CEFTAZIDIME

Main information

  • Trade name:
  • CEFTAZIDIME 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:
  • CEFTAZIDIME Pdr for Soln Inj/Inf 2 Grams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0361/033/003
  • Authorization date:
  • 08-07-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Ceftazidime2gPowderforsolutionforinjectionorinfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontains2330mgofceftazidimepentahydrate,equivalentto2gofceftazidime

Excipient:each2gvialofpowdercontains242mgofsodiumcarbonate

Thismedicinalproductcontains4.57mmol(or105mg)ofsodiumpervial

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Powderforsolutionforinjectionorinfusion

Thepowderiswhiteoroff-white

4CLINICALPARTICULARS

4.1TherapeuticIndications

Ceftazidimeisindicatedfortreatmentofthefollowingbacterialinfectionswhentheyarecausedbyceftazidime-

sensitivebacteria,andonlyifbeta-lactam-antibioticswithanarrowerspectrumcannotbeused:

-Nosocomialpneumonia

-BronchopulmonaryinfectionsincysticfibrosiscausedbyPseudomonasaeruginosa

-Meningitiscausedbyaerobicgram-negativemicroorganisms

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Posology

Thedosedependsonthedegreeofseverityoftheinfection,sensitivityandtypeofinfection,andontheage,weight

andrenalfunctionofthepatient.

Withnormalrenalfunction

Agegroup Infection Normaldose

Adults Mostindications 1gevery8hours(3g/day)or2

gevery12hours(4g/day)

Nosocomialpneumoniaand

infectionsinpatientswith

neutropaenia 2gevery8hours(6g/day)

Bronchopulmonaryinfectionsin

cysticfibrosiscausedby

Pseudomonasaeruginosa 100-150mg/kg/day,divided

into3doses;9g/daymustnot

beexceeded

Infantsandchildrenaged

overtwomonths Mostindications 30-100mg/kg/day,dividedinto

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Theplasmahalf-lifeofceftazidimemaybe3-4timesthehalflifeinadults

Elderly:InviewofthereducedclearanceofCeftazidimeinacutelyillelderlypatients,thedailydosageshouldnot

normallyexceed3g,especiallyinthoseover80yearsofage.

Thedurationoftreatmentdependsonpatientresponse.Generallytreatmentmustcontinueforatleast48hoursafter

clinicalconvalescence.

Impairedrenalfunction

Ceftazidimeisnotmetabolisedandonlyeliminatedbyglomerularfiltration.Inpatientswithimpairedrenalfunction

(i.e.creatinineclearance<50ml/min)thedoseshouldbereducedaccordingtothefollowingtabletocompensatefor

theextendedelimination.Aloadingdoseof1gofceftazidimemaybegiven,followedbyasuitablemaintenancedose

asindicatedinthetable.

*Thesevaluesareforguidanceonlyandcannotaccuratelypredicttherenalfunctionofallthepatients,particularlyin

elderlypatientswheretheserumcreatinineconcentrationmaybeduetoanoverestimatedrenalfunction

Inpatientwithacombinationofrenalinsufficiencyandseriousinfections,particularlyinpatientswithneutropaenia,a

singledose,asindicatedintheabovetable,canbeincreasedby50%orthedosingfrequencycanbesuitablyincreased.

Inthesepatientstheplasmaconcentrationofceftazidimeshouldbemonitored,ifpossible,andtheminimum

concentration(bloodsampletakenimmediatelybeforethenextdose)shouldnotexceed40mg/l.

Inchildrenwithrenalinsufficiencythecreatinineclearanceshouldbeadjustedonthebasisofbodyareaormeanbody

weight(withoutfat)andthedosingfrequencyshouldbereducedasforadults.

Patientsinhaemodialysis

Theplasmahalf-lifeofceftazidimeunderhaemodialysisvariesfrom3-5hours.Theappropriatemaintenancedoseof

ceftazidimeshouldberepeatedaftereachhaemodialysisperiod.Inpatientswithkidneyfailure,whoareundergoing

continuousatrio-venoushaemodialysisorhigh-fluxhaemofiltrationintheintensivecaredepartment,adoseof1gper

dayisrecommended,dividedintoseveraldoses.Inthecaseoflow-fluxhaemofiltrationadosespecifiedforimpaired

functionisrecommended.

Inpatientswhoareundergoingvenoushaemofiltrationandvenoushaemodialysisthedosingrecommendationsinthe

Infectedneutropenicpaediatric

patients,paediatricpatientswith

cysticfibrosisorpaediatric

patientswithmeningitis Upto150mg/kg/day(a

maximumof6gtotalperday)

dividedinto3doses

Neonatesandchildrenupto

2monthsofage Mostindications 25-60mg/kg/daydividedinto2

doses *

Creatinine

clearance

ml/min Approximateserum

creatinine*µmol/l

(mg/dl) Recommended

singledoseof

ceftazidime(g) Dosingfrequency,

indicatedinhours

50-31 150-200(1.7-2.3) 1 12

30-16 200-350(2.3-4.0) 1 24

15-6 350-500(4.0-5.6) 0.5 24

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Ceftazidimedosingguidelineduringcontinuousvenoushaemofiltration:

Themaintenancedoseisadministeredevery12hours

Ceftazidimedosingguidelineduringcontinuousvenoushaemodialysis:

Themaintenancedoseisadministeredevery12hours

Posologyinthecaseofhepaticinsufficiency

Nodoseadjustmentisrequiredunlessrenalfunctionisalsoimpaired.

Routesofadministration

Ceftazidimeshouldbeadministeredintravenously(bybolusinjection)orbydeepintramuscularinjectionintoalarge

musclemass,suchastheupperouterquadrantofthegluteusmaximusorlateralpartofthethigh.

Forpreparationofsolutionforinjection(seesection6.6).

4.3Contraindications

HypersensitivitytoCeftazidimeortoanyothercephalosporinantibiotics.

Previous,immediateand/orseverehypersensitivityreactiontopenicillinoranybeta-lactamantibiotic.

4.4Specialwarningsandprecautionsforuse

Itisrecommendedthatresultsfrombacteriaculturesandsensitivitytestsareobtainedbeforetreatmentisinitiated.This

isparticularlyimportantifceftazidimeisusedasamonotherapy.

Ceftazidimeshouldbeusedincombinationwithanotherantibioticwhentreatinginfectionsthatareprobablyduetoa

mixtureofsensitiveandresistantstrainsofbacteria.Forexample,combinationtreatmentwithanantibacterial

substancethatisactiveagainstanaerobicbacteriashouldbeconsiderediftheinfectionisassumedtobeduetoaerobic

Residualrenal

function(creatinine

clearanceml/min) Maintenancedose(mg)atanultrafiltration

rate(ml/min)of a

5 16.7 33.3 50

0 250 250 500 500

5 250 250 500 500

10 250 500 500 750

15 250 500 500 750

20 500 500 500 750

Residualrenalfunction

(creatinineclearance

ml/min) Maintenancedose(mg)atadialysatein-flowrateof a

1.0litre/hour 2.0litres/hour

Ultrafiltrationrate

(litres/hour) Ultrafilrationrate

(litres/hour)

1000

1000

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Specialcareisindicatedinpatientswhohaveexperiencedanyallergicreactiontopenicillinsoranyotherbeta-lactam-

antibioticsascross-reactionsmayoccur(forcontraindicationsduetoknownhypersensitivityreactionsseesection4.3).

SensitivebacterialstrainsofEnterobacterspp.andSerratiaspp.maydeveloparesistanceduringceftazidime

treatment.Ifitisclinicallyappropriateduringthetreatmentofsuchinfections,aperiodicsensitivitytestshouldbe

considered.

Antibiotic-associateddiarrhoea,colitisandpseudomembranouscolitisassociatedwithClostridiumdifficilehavebeen

reportedduringtheuseofceftazidime.Thesediagnosesshouldbeconsideredinanypatientwhodevelopsdiarrhoea

duringorimmediatelyaftertreatment.Ceftazidimeshouldbediscontinuedifsevereand/orbloodydiarrhoeaoccurs

duringtreatment,orasuitabletreatmentshouldbeinitiated.Peristalticinhibitorsarecontraindicated.

Ceftazidimeshouldbeusedwithcautioninpatientswithgastrointestinaldiseases,particularlycolitis.

Ceftazidimehasnotbeenshowntobenephrotoxic.However,thetotaldailydoseshouldbereducedwhenceftazidime

isadministeredtopatientswithacuteorchronicrenalinsufficiencytoavoidpossibleclinicalconsequencessuchas

convulsiveattacks(seepoint4.2).

Cephalosporinantibioticsshouldbegivenwithcautiontopatientsbeingtreatedconcomitantlywithnephrotoxicdrugs,

e.g.aminoglycosideantibioticsorstrongdiuretics(e.g.furosemide),sincethesecombinationsmayhaveanegative

influenceonrenalfunctionandhavebeenassociatedwithototoxicity(seepoints4.5and4.8).

Ceftazidimeandaminoglycosidesshouldnotbemixedinthesolutionforinjectionbecauseoftheriskforprecipitation

(seesection6.2).

TheuseofceftazidimemayresultintheproliferationofresistantmicroorganismssuchasEnterococciandCandida

spp.

Duringlong-termtreatmentwithceftazidimeitisrecommendedthatthebloodcompositionofthepatientberegularly

monitoredandthatregularbloodsamplesaretakentomonitorhepaticandrenalfunction.

Ifcopperreductionmethodsareemployed(Benedict’stest,Fehling’stest,Clinitest),minorinterferencemaybeseen

whenceftazidimeisadministered.Enzyme-basedtestsforglucosuriaarenotinfluenced,noristhealkalinepicrate

assayofcreatinine.

ThedevelopmentofapositiveCoombs’testin5%ofpatientswhenusingceftazidimemayinterferewithbloodcross-

matching.

Sodiumcontent

Thisproductcontainssodium(seesection2).

Patientsonacontrolledsodiumdietmustallowforthesodiumcontent.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Chloramphenicol,macrolidesandtetracyclineshavebeenshown,invitro¸tohaveanantagonisticeffectonceftazidime

andothercephalosporins.Theclinicalrelevanceofthisisnotknown,butifconcomitantadministrationofceftazidime

andchloramphenicol(orotherbacteriostaticsubstances:e.g.tetracycline,macrolidesorsulphonamides)isproposed,

thepossibilityofantagonismshouldbeconsidered.

Concomitanttreatmentwithnephrotoxicdrugsshouldbeavoided.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearelimitedamountsofdatafromtheuseofceftazidimeinpregnantwomen.Animalstudiesdonotindicatedirect

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development(seesection5.3).

Cautionshouldbeexercisedwhenprescribingtopregnantwomen.

Lactation

Ceftazidimeisexcretedinhumanmilkinsmallquantitiesbutattherapeuticdosesofceftazidimenoeffectsonthe

breast-fedinfantareanticipated.Ceftazidimecanbeusedduringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

Considerationshouldbegiventothefactthatdizzinessandconvulsionsmayoccurwhendrivingorusemachines.

4.8Undesirableeffects

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.

Approx.5%ofthepatientstreatedsufferfromundesirableeffects.

Organsystem

class Common(

1/100to<1/10) Uncommon(

1/1,000to<1/100) Rare(1/10,000to

<1/1,000) Veryrare

(<1/10,000)

Bloodand

lymphatic

system

disorders Eosinophilia,

thrombocytosis Thrombocytopaenia,

leucopaenia,

neutropaenia,

lymphocytosis.

PositiveCoomb’s

test Agranulocytosis,

haemolytic

anaemia

Immune

system

disorders Angioneurotic

oedema,

anaphylactic

reactions

Nervous

system

disorders Headache,

dizziness,

consciousness,

disorders,

parathesiasand

dysgeusia,

convulsions

Hepatobiliary

disorders Increasedserum

activityofliver

derivedenzymes,

e.g.gamma

glutamyl

transferase,lactate

dehydrogenase,

alkaline

phosphatase,

alanine

transminase,

aspartate

Jaundice

Gastrointestinal

disorders Nausea,vomiting,

diarrhoea,stomach

pains Thrush,

pseudomembranous

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Therehavebeenreportsofneurologicalafter-effects,includingtremor,myoclonus,convulsions,encephalopathyand

comainpatientswithimpairedrenalfunctionwhoseceftazidimedosehasnotbeensuitablyreduced.

ThereisariskofsuperinfectionswithEnterococcusandCandidastrains,forexample.

Nephrotoxicityhasbeenreportedafterconcomitantadministrationofcephalosporinsandaminoglycosideantibioticsor

strongdiuretics,e.g.furosemide.Renalfunctionshouldbecloselymonitored,particularlyifhigherdosesof

aminoglycosidearegivenorifthetreatmentisextendedbecauseofthepotentialnephro-andototoxicityof

aminoglycosideantibiotics(seepoints4.4and4.5).

4.9Overdose

Anoverdoseofceftazidimemaybeassociatedwithpain,inflammationandphlebitisatthepointofinjection.

Overdoseoradministrationofunsuitablyhighdosescombinedwithrenalinsufficiencymayresultinneurological

after-effects,includingdizziness,paraesthesias,headache,encephalopathy,convulsionsandcoma.

Abnormallaboratoryvalueswhichmayoccurafteranoverdoseincludeanincreaseinserumconcentrationsof

bilirubin,creatinine,urea,increaseintheserumactivityofliver-derivedenzymes,e.g.ASATandALAT,positive

Coombs’test,thrombocytosis,thrombocytopaenia,eosinophilia,leucopaeniaandanextensionofprothrombintime.

Generalsymptomaticandsupportiveproceduresshouldbeinstitutedtogetherwithspecificproceduresaimedat

monitoringconvulsiveattacks.Incaseofaseriousoverdose,particularlyinpatientswithrenalfailure,combined

Skinand

subcutaneous

tissuedisorders Urticariarash,

pruritus,redness,

maculopapulous

rash(exanthema) Erythema

multiforme,

Stevens-Johnson

syndrome,toxic

epidermal

necrolysis

Renaland

urinary

disorders Reductionof

glomerular

filtrationrateand

increaseinserum

concentrationof

ureaandcreatinine

Pregnancy,

puerperiumand

perinatal

conditions Vaginal

candidiasis,

vaginitis

General

disordersand

administration

siteconditions Phlebitisor

thrombophlebitis,

pains,

inflammationof

thepointof

injectionor

intravenous

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

OTHERBETA-LACTAMANTIBACTERIALS,thirdgenerationcephalosporins

ATCcode:J01DD02

Mechanismofaction

Ceftazidimeisasemi-syntheticbactericidalantibacterialsubstancebelongingtothecephalosporinclass.Likeother

beta-lactamdrugs,ceftazidimedisplaysantibacterialactivitybybindingitselftoandinhibitingtheactionofcertain

synthesisenzymes(transpeptidases)inthecellwallofthebacteria.Inhibitionofoneormoreoftheseessential

penicillin-bindingproteinsresultsinaninterruptionincellwallbiosynthesisinthefinalstageofpeptidoglycane

production,whichgivesrisetodissolutionofthecellofthebacteriumanditsdeath.

PK/PDrelationship

Theantibacterialisdependentonthetimethefreeconcentrationinserum/urineexceedstheirMIC-value.

Resistancemechanism

Bacterialresistancetoceftazidimemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbymeansofbetalactamases.Ceftazidimecanbeeffectivelyhydrolysedbysomeofthebroadspectrum

beta-lactamases(ESBLs)andbychromosomedecoded(AmpC)enzymeswhichcanbeinducedorundergostablede-

repressionincertainaerobicgram-negativestrainsofbacteria

reducedaffinityofpenicillin-bindingproteinstoceftazidime

exteriormembraneimpermeabilitywhichlimitstheaccessofceftazidimetopenicillin-bindingproteinsingram-

negativebacteria

drugeffluxpumps

Morethanoneoftheseresistancemechanismsmayoccursimultaneouslyinonesinglebacterialcell.Dependingonthe

existingmechanism(s)bacteriamaydisplaycross-resistancetoseveralorallotherbeta-lactamsand/orantibacterial

substancesbelongingtoanotherclass.

Breakpoints(accordingtoEUCAST)

ClinicalMICbreakpointsforseparatingsensitive(S)pathogensfromresistant(R)pathogensaccordingtoEUCAST

(27.04.2010)are:

Enterobacteriaceae:S<1.0mg/l;R>4mg/l

Pseudomonasspp.:S<8*mg/l;R>8mg/l

Non-speciesrelatedbreakpoints:S<4mg/l;R>8mg/l

*Thebreakpointsrelatetohighdosetherapy(2gx3)

Sensitivity

Theprevalenceofacquiredresistancemayverygeographicallyandwithtimeforselectedspeciesandlocalinformation

onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought

whenthelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsis

questionable.

Commonlysusceptiblespecies

Gram-positivemicroorganisms

Streptococcusagalactiae(groupB)

Streptococcuspyogenes

Gram-negativemicroorganisms:

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++ESBLproducingstrainsarealwaysresistant

+++Inatleastoneregiontheresistanceisover50%

#Exhibitssomein-vitroactivitytopenicillin-sensitivestrains,butthisshouldnotbereliedoninthetreatmentof

pneumococcalinfections

5.2Pharmacokineticproperties

Meanmaximumserumconcentrationsafterdifferentdosesandwithdifferentmethodsofadministrationwereas

Moraxellacatarrhalis

Proteusmirabilis ++

Proteusvulgaris

Serratialiquefaciens

Speciesforwhichacquiredresistancemaybeaproblem

Gram-positivemicroorganisms:

StaphylococcusaureusMSSA

Streptococcuspneumoniae#

Gram-negativemicroorganisms:

Escherichiacoli ++

Acinetobacterspp.

Burkholderiacepacia

Citrobacterfreundii

EnterobacteraerogenesandEnterobactercloacae

Klebsiellapneumoniae ++

Klebsiellaoxytoca ++

Morganellamorganii

Pseudomonasaeruginosa

Serratiamarcescens

Stenotrophomonasmaltophilia +++

Inherentlyresistantorganisms

Gram-positivemicroorganisms:

Enterococcusspp.

Staphylococcusaureus,methicillinresistant(MRSA)

Staphylococcus–coagulasenegative,methicillinresistant.

Anaerobes:

Bacteroidesfragilis

Clostridiumdifficile

Other:

Chlamydiaspp.

Chlamydophilaspp.

Legionellaspp.

Mycoplasmaspp.

Treponemapallidum

Intravenousbolusinjection

(after5minutes)

250mg 26mg/l

500mg 45mg/l

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*measuredinpatientswithcysticfibrosiswhosedistributionvolumemaybeincreased

Serumconcentrationsafterintravenousinfusion.

Generallytheplasmaconcentrationofceftazidimeexceeds2mg/l8hoursafterintravenousadministrationof500mg

ormore.

Afterrepeatedintravenousdosesof1and2gevery8hoursfor10days,nosignsofaccumulationofceftazidimewere

seenintheseruminpersonswithnormalrenalfunction.

Distribution

Lessthan10%ofceftazidimeisproteinbound,andthedegreeofproteinbindingisindependentoftheconcentration.

Ceftazidimeconcentrationswhicharehigherthantheminimuminhibitionconcentrationforgeneralpathogenscanbe

obtainedintissuessuchasbones,heartandgallbladder,sputum,chamberwall,synovial,pleuralandperitonealfluids.

Ceftazidimequicklypassesthroughtheplacenta.

Ceftazidimeonlypassesthroughtheblood-brainbarriertoasmallextentandlowconcentrationsareobtainedinthe

cerebrospinalfluidintheabsenceofinflammation.Therapeuticlevelsof4-20mg/mlormoreareobtainedinthe

cerebrospinalfluidinthecaseofmeningealinflammation.

Elimination

Approx.80-90%ofaceftazidimedoseiseliminatedunconvertedviathekidneysoveraperiodof24hours,which

givestohighconcentrationsintheurine.

Inpersonswithnormalrenalfunctionthehalflifeofceftazidimeisapprox.2hoursafterintravenousorintramuscular

administration.

Impairedliverfunctionhadnoeffectonthepharmacokineticsofceftazidimeinpersonswhoreceived2gintravenously

every8hoursfor5days.Doseadjustmentisnotthereforenecessaryinpatientswithimpairedhepaticfunctionunless

therenalfunctionisalsoimpaired.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeat

dosetoxicity,genotoxicity,toxicitytoreproduction.Carcinogenicitystudieshavenotbeenperformedwithceftazidime.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

2g 170mg/l

3g 200-300mg/l*

Ceftazidime

Intravenous

infusiondose Serumconcentrations(µg/ml)

0.5hour 1hour 2hours 4hours 8hours

500mg 42 25 12 6 2

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6.2Incompatibilities

Ceftazidimeandaminoglycosidesmustnotbemixedinthesameinfusionsolutionduetotheriskofprecipitation.

Cannulaeandcathetersforintravenousapplicationmustberinsedwithisotonicsaltwaterbetweentheadministration

ofceftazidimeandvancomycintoavoidprecipitation.

Thismedicinalproductmustnotbemixedwithothermedicinalproductsexceptthosementionedinsection6.6.

6.3Shelflife

Vialbeforebreakingopen:

1year

Vialafterbreakingopen:

Theproductshouldbeusedimmediately

Afterreconstitution:

Theproductshouldbeusedimmediately

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuser.

Chemicalandphysicalin-usestabilityhasbeendemonstratedfor:

6hoursat2ºC-8oCwhenpreparedin0.9%(9mg/ml)SodiumChlorideInjectionand5%(50mg/ml)Dextrose

Injection

12hoursat2ºC-8oCwhenpreparedinSterileWaterforInjection

12hoursat2ºC-8oCwhenpreparedin5%(50mg/ml)DextroseInjection,CompoundSodiumLactateInjection,

Dextran40Injection10%in0.9%(9mg/ml)SodiumChlorideInjectionandDextran40Injectionin10%in5%

(50mg/ml)DextroseInjection

12hoursat2ºC-8oCwhenCeftazidimeforInjection2g(4mg/mL)ispreparedwithCefuroximeSodium

(3mg/mL),Heparin(10µ/mL),PotassiumChloride(10mEq/L)andCloxacillinSodium(4mg/mL)in0.9%

(9mg/ml)SodiumChlorideInjection.

24hoursat2ºC-8oCwhenpreparedin0.9%(9mg/ml)SodiumChlorideInjection

6.4Specialprecautionsforstorage

Unopened:

Storebelow25°C

Keepthevialintheoutercartoninordertoprotectfromlight

Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

6.5Natureandcontentsofcontainer

2gpowderforinjectionorinfusion

Clear,colourlesstypeIglassvial(50ml)withbromobutylrubberstopperandpolypropyleneflip-offaluminiumseal,

32mmorangecoloured,bothsideslacquered.Thevialsareplacedincartons.Packsizes:boxesofone,fiveorten

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6.6Specialprecautionsfordisposalandotherhandling

Disposal

Forsingleuseonly.Discardanyunusedsolution.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

Thedilutionistobemadeunderasepticconditions.Thesolutionistobeinspectedvisuallyforparticulatematterand

discolorationpriortoadministration.Thesolutionshouldonlybeusedifthesolutionisclearandfreefromparticles.

Instructionsforreconstitution:

PreparationofsolutionsofCeftazidime

*SterileWaterforInjection

**Note:Additionshouldbeintwostages

Note:Use0.9%(9mg/ml)SodiumChlorideInjection,5%(50mg/ml)DextroseInjection,5%(50mg/ml)Dextroseand

0.9%(9mg/ml)SodiumChlorideInjection,Dextran40InjectionBP10%in0.9%(9mg/ml)SodiumChlorideInjection,

Dextran40InjectionBP10%in5%(50mg/ml)DextroseInjectionandCompoundSodiumLactateInjectionasSterile

WaterforInjectionproduceshypotonicsolutionsatthisconcentration

CompatibilityofCeftazidimeforInjection2g(4mg/mL)hasbeendemonstratedwithCefuroximeSodium(3mg/mL),

Heparin(10µ/mL),PotassiumChloride(10mEq/L)andCloxacillinSodium(4mg/mL)in0.9%(9mg/ml)Sodium

ChlorideInjection.

Allvialsassuppliedareunderreducedpressure.

Whenceftazidimeisdissolved,carbondioxideisreleasedandapositivepressuredevelops.Foreaseofuse,followthe

recommendedtechniquesofreconstitutiondescribedbelow.

Preparationfordirectadministrationfor2g

Thefollowingreconstitutionguidelinesshouldbefollowed:

1.Insertthesyringeneedlethroughtheoriginalvialclosureandinjecttherecommendedvolumeofdiluent.The

vacuummayassistentryofthediluent.

2.Removethesyringeneedle.

3.Shaketheoriginalvialtodissolvethecontent.Carbondioxideisreleasedandaclearsolutionwillbeobtainedin

about1to2minutes.

4.Inverttheoriginalvial.Withthesyringeplungerfullydepressed,inserttheneedlethroughthevialclosureand

withdrawthetotalvolumeofsolutionintothesyringe(thepressureinthevialmayaidwithdrawal).Ensurethatthe

needleremainswithinthesolutionanddoesnotentertheheadspace.

5.Thewithdrawnsolutionmaycontainsmallbubblesofcarbondioxide;theymaybedisregarded.

Forintravenousinjection,thesolutionmustbeadministereddirectlyintotheveinorintroducedintothetubingofthe

givingsetifthepatientisreceivingparenteralfluid(seeaboveforcompatiblefluids).

Preparationforadministrationof2gvialsbyinfusion

Amountofdiluentstobe

added(ml) Approximateceftazidime

concentration(mg/ml)

Intravenous-Injection

10.0* 170

Intravenous-Injection

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Prepareusingatotalof50mlofcompatiblediluent,addedinTWOstagesasbelow:

1.Insertthesyringeneedlethroughthevialclosureandadd10mlofdiluent.

Thevacuummayassistentryofthediluent.

2.Removethesyringeneedle.

3.Shaketheoriginalvialtodissolvethecontent.Carbondioxideisreleasedandaclearsolutionwillbeobtainedin

about1to2minutes.

4.Donotinsertagasreliefneedleuntiltheproducthasdissolved.Insertagasreliefneedlethroughthevialclosureto

relivetheinternalpressure.

5.Transferthereconstitutedsolutiontothefinaldeliveryvehicle,makinguptoatotalvolumeofatleast50ml,and

administerbyintravenousinfusionover15-30minutes.

Pleaserefertosection6.3forinusestabilityofthereconstitutedproduct.

Extemporaneoussolutionsforpaediatricsingledosesaretobereconstitutedwiththemostadequatestrengthinorderto

reduceasfaraspossiblevolumestobediscarded.Multipleuseofthesingledosecontainersisnotappropriate.The

reconstitutedproductshouldbeusedimmediately(seesection6.3).

Solutionsrangefromlightyellowtoamberdependingonconcentration,diluentandstorageconditionsused.Within

thestatedrecommendations,productpotencyisnotadverselyaffectedbysuchcolourvariations.

Beforeadministration,thereconstitutedanddilutedsolutionsshouldbeinspectedvisuallyforparticulatematterand

discoloration.Onlyclear,andcolourlesssolutionfreefromparticlesshouldbeused.

7MARKETINGAUTHORISATIONHOLDER

MartindalePharmaceuticalsLtd

BamptonRoad

HaroldHill

Romford

RM38UG

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA361/33/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8thJuly2011

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 18/07/2011 CRN 2103075 page number: 12