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ZithromaxPowderforOralSuspension
SummaryofProductCharacteristicsUpdated13Jan2015|PfizerLimited

1.Nameofthemedicinalproduct
Zithromax200mgin5mlsuspension

2.Qualitativeandquantitativecomposition
Activeingredient:azithromycin.
ZithromaxPowderforOralSuspensionisadryblendofazithromycindihydrate209.64mg/5mlcontainingthe
equivalentof200mgazithromycinbaseper5mlonreconstitutionwithwater.
Excipientswithknowneffect
Sucrose
Forthefulllistofexcipients,seesection6.1.

3.Pharmaceuticalform
ZithromaxPowderforOralSuspensionisadrypowderwhichreconstituteswithwatertogiveacherry/bananaflavoured
suspensionwithaslightvanillaodour.

4.Clinicalparticulars
4.1Therapeuticindications
Azithromycinisindicatedforthetreatmentofthefollowinginfectionswhenknownorlikelytobeduetooneormore
susceptiblemicroorganisms(seesection5.1):
bronchitis
communityacquiredpneumonia
sinusitis
pharyngitis/tonsillitis(seesection4.4regardingstreptococcalinfections)
otitismedia
skinandsofttissueinfections
uncomplicatedgenitalinfectionsduetoChlamydiatrachomatisandNeisseriagonorrhoeae.
Considerationsshouldbegiventoofficialguidanceregardingtheappropriateuseofantibacterialagents.
4.2Posologyandmethodofadministration
Methodofadministration:
Zithromaxshouldbegivenasasingledailydose.
ZithromaxSuspensioncanbetakenwithfood.
Childrenover45kgbodyweightandadults,includingelderlypatients:Thetotaldoseofazithromycinis1500mg
whichshouldbegivenoverthreedays(500mgoncedaily).
InuncomplicatedgenitalinfectionsduetoChlamydiatrachomatis,thedoseis1000mgasasingleoraldose.For
susceptibleNeisseriagonorrheatherecommendeddoseis1000mgor2000mgofazithromycinincombinationwith250
or500mgofceftriaxoneaccordingtolocalclinicaltreatmentguidelines.Forpatientswhoareallergictopenicillinand/or
cephalosporins,prescribersshouldconsultlocaltreatmentguidelines.
Inchildrenunder45kgbodyweight:ZithromaxSuspensionshouldbeusedforchildrenunder45kg.Thereisno
informationonchildrenlessthan6monthsofage.Thedoseinchildrenis10mg/kgasasingledailydosefor3days:
Upto15kg(lessthan3years):Measurethedoseascloselyaspossibleusingthe10mloraldosingsyringeprovided.
Thesyringeisgraduatedin0.25mldivisions,providing10mgofazithromycinineverygraduation.
Forchildrenweighingmorethan15kg,ZithromaxSuspensionshouldbeadministeredusingthespoonprovided
accordingtothefollowingguidance:
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1525kg(37years):5ml(200mg)givenas1x5mlspoonful,oncedailyfor3days.
2635kg(811years):7.5ml(300mg)givenas1x7.5mlspoonful,oncedailyfor3days.
3645kg(1214years):10ml(400mg)givenas1x10mlspoonful,oncedailyfor3days.
Over45kg:Doseasperadults.
Seesection6.5forappropriatepacksizetousedependingonage/bodyweightofchild.
ThespeciallysuppliedmeasureshouldbeusedtoadministerZithromaxsuspensiontochildren.
Renalfailure:
Nodoseadjustmentisnecessaryinpatientswithmildtomoderaterenalimpairment(GFR1080ml/min).Caution
shouldbeexercisedwhenazithromycinisadministeredtopatientswithsevererenalimpairment(GFR<10ml/min)
(seesection4.4andsection5.2).
Hepaticfailure:
Sinceazithromycinismetabolisedintheliverandexcretedinthebile,thedrugshouldnotbegiventopatientssuffering
fromsevereliverdisease.Nostudieshavebeenconductedregardingtreatmentofsuchpatientswithazithromycin(see
section4.4).
ZithromaxSuspensionisfororaladministrationonly.
4.3Contraindications
Zithromaxiscontraindicatedinpatientswithaknownhypersensitivitytoazithromycinoranymacrolideorketolide
antibiotics,erythromycin,ortoanyoftheexcipientsthereofas(forexample)listedinsection6.1.
4.4Specialwarningsandprecautionsforuse
Hypersensitivity
Aswitherythromycinandothermacrolides,rareseriousallergicreactionsincludingangioneuroticoedemaand
anaphylaxis(rarelyfatal),havebeenreported.Someofthesereactionswithazithromycinhaveresultedinrecurrent
symptomsandrequiredalongerperiodofobservationandtreatment.
Hepatotoxicity
Sincetheliveristheprincipalrouteofeliminationforazithromycin,theuseofazithromycinshouldbeundertakenwith
cautioninpatientswithsignificanthepaticdisease.Casesoffulminanthepatitispotentiallyleadingtolifethreatening
liverfailurehavebeenreportedwithazithromycin(seesection4.8).Somepatientsmayhavehadpreexistinghepatic
diseaseormayhavebeentakingotherhepatotoxicmedicinalproducts.
Incaseofsignsandsymptomsofliverdysfunction,suchasrapiddevelopingastheniaassociatedwithjaundice,dark
urine,bleedingtendencyorhepaticencephalopathy,liverfunctiontests/investigationsshouldbeperformed
immediately.Azithromycinadministrationshouldbestoppedifliverdysfunctionhasemerged.
Ergotderivatives
Inpatientsreceivingergotderivatives,ergotismhasbeenprecipitatedbycoadministrationofsomemacrolide
antibiotics.Therearenodataconcerningthepossibilityofaninteractionbetweenergotandazithromycin.However,
becauseofthetheoreticalpossibilityofergotism,azithromycinandergotderivativesshouldnotbecoadministrated.
ProlongationoftheQTinterval
ProlongedcardiacrepolarisationandQTinterval,impartingariskofdevelopingcardiacarrhythmiaandtorsadesde
pointes,havebeenseenintreatmentwithothermacrolides.Asimilareffectwithazithromycincannotbecompletely
ruledoutinpatientsatincreasedriskforprolongedcardiacrepolarisation(seesection4.8)thereforecautionisrequired
whentreatingpatients:
WithcongenitalordocumentedQTprolongation
CurrentlyreceivingtreatmentwithotheractivesubstanceknowntoprolongQTintervalsuchasantiarrhytmicsof
classesIaandIII,cisaprideandterfenadine
Withelectrolytedisturbance,particularlyincaseofhypokalaemiaandhypomagnesemia
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Withclinicallyrelevantbradycardia,cardiacarrhythmiaorseverecardiacinsufficiency.
Superinfection
Aswithanyantibioticpreparation,observationforsignsofsuperinfectionwithnonsusceptibleorganismsincludingfungi
isrecommended.
Clostridiumdifficileassociateddiarrhoea
Clostridiumdifficileassociateddiarrhoea(CDAD)hasbeenreportedwithuseofnearlyallantibacterialagents,including
azithromycin,andmayrangeinseverityfrommilddiarrhoeatofatalcolitis.StrainsofC.difficileproducinghypertoxinA
andBcontributetothedevelopmentofCDAD.HypertoxinproducingstrainsofC.difficilecauseincreasedmorbidity
andmortality,astheseinfectionscanberefractorytoantimicrobialtherapyandmayrequirecolectomy.Therefore,
CDADmustbeconsideredinpatientswhopresentwithdiarrhoeaduringorsubsequenttotheadministrationofany
antibiotics.CarefulmedicalhistoryisnecessarysinceCDADhasbeenreportedtooccurovertwomonthsafterthe
administrationofantibacterialagents.Discontinuationoftherapywithazithromycinandtheadministrationofspecific
treatmentforC.difficileshouldbeconsidered.
Streptococcalinfections
Penicillinisusuallythefirstchoicefortreatmentofpharyngitis/tonsillitisduetoStreptococcuspyogenesandalsofor
prophylaxisofacuterheumaticfever.Azithromycinisingeneraleffectiveagainststreptococcusintheoropharynx,but
nodataareavailablethatdemonstratetheefficacyofazithromycininpreventingacuterheumaticfever.
Renalimpairment
Inpatientswithsevererenalimpairment(GFR<10ml/min)a33%increaseinsystemicexposuretoazithromycinwas
observed(seesection5.2).
Myastheniagravis
Exacerbationsofthesymptomsofmyastheniagravisandnewonsetofmyastheniasyndromehavebeenreportedin
patientsreceivingazithromycintherapy(seesection4.8).
Diabetes
Cautionindiabeticpatients:5mlofreconstitutedsuspensioncontains3.87gofsucrose.
Duetothesucrosecontent(3.87g/5mlofreconstitutedsuspension),thismedicinalproductisnotindicatedfor
personswithfructoseintolerance(hereditaryfructoseintolerance),glucosegalactosemalabsorptionorsaccharase
isomaltasedeficiency.
ZithromaxSuspensionisfororaladministrationonly.
4.5Interactionwithothermedicinalproductsandotherformsofinteraction
Antacids:Inapharmacokineticstudyinvestigatingtheeffectsofsimultaneousadministrationofantacidwith
azithromycin,noeffectonoverallbioavailabilitywasseen,althoughpeakserumconcentrationswerereducedby
approximately24%.Inpatientsreceivingbothazithromycinandantacids,thedrugsshouldnotbetaken
simultaneously.
Cetirizine:Inhealthyvolunteers,coadministrationofa5dayregimenofazithromycinwithcetirizine20mgatsteady
stateresultedinnopharmacokineticinteractionandnosignificantchangesintheQTinterval.
Didanosine(Dideoxyinosine):Coadministrationof1200mg/dayazithromycinwith400mg/daydidanosinein6HIV
positivesubjectsdidnotappeartoaffectthesteadystatepharmacokineticsofdidanosineascomparedwithplacebo.
Digoxin:Someofthemacrolideantibioticshavebeenreportedtoimpairthemicrobialmetabolismofdigoxininthegut
insomepatients.Inpatientsreceivingconcomitantazithromycin,arelatedazalideantibiotic,anddigoxinthepossibility
ofraiseddigoxinlevelsshouldbeborneinmind.
Zidovudine:Single1000mgdosesandmultiple1200mgor600mgdosesofazithromycinhadlittleeffectonthe
plasmapharmacokineticsorurinaryexcretionofzidovudineoritsglucuronidemetabolite.However,administrationof
azithromycinincreasedtheconcentrationsofphosphorylatedzidovudine,theclinicallyactivemetabolite,inperipheral
bloodmononuclearcells.Theclinicalsignificanceofthisfindingisunclear,butitmaybeofbenefittopatients.
AzithromycindoesnotinteractsignificantlywiththehepaticcytochromeP450system.Itisnotbelievedtoundergothe
pharmacokineticdruginteractionsasseenwitherythromycinandothermacrolides.HepaticcytochromeP450induction
orinactivationviacytochromemetabolitecomplexdoesnotoccurwithazithromycin.
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Ergotderivatives:Duetothetheoreticalpossibilityofergotism,theconcurrentuseofazithromycinwithergot
derivativesisnotrecommended.(Seesection4.4).
Pharmacokineticstudieshavebeenconductedbetweenazithromycinandthefollowingdrugsknowntoundergo
significantcytochromeP450mediatedmetabolism.
Atorvastatin:Coadministrationofatorvastatin(10mgdaily)andazithromycin(500mgdaily)didnotaltertheplasma
concentrationsofatorvastatin(basedonaHMGCoAreductaseinhibitionassay).
Carbamazepine:Inapharmacokineticinteractionstudyinhealthyvolunteers,nosignificanteffectwasobservedonthe
plasmalevelsofcarbamazepineoritsactivemetaboliteinpatientsreceivingconcomitantazithromycin.
Cimetidine:Inapharmacokineticstudyinvestigatingtheeffectsofasingledoseofcimetidine,given2hoursbefore
azithromycin,onthepharmacokineticsofazithromycin,noalterationofazithromycinpharmacokineticswasseen.
CoumarinTypeOralAnticoagulants:Inapharmacokineticinteractionstudy,azithromycindidnotalterthe
anticoagulanteffectofasingle15mgdoseofwarfarinadministeredtohealthyvolunteers.Therehavebeenreports
receivedinthepostmarketingperiodofpotentiatedanticoagulationsubsequenttocoadministrationofazithromycinand
coumarintypeoralanticoagulants.Althoughacausalrelationshiphasnotbeenestablished,considerationshouldbe
giventothefrequencyofmonitoringprothrombintimewhenazithromycinisusedinpatientsreceivingcoumarintype
oralanticoagulants.
Ciclosporin:Inapharmacokineticstudywithhealthyvolunteersthatwereadministereda500mg/dayoraldoseof
azithromycinfor3daysandwerethenadministeredasingle10mg/kgoraldoseofciclosporin,theresultingciclosporin
CmaxandAUC05werefoundtobesignificantlyelevated(by24%and21%respectively),howevernosignificant
changeswereseeninAUC0.Consequently,cautionshouldbeexercisedbeforeconsideringconcurrentadministration
ofthesedrugs.Ifcoadministrationofthesedrugsisnecessary,ciclosporinlevelsshouldbemonitoredandthedose
adjustedaccordingly.
Efavirenz:Coadministrationofa600mgsingledoseofazithromycinand400mgefavirenzdailyfor7daysdidnot
resultinanyclinicallysignificantpharmacokineticinteractions.
Fluconazole:Coadministrationofasingledoseof1200mgazithromycindidnotalterthepharmacokineticsofasingle
doseof800mgfluconazole.Totalexposureandhalflifeofazithromycinwereunchangedbythecoadministrationof
fluconazole,however,aclinicallyinsignificantdecreaseinCmax(18%)ofazithromycinwasobserved.
Indinavir:Coadministrationofasingledoseof1200mgazithromycinhadnostatisticallysignificanteffectonthe
pharmacokineticsofindinaviradministeredas800mgthreetimesdailyfor5days.
Methylprednisolone:Inapharmacokineticinteractionstudyinhealthyvolunteers,azithromycinhadnosignificant
effectonthepharmacokineticsofmethylprednisolone.
Midazolam:Inhealthyvolunteers,coadministrationofazithromycin500mg/dayfor3daysdidnotcauseclinically
significantchangesinthepharmacokineticsandpharmacodynamicsofasingle15mgdoseofmidazolam.
Nelfinavir:Coadministrationofazithromycin(1200mg)andnelfinaviratsteadystate(750mgthreetimesdaily)
resultedinincreasedazithromycinconcentrations.Noclinicallysignificantadverseeffectswereobservedandnodose
adjustmentisrequired.
Rifabutin:Coadministrationofazithromycinandrifabutindidnotaffecttheserumconcentrationsofeitherdrug.
Neutropeniawasobservedinsubjectsreceivingconcomitanttreatmentofazithromycinandrifabutin.Although
neutropeniahasbeenassociatedwiththeuseofrifabutin,acausalrelationshiptocombinationwithazithromycinhas
notbeenestablished(seesection4.8.).
Sildenafil:Innormalhealthymalevolunteers,therewasnoevidenceofaneffectofazithromycin(500mgdailyfor3
days)ontheAUCandCmax,ofsildenafiloritsmajorcirculatingmetabolite.
Terfenadine:Pharmacokineticstudieshavereportednoevidenceofaninteractionbetweenazithromycinand
terfenadine.Therehavebeenrarecasesreportedwherethepossibilityofsuchaninteractioncouldnotbeentirely
excludedhowevertherewasnospecificevidencethatsuchaninteractionhadoccurred.
Theophylline:Thereisnoevidenceofaclinicallysignificantpharmacokineticinteractionwhenazithromycinand
theophyllinearecoadministeredtohealthyvolunteers.
Triazolam:In14healthyvolunteers,coadministrationofazithromycin500mgonDay1and250mgonDay2with
0.125mgtriazolamonDay2hadnosignificanteffectonanyofthepharmacokineticvariablesfortriazolamcompared
totriazolamandplacebo.
Trimethoprim/sulfamethoxazole:Coadministrationoftrimethoprim/sulfamethoxazoleDS(160mg/800mg)for7days
withazithromycin1200mgonDay7hadnosignificanteffectonpeakconcentrations,totalexposureorurinary
excretionofeithertrimethoprimorsulfamethoxazole.Azithromycinserumconcentrationsweresimilartothoseseenin
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otherstudies.
4.6Fertility,pregnancyandlactation
Pregnancy
Animalreproductionstudieshavebeenperformedatdosesuptomoderatelymaternallytoxicdoseconcentrations.In
thesestudies,noevidenceofharmtothefoetusduetoazithromycinwasfound.Thereare,however,noadequateand
wellcontrolledstudiesinpregnantwomen.Becauseanimalreproductionstudiesarenotalwayspredictiveofhuman
response,azithromycinshouldbeusedduringpregnancyonlyifclearlyneeded.
Breastfeeding
Therearenodataonsecretioninbreastmilk.Asmanydrugsareexcretedinhumanmilk,azithromycinshouldnotbe
usedinthetreatmentofalactatingwomanunlessthephysicianfeelsthatthepotentialbenefitsjustifythepotential
riskstotheinfant.
4.7Effectsonabilitytodriveandusemachines
ThereisnoevidencetosuggestthatZithromaxmayhaveaneffectonapatient'sabilitytodriveoroperatemachinery.
4.8Undesirableeffects
Zithromaxiswelltoleratedwithalowincidenceofsideeffects.
Thesectionbelowliststheadversereactionsidentifiedthroughclinicaltrialexperienceandpostmarketingsurveillance
bysystemorganclassandfrequency.Adversereactionsidentifiedfrompostmarketingexperienceareincludedin
italics.Thefrequencygroupingisdefinedusingthefollowingconvention:Verycommon(1/10)Common(1/100to
<1/10)Uncommon(1/1,000to<1/100)Rare(1/10,000to<1/1,000)VeryRare(<1/10,000)andNotknown(cannot
beestimatedfromtheavailabledata).Withineachfrequencygrouping,undesirableeffectsarepresentedinorderof
decreasingseriousness.
Adversereactionspossiblyorprobablyrelatedtoazithromycinbasedonclinicaltrialexperienceandpost
marketingsurveillance:
InfectionsandInfestations
Uncommon(1/1,000to<1/100)
Candidiasis,oralcandidiasis,vaginalinfection
Notknown(cannotbeestimatedfromavailabledata)
Pseudomembranouscolitis(seesection4.4)
BloodandLymphaticSystemDisorders
Uncommon(1/1,000to<1/100)
Leukopenia,neutropenia
Notknown(cannotbeestimatedfromavailabledata)
Thrombocytopenia,haemolyticanaemia
ImmuneSystemDisorders
Uncommon(1/1,000to<1/100)
Angioedema,hypersensitivity
Notknown(cannotbeestimatedfromavailabledata)
Anaphylacticreaction(seesection4.4)
MetabolismandNutritionDisorders
Common(>1/100<1/10)
Anorexia

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PsychiatricDisorders
Uncommon(1/1,000to<1/100)
Nervousness
Rare(>1/10,000<1/1,000)
Agitation
Notknown(cannotbeestimatedfromavailabledata)
Aggression,anxiety
NervousSystemDisorders
Common(>1/100<1/10)
Dizziness,headache,paraesthesia,dysgeusia
Uncommon(1/1,000to<1/100)
Hypoaesethesia,somnolence,insomnia
Notknown(cannotbeestimatedfromavailabledata)
Syncope,convulsion,psychomotorhyperactivity,anosmia,ageusia,parosmia,Myastheniagravis(seesection4.4)
EyeDisorders
Common(>1/100<1/10)
Visualimpairment
EarandLabyrinthDisorders
Common(>1/100<1/10)
Deafness
Uncommon(1/1,000to<1/100)
Hearingimpaired,tinnitus
Rare(>1/10,000<1/1,000)
Vertigo
CardiacDisorders
Uncommon(1/1,000to<1/100)
Palpitations
Notknown(cannotbeestimatedfromavailabledata)
Torsadesdepointes(seesection4.4),arrhythmia(seesection4.4)includingventriculartachycardia
VascularDisorders
Notknown(cannotbeestimatedfromavailabledata)
Hypotension
GastrointestinalDisorders
Verycommon(1/10)
Diarrhoea,abdominalpain,nausea,flatulence
Common(>1/100<1/10)
Vomiting,dyspepsia
Uncommon(>1/1,000<1/100)
Gastritis,constipation
Notknown(cannotbeestimatedfromavailabledata)
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Pancreatitis,tonguediscolouration
HepatobiliaryDisorders
Uncommon(>1/1,000<1/100)
Hepatitis
Rare(>1/10,000<1/1,000)
Hepaticfunctionabnormal
Notknown(cannotbeestimatedfromavailabledata)
Hepaticfailure(seesection4.4),whichhasrarelyresultedindeath,hepatitisfulminant,hepaticnecrosis,jaundice
cholestatic
SkinandSubcutaneousTissueDisorders
Common(>1/100<1/10)
Pruritusandrash
Uncommon(>1/1,000<1/100)
StevensJohnsonsyndrome,photosensitivityreaction,urticaria
Notknown(cannotbeestimatedfromavailabledata)
Toxicepidermalnecrolysis,erythemamultiforme
Musculoskeletal,ConnectiveTissueDisorders
Common(>1/100<1/10)
Arthralgia
RenalandUrinaryDisorders
Notknown(cannotbeestimatedfromavailabledata)
Renalfailureacute,nephritisinterstitial
GeneraldisordersandAdministrationSiteConditions
Common(>1/100<1/10)
Fatigue
Uncommon(>1/1,000<1/100)
Chestpain,oedema,malaise,asthenia
Investigations
Common(>1/100<1/10)
Lymphocytecountdecreased,eosinophilcountincreased,bloodbicarbonatedecreased
Uncommon(>1/1,000<1/100)
Aspartateaminotransferaseincreased,alanineaminotransferaseincreased,bloodbilirubinincreased,bloodurea
increased,bloodcreatinineincreased,bloodpotassiumabnormal
Notknown(cannotbeestimatedfromavailabledata)
ElectrocardiogramQTprolonged(seesection4.4)
Reportingofsuspectedadversereactions
Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued
monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany
suspectedadversereactionsviatheYellowCardSchemeatwww.mhra.gov.uk/yellowcard.
4.9Overdose
Adverseeventsexperiencedinhigherthanrecommendeddosesweresimilartothoseseenatnormaldoses.The
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typicalsymptomsofanoverdosewithmacrolideantibioticsincludereversiblelossofhearing,severenausea,vomiting
anddiarrhoea.Intheeventofoverdose,theadministrationofmedicinalcharcoalandgeneralsymptomatictreatment
andsupportivemeasuresareindicatedasrequired.

5.Pharmacologicalproperties
5.1Pharmacodynamicproperties
Generalproperties
Pharmacotherapeuticgroup:Antibacterialsforsystemicuse.ATCcode:J01FA10
Modeofaction:
Zithromaxisamacrolideantibioticbelongingtotheazalidegroup.Themoleculeisconstructedbyaddinganitrogen
atomtothelactoneringoferythromycinA.Thechemicalnameofazithromycinis9deoxy9aaza9amethyl9a
homoerythromycinA.Themolecularweightis749.0.Themechanismofactionofazithromycinisbaseduponthe
suppressionofbacterialproteinsynthesisbymeansofbindingtotheribosomal50ssubunitandinhibitionofpeptide
translocation.
Mechanismofresistance:
Resistancetoazithromycinmaybeinherentoracquired.Therearethreemainmechanismsofresistanceinbacteria:
targetsitealteration,alterationinantibiotictransportandmodificationoftheantibiotic.
Azithromycindemonstratescrossresistancewitherythromycinresistantgrampositiveisolates.Adecreasein
macrolidesusceptibilityovertimehasbeennotedparticularlyinStreptococcuspneumoniaeandStaphylococcus
aureus.Similarly,decreasedsusceptibilityhasbeenobservedamongStreptococcusviridansandStreptococcus
agalactiae(GroupB)streptococcusagainstothermacrolidesandlincosamides.
Breakpoints
AzithromycinsusceptibilitybreakpointsfortypicalbacterialpathogenspublishedbyEUCASTare:
Organism

MICbreakpoints(mg/L)
Susceptible(S)

Resistant(R>)

Staphylococcusspp.

StreptococcusgroupsA,B,CandG

0.25

0.5

Streptococcuspneumoniae

0.25

0.5

Haemophilusinfluenzae

0.12

Moraxellacatarrhalis

0.25

0.5

Neisseriagonorrhoeae

0.25

0.5

Susceptibility
Theprevalenceofacquiredresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformation
onresistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesought
whenthelocalprevalenceofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsis
questionable.
Table:AntibacterialspectrumofAzithromycin
Commonlysusceptiblespecies
AerobicGrampositivemicroorganisms
Staphylococcusaureus
Methycillinsusceptible
Streptococcuspneumoniae
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Penicillinsusceptible
Streptococcuspyogenes(GroupA)
AerobicGramnegativemicroorganisms
Haemophilusinfluenzae
Haemophilusparainfluenzae
Legionellapneumophila
Moraxellacatarrhalis
Neisseriagonorrhoeae
Pasteurellamultocida
Anaerobicmicroorganisms
Clostridiumperfringens
Fusobacteriumspp.
Prevotellaspp.
Porphyromonasspp.
Othermicroorganisms
Chlamydiatrachomatis
Speciesforwhichacquiredresistancemaybeaproblem
AerobicGrampositivemicroorganisms
Streptococcuspneumoniae
Penicillinintermediate
Penicillinresistant
Inherentlyresistantorganisms
AerobicGrampositivemicroorganisms
Enterococcusfaecalis
StaphylococciMRSA,MRSE*
Anaerobicmicroorganisms
Bacteroidesfragilisgroup
*Methycillinresistantstaphylococcihaveaveryhighprevalenceofacquiredresistancetomacrolidesandhavebeen
placedherebecausetheyarerarelysusceptibletoazithromycin.
5.2Pharmacokineticproperties
Absorption
Bioavailabilityafteroraladministrationisapproximately37%.Peakplasmaconcentrationsareattained23hoursafter
takingthemedicinalproduct.
Distribution
Orallyadministeredazithromyciniswidelydistributedthroughoutthebody.Inpharmacokineticstudiesithasbeen
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demonstratedthattheconcentrationsofazithromycinmeasuredintissuesarenoticeablyhigher(asmuchas50times)
thanthosemeasuredinplasma,whichindicatesthattheagentstronglybindstotissues.
Bindingtoserumproteinsvariesaccordingtoplasmaconcentrationandrangesfrom12%at0.5microgram/mlupto
52%at0.05microgramazithromycin/mlserum.Themeanvolumeofdistributionatsteadystate(VVss)hasbeen
calculatedtobe31.1l/kg.
Elimination
Theterminalplasmaeliminationhalflifecloselyreflectstheeliminationhalflifefromtissuesof24days.
Approximately12%ofanintravenouslyadministereddoseofazithromycinisexcretedunchangedinurinewithinthe
followingthreedays.Particularlyhighconcentrationsofunchangedazithromycinhavebeenfoundinhumanbile.Alsoin
bile,tenmetabolitesweredetected,whichwereformedthroughNandOdemethylation,hydroxylationofdesosamine
andaglyconeringsandcleavageofcladinoseconjugate.Comparisonoftheresultsofliquidchromatographyand
microbiologicalanalyseshasshownthatthemetabolitesofazithromycinarenotmicrobiologicallyactive.
Inanimaltests,highconcentrationsofazithromycinhavebeenfoundinphagocytes.Ithasalsobeenestablishedthat
duringactivephagocytosishigherconcentrationsofazithromycinarereleasedfrominactivephagocytes.Inanimal
modelsthisresultsinhighconcentrationsofazithromycinbeingdeliveredtothesiteofinfection.
5.3Preclinicalsafetydata
Phospholipidosis(intracellularphospholipidaccumulation)hasbeenobservedinseveraltissues(e.g.eye,dorsalroot
ganglia,liver,gallbladder,kidney,spleen,and/orpancreas)ofmice,rats,anddogsgivenmultipledosesof
azithromycin.Phospholipidosishasbeenobservedtoasimilarextentinthetissuesofneonatalratsanddogs.The
effecthasbeenshowntobereversibleaftercessationofazithromycintreatment.Thesignificanceofthefindingfor
animalsandforhumansisunknown.
Carcinogenicpotential:
Longtermstudiesinanimalshavenotbeenperformedtoevaluatecarcinogenicpotentialasthedrugisindicatedfor
shorttermtreatmentonlyandtherewerenosignsindicativeofcarcinogenicactivity.
Mutagenicpotential:
Therewasnoevidenceofapotentialforgeneticandchromosomemutationsininvivoandinvitrotestmodels.
Reproductivetoxicity:
Inanimalstudiesforembryotoxiceffectsofthesubstance,noteratogeniceffectwasobservedinmiceandrats.Inrats,
azithromycindosesof100and200mg/kgbodyweight/dayledtomildretardationoffetalossificationandinmaternal
weightgain.Inperiandpostnatalstudiesinrats,mildretardationfollowingtreatmentwith50mg/kg/dayazithromycin
andabovewasobserved.

6.Pharmaceuticalparticulars
6.1Listofexcipients
ZithromaxPowderforOralSuspensioncontains:Hydroxypropylcellulose,sodiumphosphatetribasicanhydrous,
sucrose,xanthangum.Flavours:artificialbanana,artificialcherry,artificialcremedevanilla.
6.2Incompatibilities
Noneknown
6.3Shelflife
ZithromaxPowderforOralSuspension:3years.
Oncereconstitutedwithwater,ZithromaxSuspensionhasashelflifeof5days.
6.4Specialprecautionsforstorage
None
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6.5Natureandcontentsofcontainer
ZithromaxPowderforOralSuspensionisavailableas:
600mg(15ml)Pack:(Recommendedforuseinchildrenupto7years(25kg)).
Packsofpowderequivalentto600mgazithromycininapolypropylenecontainerwithchildresistantscrewcap(withor
withoutatamperevidentseal),inacartonbox.Packcontainsadoubleendedmultidosingspoon1and10mloral
dosingsyringewithdetachableadaptor.Reconstitutewith9mlofwatertogive15mlsuspension.
900mg(22.5ml)Pack:(Recommendedforuseinchildrenagedfrom811years(2635kg)).
Packsofpowderequivalentto900mgazithromycininapolypropylenecontainerwithchildresistantscrewcap(withor
withoutatamperevidentseal),inacartonbox.Packcontainsadoubleendedmultidosingspoon1.Reconstitutewith
12mlofwatertogive22.5mlsuspension.
1200mg(30ml)Pack:(Recommendedforuseinchildrenagedfrom1214years(3645kg)).
Packsofpowderequivalentto1200mgazithromycininapolypropylenecontainerwithchildresistantscrewcap(withor
withoutatamperevidentseal)inacartonbox.Packcontainsadoubleendedmultidosingspoon1.Reconstitutewith15
mlofwatertogive30mlsuspension.
1500mg(37.5ml)Pack:
Packsofpowderequivalentto1500mgazithromycininapolypropylenecontainerwithchildresistantscrewcapand
tamperevidentseal,inacartonbox.Packcontainsadoubleendedmultidosingspoon1.Reconstitutewith19mlof
watertogive37.5mlsuspension.
Multidosingspoondeliversdosesasfollows:
Smallendtograduation

2.5ml(100mg)

brimful

5ml(200mg)

Largeendtograduation

7.5ml(300mg)

brimful

10ml(400mg)

Eachpackcontainsapatientinformation/instructionleaflet.
Notallpacksizesmaybemarketed.
6.6Specialprecautionsfordisposalandotherhandling
Whendispensingthe15mlpack,adviceshouldbegivenastowhetherthedoseshouldbemeasuredusingtheoral
dosingsyringeorthespoonprovidedandoncorrectusage.Ifthedoseistobegivenusingtheoraldosingsyringe,
beforedispensingthesyringeadaptorshouldbedetachedfromthesyringeandinsertedintothebottleneckandthecap
replaced.
Whendispensing22.5ml,30mland37.5mlpacks,adviceshouldbegivenastothecorrectusageofthemultidosing
spoon.
Anyunusedmedicinalproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7.Marketingauthorisationholder
PfizerLimited
RamsgateRoad
Sandwich
KentCT139NJ
UnitedKingdom

8.Marketingauthorisationnumber(s)
PL00057/0336

9.Dateoffirstauthorisation/renewaloftheauthorisation
25September1996/22December2005
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10.Dateofrevisionofthetext
01/2015
Ref19_2

CompanyContactDetails
PfizerLimited
Address
RamsgateRoad,Sandwich,Kent,CT139NJ

Telephone
+44(0)1304616161

Fax
+44(0)1304656221

MedicalInformationWebsite
www.pfizermedicalinformation.co.uk

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