ERYTHROMYCIN 1G POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION.

Main information

  • Trade name:
  • ERYTHROMYCIN 1G POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION.
  • Dosage:
  • 1 Grams
  • Pharmaceutical form:
  • Pdr for Soln for Infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ERYTHROMYCIN 1G POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION.
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0437/025/001
  • Authorization date:
  • 17-04-1992
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0437/025/001

CaseNo:2055150

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

HOSPIRAUKLtd

Queensway,RoyalLeamingtonSpa,WarwickshireCV313RW,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Erythromycin1gPowderforConcentrateforSolutionforInfusion

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom17/09/2008.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Erythromycin1gPowderforConcentrateforSolutionforInfusion.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvial,beforereconstitutioncontains:

Erythromycin1g(aslactobionate)

Whenreconstitutedasdirectedinsection6.6(Specialprecautionsfordisposalofausedmedicinalproductorwaste

materialsderivedfromsuchmedicinalproductandotherhandlingoftheproduct),eachvialprovidesaconcentratefor

solutionforinfusioncontaining50mg/mlerythromycin(aslactobionate).

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Powderforconcentrateforsolutionforinfusion.

Awhitepowderorplug.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Upperrespiratorytractinfections(tonsillitis,pharyngitis,sinusitis,secondarybacterialinfections).

Lowerrespiratorytractinfections(pneumonia,bronchitis,primaryatypicalpneumonia,Legionnaire'sdisease).

Skinandsofttissueinfections(furunculosis,erysipelas).

Otherinfections-diphtheriacarriersandcasesasanadjuncttoantitoxin,syphilisandgonorrhoea(incasesof

penicillinallergy),subacutebacterialendocarditis,otitismedia.

4.2Posologyandmethodofadministration

Intravenousadministrationoferythromycinissuitabletopatientswhoareunabletotolerateoralmedicationorwhenit

isnecessarytoproduceahighbloodconcentrationtocontrolsevereinfections.Oraladministrationshouldreplace

parenteraladministrationassoonaspracticable.

DuetothelocalirritativeeffectsoferythromycinaswellasreportsofQTintervalprolongationandventricular

arrhythmias(someofwhichhavebeenfatal)beingassociatedwithelevatedserumconcentrationsoferythromycin,the

drugmustnotbeadministeredrapidlybydirextintravenousinjection(IVpush).

ForcontinuousI.V.infusiontheconcentratedsolutionshouldbedilutedtoaconcentrationof1mgperml.Ifrequired,

solutionstrengthsupto5mg/ml(0.5%solution)maybeused,butshouldnotbeexceeded.Higherconcentrationsmay

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ForintermittentI.V.infusiontheappropriatedailydosecanbegivenas4dosesonceevery6hours.Theerythromycin

concentrationshouldnotexceed5mgpermlandtheinfusionshouldbeadministeredover60minutes,asarapid

infusionismorelikelytobeassociatedwitharrhythmiasorhypotension.Alongerperiodofinfusionshouldbeusedin

patientswithriskfactorsorpreviousevidenceofarrhythmias.Notlessthan100mlofdiluentshouldbeusedfor

preparingintermittentI.V.solutions.

Intravenoustherapyshouldbereplacedbyoraladministrationattheappropriatetime.

Adults:Theusualadultdoseistheequivalentof25-50mg/kgperdayindivideddosesoferythromycin,by

intravenousinfusionevery6hours,ortheequivalentof1to2goferythromycindailybyintermittentintravenous

infusionover20to60minutesevery6hoursorbyinfusionover24hours.Theequivalentof4gramdailyhasbeen

recommendedforsevereinfections.

SmallvolumeI.V.infusion,minimumvolume100ml,isthepreferredmethodsoastominimisevenousirritation.

Children:25-50mgperkgbyintravenousinjection,dailyindivideddoses.

Elderly:Useadultdosagewithcare,takingintoconsiderationanyimpairmentinliverorbiliaryfunctions.

Patientswithimpairedhepaticfunction:Inthepresenceofnormalhepaticfunction,erythromycinisconcentratedin

theliverandexcretedinthebile.Althoughtheeffectofhepaticdysfunctionontheexcretionoferythromycinandits

half-lifeinsuchpatientsisnotknown,cautionshouldbeexercisedinadministeringtheantibioticinsuchcases.

Patientswithimpairedrenalfunction:Thelowproportionofrenalexcretionwouldsuggestthatdosage

modificationinpatientswithimpairedrenalfunctionmaynotbenecessary.Inseverelyimpairedpatientshowever,

toxicityhasbeenreportedanddosageadjustmentinthesecasesmaybewarranted.

4.3Contraindications

PatientswithknownhypersensitivitytoEyrthromycin.

Erythromyciniscontraindicatedwitheitherastemizoleorterfenadine.

ProlongationoftheQTintervalanddevelopmentofventriculararrhythmias(someofwhichhavebeenfatal),including

atypicalventriculartachycardia(torsadesdepointes),havebeenreportedwiththeintravenousadministrationof

erythromycin.Limiteddatasuggestthattheseadverseeffectsmaybeassociatedwithabnormallyelevatedserum

erythromycinconcentrationsfollowingrapidadministration.Erythromycinthereforemustnotbeadministeredrapidly

bydirectintravenousinjection(IVpush).

4.4Specialwarningsandprecautionsforuse

Allergicreactionsrangingfromurticariatoanaphylaxishavebeenreportedwithintravenouserythromycin.

Superinfectionmayoccurwithprolongeduse,givingrisetoovergrowthofnonsusceptibleorganisms.

Erythromycinisexcretedprincipallyviatheliverandcautionshouldbeexercisedwhenusingerythromycininpatients

withadegreeofhepaticimpairmentorconcomitantlyreceivingpotentiallyhepatotoxicagents.

Extravasationshouldbeavoided.Theinfusionshouldbeslowtoavoidpainalongthevein.

Cautionmustbeexercisedintheadministrationofparenteralfluids,especiallythosecontainingsodiumions,to

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TherehavebeenreportsofInfantileHypertrophicPyloricStenosis(IHPS)occurringininfantsfollowingerythromycin

therapy.Inonecohortof157newbornswhoweregivenerythromycinforpertussisprophylaxis,sevenneonates(5%)

developedsymptomsofnon-bilious,vomitingorirritabilitywithfeedingandweresubsequentlydiagnosedashaving

IHPSrequiringsurgicalpyloromyotomy.Sinceerythromycinmaybeusedinthetreatmentofconditionsininfants

whichareassociatedwithsignificantmortalityormorbidity(suchaspertussisorchlamydia),thebenefitof

erythromycintherapyneedstobecarefullyconsideredagainstthepotentialriskofdevelopingIHPS.Patientsshouldbe

informedtocontacttheirphysicianifvomitingorirritabilityoccurs.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Penicillin:Erythromycin,inlowbacteriostaticconcentrations,mayinhibittheactionsofbactericidaldrugs.Inhigh

concentrations,erythromycinmayactsynergisticallywithpenicillin.

Useoferythromycininpatientsreceivingdigoxin,warfarin,carbemazepineorhighdosesoftheophyllinemayresultin

potentiationoftheeffectsduetoimpairmentofexcretion.Additionallyareporthasbeennotedonthepotentiationof

vinblastinewithconcomitanterythromycintherapy.

Increasedplasmalevelsofcyclosporinmayoccurinpatientsonerythromycin.

Ergotismhasbeenreportedinpatientsreceivingerythromycinincombinationwithergot.

Concomitantuseoferythromycinwithterfenadineorastemizoleislikelytoresultinanenhancedriskofcardiotoxicity

withthesedrugs.Theconcomitantuseoferythromycinwitheitherastemizoleorterfenadineistherefore

contraindicated.

4.6Pregnancyandlactation

UseinPregnancyandLactation

Erythromycinshouldnotbeadministeredtopregnantwomenunlessthebenefitsoutweighthepotentialrisks.

Erythromycincrossestheplacentaandgivesrisetofoetalplasmalevelswhichareapproximately5-20%ofmaternal

limits.Howevertherisksassociatedwiththisphenomenonhavenotbeenclearlyestablished.

Erythromycinisnotrecommendedfornursingmothersunlesstheexpectedbenefitsoutweighthepotentialrisks.In

lactatingwomen,erythromycinissecretedintobreastmilkinquantitiesofbetween0.5and6.2micrograms/ml.

Thesequantitiesarenotknowntobeharmful.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

ProlongationoftheQTintervalanddevelopmentofventriculararrhythmias(someofwhichhavebeenfatal)including

atypicalventriculartachycardia(torsadesdepointes),havebeenreportedwiththeintravenousadministrationof

erythromycin.Limiteddatasuggestthattheseadverseeffectsmaybeassociatedwithabnormallyelevatedserum

erythromycinconcentrationsfollowingrapidadministration.

Auditory/Vestibular:Inveryhighdoses,erythromycinmaycausetransientperceptivedeafness.CasesofInfantile

HypertrophicPyloricStenosis(IHPS)occurringininfantsfollowingerythromycintherapyhavebeenreported(see

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4.9Overdose

Thetoxicityislow.Overdosagemaybeassociatedwithototoxicity.Nospecifictreatmenthasbeenproposedotherthan

generalsupportivemeasures.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Erythromycinbindstotheribosomesofbacteriaandaffectsproteinsynthesiswithoutaffectingnucleicacidsynthesis.

Erythromycindoesnotbindtocytoplasmicmembranesofthehostcells.Thisisapossibleexplanationofitslow

toxicityandsafetyrecord.

Erythromycinisbacteriostaticandbactericidaldependingonitsconcentrationandthetypeoforganism.Itinhibits

proteinsynthesisbybindingtoribosmalsubunits,inhibitingtranslocationofaminocyltransferRNAandinhibiting

polypeptidesynthesiswithoutcausinganyalterationinthenucleicacidcycle.

5.2Pharmacokineticproperties

Distribution:

Theapparentvolumeofdistributionoferythromycinisaround45%ofbodyweightinnormalsubjects.Thislarge

distributionvolumeisconsistentwiththeextensivetissuepenetrationoferythromycin.

Erythromycindiffusesreadilyintomostbodyfluids,exceptthecerebrospinalfluid.However,incasesofmeningeal

inflammation,higherconcentrationsareapparent.

Metabolism:

Instudiesusingrabbitmicrosomesithasbeenshownthaterythromycinisdemethylatedtodes-N-methylerythromycin

andformaldehyde.

Excretion:

Inthepresenceofnormalhepaticfunction,erythromycinisconcentratedintheliverandexcretedinthebile;theeffect

ofhepaticdysfunctiononexcretionoferythromycinbytheliverisnotknown.

From12%to15%ofintravenouslyadministerederythromycinisexcretedinactiveformintheurine.

Thedrugisalsoexcretedinthefaeces.

Half-Life:

Theplasmaeliminationhalf-lifeinpatientswithnormalrenalfunctionisabout2hours.Insevererenalimpairmentthe

half-lifemaybeprolongedtobetween4and7hours.

5.3Preclinicalsafetydata

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumhydroxide(forpH-adjustment)

Lactobionicacidsolution(forpH-adjustment)

6.2Incompatibilities

Erythromycinshouldnotbereconstitutedwithinorganicsaltsolutions.Useonlywaterforinjections.

ThestabilityofsolutionsoferythromycinlactobionateisadverselyaffectedbelowpH5.5.5mlofsterile8.4%sodium

bicarbonatesolutionwillneutralise1litreofGlucoseInjectionBPandshouldbeaddedtothebagpriortotheaddition

oferythromycinlactobionate.

6.3ShelfLife

Aspackagedforsale–2years

Afterreconstitutionwithsterilewaterforinjections,chemicalandphysicalin-usestabilityhasbeendemonstratedfor

72hoursat2 o

Cto8 o

Afterfurtherdilutionwith0.9%sodiumchloride,chemicalandphysicalin-usestabilityhasbeendemonstratedfor72

hoursat2 o

Cto8 o

C.Orafterfurtherdilutionwith5%w/vbufferedglucosesolution,chemicalandphysicalin-use

stabilityhasbeendemonstratedfor24hoursat25 o

C.(Seesection6.6,Specialprecautionsfordisposalofaused

medicinalproductorwastematerialsderivedfromsuchmedicinalproductandotherhandlingoftheproduct,for

informationonreconstitutionanddilutionmethods)

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in-usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandshouldnotbelongerthan24hoursata

temperaturenotexceeding2 o

Cto8 o

C,unlessreconstitution/dilution(etc)hastakenplaceincontrolledandvalidated

asepticconditions.

Containsnopreservative.Forsingleuse.Discardanyunusedcontents.

6.4Specialprecautionsforstorage

Aspackagedforsale–Donotstoreabove25°C.Keepvialintheoutercarton.

Afterreconstitution/dilutionseesection6.3,Shelflife

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Erythromycinlactobionatevialslabeledascontaining1gramoferythromycinshouldbeinitiallyreconstitutedby

adding20mlofSterileWaterforInjectionsBPwithoutpreservative,toprovideasolutioncontaining50mgperml.

Nootherdiluentshouldbeusedtopreparethisinitialsolution.Itisimportanttoensurethattheproductiscompletely

dissolvedbyvigorousshakingbeforetransferringtoinfusioncontainers.

Priortoadministrationtheconcentratedsolutionmustbefurtherdilutedinglassorflexibleplasticcontainersof0.9%

sodiumchlorideinjection.If,forclinicalreasons,0.9%salineisnotsuitable,thenneutralisedGlucoseIntravenous

InfusionBP5%w/vmaybeused.Neutralisedglucosesolutionispreparedbytheadditionof5mlofsterile8.4%w/v

sodiumbicarbonatesolutiontoeachlitreofGlucoseIntravenousInjectionBP5%w/v.

Itisnecessarytobuffertheglucosesolutioninthiswaybecausethestabilityoferythromycinlactobionateisadversely

affectedbelowpH5.5.

Subsequentdilutionintoinfusionfluidsshouldbemadepriortoadministration.RecommendedfluidsareSodium

ChlorideInjectionBP0.9%orGlucose5%InjectionBP.

Itisrecommendedthataclarifyingfilterisusedtominimisetheparticulatelevelsinresultantinfusions.

7MARKETINGAUTHORISATIONHOLDER

HospiraUKLimited

Queensway

RoyalLeamingtonSpa

WarwickshireCV313RW

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0437/025/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 17April1992

Dateoflastrenewal: 17April2007

10DATEOFREVISIONOFTHETEXT

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