CEFAGER

Main information

  • Trade name:
  • CEFAGER Powder for Oral Suspension 125 MG/5ml
  • Dosage:
  • 125 MG/5ml
  • Pharmaceutical form:
  • Powder for Oral Suspension
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CEFAGER Powder for Oral Suspension 125 MG/5ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/045/001
  • Authorization date:
  • 08-03-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0577/045/001

CaseNo:2051195

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDermottLaboratoriesLtdt/aGerardLaboratories

35/36BaldoyleIndustrialEstate,GrangeRoad,Dublin13,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CefagerPowderforOralSuspension125mg/5ml

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom18/02/2009until12/12/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CefagerPowderforOralSuspension125mg/5ml.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

WhenreconstitutedasdirectedinSection6.6,each5mldosecontainscefaclor(asmonohydrate)125mg.

CefagerpowderfororalsuspensionalsocontainsSorbitol(E420).

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Powderfororalsuspension.

Anoff-white,sugar-free,strawberry-flavouredproduct.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cefaclorisindicatedforthetreatmentofthefollowinginfectionsduetosusceptiblemicro-organisms:

Respiratorytractinfections,includingpneumoniabronchitis,exacerbationofchronicbronchitis,pharyngitisand

tonsillitis,andaspartofthemanagementofsinusitis.

Otitismedia.Skinandsofttissueinfections.Acuteandchronicurinarytractinfections,includingpyelonephritisand

cystitis.

Cefaclorisgenerallyeffectiveintheeradicationofstreptococcifromthenasopharynx;however,dataestablishing

efficacyinthesubsequentpreventionofeitherrheumaticfeverorbacterialendocarditisarenotavailable.

4.2Posologyandmethodofadministration

Cefaclorisadministeredorally.

Adults:

Theusualadultdosageis250mgevery8hours.

Formoresevereinfectionsthisdosemaybedoubledto500mgevery8hours.However,themaximumdailydose

shouldnotexceed4g,whichhasbeenadministeredsafelytonormalsubjectsfor28days.

Forpatientsundergoingregularhaemodialysisaloadingdoseof250mg-1gshouldbeadministeredpreceding

dialysis.Atherapeuticdoseof250mg-500mgshouldbegivenevery6to8hoursduringinterdialyticintervals.

Cefaclormaybeadministeredinthepresenceofimpairedrenalfunction.Undersuchconditionsdosageisusually

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Theelderly

Asforadults.

Children:

Theusualrecommendeddailydosageforchildrenis20mg/kg/dayindivideddoseseveryeighthours.Forbronchitis

andpneumonia,thedosageis20mg/kg/dayindivideddosesadministeredthreetimesdaily.Forotitismediaand

pharyngitisthetotaldailydosagemaybedividedandadministeredevery12hours.Safetyandefficacyhavenotbeen

establishedforuseininfantsagedlessthanonemonth.

CefaclorforOralSuspension 125mg/5ml

<1year(9kg) 2.5mlt.i.d

1–5years(9–18kg) 5.0mlt.i.d

Inmoreseriousinfections,otitismedia,sinusitisandinfectionscausedbylesssusceptibleorganisms,40mg/kg/dayin

divideddosesisrecommendeduptoadailymaximumof1g.

Inthetreatmentofbeta-haemolyticstreptococcalinfections,therapyshouldbecontinuedforatleast10days.

4.3Contraindications

PatientswithahistoryofhypersensitivitytoCefaclorortoanyothercephalosporins.

Patientswithahistoryofhypersensitivitytotheotherconstituents

Patientswithahistoryofsevereallergyorasthmashouldbecloselymonitored.

4.4Specialwarningsandprecautionsforuse

BeforetherapywithCefaclorisinstituted,carefulinquiryshouldbemadetodeterminewhetherthepatienthashad

previoushypersensitivityreactionstoCefaclor,cephalosporinsorotherdrugs.Ifthisproductistobegivento

penicillin-sensitivepatients,cautionshouldbeexercisedbecausecross-sensitivityamongbeta-lactamantibioticshas

beenclearlydocumentedandmayoccurinupto10%ofpatientswithahistoryofpenicillinallergy.Ifanallergic

reactiontoCefacloroccurs,discontinuethedrug.Seriousacutehypersensitivityreactionsmayrequireemergency

treatmentmeasures.

Patientswithsevererenalimpairmentshouldbemonitoredcloselyalthoughadjustmentofthedoseisnotusually

required.Thehalf-lifeofCefaclorinanuricpatientsis2.3to2.8hourscomparedto0.6to0.9hoursinnormal

subjects.

ProlongeduseofCefaclormayencouragethegrowthofnon-susceptibleorganisms.Appropriatemeasuresshouldbe

takenifsuperinfectiontakesplaceduringtreatmentwithCefaclor.

Pseudomembranouscolitisisacommonsideeffectofbroad-spectrumantibiotictreatment.Thisshouldbeconsidered

whendiagnosingcasesofdiarrhoeainpatientstakingCefaclor.Thistypeofcolitismayrangefrommildtolife-

threatening.Mildcolitisisusuallyalleviatedbydiscontinuingthedrug.Moreappropriatemeasuresmayberequired

inmoderatetoseverecases.

Cautionshouldbeexercisedwhenprescribingbroadspectrumantibioticstopersonswithahistoryofgastrointestinal

disease,especiallycolitis.

Each5mldoseofCefaclorOralSuspensioncontains786mgofsorbitol.Itmaythereforebeunsuitableinhereditary

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

FalsepositiveCoombs'testshavebeenreportedduringtreatmentwithcephalosporins.Thisshouldbetakeninto

accountwhencross-matchingfortransfusion.Falsepositivesshouldalsobeconsideredwhentestingnew-borninfants'

bloodgroupswhosemothersweretakingcephalosporinantibioticspriortoparturition.

FalsepositiveshavealsobeenreportedforglucoseinurinewhenusingBenedict'sorFehling'ssolutionsorwithcopper

sulphatetesttablets.

TherenalexcretionofCefaclorisinhibitedbyprobenecid.

InpatientstakingCefaclorandwarfarinconcurrentlytherehavebeensomerarecasesofincreasedprothrombintime

eitherwithorwithoutclinicalbleeding.Adoseadjustmentmaybenecessaryandsuchpatientsshouldbemonitored

closely.

Theconcomitantuseofbacteriostaticantibioticsmayinterferewiththebactericidaleffectsofotherantibioticssuchas

beta-lactams.

4.6Pregnancyandlactation

CareshouldbetakenwhenprescribingCefaclorforpregnantwomen,inparticularduringthefirstthreemonths.

Animalstudieshavenotshownanyevidenceofimpairedfertilityorteratogenicityalthoughtherearenoadequateor

well-controlledtrialsinhumanvolunteers.

TherehavebeensmalllevelsofCefaclordetectedinthebreastmilkofnursingmothersfollowingsingledosesof500

mgCefaclor.Traceamountsarestilldetectableafter1hourandtheaverageamountofCefaclordeterminedafter5

hoursis0.2µg/ml.TheeffectofthisresidualCefacloronnursinginfantsisnotknownandconsequentlycareshould

betakenwhenprescribingfornursingwomen.

4.7Effectsonabilitytodriveandusemachines

ItisunlikelythatCefaclorwillaffectthepatient’sabilitytodriveand/oroperatemachinery.

4.8Undesirableeffects

Gastro-intestinal

Diarrhoeaisacommonside-effectalthoughitisnotusuallysevereenoughtodiscontinuetherapy.Colitisandrare

casesofpseudo-membranouscolitishavealsobeenreported.Nauseaandvomitinghavelikewisebeendescribed.

Transienthepatitisandcholestaticjaundiceareinfrequentlyfoundaswithsomepenicillinsandothercephalosporins.

Hypersensitivity:

Hypersensitivityreactionshaveoccurredinpatientsincludingmorbilliformrashes.Pruritus,urticariaandapositive

Coombs’testarefoundinlessthan1in200treatedpatients.

TherehavebeenreportsofgeneralisedreactionssimilartoserumsicknesswiththeuseofCefaclor.Theseare

characterisedbythepresenceoferythema,multiformrashandothersignsaffectingtheskin,accompaniedby

arthritis/arthralgia,withorwithoutfever.Theymaybedistinguishedfromclassicalserumsicknessinthat

lymphadenopathyandproteinuriaarerarelyfound,nocirculatingimmunecomplexesarepresentandthereistodateno

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Whilestudiesonthisareunderway,the"serumsicknesslike"reactionappearstobeduetohypersensitivityandoccurs

moreofteninasecondorsubsequenttreatmentcyclewithCefaclor.Thesereactionshavebeenreportedwithgreater

frequencyinchildrencomparedwithadultswithanincidenceof1in200(0.5%)inaclinicalstudy,in2outof8346

(0.024%)inotherclinicalstudies(withanincidenceinchildrenof0.055%)andfinallyin1in38,000(0.0003%)as

spontaneousevents.Thesignsandsymptomsareevidentafewdaysafterthestartoftreatmentandceaseafewdays

afteritsconclusion.Thesereactionshaveonlyoccasionallynecessitatedhospitalisationwhichisgenerallyshort(on

averagefrom2to3daysaccordingtothe"Post-MarketingSurveillance"studies).

Thesymptomsatthetimeofhospitaladmissionrangedfrommildtosevereandweremoresevereinchildren.Anti-

histaminesandglucocorticoidsresolvethesignsandsymptoms.Serioussequelaehavenotbeenreported.Moresevere

hypersensitivityreactions,includingtheSteven's-Johnsonsyndrome,toxicepidermalnecrolysisandanaphylaxis,may

bemorereadilyseeninpatientsallergictopenicillins.Symptomsofanaphylactoidreactionscanappearasindividual

symptomsincludingangiodema,asthenia,oedema(faceandjoints),dyspnoea,orvasodilation.Inrarecasesthe

symptomsofhypersensitivitycanrecuroveranumberofmonths.

Other:

EventsrelatedtotreatmentwithCefaclorincludeeosinophilia,genitalpruritisandvaginitis;andrarely,

thrombocytopeniaandreversibleinterstitialnephritis,paraesthesias,syncope,vaginalmoniliasis,nervousness,

dizziness,hallucinations.Therehavebeenreportsofcasesofhaemolyticanaemiafollowingtreatmentwith

cephalosporins.

CentralNervousSystem:reversiblehyperactivity,insomnia,mentalconfusion,hypertonia,afeelingofinstabilityand

staggering,andsomnolencehavebeenreportedoccasionally.Thesewerereversibleoncessationoftreatmentandthe

causalrelationshiptotreatmentisnotcertain.

Transientchangesinbiochemicalvalueshavealsobeenreportedand

thecausalrelationshiptotreatmentisnotcertain.

Changesinliverfunction:therehavebeenreportsofmildincreasesinSGOTandSGPToralkalinephosphataseand

thecausalrelationshiptotreatmentisnotcertain.

Haematologicalchanges:aswithotherbeta-lactamantibiotics,therehavebeenreportsoftransientlymphocytosis,

leucopeniaand,rarely,haemolyticanaemiaandreversibleneutropeniaofpossibleclinicalsignificance.Therehave

beeninfrequentreportsofanincreaseintheprothrombintimewithorwithoutclinicalbleedinginpatientswhowere

takingCefaclorandwarfarinsodiumatthesametime.

Renalchanges:therehavebeenreportsofmildincreasesinserumureaandcreatinineorchangesinurinalysis.

4.9Overdose

Symptoms:

Symptomsoftoxicityfollowinganoverdosemayincludenausea,vomiting,epigastricdistressanddiarrhoea.The

severityoftheepigastricdistressandthediarrhoeaisproportionaltothedosetaken.Ifothersymptomsarenotedthey

areprobablysecondarytotheunderlyingpathology,toanallergicreactionortoanotherintoxication.

Treatment:

Gastrointestinaldecontaminationisnotrequiredunless5timesthenormaltotaldailydosehasbeenconsumed.

Intestinalabsorptionmaybereducedbygivingactivatedcharcoalwhichmay,inmanycases,moreeffectivethan

inducedvomitingorgastriclavage.Activatedcharcoalshouldthereforebeconsideredeitherasanalternative

treatmentorinconjunctionwithgastricemptying.Thepatient'sairwayshouldbecarefullymonitoredifthestomachis

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Thepatient'sventilationandpulmonaryperfusion,vitalsigns,bloodgasanalysis,serumelectrolysis,etc.,shouldalso

beconscientiouslymonitored.

Thebenefitofforceddiuresis,peritonealdialysis,haemodialysisorhaemoperfusionwithcharcoalhasnotbeen

establishedforoverdosesofCefaclor.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Thecephalosporinmodeofactionissimilartopenicillininthatthereisinhibitionofcellwallsynthesis.Thelaststage

ofpeptidoglycansynthesisinthebacterialcellwallisacross-linkingreactioneffectedbyatranspeptidaseenzyme.It

isprobablethatcephalosporinsinhibitthistranspeptidaseenzymebyacylatingitinthesamewayaspenicillins

Breakpoints

ThefollowingMICbreakpointsseparatingsusceptiblefromintermediately/moderatelysusceptiblefromresistant

organismsaresuggested:

Sislessthanorequalto8mg/LandRisgreaterthanorequalto32mg/Lforallbacterialisolates.

5.2Pharmacokineticproperties

Cefaclorisrapidlyabsorbedfromthegastrointestinaltract,plasmalevelsof18-33mg/lbeingfoundaftera1gdose

and13-19mg/lafter500mg.Itisunstableinserumat37 °

C,lessthan10%ofactivityremainingatsixhoursand

Susceptible

Grampositiveaerobes

Staphylococcusspp.(includingmethicillin-susceptible)

Streptococcuspneumoniae

Streptococcuspyogenes(groupA haemolyticstreptococci

Gram-negativeaerobes

Moraxellacatarrhalis

Escherichiacoli

Haemophilusinfluenzae

Klebsiellaspp.

Proteusmirabilis

Resistant

Gram-positiveaerobes

Staphylococcusspp.(methicillinresistant)

Enterococcusspp.

Gram-negativeaerobes

Acinetobacterspp.

Enterobacterspp.

Morganellamorganii

Proteusvulgaris

Providenciarettgeri

Pseudomonasspp.

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Therewasnoevidenceofaccumulationafter10daysinmultipledosevolunteerstudies.Thepresenceoffoodmay

arrestCefaclorabsorptiontemporarilybutthetotalamountabsorbedshouldremainthesame.Innormalfasting

subjects,ameanpeakvalueof16.5mg/lwasreducedto10.8mg/lat48minwhenthedrugwasadministeredwith

food.FurthermorethesevaluesgreatlyexceedtheMICforsusceptibleorganismsandtheurinaryexcretioninthefirst

sixhoursisnotaffected.Theplasmahalflifeis29-60min(mean48min).Thevolumeofdistributionis0.37 ±

0.114.1kg.Plasmaproteinbindingis24.6 ±

3.5%.

Inchildrenagedfourmonthstofiveyears(average1.9years)dosesof10mg/kgproducedlevelsat13minutesinthe

serumof10.8mg/linfastingpatientsand6.7mg/linpatientswhoreceivedfood.Verylittleofthedrugreachesthe

CSF.Intwopatientsgivenasingledoseof250mg,peaklevelsinbreastmilkwere1.8and0.5mgaftertwoandfour

hoursrespectively.Peaklevelsdetectedinaqueoushumor,interstitialfluid,middleearaspirateandsalivahavebeen

foundtobebetween0.5and1mg/l.Lowerlevelsinsputum(around0.5mg/l)havebeenfound.

Excretioninurineisthemaineliminationpathwithbetween43and97%oftheadministereddoseisexcretedinthe

first8hours.38-54%ofexcretiontakesplaceinthefirsttwohours,producingpeakvaluesinexcessof900mg/l.

Mostofthedrugiseliminatedunchangedintheurine.Asmallproportionofthedose,upto15%,ismetabolisedor

otherwisedegraded.Inpatientswithseverelyimpairedrenalfunctionreceivingasingledoseof500mgCefaclorby

mouthwhilefasting,peakplasmalevelsrangedfrom12to23mg/landtheplasmahalflifefrom1.9to3.5hours.

Theminimumbactericidalconcentration(MBC),dependingontheorganismtested,isusuallytwotoeighttimesthe

minimuminhibitoryconcentration(MIC).ThereisnoevidencethatmeasuringplasmaconcentrationsofCefaclorisof

anyrelevanceinroutineclinicalpractice.

5.3Preclinicalsafetydata

Cefaclorhasshownlowtoxicityinmice,rats,dogsandmonkeys.Subacuteandchronictoxicitystudiesinrodentsand

dogsdemonstratethatthedrugiswelltolerated.Cefaclorisnotteratogenictomiceindosesashighas1mg/kgnorto

ratsindosesupto1000mg/kgdaily.Nocarcinogeniceffectshavebeenobservedinchroniconeyeartoxicitystudies

inrats.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sorbitol(E420)

Simethicone

Xanthangum

Strawberryflavour

Sodiumlaurylsulphate

Mannitol

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Shelflifefortheproductaspackagedforsale:

2years.

Shelflifeafterreconstitutionaccordingtodirections:

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6.4Specialprecautionsforstorage

Fortheproductaspackagedforsale:

Donotstoreabove25 °

C.Keepcontainerintheoutercarton.Keepcontainertightlyclosed.

Afterreconstitution:

Storeinarefrigerator(2-8 °

6.5Natureandcontentsofcontainer

Thisproductissuppliedina60ml,75ml,100mlora150mlHighDensityPolyethylene(HDPE)bottlewithachild-

proofpolypropylene/polyethylene(PP/PE)screw-cap.

Theinsideofthecapislinedwithasarandisc(PVdC).

A5ml,CEcertified,graduatedpolypropyleneoralsyringefordosingissupplied.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Thereconstitutionisusuallyperformedbythedispensingpharmacist.

Shakethebottlewellbeforeaddinganywatertoloosenthepowder.

Forthe150mlbottlesize:

Add116mlwaterintwoportions,shakingwellbetweenadditionstoensureahomogenoussuspension.

Forthe100mlbottlesize:

Add77mlwaterintwoportions,shakingwellbetweenadditionstoensureahomogenoussuspension.

Forthe75mlbottlesize:

Add58mlwaterintwoportions,shakingwellbetweenadditonstoensureahomogenoussuspension.

Forthe60mbottlesize

Add47mlwaterintwoportions,shakingwellbetweenadditionstoensureahomogenoussuspension.

Thereconstitutedsuspensionshouldbestoredinarefrigerator.Discardanyremainingsolutionafter14days.

Thereconstitutedsuspensionisintheformofanoff-whitesuspension.

Shakethebottlethoroughlybeforeuse.

InstructionforusebythepatientareincludedinthepatientInformationLeafletandpertaintotheuseofanoral

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7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLimited

T/AGerardLaboratories

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA0577/045/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 8March2002

Dateoflastrenewal: 13December2005

10DATEOFREVISIONOFTHETEXT

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