CEFTAL

Main information

  • Trade name:
  • CEFTAL Coated Tablets 125 Milligram
  • Dosage:
  • 125 Milligram
  • Pharmaceutical form:
  • Coated Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CEFTAL Coated Tablets 125 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/101/001
  • Authorization date:
  • 13-10-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0711/101/001

CaseNo:2082950

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

RowexLtd

Bantry,Co.Cork,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Ceftal125mgcoatedtablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom28/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 28/07/2010 CRN 2082950 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Ceftal125mgcoatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Ceftal125mgcontains150.36mgcefuroximeaxetilwhichisequivalentto125mgcefuroximepertablet

Excipients:aspartame(E951)0.2mg

Forafulllistofexcipients:seesection6.1.

3PHARMACEUTICALFORM

Coatedtablets

Whitetoslightlyyellowish,biconvex,oblongtablets

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cefuroximeaxetilisindicatedforthetreatmentofmildtomoderatelysevereinfectionscausedbymicro-organisms

susceptibletocefuroxime,suchas:

upperrespiratorytractinfections:acuteotitismedia,sinusitis,tonsillitisandpharyngitis

acutebronchitis,acuteexacerbationsofchronicbronchitis

loweruncomplicatedurinarytractinfections:cystitis

skinandsofttissueinfections:furunculosis,pyodermaandimpetigo

treatmentofearlystageLymedisease(stadiumI)andsubsequentpreventionoflatecomplicationsinadultsand

childrenabove12yearsofage.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2Posologyandmethodofadministration

CeftalTabletsarecoatedtomasktheirtaste:theyshouldnotbechewed.

Theusualdurationoftherapyis7days(rangingfrom5to10days).Incaseofpharyngotonsillitiscausedby

Streptococcuspyogenesatherapydurationofatleast10daysisindicated.ThedurationoftreatmentofearlyLyme

diseaseshouldbe20days.InordertoachieveoptimumabsorptionCeftalTabletsshouldbetakenshortlyaftermeals.

Thedosagedependsontheseverityoftheinfection.Forsevereinfectionsparenteralformsofcefuroximeare

recommended.Whereappropriatecefuroximeaxetiliseffectivewhenusedfollowinginitialparenteralcefuroxime

sodiuminthetreatmentofpneumoniaandacuteexacerbationsofchronicbronchitis.

Dosageschedulefortablets:

Adultsandchildrenover12yearsofage Dosage

Upperrespiratorytractinfections 250(–500)mgtwicedaily

Lowerrespiratorytractinfections 500mgtwicedaily

Loweruncomplicatedurinarytractinfections 125–250mgtwicedaily

Skinandsofttissueinfections 250–500mgtwicedaily

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Childrenunder5yearsofage:

CeftalTabletsarenotsuitableforuseinchildrenundertheageof5.Forpatientsinthisagegroupitisadvisedtouse

anoralsuspension.Thereisnoexperienceinchildrenunder3monthsofage.

Dosageregimeninrenalimpairment,indialysispatientsandelderly:

Nospecialprecautionsarenecessaryinpatientswithrenalimpairment,orinelderlypatientsifthedailydosagedoes

notexceed1gram.Inpatientswithrenalimpairmentandcreatinineclearancebelow20ml/minCeftalTabletsshould

bedosedcarefully.Patientsundergoinghaemodialysiswillrequireasupplementarydoseofcefuroximeattheendof

eachdialysistreatment.

4.3Contraindications

Hypersensitivitytocefuroxime,othercephalosporinsortoanyoftheexcipients.

Previousimmediateand/orseverehypersensitivityreactiontoapenicillinortoanyothertypeofbeta-lactammedicinal

products.

4.4Specialwarningsandprecautionsforuse

Ifafteradministrationofcefuroximeaxetilsensitivityreactionsoccur,theuseshouldbediscontinuedimmediatelyand

anappropriatetreatmentshouldbeestablished.

Specialcareisindicatedinpatientswhohaveexperiencedanallergicreactiontopenicillinsorotherbeta-lactams.

Aswithotherbroadspectrumantibiotics,prolongeduseofcefuroximeaxetilmayresultintheovergrowthofnon-

susceptibleorganisms(e.g.,candida,enterococciandclostridiumdifficile,whichmayrequireinterruptionoftreatment.

Inpatientswhodevelopseverediarrhoeaduringorafteruseofcefuroximeaxetil,theriskoflifethreatening

pseudomembranouscolitisshouldbetakenintoaccount.Theuseofcefuroximeaxetilshouldbediscontinuedandthe

appropriatetreatmentestablished.Theuseofpreparationsinhibitingtheintestinalperistaltismiscontra-indicated(see

section4.8).

A20-daytreatmentofLymediseasemaycausethefrequencyofdevelopingdiarrhoeatoincrease.

Longtermuseofcefuroximeaxetilmayleadtoanexcessofpathogensresistanttocefuroximeaxetil.Itisofhigh

importancethatthepatientiscarefullychecked.Ifasuperinfectionoccursduringtreatment,appropriatemeasures

shouldbetaken(seesection4.8).

Theuseofcefuroximeaxetilisnotrecommendedinpatientswithsevereintestinaltractdisordersaccompaniedby

vomitinganddiarrhoea,sinceinthesesituationsasufficientabsorptioncannotbeguaranteed.Administrationofa

parenteralformulationofcefuroximeshouldbeconsidered.

TheJarisch-HerxheimerreactionhasbeenreportedfollowingcefuroximeaxetiltreatmentofLymedisease.The

reactionresultsdirectlyfromthebactericidalactivityofcefuroximeaxetilonthespirochaeteBorreliaburgdorferi.

Patientsshouldbeinformedofthiscommonandusuallyself-limitedreactionbeingaconsequenceofantibiotic

treatmentofLymedisease.

SimultaneoususeofmedicinesenhancingthepHofthestomachisnotrecommended(seesection4.5).

Thereisnoclinicalexperiencewiththeuseofcefuroximeaxetilinchildrenundertheageof3months.Withrespectto

thetreatmentofearlyLymediseasethereisonlyclinicalexperiencewithchildrenfromtheageof12andwithadults.

Specialcareshouldbetakenwithphenylketonuricpatientsbecauseoftheaspartamecontainingcoating.

Childrenfrom5to12yearsofage

Above-mentionedindications,ifrelevantfor

thisgroupofchildren 125–250mgtwicedaily

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Eithertheglucoseoxidaseorthehexokinasemethodsarerecommendedtodeterminethebloodandplasmaglucose

levelsinpatientsreceivingcefuroximeaxetil.Cefuroximedoesnotinterfereinthealkalinepicrateassayforcreatinine

(seesection4.5).

Duringthetreatmentwithcefuroximesodium,somechildrenhaveexperiencedslighttomoderatehearingloss.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SimultaneoususeofmedicinesenhancingthepHofthestomachdecreasesthebioavailabilityofcefuroximeaxetil.Itis

recommendedtoavoidthiscombination(seesection4.4).

Sincebacteriostaticdrugsmayinterferewiththebactericidalactionofcephalosporins,itisadvisabletoavoidgiving

tetracyclines,macrolides,orchloramphenicolinconjunctionwithcefuroximeaxetil.

Theconcomitantadministrationofprobenicidcanproducehigherandsustainedconcentrationsofcefuroximeinthe

serumandinthebile.

Cefuroximemayinterferewiththedeterminationofglucoseinurinewithcoppercontainingreagentia(Benedict-or

Fehling-solution,Clinitest).Forthedeterminationofblood-andplasmasugarlevelsinpatientsreceivingcefuroxime

axetil,theglucose-oxidase-orhexokinasemethodisrecommended(seesection4.4).

TheuseofcefuroximeaxetilmaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(seesection4.8).

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingpotentdiuretics,

aminoglycosides,oramphotericinasthesecombinationsincreasestheriskofnephrotoxicity.

4.6Pregnancyandlactation

Useinpregnancy

Therearenotsufficientdataontheuseofcefuroximeaxetilduringpregnancytoassessitspossibleharmfulness.Sofar,

animaltestshavenotyieldedevidenceofharmfulness.Cefuroximecrossestheplacenta.Cefuroximeaxetilshouldnot

beusedduringpregnancyunlessconsideredessentialbythephysician.

Useduringlactation

Cefuroximeisexcretedtoasmalldegreeinhumanmilk;breastfeedingshouldbeavoidedinwomenusingcefuroxime

axetil.

4.7Effectsonabilitytodriveandusemachines

Therearenostudiesoftheeffectofcefuroximeaxetilontheabilitytodriveandtohandlemachines.

However,anyeffectsarenottobeexpected.

4.8Undesirableeffects

Common(1/100to<1/10)

Uncommon(1/1,000to<1/100)

Rare(1/10,000to<1/1,000)

Veryrare(<1/10,000)

Infectionsandinfestations:

Rare

Pseudomembranouscolitis

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Candida,EnterococciandClostridiumdifficile(seesection4.4).

Bloodandthelymphaticsystemdisorders

Rare

Decreasedhaemoglobinconcentration,eosinophilia,leucopenia,neutropeniaandthrombocytopenia

Veryrare

Haemolyticanemia

Immunesystemdisorders:

Common

Jarisch-HerxheimerreactionfollowingcefuroximeaxetiltreatmentofLymedisease(seesection4.4).

Rare

Serumsickness

Veryrare

Anaphylaxis

Nervoussystemdisorders

Uncommon

Headache,dizziness

Veryrare

Restlessness,nervousness,confusion

Gastrointestinaldisorders:

Common

Diarrhoea,nauseaandvomiting.Thefrequencyofdiarrhoeaisrelatedtotheadministereddoseandmayrateupto10%

withtablets.Theincidenceisevenhigher(approx.13%)atprolongedtreatmentof20daysofearlyLymedisease.

Hepato-biliarydisorders:

Rare

Transientincreasesofhepaticenzymelevels(AST,ALTandLDH)andserumbilirubin.

Veryrare

Jaundice.

Skinandsubcutaneoustissuedisorders:

Common

Skinrashes,urticaria,pruritus.

Veryrare

Erythemamultiforme,Stevens-Johnsonsyndromeandtoxicepidermalnecrolysis

Renalandurinarydisorders

Common

Increasedlevelsofcreatinineandureainserum,especiallyinpatientswithimpairedrenalfunction.

Uncommon

Acuteinterstitialnephritis

Generaldisordersandadministrationsiteconditions:

Rare

Drugfever

Investigations

TheuseofcefuroximeaxetilmaybeaccompaniedbyafalsepositiveCoombstest.Thismayinterferewiththe

performanceofcrossmatchingtestswithblood(seesection4.5).

4.9Overdose

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levelscanbereducedbyhaemodialysisandperitonealdialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Generalproperties:

ATCclassification

Pharmacotherapeuticgroup:cephalosporinsandrelatedsubstances

ATC-Code:J01DC02

Modeofaction

Cefuroximeaxetilowesitsinvivobactericidalactivitytotheparentcompoundcefuroxime.Allcephalosporins(-

lactamantibiotics)inhibitcellwallproductionandareselectiveinhibitorsofpeptidoglycansynthesis.Theinitialstepin

drugactionconsistsofbindingofthedrugtocellreceptors,calledPenicillin-BindingProteins.Aftera -lactam

antibiotichasboundtothesereceptors,thetranspeptidationreactionisinhibitedandpeptidoglycansynthesisis

blocked.Bacteriallysisistheendresult.

Mechanismofresistance

Bacterialresistancetocefuroximemaybeduetooneormoreofthefollowingmechanisms:

hydrolysisbybeta-lactamases.Cefuroximemaybeefficientlyhydrolysedbycertainoftheextended-spectrum

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

derepressedincertainaerobicgram-negativebacterialspecies

reducedaffinityofpenicillin-bindingproteinsforcefuroxime

outermembraneimpermeability,whichrestrictsaccessofcefuroximetopenicillinbindingproteinsingram-

negativeorganisms

drugeffluxpumps

Methicillin-resistantstaphylococci(MRS)areresistanttoallcurrentlyavailable -lactamantibioticsincluding

cefuroxime.

Penicillin-resistantStreptococcuspneumoniaearecross-resistanttocephalosporinssuchascefuroximethrough

alterationofpenicillinbindingproteins.

Beta-lactamasenegative,ampicillinresistant(BLNAR)strainsofH.influenzaeshouldbeconsideredresistantto

cefuroximedespiteapparentinvitrosusceptibility.

StrainsofEnterobacteriaceae,inparticularKlebsiellaspp.andEscherichiacolithatproduceESBLs(extended

spectrum-lactamase)maybeclinicallyresistanttotherapywithcephalosporinsdespiteapparentinvitrosusceptibility

andshouldbeconsideredasresistant.

Breakpoints:

AccordingtotheNCCLS(NationalCommitteeonClinicalLaboratoryStandards)in2001thefollowingbreakpoints

havebeendefinedforcefuroximeaxetil:

Enterobacteriaceae: ≤4µg/mlsusceptible,≥32µg/mlresistant

Staphylococcusspp.: ≤4µg/mlsusceptible,≥32µg/mlresistant

Haemophilusspp.: ≤4µg/mlsusceptible;≥16µg/mlresistant

Streptococcuspneumoniae: ≤1µg/mlsusceptible,≥4µg/mlresistant

Streptococcusspp.otherthanS.pneumoniae:

Streptococcalisolatessusceptibletopenicillin(MIC

≤0.12µg/ml)maybeconsideredsusceptibletocefuroxime.

Susceptibility:

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspeciesandlocalinformationon

resistanceisdesirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhen

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5.2Pharmacokineticproperties

Absorption:Afteroraladministrationcefuroximeaxetilisabsorbedfromthegastrointestinaltractandrapidly

hydrolysedintheintestinalmucosaandbloodcausingthereleaseoftheactivecompoundcefuroximeintothe

circulation.OptimumabsorptionoccurswhenCefuroximaxetilistakenshortlyafterameal(50-60%).Underthese

circumstancesmaximumserumconcentrationisachievedafter2-3hours.

Distribution:Cefuroximeiswidelydistributedinthebodyincludingpleuralfluid,sputum,bone,synovialfluid,and

aqueoushumour,butonlyachievestherapeuticconcentrationsintheCSFwhenthemeningesareinflamed.About50%

ofcefuroximeinthecirculationisboundtoplasmaproteins.Itdiffusesacrosstheplacentaandhasbeendetectedin

breastmilk.

Metabolism:Cefuroximeisnotmetabolised.

Commonlysusceptiblespecies

Aerobes,Grampositive:

Staphylococcusaureus(methicillin-susceptible)

Coagulase-negativestaphylococci(methicillin-susceptible)

Streptococcusagalactiae

Streptococcuspneumoniae

Streptococcuspyogenes

Aerobes,Gramnegative:

Escherichiacoli

Haemophilusinfluenzae

Klebsiellaspecies

Moraxellacatarrhalis

Proteusmirabilis

Proteusrettgeri

Anaerobes,

Peptococcusspecies

Peptostreptococcusspecies

Otherorganisms:

Borreliaburgdorferi.

Speciesforwhichresistancemaybeaproblem

Acinetobacterspecies

Citrobacterspecies

Enterobacterspecies

Morganellamorganii

Resistant

Bacteroidesfragilis

Clostridiumdifficile

Enterococci

Listeriamonocytogenes

Proteusvulgaris

Pseudomonasspecies

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about50%throughrenaltubularsecretionwithin24hours,withthemajoritybeingeliminatedwithin6hours;high

concentrationsareachievedintheurine.Smallamountsofcefuroximeareexcretedinbile.

Probenecidcompeteswithcefuroximeforrenaltubularsecretionresultinginhigherandmoreprolongedplasma

concentrationsofcefuroxime.Theplasmahalf-liferangesbetween60and90minutesandisprolongedinpatientswith

renalimpairmentandinneonates.

Dialysiscausesthedecreaseofcefuroximeserumlevels.

5.3Preclinicalsafetydata

Preclinicaleffectswereobservedindosagesfarabovethemaximalhumandosagewhicharethereforehardlyrelevant

fortheclinicaluseofcefuroximeaxetil.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Core

Sodiumlaurilsulfate,

Copovidone,

Croscarmellosesodium(E468),

Magnesiumstearate(E470B),

Colloidalanhydroussilica(E551),

Granulatedmannitol(E421),

Microcrystallinecellulose(E460),

Crospovidone(E1202),

Talc(E553B).

Coating

Mannitol(E421),

Solublestarch(potato),

Talc(E553B),

Titaniumdioxide(E171),

Aspartame(E951)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Al/Alstrip:3years

Al/Alblister:3years

6.4Specialprecautionsforstorage

Al/Alstrip:Storeintheoriginalpackaginginordertoprotectfrommoisture

Al/Alblister:Storeintheoriginalpackaginginordertoprotectfrommoisture

Thismedicinalproductdoesnotrequireanyspecialtemperaturestorageconditions

6.5Natureandcontentsofcontainer

Al/Alstrippackaging

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Packsizes:

8,10,12,14,24tablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RowexLtd

Bantry

CoCork

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA711/101/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13October2006

Lastdateofrenewal:26January2010

10DATEOFREVISIONOFTHETEXT

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