AZACTAM

Main information

  • Trade name:
  • AZACTAM Pdr for Soln Inj/Inf 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Pdr for Soln Inj/Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AZACTAM Pdr for Soln Inj/Inf 500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0002/052/001
  • Authorization date:
  • 05-03-1985
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0002/052/001

CaseNo:2049681

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

Bristol-MyersSquibbPharmaceuticalsLtd

Swords,Co.Dublin,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Azactam500mgPowderforSolutionforInjectionorInfusion,vial

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom11/08/2008until04/03/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Azactam500mgPowderforSolutionforInjectionorInfusion,vial

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontains500mgaztreonam.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Powderforsolutionforinjectionorinfusion

Asterilewhitetooff-white,sodium-freepowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ThetreatmentofthefollowinginfectionscausedbysusceptibleaerobicGram-negativemicro-organisms:

Urinarytractinfections:Includingpyelonephritisandcystitis(initialandrecurrent)andasymptomaticbacteriuria,

includingthoseduetopathogensresistanttotheaminoglycosides,cephalosporinsorpenicillins.

Gonorrhoea:Acuteuncomplicatedurogenitaloranorectalinfectionsincludinginfectionsduetobeta-lactamase

producingornon-producingstrainsofN.gonorrhoeae.

Lowerrespiratorytractinfections:Includingpneumonia,bronchitisandlunginfectionsinpatientswithcysticfibrosis.

Bacteraemia/septicaemia.

MeningitiscausedbyHaemophilusinfluenzaeorNeisseriameningitidis.SinceAzactamprovidesonlyGram

negativecover,itshouldnotbegivenaloneasinitialblindtherapy,butmaybeusedwithanantibioticactive

againstGrampositiveorganismsuntiltheresultsofsensitivitytestsareknown.

Boneandjointinfections.

Skinandsofttissueinfections:Includingthoseassociatedwithpostoperativewounds,ulcersandburns.

Intra-abdominalinfections:Peritonitis.

Gynaecologicalinfections:Pelvicinflammatorydisease,endometritis,andpelviccellulitis.

Azactamisindicatedforadjunctivetherapytosurgeryinthemanagementofinfectionscausedbysusceptible

organisms,includingabscesses,infectionscomplicatinghollowviscousperforations,cutaneousinfectionsand

infectionsofseroussurfaces.

Bacteriologicalstudiestodeterminethecausativeorganism(s)andtheirsensitivitytoaztreonamshouldbeperformed.

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Inpatientsatriskofinfectionsduetonon-susceptiblepathogens,additionalantibiotictherapyshouldbeinitiated

concurrentlywithAzactamtoprovidebroad-spectrumcoveragebeforeidentificationandsusceptibilitytestingresults

ofthecausativeorganism(s)areknown.Basedontheseresults,appropriateantibiotictherapyshouldbecontinued.

SomepatientswithseriousPseudomonasinfectionsmaybenefitfromconcurrentuseofAzactamandan

aminoglycosidebecauseoftheirsynergisticaction.Ifsuchconcurrenttherapyisconsideredinthesepatients,

susceptibilitytestsshouldbeperformedinvitrotodeterminetheactivityincombination.Theusualmonitoringof

serumlevelsandrenalfunctionduringaminoglycosidetherapyapplies.

4.2Posologyandmethodofadministration

Intramuscularorintravenousinjectionorintravenousinfusion.

Adults:

ThedoserangeofAzactamis1to8gdailyinequallydivideddoses.Theusualdoseis3to4gdaily.Themaximum

recommendeddoseis8gdaily.Thedosageandrouteofadministrationshouldbedeterminedbythesusceptibilityof

thecausativeorganisms,severityofinfection,andtheconditionofthepatient.

DosageGuide:

Theintravenousrouteisrecommendedforpatientsrequiringsingledosesgreaterthan1g,orthosewithbacterial

septicaemia,localisedparenchymalabscess(e.g.intra-abdominalabscess),peritonitis,meningitisorothersevere

systemicorlife-threateninginfections.BecauseoftheseriousnatureofinfectionsduetoPs.aeruginosa,adosageof

2gevery6to8hoursisrecommended,atleastforinitialtherapyinsystemicinfectionscausedbythisorganism.

Children:

Theusualdosageforpatientsolderthanoneweekis30mg/kg/doseevery6or8hours.Forsevereinfectionsin

patients2yearsofageorolder,50mg/kg/doseevery6to8hoursisrecommended.Thetotaldailydoseshouldnot

exceed8g.Dosageinformationisnotyetavailablefornew-bornslessthan1weekold.

Elderly:

Elderlypatientswithacreatinineclearanceinexcessof30ml/minshouldreceivethenormalrecommendeddose.If

renalfunctionisbelowthislevel,thedosagescheduleshouldbeadjusted(seeRenalImpairment).

Estimatedcreatinineclearanceshouldbeusedtodetermineappropriatedosage,sinceserumcreatinineisnotan

accuratemeasurementofrenalfunctioninthesepatients.

RenalImpairment:

Inpatientswithimpairedrenalfunctionthenormalrecommendedinitialdoseshouldbegiven.Thisshouldbefollowed

TypeofInfection Dosage

Frequency

(hr) Route

Urinarytract 0.5-1 8-12 IMorIV

Gonorrhoea/cystitis 1 singledose IM

CysticFibrosis 2 6-8 IV

Severeorlife-threateninginfections

either 1 8 IMorIV

EstimatedCreatinineClearance MaintenanceDose

10-30 Halftheinitialdose

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Thenormaldoseintervalshouldnotbealtered.

Inpatientsonhaemodialysis,asupplementaryone-eighthoftheinitialdoseshouldbegivenaftereachdialysis.

Reconstitution:

AzactamforInjectionissuppliedin15mlvials.Upontheadditionofthediluentthecontentsshouldbeshaken

immediatelyandvigorously.VialsofreconstitutedAzactamarenotintendedformulti-doseuse,andanyunused

solutionfromasingledosemustbediscarded.Dependingonthetypeandamountofdiluent,thepHrangesfrom

4.5to7.5,andthecolourmayvaryfromcolourlesstolightstraw-yellow,whichmaydevelopaslightpinktinton

standing;howeverthisdoesnotaffectthepotency.

Forintramuscularinjection:Foreachgramofaztreonamaddatleast3mlofWaterforInjectionsPhEuror0.9%

SodiumChlorideInjectionBPandshakewell.

Azactamisgivenbydeepinjectionintoalargemusclemass,suchastheupperouterquadrantofthegluteusmaximus

orthelateralpartofthethigh.

Forintravenousinjection:Tothecontentsofthevialadd6to10mlofWaterforInjectionsPhEur,andshakewell.

Slowlyinjectdirectlyintotheveinoveraperiodof3to5minutes.

Forintravenousinfusion:Eachgramofdrugshouldbereconstitutedinitiallywithatleast3mlofWaterfor

Injections.Thissolutionshouldthenbedilutedintheappropriateinfusionsolutiontoaconcentrationnot

exceeding1gofdrugper50mlofsolution.Theinfusionshouldbeadministeredover20-60minutes.

Appropriateinfusionsolutionsinclude:

0.9%SodiumChlorideInjectionBP;

5%GlucoseIntravenousInfusionBP;

5%,10%MannitolIntravenousInfusionBP;

SodiumLactateIntravenousInfusionBP;

0.9%,0.45%or0.2%SodiumChlorideand5%GlucoseIntravenousInfusionBP;

CompoundSodiumChlorideInjectionBPC1959(Ringer’sSolutionforInjection);

CompoundSodiumLactateIntravenousInfusionBP(Hartmann’sSolutionforInjection).

AvolumecontroladministrationsetmaybeusedtodelivertheinitialsolutionofAzactamintoacompatibleinfusion

solutionbeingadministered.WithuseofaY-tubeadministrationset,carefulattentionshouldbegiventothecalculated

volumeofAzactamsolutionrequiredsothattheentiredosewillbeinfused.

WithintermittentinfusionofAzactamandanotherdrugviaacommondeliverytube,thetubeshouldbeflushedbefore

andafterdeliveryofAzactamwithanyappropriateinfusionsolutioncompatiblewithbothdrugsolutions.Exceptfor

theantibioticsdescribedbelow,thedrugsshouldnotbedeliveredsimultaneously.

IntravenousinfusionsolutionsofAzactamforInjectionpreparedwith0.9%SodiumChlorideInjectionBPor5%

GlucoseIntravenousInfusionBP,towhichclindamycinphosphate,gentamicinsulphate,tobramycinsulphate,or

cephazolinsodiumhavebeenaddedatconcentrationsusuallyusedclinically,arestableforupto24hoursina

refrigerator(2-8°C).Ampicillinsodiumadmixtureswithaztreonamin0.9%SodiumChlorideInjectionBParestable

for24hoursinarefrigerator(2-8°C);stabilityin5%GlucoseIntravenousInfusionBPiseighthoursunder

Single-Dose

VialSize VolumeofDiluent

tobeadded

0.5g 1.5ml

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Ifaztreonamandmetronidazolearetobeusedtogether,theyshouldbeadministeredseparatelyasacherryredcolour

hasbeenobservedafterstorageofsolutionscontainingcombinationsofthetwoproducts.

4.3Contraindications

PatientswithaknownhypersensitivitytoaztreonamorL-arginine.

Aztreonamiscontraindicatedinpregnancy.Aztreonamcrossestheplacentaandentersthefoetalcirculation.

4.4Specialwarningsandprecautionsforuse

Precautions

Thebiologicalhalf-lifeisprolongedinpatientswithrenalinsufficiencyorcreatinineclearanceoflessthan30ml/min.

Dosageadjustmentsshouldbebasedoncreatinineclearance.

Insofarastheelderlymayhaveasignificantdegreeofrenaldysfunction,dosageofthedrugshouldbeundertaken

withparticularcare.(Seesectionondosageandadministrationintheelderly).

Concurrenttherapywithotherantimicrobialagentsandaztreonamisrecommendedasinitialtherapyinseriouslyill

patientswhoareatriskofhavinganinfectionduetopathogensthatmaynotbesusceptibletoaztreonam.

Experienceinpatientswithimpairedhepaticfunctionislimited.Appropriatemonitoringofliverfunctioninsuch

patientsisrecommendedduringtherapy.

Specificstudieshavenotshownsignificantcross-reactivitybetweenaztreonamandeitherpenicillinsor

cephalosporins.TheincidenceofhypersensitivitytoAzactaminclinicaltrialshasbeenverylowbutcautionshouldbe

exercisedinpatientswithahistoryofhypersensitivityuntilfurtherexperienceisgained.Itisrecommendedthat

prothrombintimesshouldbemonitoredifthepatientisonconcomitantanticoagulanttherapy.

Prolongeduseoftheantibioticmayresultinsuperinfectionbyorganismsresistanttothedrug.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Single-dosepharmacokineticstudieshavenotshownanysignificantinteractionbetweenaztreonamandgentamicin,

cephradine,clindamycinormetronidazole.

Nodisulfiram-likereactionswithalcoholingestionhavebeenreported.

4.6Pregnancyandlactation

Aztreonamiscontraindicatedinpregnancy.Aztreonamisexcretedinbreastmilkinconcentrationsthatarelessthan

1%ofthoseinsimultaneouslyobtainedmaternalserum.Lactatingmothersshouldrefrainfrombreastfeedingduring

thecourseoftherapy.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

ThefollowingsideeffectshavebeenreportedfromAzactamtherapy:

Azactamisgenerallywell-tolerated.

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epidermalnecrolysis.

Haematological:Eosinophilia;increasesinprothrombinandpartialthromboplastintimehaveoccurred.Therehave

beenisolatedreportsofthrombocytopenia,neutropenia,anaemia,bleedingandpancytopenia.

Hepatobiliary:Jaundiceandhepatitis;transientelevationsofhepatictransaminasesandalkalinephosphatase(without

overtsignsorsymptomsofhepatobiliarydysfunction).

Hypersensitivity:Anaphylaxis,angioedema,bronchospasm.

Gastrointestinal:Diarrhoea;veryrarelypseudomembranouscolitisorgastrointestinalbleeding,nauseaand/or

vomiting,abdominalcramps,mouthulcerandalteredtaste.

Localreactions:Phlebitisanddiscomfortatthei.v.injectionsite;discomfortatthei.m.injectionsite.

Rareinstancesofthefollowingeventshavebeenreported:Vaginitis,candidosis,seizures,dyspnoea,bronchospasm,

hypotension,weakness,confusion,dizziness,vertigo,sweating,headache,breasttenderness,halitosis,muscleaches,

fevermalaise,sneezingandnasalcongestion;transientincreasesinserumcreatinine.

4.9Overdose

Therehavebeennoreportedcasesofoverdosage.Ifnecessary,aztreonamcanberemovedfromthebodyby

haemodialysisand/orperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Aztreonamisamonocyclicbeta-lactam(monobactam)anti-infectivewithbactericidalactivityagainstaspectrumof

mostGram-negativeaerobicpathogens,includingPseudomonasaeruginosa.

AztreonamisactiveinvitroagainstmoststrainsofthefollowingGram-negativemicro-organisms:

Escherichiacoli,Enterobacterspecies,Klebsiellaspecies,(includingK.pneumoniaeandK.oxytoca),Proteus

mirabilis,Proteusvulgaris,Morganellamorganii,Providenciaspecies(includingP.stuartiiandP.rettgeri),

Pseudomonasspecies(includingPs.aeruginosa),Serratiamarcescens,Neisseriagonorrhoeae(including

penicillinase-producingstrains),Haemophilusinfluenzae(includingampicillin-resistantandotherpenicillinase-

producingstrains),Neisseriameningitidis,Citrobacterspecies.

Aztreonamdoesnotincludebeta–lactamaseactivityanditishighlyresistanttohydrolysisbythebeta-lactamases

producedbymostpathogens.

Certainantibiotics(e.g.cefoxitin,imipenem)mayinducehighlevelsofbeta-lactamaseinvitroinsomegram-negative

aerobessuchasEnterobacterandPseudomonasspecies,resultinginantagonismtoaztreonam.

5.2Pharmacokineticproperties

Aztreonamisthefirstmemberofanewclassofantibiotics,themonobactams.Ithasbeensynthesisedasamonocyclic

beta-lactamantibioticinwhichthesulphonicacidsubstituentinthe1-positionofthenuclearringactivatesthebeta-

lactammoiety.

Whilethedrugmayundergosomemetabolismintheliver,itisexcretedmostlyunchangedthroughbileandappearsto

undergomuchofitsbiotransformationinthegutlumen.Excretiondependsprincipallyonrenalpathways.

Single30-minutei.v.infusionsof0.5g,1.0g,and2.0ginhealthyvolunteersproducedimmediateserumlevelsof54,

90and240mg/l,andsingle3-minutei.v.injectionsofthesamedosesproducedpeaklevelsof58,125and242mg/l.

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doses,theserumconcentrationsarecomparableat1hour(1.5hoursfromthestartofi.v.infusion),withsimilarslopes

ofserumconcentrationsthereafter.

Theserumhalf-lifeofaztreonamaveraged1.7hoursinsubjectswithnormalrenalfunction,independentofthedose

androute.Inhealthysubjects60-70%ofasinglei.m.ori.v.dosewasrecoveredintheurineby8hours,andurinary

excretionwasessentiallycompleteby12hours.Inrenaldysfunction,thesetimesmaybeconsiderablyprolonged.

Aswithotherantibiotics,inthetreatmentofacutepulmonaryexacerbationsinpatientswithcysticfibrosis,while

clinicalimprovementisusuallynoted,lastingbacterialeradicationsmaynotbeachieved.

Unlikebroadspectrumantibiotics,aztreonamproducesnoeffectsonthenormalanaerobicintestinalflora.

5.3Preclinicalsafetydata

Aztreonamwaswelltoleratedinacomprehensiveseriesofpreclinicaltoxicityandsafetystudies.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

L-arginine(780mgpergofaztreonam)

6.2Incompatibilities

Azactamshouldnotbephysicallymixedwithanyotherdrug,antibioticordiluentexceptthoselistedinthedosageand

administrationsectionunderreconstitutionforintravenousinfusion.

6.3ShelfLife

(a)Productunopened: 3years.

(b)Reconstitutedproduct: SeeSection4.2Reconstitution.

Stabilityafterdilutionininfusionfluids:

Itisgoodpracticetoreconstituteimmediatelybeforeuse.Ifthisisnotpossible,Azactamisstablefor24hours(8hours

forglucoseintravenousinfusion)ifstoredinarefrigerator(2-8 o

C)whenreconstitutedwiththerecommendedinfusion

solutionstoafinalconcentrationnotexceeding2%w/v.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat

2to8ºCunlessreconstitution/dilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.4Specialprecautionsforstorage

Storagebeforereconstitution:

Donotstoreabove25 o

Storageafterreconstitution:

SeeSections4.2and6.3.

6.5Natureandcontentsofcontainer

TypeIIIPh.Eur.clearglassvial,closedwithsiliconedgreybutylrubberclosure,sealedwithaluminiumseal:packof

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forsingleuseonly.

Anycontentofproductremainingafteruseshouldbediscarded.

Fordetailedinstructionsonthereconstitutionoftheproduct,seeSection4.2.

7MARKETINGAUTHORISATIONHOLDER

Bristol-MyersSquibbPharmaceuticalsLimited

Swords

Co.Dublin

8MARKETINGAUTHORISATIONNUMBER

PA2/52/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:05March1985

Dateoflastrenewal:05March2005

10DATEOFREVISIONOFTHETEXT

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