminfusion:2gcefotaximeisdissolvedin40to50mlwaterforinjectionoracompatibleinfusionsolution

(seesection6.6Instructionsforuseandhandling)andsubsequentlyi.v.infusedoverapproximately20minutes.

Forinfusionbyintravenousdrip,2gcefotaximeisdissolvedin100mlsodiumchloride9mg/ml(0.9%)orglucose50

mg/ml(5%)solutionandsubsequentlyi.v.infusedover50to60minutes.Anothercompatibleinfusionsolutioncan

alsobeusedforthesolution.

Intramuscularinjection

Forintramuscularinjection,0.5gCefotaxime500mgpowderforsolutionforinjectionand1gCefotaxime1gpowder

forsolutionforinjectionisdissolvedin2and4mlwaterforinjection,respectively.Afterwards,theinjectionshould

takeplacedeepintotheglutealmuscle.Painwiththei.m.injectioncanbeavoidedbydissolvingCefotaxime500mg

powderforsolutionforinjectionin2mlorCefotaxime1gpowderforsolutionforinjectionin4mlof1%lidocaine

solution.Anintravascularinjectionistobeavoidedinthiscasebecauseofpossibleadverseeffects.IfCefotaximeis

intramuscularlyadministeredafterreconstitutionwithlidocaine,theSPCoflidocaineshouldbecheckedforthe

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Combinationtherapy

Acombinationtherapyofcefotaximewithaminoglycosidesisindicatedwithoutavailabilityofanantibiograminthe

caseofsevere,life-threateninginfections.Kidneyfunctionmustbemonitoredwhenusingincombinationwith

aminoglycosides.

Thedurationofthetreatmentdependsonthecourseoftheillness.

4.3Contraindications

Hypersensitivitytocefotaximeortoanyofthecephalosporins.

Previousimmediateand/orseverehypersensitivityreactiontopenicillinortoanyothertypeofbeta-lactamdrug.

4.4Specialwarningsandprecautionsforuse

Cefotaximeshouldbegivenwithcautiontopatientswhohavehadanyothertypeofhypersensitivityreactiontoa

penicillinoranyotherbeta-lactamdrug.Beforetherapywithcefotaximeisinstituted,carefulinquiryshouldbemadeto

determinewhetherthepatienthadanyprevioushypersensitivityreactionstocefotaxime,anyothercephalosporin,orto

anypenicillinorotherbeta-lactamdrug.

Cefotaximeshouldbeusedwithcautioninpatientswithallergicdiathesesandasthma.

Antibiotic-associateddiarrhoea,colitisandpseudomembranouscolitishaveallbeenreportedwiththeuseof

cefotaxime.Thesediagnosesshouldbeconsideredinanypatientwhodevelopssevereand/orbloodydiarrhoeaduring

orshortlyaftertreatment.

ThepresenceofClostridiumdifficileshouldbeinvestigatedandcefotaximeshouldbediscontinuedimmediately.

Appropriatetreatmentmeasuresshouldbeinitiatedincludingspecificantibiotictherapyifconsiderednecessary.

Antiperistalticsarecontraindicated.

Cefotaximeshouldbeusedwithcautioninindividualswithaprevioushistoryofgastro-intestinaldisease,particularly

colitis.

Aswithothercephalosporins,prolongeduseofcefotaximemayresultintheovergrowthofnon-susceptibleorganisms,

suchasenterococciandCandidaspp.

Sincehaematologicalabnormalitiesmaydevelopduringtreatmentwithcefotaxime,bloodcountshouldbemonitoredif

treatmentlastsforlongerthan7days.Incasesofneutropenia(<1400neutrophils/mm 3

),treatmentshouldbe

interrupted.

Fastinfusionintoacentralveincancausearrhythmia.

Patientswithsevererenaldysfunction(creatinineclearanceof20ml/minuteorless)requiredoseadjustment.See

section4.2.

Ifcefotaximeisintramuscularlyadministeredafterreconstitutionwithlidocaine,theSPCoflidocaineshouldbe

checkedforthenecessaryproductinformation.

Thisproductcontainssodium,whichshouldbetakenintoaccountwhenprescribingtopatientsrequiringsodium

restriction.Cefotaxime2gpowderforsolutionforintravenousinfusioncontains2096mgcefotaxim-sodiumwhichis

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cefotaxime/otherantibiotics

Asfaraspossible,cefotaximeshouldnotbecombinedwithsubstanceshavingabacteriostaticaction(e.g.tetracycline,

erythromycin,chloramphenicolorsulfonamides),sinceanantagonisticeffecthasbeenobservedregardingtheanti-

bacterialeffectinvitro.Asynergisticeffectcanresultwithacombinationwithaminoglycosides.

Anincreasedriskofoto-andnephrotoxicityhavebeenreportedwhenhighdosesofcephalosporinshavebeenused

concomitantlywithaminoglycosides.Adoseadjustmentmaybenecessary,andthekidneyfunctionmustbemonitored

(see4.2Posologyandmethodofadministration).

Cefotaxime/probenecid

Thesimultaneousadministrationofprobenecidleadstohigher,moreprolongedconcentrationsofcefotaximeinthe

serumbyinhibitingrenalclearance.

Cefotaxime/potentiallynephrotoxicdrugsandloopdiuretics

Incombinationwithpotentiallynephrotoxicdrugs(forexample,aminoglycosideantibiotics,polymyxinBandcolistin)

andwithloopdiureticsthekidneyfunctionshouldbemonitored,sincethenephrotoxicityofthesesubstancesquoted

maybeaccentuated.

Influenceonlaboratorydiagnostictests

FalsepositivesmayoccurintheCoombs-testinrarecasesduringtreatmentwithcefotaxime.

Inglucosedeterminationsinurineandblood,falsepositiveaswellasfalsenegativeresultsmayalsobeobtained,

dependingonthemethod;thesemaybeavoidedbytheuseofenzymaticmethods.

4.6Fertility,pregnancyandlactation

Pregnancy

Cefotaximecrossestheplacenta.Althoughreproductionstudiesinanimalshavenotrevealedanyevidenceofharmto

thefoetus,cefotaximeshouldbeusedduringpregnancyonlyifclearlyneededandtheexpectedbenefittothemother

outweighsanypotentialrisktothefoetus.

Lactation

Cefotaximeisexcretedinhumanmilkinlowconcentrations.

Useduringlactationcanleadininfantstoaneffectonthephysiologicalintestinalflorawithdiarrhoea,to

Saccharomycescolonisationandmayalsoleadintosensitisation.Cautionshouldbeexercisedwhenadministeredto

nursingwomen.Adecisionshouldbemadewhethertodiscontinuenursingordiscontinuetreatmenttakinginto

accounttheimportanceofcefotaximetothenursingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectontheabilitytodriveandusemachineshavebeenperformed.

Inindividualcases,inadministrationofhighdosesandparticularlywithsimultaneouskidneyfunctionimpairment,

attacksofcramp(tonic/clonic),musclespasms(myoclonias)andgiddinesshavebeenreported.Theindicatedactivities

shouldthereforebediscontinuedunderthesecircumstances.

4.8Undesirableeffects

Adversereactionstocefotaximehaveoccurredrelativelyinfrequentlyandhavegenerallybeenmildandtransientand

occurinabout5%ofpatientstreatedwithcefotaxime.

Thesideeffects,describedbelow,areclassifiedaccordingtofollowingfrequencies:

Verycommon:>10%;Common:>1%,<10%;Uncommon:>0.1%,<1%;Rare:>0.01%,<0.1%;Veryrare,including

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Bloodandlymphaticsystemdisorders

Rare

Haemolyticanaemia,granulocytopenia,leukocytopenia,eosinophilia,thrombocytopenia.Agranulocytosismay

develop,particularlyafterprolongedtherapy.Theseoccurrencesarereversible.Iftherapylastsformorethan7days

bloodpicturechecksshouldbeinstituted.

Immunesystemdisorders

Rare

Severeacutehypersensitivityreaction(anaphylaxis).Ananaphylacticshockislifethreateningandnecessitates

correspondingemergencymeasures.

Allergicskin-reactions(e.g.urticaria,exanthema),itchinganddrug-fevers.

Veryrare,includingisolatedcases

Erythemamultiforme(mildtosevereformsi.eStevens-Johnsonssyndrome)andtoxic-epidermalnecrolysis.

Inpatientswithaninclinationtoallergiesanallergicreactionismorelikely.

Nervoussystemdisorders

Rare

Seizureshavebeenreported,especiallywithhighdosesandinpatientswithrenalfunctionimpairment.

Cardiacdisorders

Veryrare

Averysmallnumberofcasesofarrhythmiashaveoccurredfollowingrapidbolusinfusionthroughacentralvenous

catheter.

Gastrointestinaldisorders

Common

Gastrointestinaldisturbances,likelossofappetite,nausea,sickness,stomachacheordiarrhoea,whichareusuallymild

innatureandfrequentlyfadeawayduringorotherwiseafterterminationofthetherapy.

Rare

Pseudomembranouscolitis.Seealsosection4.4Specialwarningsandprecautionsforuse.

Renalandurinarydisorders

Rare

Increasedserumcreatinineandureaconcentrations,

Veryrare,includingisolatedcases

Acuteinterstitialnephritis

Hepato-biliarydisorders

Rare

Slight,transientincreasesinserumbilirubinand/orliverenzymes(SGOT,SGPT,GammaGT,alkalinephosphatase,

LDH).

Generaldisordersandadministrationsiteconditions

Common

Transientpainmaybeexperiencedatthesiteofinjection.Thisismorelikelytooccurwithhigherdoses.Occasionally,

phlebitishasbeenreportedinpatientsreceivingintravenouscefotaxime.However,thishasrarelybeenacausefor

discontinuationoftreatment.

Painandhardeningofthetissue(induration)occasionallyariseattheinjectionsiteafterintramuscularinjection.

Otheradvice

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4.9Overdose

Intheeventofoverdosingitmaybenecessary,inadditiontoremovingthedrug,totakestepstoaccelerateelimination.

Cefotaximeishaemodialysable.

a)symptomsofoverdosing

Intoxication,sensustrictu,isnotknowninman.Withcertainriskpatternsandwiththeadministrationofveryhigh

doses,centralnervoussystemexcitationconditions,myocloniaandcrampcanoccur,ashavealsobeendescribedfor

otherbetalactams.Theriskoftheappearanceoftheseundesirableeffectsisincreasedinpatientswithseverely

restrictedkidneyfunction,epilepsyandmeningitis.

b)emergencymeasures

Centrallyinitiatedcrampscanbetreatedwithdiazepamorphenobarbital,butnotwithphenytoin.Withanaphylactic

reactionstheusualemergencymeasuresmustbecommenced,preferablywiththefirstindicationsoftheshock.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticalgroup:Thirdgenerationcephalosporins.

ATCclassification:J01DD01

Modeofaction

Cefotaximeinhibitstheactionofcertainbacterialcellwallsyntheticenzymesandsointerruptscellwallbiosynthesis.

Bacterialcelllysisresults.

Mechanismsofresistance

Bacterialresistancetocefotaximemaybeduetooneormoreofthefollowingmechanisms:

Hydrolysisby-lactamases.Cefotaximemaybeefficientlyhydrolysedbytheproductionofcertainextended-

spectrum-lactamases.Also,theinductionand/orconstitutiveexpressionofchromosomally-encoded(AmpC)

enzymescanefficientlyhydrolysethedrug

Animpermeability-basedmechanismofresistance

Effluxpumpmechanisms.

Morethanoneofthesepossiblemechanismsmayco-existinasinglebacterium.

Cefotaxime-resistantbacteriamayexhibitvaryingdegreesofcross-resistancewithother-lactams.Cefotaxime-

resistantgram-negativebacteriashowcompletecross-resistancetootherbroad-spectrumthirdgeneration

cephalosporins(e.g.ceftazidime,ceftriaxone).

Theuseofcefotaximeasmonotherapyininfectionscausedbygramnegativebacteriacontaininginducibleencoded

AmpC-like-lactamaseslikeEnterobactercloacae,Enterobacterspp.,Serratiaspp.,andCitrobacterspp.shouldbe

discourageddespiteapparentinvitrosusceptibility,asmutantswithstablydepressed(hyperproduced)-lactamasemay

beselectedduringtherapy.

Breakpoints

NationalCommitteeforClinicalLaboratoryStandards(NCCLS):

Enterobacteriaceae*,PseudomonasaeruginosaandotherNon-Fermenters,Staphylococcusspp.:susceptible 8mg/l;

intermediate16-32mg/l;resistant 64mg/l

Haemophilusinfluenzae:susceptible 2mg/l

Neisseriagonorrhoeae:susceptible 0.5mg/l

Streptococcuspneumoniae(non-meningitis):susceptible 1mg/l;intermediate2mg/l;resistant 4mg/l

Streptococcuspneumoniae(meningitis):susceptible 0.5mg/l;intermediate1mg/l;resistant 2mg/l

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Streptococcusspp.(viridansgroup):susceptible 1mg/l;intermediate2mg/l;resistant 4mg/l.

*StrainsofEscherichiacoliandKlebsiellaspp.thatproduceESBLsmaybeclinicallyresistanttotherapywith

cefotaximedespiteinvitrosusceptibility.

In-vitroantibacterialspectrum

Ageneraloverviewoftheantibacterialspectrumofcefotaximeisgivenbelow.Itshouldbeconsideredthatthe

prevalenceofacquiredresistancemayvarygeographicallywithintheEuropeanUnionandwithtimeforselected

species,sothatlocalinformationonresistanceisdesirable,particularlywhentreatingsevereinfections.The

informationgiveninthetablebelowprovidesanapproximateguidanceontheprobabilitieswhethermicroorganisms

willbesusceptibletocefotaxime.

Commonlysusceptiblespecies

Grampositiveaerobes

Staphylococcusaureus(MSSA)

Streptococcusagalactiae

Streptococcuspneumoniae(includingpenicillinresistant

strains)

Streptococcuspyogenes

Gram-negativeaerobes

Haemophilusinfluenzae

Moraxellacatarrhalis°

Morganellamorganii

Neisseriagonorrhoeae°

Neisseriameningitidis°

Proteusmirabilis %

Speciesforwhichacquiredresistancemaybeaproblem

Gram-positiveaerobes

Staphylococcusaureus

Staphylococcusepidermidis +

Staphylococcushaemolyticus +

Staphylococcushominis +

Gram-negativeaerobes

Citrobacterfreundii

Enterobacteraerogenes

Enterobactercloacae

Escherichiacoli %

Klebsiellaoxytoca %

Klebsiellapneumoniae %

Proteusvulgaris

Serratiamarcescens

Anaerobes

Bacteroidesfragilis

Inherentlyresistantspecies

Gram-positiveaerobes

Enterococcusspp.

Listeriamonocytogenes

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°Nocurrentsurveillancedataavailable.Susceptibilityisanticipatedaccordingtothecurrentscientificknowledge.

Inatleastoneregionresistancerateisabove50%.

ExtendedSpectrumbeta-lactamase(ESBL)producingstrainsarealwaysresistant.

resistancerates<10%incommunityacquiredinfections

5.2Pharmacokineticproperties

Cefotaximeisappliedparenterally.

Absorption

Afterintravenousinjectionof1gcefotaxime,theserumconcentrationsafter5minamountedtoabout81-102mg/land

after15minto46mg/l.Eightminutesafterintravenousinjectionof2gcefotaxime,serumconcentrationsof167-214

mg/lwererecorded.Afterintramuscularadministration,themaximumserumconcentrations(approximately20mg/l

after1g)werereachedwithin30minutes.

Distribution

Theapparentdistributionvolumeis21-37l.

Withinfectedmeninges,cefotaximeanddesacetyl-cefotaximepenetrateintothefluidspaceandthenreach

therapeuticallyeffectiveconcentrationsthere(e.g.withinfectionswhicharecausedbygram-negativebacteriaand

pneumococci).

Theserumproteinbindingamountstoapproximately25-40%.

Cefotaximepervadestissuerapidly,passestheplacentabarrierandreacheshighconcentrationsinfoetaltissues(upto6

mg/kg).Itisonlyexpressedatalowpercentageinthemother'smilk(concentrationsinthemother'smilk:0.4mg/lafter

2g).

Metabolism

Cefotaximeismetabolizedtoaconsiderableextentinman.Approximately15-25%ofaparenteraldoseisexcretedas

O-desacetyl-cefotaxime.Themetabolitepossessesanti-bacterialactivity.

Inadditiontodesacetyl-cefotaxime,therearetwootherinactivelactones.Fromdesacetyl-cefotaxime,alactoneis

producedasanephemeralintermediate,whichstillcannotbeproveneitherintheurineorintheplasma,becauseitis

subjecttoarapidconversiontostereoisomersoftheringopening(beta-lactamring)lactone.Thesearelikewise

Gram-negativeaerobes

Acinetobacterbaumannii

Pseudomonasaeruginosa

Stenotrophomonasmaltophilia

Anaerobes

Clostridiumdifficile

Others

Chlamydiaspp.

Chlamydophilaspp.

Legionellapneumophilia

Mycoplasmaspp.

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Excretion

Theexcretionofcefotaximeanddesacetyl-cefotaximetakesplacemainlybytherenalroute.Asmallpercentage

(approximately2%)iseliminatedwithbile.Inurinecollectedover6-hours,40-60%ofadosewasrecoveredin

unchangedformandapproximately20%asdesacetyl-cefotaxime.Afterintravenousadministrationofradioactively

markedcefotaximesomewhatmorethan80%wasrecoveredintheurine,fromit,50-60%appearedasunchanged

mothersubstanceandtheremainderasthreemetabolites.

Thetotalclearanceofthecefotaximeamountsto240-390ml/minandtherenalclearanceto130-150ml/min.

Theserumhalf-livesofcefotaximeanditsactivemetaboliteamountto50-80minutesand125minutes,respectively.In

geriatricpatients(>80years),thehalf-liveswerefoundtobe120-150minutesand5hoursfortheactivemetabolite.

Withseverekidneymalfunctions(creatinineclearance3-10mi/min)thehalf-lifeofthecefotaximecanbeextendedto

2.5-10hours.Cefotaximeonlyaccumulatesundertheseconditionstoasmallextent,incontrasttotheactiveand

inactivemetabolites.

Bothcefotaximeanddesacetyl-cefotaximearetoalargeextentremovedfromthebloodbyhaemodialysis.

5.3Preclinicalsafetydata

Thetoxicityofcefotaximeaftersingledosesisverylow.Cefotaximehasnomutagenicpotential,asindicatedbya

negativemicronucleustest.Studiesinratsandmicegavenoindicationofcefotaximehavingteratogenicproperties.

Fertilitywasnotimpaired.Inperinatalandpostnatalstudiesinrats,pupsborntothehighdoseanimalshad

significantlylowerweightsatbirthandremainedsmallerthancontrolpupsduringthe21daysofnursing.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Notapplicable.

6.2Incompatibilities

Cefotaximeshouldnotbemixedinalkalinesolutionssuchassodiumbicarbonateinjection.

Cefotaximeshouldalsonotbeadmixedwithaminoglycosides.However,theymaybeadministeredseparatelytothe

samepatient.

6.3Shelflife

Unopened

2years

Openedandreconstitutedproduct

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Discardanyunusedsolution.Ifnot

usedimmediately,in-usestoragetimesandconditionspriortousearetheresponsibilityoftheuser.

Chemicalandphysicalin-usestabilityhasbeendemonstratedfor6hoursat2-8ºC,whendissolvedinwaterfor

injectionand1%lidocaineHClsolution.Whenreconstitutedwithothercompatiblesolutions(seesection6.6),the

productshouldbeusedimmediately.

Thecolourofthesolutionmaychangetolightyellow,however,theefficacyandsafetyoftheantibioticarenot

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6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Keepthevialintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

TransparenttypeIIglassvialwithbromobutylrubberstopperandaluminiumsealwithaflipoffcap,containing

cefotaximesodium,equivalentto2gcefotaxime.

Thevialsarepackedinacartonboxcontaining1,5or10vials.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Theproductiscompatiblewiththefollowingsolutions:

WaterforInjections

Sodiumchloride9mg/ml(0.9%w/v),solutionforinfusion

Glucose50mg/ml(5%w/v),solutionforinfusion

LidocaineHCl10mg/ml(1%w/v),solutionforinjection(seealsosection4.4Specialwarningsandprecautions

foruse).

Thecompatibilitywithotherinfusionfluidsshouldbecheckedbeforeuse.

Reconstitutethepowderwiththesolventbyshakingvigorouslyforatleast30secondstoensurecompletedissolution.

Seealsosection4.2Posologyandmethodofadministrationforfurtherinstructions.Onlyclearsolutions,practically

freefromparticles,shouldbeused.

Forsingleuseonly.Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocal

requirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharma

Computerweg10

P.O.Box43028

3540AAUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA749/12/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10thNovember2006

Dateoflastrenewal:12thJuly2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 22/11/2011 CRN 2079247 page number: 11