CEFTAZIDIME

Main information

  • Trade name:
  • CEFTAZIDIME Pdr for Soln for Injection 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Pdr for Soln for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CEFTAZIDIME Pdr for Soln for Injection 500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/178/001
  • Authorization date:
  • 06-03-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Ceftazidime500mgpowderforsolutionforinjection.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontains582mgceftazidimepentahydratecorrespondingto500mgceftazidime

Excipients:

25.6mg(1.11mmol)ofsodium/vialofpowderforsolutionforinjection

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Powderforsolutionforinjection

Thepowderiswhiteoroff-white.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Ceftazidimeisindicatedfortheparenteraltreatmentofthefollowingbacterialinfectionswhencausedbypathogens

susceptibletoceftazidime(seesection5.1)onlyifpenicillinorapenicillinderivativewithanarrowerspectrumcannot

beused:

Nosocomialpneumonia

Lowerrespiratorytractinfectionsinpatientswithcysticfibrosis.

MeningitisowingtoaerobicGram-negativeorganisms.

Itisrecommendedthattheresultsofbacterialculturesandsusceptibilitytestsareknownbeforecommencingtreatment.

Thisisespeciallyimportantifceftazidimeistobeusedasmonotherapy.

Ceftazidimeshouldbeusedincombinationwithanadditionalantibacterialagent(s)whentreatinginfectionsthatare

likelytobeduetoamixtureofsusceptibleandresistantbacterialspecies.Forexample,combinationtherapywithan

antibacterialagentthatisactiveagainstanaerobicbacteriashouldbeconsideredwhentheinfectionisthoughttobedue

toaerobicandanaerobicbacteria.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

Routesofadministration:

250mg,500mgand1000mgPowdersolutionforinjection:

Intravenoususe

Intramuscularuse(onlyexceptionalclinicalsituations)

1g,2gand3gPowderforsolutionforinfusion:

Intravenoususe

Posology

Thedosagedependsupontheseverity,sensitivityandtypeofinfectionandtheage,weightandrenalfunctionofthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 1

Inthepresenceofnormalrenalfunction:

Inacutelyillelderlypatientstheclearanceoftheceftazidimeisusuallydecreased

Serumhalf-lifeofceftazidimecanbe3to4timesthatofadults.

Thedurationoftherapydependsonthepatientresponse.Ingeneral,treatmentshouldbecontinuedforatleast48hours

afterclinicalrecovery.

Impairedrenalfunction

Ceftazidimeisnotmetabolisedandisonlyeliminatedbyglomerularfiltration.Forpatientswithimpairedrenal

function(i.e.creatinineclearance<50ml/min)thedoseshouldbereducedaccordingtothefollowingtable-,inorderto

compensatefortheprolongedelimination:aninitialloadingdoseof1gofceftazidimemaybegiven,followedbyan

appropriatemaintenancedoseasinthetable:

*Thesevaluesareguidelinesandmaynotaccuratelypredictrenalfunctioninallpatientsespeciallyin

theelderlyinwhomtheserumcreatinineconcentrationmayoverestimaterenalfunction.

Inpatientswithacombinationofrenalinsufficiencyandsevereinfections,especiallypatientswhohaveneutropenia,

theunitdosegiveninthetableabovemaybeincreasedby50%orthedosingfrequencyincreasedappropriately.In

suchpatients,ifpossible,theserumconcentrationofceftazidimeshouldbemonitoredandtroughconcentrations(blood

sampletakenimmediatelybeforenextdose)shouldnotexceed40mg/litre.

Inchildrenwithrenalinsufficiencythecreatinineclearanceshouldbeadjustedforbodysurfaceareaorleanbodymass

andthedosingfrequencyreducedasforadults.

Inpatientsonhaemodialysis

Theserumhalf-lifeofceftazidimeduringhaemodialysisrangesfrom3to5hours.Theappropriatemaintenancedoseof

AgeGroup Infection UsualDose

Adults Mostuses 1g8-hourly(3g/day)OR

2g12-hourly(4g/day)

Nosocomialpneumonia.

Severeinfectionsand

infectionsinneutropenic

patients 2g8-hourly(6g/day)

Lowerrespiratorytractinfectionin

patientswithcysticfibrosis. 100-150mg/kg/dayinthree

divideddoses;nottoexceed

9g/day

Elderly Allinfections,especiallyin

those>80years Nottoexceed3gdailytotal 1

Infants>2

months,toddlersand

children Mostuses 30-100mg/kg/dayintwoorthreedivided

doses

Severeinfections Upto150mg/kg/day(max6gtotalperday)

inthree

divideddoses

Newborninfantsand

infants<2months Mostuses 25-60mg/kg/dayintwodivided

doses 2

Creatinineclearance

ml/min Approx.serumcreatinine*µmol/l

(mg/dl) Recommendedunitdose

ofceftazidime(g) Frequencyofdosing

(hourly)

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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 2

Forpatientsinrenalfailureoncontinuousarteriovenoushaemodialysisorhigh-fluxhaemofiltrationinintensive

therapyunits,itisrecommendedthatthedosageshouldbe1gdailyindivideddoses.Forlow-fluxhaemofiltrationitis

recommendedthatthedosageshouldbethatsuggestedunderimpairedrenalfunction.

Forpatientsonvenoushaemofiltrationandvenoushaemodialysis,followthedosagerecommendationsinthetables

below:

Continuousvenoushaemofiltrationdosageguidelinesforceftazidime

Maintenancedosetobeadministeredevery12hours

Ceftazidimedosageguidelinesduringcontinuousvenoushaemodialysis

Maintenancedosetobeadministeredevery12hours

Dosageinhepaticinsufficiency

Nodoseadjustmentisrequiredunlessthereisconcomitantrenalinsufficiency.

Methodofadministration

Onlyfor250mg,500mgand1000mgpowdersolutionforinjection

Ceftazidimemaybegivenintravenouslybyslowbolusinjectionoverafewminutesorbydeepintramuscularinjection

intoalargemusclemass,suchastheupperouterquadrantofthegluteusmaximusorlateralpartofthethigh.

Theintramuscularmethodofadministrationisreservedtoexceptionalclinicalsituationsandshouldundergoarisk-

benefitassessment.

Onlyfor1g,2gand3gPowderforsolutionforinfusion

Ceftazidimemaybegivenintravenouslybyinfusionover20-30minutes.

For250mg,500mgand100mgPowdersolutionforinjectiononly:

Incaseoftheuseofthelocalanaestheticlidocainehydrochloridesolution1%asdiluentofCeftazidimefor

intramuscularinjection,theSummaryofProductCharacteristicsoflidocainehydrochloride1%solutionshouldbe

takenintoaccount.

Residualrenalfunction

(creatinineclearance

ml/min) Maintenancedose(mg)foraultrafiltrationrate(ml/min)of a

16.7 33.3 50

Residualrenalfunction

(creatinineclearance

ml/min) Maintenancedose(mg)foradialysateinflowrateof a

1.0litre/hour 2.0litres/hour

Ultrafiltrationrate(litre/hour) Ultrafiltrationrate(Litre/hour)

1000

1000

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 3

4.3Contraindications

Hypersensitivitytoceftazidime,toanyofthecephalosporinsortosodiumcarbonate.

Previousimmediateand/orseverehypersensitivityreactiontopenicillinortoanyothertypeofbeta-lactamdrug.

4.4Specialwarningsandprecautionsforuse

Beforetherapywithceftazidimeisinstituted,carefulinquiryshouldbemadetodeterminewhetherthepatienthashad

anyprevioushypersensitivityreactionstoceftazidime,cephalosporins,penicillins,orotherbeta-lactamdrugs.

Ceftazidimeiscontraindicatedinpatientswhohavehadaprevioushypersensitivityreactiontoanycephalosporin.Itis

alsocontraindicatedinpatientswhohavehadapreviousimmediateand/oranyseverehypersensitivityreactiontoany

penicillinortoanyotherbeta-lactamdrug.Ceftazidimeshouldbegivenwithcautiontopatientswhohavehadany

othertypeofhypersensitivityreactiontoapenicillinoranyotherbeta-lactamdrug.

Aswithotherextended-spectrumcephalosporinsandpenicillins,someinitiallysusceptiblestrainsofEnterobacterspp.

andSerratiaspp.maydevelopresistanceduringceftazidimetherapy.Whenclinicallyappropriateduringtherapyof

suchinfections,periodicsusceptibilitytestingshouldbeconsidered.

Antibiotic-associateddiarrhoea,colitisandpseudomembranouscolitislinkedtoClostridumDifficilehaveallbeen

reportedwiththeuseofceftazidime.Thesediagnosesshouldbeconsideredinanypatientwhodevelopsdiarrhoea

duringorshortlyaftertreatment.Ceftazidimeshouldbediscontinuedifsevereand/orbloodydiarrhoeaoccursduring

treatmentandappropriatetherapyinstituted.Anti-peristalticsarecontraindicated.

Ceftazidimeshouldbeusedwithcautioninindividualswithaprevioushistoryofgastro-intestinaldisease,particularly

colitis.

Ceftazidimehasnotbeenshowntobenephrotoxic.However,thetotaldailydosageshouldbereducedwhen

ceftazidimeisadministeredtopatientswithacuteorchronicrenalinsufficiencyinordertoavoidpotentialclinical

consequences,suchasseizures(seesection4.2).

Cephalosporinantibioticsshouldbegivenwithcautiontopatientsreceivingconcurrenttreatmentwithnephrotoxic

drugssuchasaminoglycosideantibioticsorpotentdiuretics(suchasfrusemide)asthesecombinationsmayhavean

adverseeffectonrenalfunctionandhavebeenassociatedwithototoxicity(seesection4.5and4.8).

Aswithothercephalosporins,useofceftazidimemayresultintheovergrowthofresistantorganisms,suchas

EnterococciandCandidaspp.

Duringlong-termtreatmentwithceftazidime,itisrecommendedthereareregularchecksonthecellularcompositionof

thepatient’sbloodandthatthereareregularbloodtestsofliverandrenalfunction.

Slightinterferencewithcopperreductionmethods(Benedict'stest,Fehling'stest,Clinitest)maybeobservedwhen

ceftazidimeisgiven.Enzyme-basedtestsforglycosuriaarenotaffected,noristhealkalinepicrateassayforcreatinine.

ThedevelopmentofapositiveCoombs'testassociatedwiththeuseofceftazidimeinabout5%ofpatientsmay

interferewiththecross-matchingofblood.

Sodiumcontent:

Ceftazidime500mgcontains25.6mg(1.11mmol)sodiumpervial.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 4

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Invitro,chloramphenicol,macrolides,andtetracyclineshavebeenshowntobeantagonistictoceftazidimeandother

cephalosporins.

Theclinicalrelevanceofthisfindingisunknown,butifconcurrentadministrationofceftazidimewithchloramphenicol

(orotherbacteriostaticagents:e.g.tetracycline,macrolides,orsulfonamides)isproposed,thepossibilityofantagonism

shouldbeconsidered.

Concomitanttreatmentwithnephrotoxicmedicinalproductsshouldbeavoided(seesections4.4and4.8).

4.6Fertility,pregnancyandlactation

Pregnancy

Thereisnoevidenceofembryotoxicityorteratogenicityinanimalstudies,butthereisnoexperienceofsafetyinuse

duringhumanpregnancy.Ceftazidimeshouldthereforeonlybeusedduringpregnancyifconsideredessentialbythe

physician.

Lactation

Ceftazidimeisexcretedinhumanmilkinlowconcentrationsandshouldbeusedwithcautioninnursingmothers.

Diarrhoeaandfungusinfectionofthemucousmembranescouldoccurinthebreast-fedinfant,sothatnursingmight

havetobediscontinued.Theinfantmayalsobecomeallergictoceftazidime.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

Thepossibilitythatdizzinessandconvulsionsmayoccurshouldbetakenintoaccountwhendrivingoroperating

machinery.

4.8Undesirableeffects

Approximately5%ofthetreatedpatientsexperienceundesirableeffects.

Organsystem

class Common

(1/100to<1/10) Uncommon

(1/1,000to<

1/100) Rare

(1/10,000to

<1,000) Veryrare

(<10,000)

Bloodand

lymphaticsystem

disorders Eosinophilia,

thrombocytopenia,

thrombocytosis,

leukopenia,

neutropenia,

lymphocytosis.

PositiveCoombs’s

test. Agranulocytosis,

haemolytic

anaemia.

Immunesystem

disorders Angioneurotic

oedema,

Anaphylactic

reactions

Nervoussystem

disorders Headache,

dizziness,

disturbancesinthe

degreeof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 5

Therehavebeenreportsofneurologicalsequelae,includingtremor,myoclonia,convulsions,encephalopathyandcoma

inpatientswithrenalimpairmentinwhomthedoseofceftazidimehasnotbeenappropriatelyreduced.

Thereisariskofsuper-infectionswithe.g.EnterococcusandCandidaspecies.

Nephrotoxicityhasbeenreportedfollowingconcomitantadministrationofcephalosporinsandaminoglycoside

Paresthesiaand

dysgeusia,cramps.

Gastrointestinal

disorders Nausea,vomiting,

diarrhoea,

abdominalpain. Oralthrush,

pseudo-

membranous

colitis.

Renalandurinary

disorders Reductionof

glomerular

filtrationrateand

increaseinserum

concentrationof

urea,and

creatinine.

Skinand

subcutaneous

tissuedisorders Urticarialrash,

pruritus,flush,

Maculopapularrash

(exanthema). Erythema

multiforme,

Stevens-Johnsons

syndrome,toxic

epidermal

necrolysis.

Generaldisorders

administrationsite

conditions Phlebitisor

thrombophlebitis,

pain,inflammation

atthesiteof

injectionafter

intravenous

administration Fever

Genitals Vaginal

candidiasis,

vaginitis

Hepato-biliary

disorders Increasedserum

activitiesofliver-

derivedenzymes

suchasgamma-

glutamyl

transferase,lactate

dehydrogenase,

alkaline

phosphatase,

alanine

transaminase,

aspartate

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 6

Renalfunctionshouldbecarefullymonitored,especiallyifhigherdosagesoftheaminoglycosidearetobe

administeredoriftherapyisprolonged,becauseofthepotentialnephrotoxicityandototoxicityofaminoglycoside

antibiotics(see4.4and4.5).

4.9Overdose

Anoverdoseofceftazidimemaybeassociatedwithpain,inflammationandphlebitisattheinjectionsite.

Overdoseortheadministrationofinappropriatelylargedosesinthepresenceofrenalinsufficiencycanleadto

neurologicalsequelaeincludingdizziness,paraesthesiae,headache,encephalopathy,convulsionandcoma.

Laboratoryabnormalitiesthatmayoccurafteranoverdoseincludeincreasesintheserumconcentrationsofbilirubin,

creatinine,urea,increaseintheserumactivitiesofliverderivedenzymessuchasASTandALT,apositiveCoombs'

test,thrombocytosis,thrombocytopenia,eosinophilia,leucopeniaandprolongationoftheprothrombintime.

Generalsymptomaticandsupportivemeasuresshouldbeinstituted,togetherwithspecificmeasurestocontrolany

seizures.Incasesofsevereoverdose,especiallyinapatientwithrenalfailure,combinedhaemodialysisand

haemoperfusionmaybeconsideredifresponsetomoreconservativetherapyfails.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Thirdgenerationcephalosporins,ATCcode:J01DD02

Modeofaction

Ceftazidimeisasemi -syntheticbactericidalantibacterialagentofthecephalosporinclass.Likeotherbeta-lactam

drugs,ceftazidimeexertsantibacterialactivitybybindingtoandinhibitingtheactionofcertainbacterialcellwall

syntheticenzymes(transpeptidases).Inhibitionofoneormoreoftheseessentialpenicillin-bindingproteinsresultsin

theinterruptionofcellwallbiosynthesisatthefinalstageofpeptidoglycanproduction,resultinginbacterialcelllysis

anddeath.

Mechanismsofresistance

Bacterialresistancetoceftazidimemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbybeta -lactamases.Ceftazidimemaybeefficientlyhydrolysedbycertainoftheextended-spectrum

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

derepressedincertainaerobicGram -negativebacterialspecies

reducedaffinityofpenicillin -bindingproteinsforceftazidime

outermembraneimpermeability,whichrestrictsaccessofceftazidimetopenicillin-bindingproteinsin

Gram -negativeorganisms

drugeffluxpumps

Morethanoneofthesemechanismsofresistancemayco -existinasinglebacterialcell.Dependingonthemechanism

(s)present,bacteriamayexpresscross -resistancetoseveralorallotherbeta-lactamsand/orantibacterialdrugsof

otherclasses.

Breakpoints(accordingtoEUCAST)

ClinicalMICbreakpointstoseparatesusceptible(S)pathogensfromresistant(R)pathogensbyEUCAST(31.03.2006)

are:

Enterobacteriaceae:S1.0mg/l;R>8mg/l.

Pseudomonasspp.:S8mg/l;R>8mg/l.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 7

Susceptibility

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.

Resistancerateswerederivedfromthepercentagesusceptibility,thusintermediateandresistantstrainswereincluded.

Commonlysusceptiblespecies,i.e.resistance<10%inallEUMemberStates +

Gram-positivemicro-organisms:

Streptococcusagalactiae(GroupB)

Streptococcuspyogenes

Gram-negativemicro-organisms:

Escherichiacoli ++

Haemophilusinfluenzae

Moraxellacatarrhalis

Proteusmirabilis ++

Proteusvulgaris

Serratialiquefaciens

Speciesforwhichacquiredresistancemaybeaproblem,i.e.resistance>10%inatleastoneoftheEUMember

States +

:

Gram-positivemicro-organisms:

StaphylococcusaureusMSSA

Streptococcuspneumoniae#

Gram-negativemicro-organisms:

Acinetobacterspp.

Burkholderiacepacia

Citrobacterfreundii

EnterobacteraerogenesandEnterobactercloacae

Klebsiellapneumoniae ++

Klebsiellaoxytoca ++

Morganellamorganii

Pseudomonasaeruginosa

Serratiamarcescens

Stenotrophomonasmaltophilia +++

Streptococcuspneumoniae(Penicillin-intermediateand-resistant)

Inherentlyresistantorganisms

Gram-positivemicro-organisms:

Enterococcusspp.

Staphylococcusaureus,methicillinresistant(MRSA)

Staphylococcus–coagulasenegative,methicillinresistant

Anaerobes:

Bacteroidesfragilis

Clostridiumdifficile

Other:

Chlamydiaspp.

Chlamydophilaspp.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 8

Mycoplasmaspp.

Treponemapallidum

+

Basedonpublisheddatafromseveraldifferentsources

++

ESBLproducingstrainsarealwaysresistant

+++

Inatleastoneregionresistanceratesabove50%.

Showssomein-vitroactivityagainstpenicillin-susceptiblestrainsbutshouldnotbereliedupontotreatpneumococcal

infections.

5.2Pharmacokineticproperties

Theserummeanpeaklevelsofceftazidimeafterdifferentdosesandmodesofadministrationtosubjectswithnormal

renalfunctionwereasfollows:

*measuredincysticfibrosispatients,inwhomthevolumeofdistributionmightbeincreased

Serumconcentrationsfollowingintravenousinfusion:

Ingeneral,plasmaconcentrationsat8hoursafterintravenousorintramuscularadministrationof500mgormore

ceftazidimeareinexcessof2mg/l.Followingmultipleintravenousdosesof1gand2gevery8hoursfor10days,there

wasnoevidenceofaccumulationofceftazidimeintheserumofindividualswithnormalrenalfunction.

Distribution

Lessthan10%ofceftazidimeisproteinboundandthedegreeofproteinbindingisindependentofconcentration.

Concentrationsofceftazidimeinexcessoftheminimuminhibitorylevelsofcommonpathogenscanbeachievedin

tissuessuchasbone,heart,bile,sputum,aqueoushumour,synovial,pleuralandperitonealfluids.

Transplacentaltransferoftheantibioticreadilyoccurs.

Ceftazidimepenetratestheintactblood-brainbarrierpoorlyandlowlevelsareachievedintheCSFintheabsenceof

inflammation.Therapeuticlevelsof4to20mg/lormoreareachievedintheCSFwhenthemeningesareinflamed.

Elimination

Approximately80%to90%ofadoseofceftazidimeisexcretedunchangedbythekidneysovera24-hourperiod,

resultinginhighurinaryconcentrations.

Insubjectswithnormalrenalfunction,thehalf-lifeofceftazidimeisapproximately2hoursafterintravenousor

intramuscularadministration.

Thepresenceofhepaticdysfunctionhadnoeffectonthepharmacokineticsofceftazidimeinindividualswhoreceived

2gintravenouslyevery8hoursfor5days.Therefore,dosageadjustmentisnotrequiredforpatientswithhepatic

Intramuscularinjection

(after1hour) Intravenousbolus-injection

(after5minutes)

250mg

500mg

1g

2g

3g 18mg/l

39mg/l 26mg/l

45mg/l

90mg/l

170mg/l

200-300mg/l*

Ceftazidime

intravenousdose SerumConcentrations(µg/ml)

0.5hour 1hour 2hour 4hour 8hour

500mg 42 25 12 6 2

1g 60 39 23 11 3

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 9

5.3Preclinicalsafetydata

Longtermstudiesinanimalshavenotbeenperformedtoevaluatecarcinogenicpotential.However,amouse

micronucleustestandanAmestestwerebothnegativeformutageniceffects.

Theteratogenicityofceftazidimehasbeenstudiedinrabbits(i.m)andinmice(s.c.).Embryotoxicityandtoxicityto

rabbitsweredetected,butnoteratogeniceffects.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumcarbonate,anhydrous(E500)

6.2Incompatibilities

CeftazidimeshouldnotbemixedwithsolutionswithapHabove7.5forexamplesodiumbicarbonatesolutionfor

injection.Ceftazidimeandaminoglycosidesshouldnotbemixedinthesolutionforinfusionbecauseoftheriskfor

precipitation.

Cannulaeandcathetersforintravenoususeshouldbeflushedwithphysiologicalsalt-solutionbetweenadministrations

ofceftazidimeandvancomycintoavoidprecipitation.

6.3Shelflife

Vialbeforeopening:3years.

Vialafterfirstopening:Theproductshouldbeusedimmediately.

Afterreconstitution:Theproductshouldbeusedimmediately.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat2

to8ºC,unlessreconstitutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Unopened:Storebelow25°C.Keepvialintheoutercarton

Forstorageconditionsofthereconstitutedmedicinalproduct,seesection6.3.

6.5Natureandcontentsofcontainer

Nature:

ClearcolourlesstypeIII.Injectionvial(15ml)closedwithbromobutylrubberclosureandpolypropyleneflip-off

aluminiumcap.

Packsizes:10x1vial.

6.6Specialprecautionsfordisposalandotherhandling

Forsingleuseonly.Discardanyunusedsolution.

Thedilutionistobemadeunderasepticconditions.Thesolutionistobeinspectedvisuallyforparticulatematterand

discolorationpriortoadministration.Thesolutionshouldonlybeusedifthesolutionisclearandfreefromparticles.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 10

Thetablebelowshowstheamountofsolventtobeaddedforpreparingofasolutionforinjection/infusionand

approximatesolutionconcentrations(thismaybeusefulwhenfractionaldosesarerequired):

*Note:Additionofsolventshouldbeperformedintwostages.

Astheproductdissolves,carbondioxideisreleasedandapositivepressuredevelops.Hence,itisrecommendedthat

thefollowingtechniquesofreconstitutionareadopted.

For250mg,500mgand1000mgintramuscular,intravenoussolutionforinjection

Injectthediluentandshakewelltodissolve.

Carbondioxideisreleasedastheantibioticdissolves,generatingpressurewithinthevial.Thesolutionwill

becomeclearwithin1to2minutes.

Invertthevialandcompletelydepressthesyringeplungerpriortoinsertion.

Inserttheneedlethroughthevialstopper.Besuretheneedleremainswithinthesolutionandwithdrawcontents

ofthevialintheusualmanner.Pressureinthevialmayaidwithdrawal.

Thewithdrawnsolutionmaycontaincarbondioxidebubbles,whichshouldbeexpelledfromthesyringebefore

injection.

For1g,2gand3gsolutionforinfusion

Inject10mlofthediluentfor1gand2gvial;and15mlfor3gvial;shaketodissolve.

Carbondioxideisreleasedastheantibioticdissolves,generatingpressurewithinthevial.Thesolutionwill

becomeclearwithin1to2minutes.

Insertaventneedletoreleasepressurebeforeaddingofafurther40mlofdiluentfor1gand2gvialand60ml

for3gvial.Adddiluentandthenremovetheventneedle.

Additionalpressurethatmaydevelopinthevialespeciallyafterstorageshouldberelievedpriortoadministration

Ceftazidime Solventforintramuscular

injection Solventforintravenousinjection Solventforintravenousinfusion

Amountof

diluenttobe

added Approximate

concentration

(mg/ml) Amountof

diluenttobe

added Approximate

concentration

(mg/ml) Amountof

diluenttobe

added Approximate

concentration

(mg/ml)

250mg

500mg

1000mg

1g

2g

1.0ml

1.5ml

3.0ml

------

------

------

------

2.5ml

5.0ml

10.0ml

10.0ml

10.0ml

------

------

------

50.0ml*

50.0ml*

------

------

------

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 11

NOTE:Topreserveproductsterility,itisimportantthataventneedleisnotinsertedthroughthevialclosurebeforethe

producthasdissolved.

Thesesolutionsmaybegivendirectlyintotheveinorintroducedintothetubingofagivingsetifthepatientis

receivingparenteralfluids.

Byslowbolusinjectionoverafewminutesorbyinfusionover20-30minutes.

Otherinformation

Thecolouroftheceftazidimesolutionsrangefromlightyellowtoamberdependingontheconcentration,diluentand

storageconditionsused.Withinthestatedrecommendations,theproductpotencyisnotadverselyaffectedbysuch

colourvariation.

Ceftazidimepowderforinjectionorinfusionmaybemixedinthefollowingsolutionsforinfusion:

0.9%sodiumchloridesolution(physiologicsalinesolution)

5%glucosesolution

0.9%sodiumchloride+5%glucosesolution

Onlyfor250mg,500mgand1000mgpowdersolutionforinjection

Whenreconstitutedforintramuscularuse,theinjectioncanalsobedilutedwith1%lidocainesolutions.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLimited

WaterfordRoad

Clonmel

Co.Tipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA126/178/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:6 th

March2009

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 12/03/2012 CRN 2108136 page number: 12