CLAFORAN

Main information

  • Trade name:
  • CLAFORAN Pdr for Soln for Injection 2 Grams
  • Dosage:
  • 2 Grams
  • Pharmaceutical form:
  • Pdr for Soln for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLAFORAN Pdr for Soln for Injection 2 Grams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0540/037/004
  • Authorization date:
  • 09-01-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0540/037/004

CaseNo:2059853

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

TransferredfromPA0006/024/004.

sanofi-aventisIrelandLimited

CitywestBusinessCampus,Dublin24,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

ClaforanPowderforsolutionforInjection2g

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/01/2009until17/12/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ClaforanPowderforsolutionforInjection2g

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachvialcontainscefotaximesodiumequivalentto2gcefotaximebase.

EachgramofClaforancontainsapproximately48mg(2.09mmol)ofsodium.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Powderforsolutionforinjectionorinfusion.

Awhitetopaleyellow-whitecrystallinepowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Properties:Claforanisabroad-spectrumbactericidalcephalosporinantibiotic.Claforanisexceptionallyactivein

vitroagainstGram-negativeorganismssensitiveorresistanttofirstorsecondgenerationcephalosporins.Itissimilar

toothercephalosporinsinactivityagainstGram-positiveorganisms.

Indication:Claforanisindicatedinthetreatmentofthefollowinginfectionseitherbeforetheinfectingorganismhas

beenidentifiedorwhencausedbybacteriaofestablishedsensitivity:

Septicaemias

RespiratoryTractInfectionssuchasacuteandchronicbronchitis,bacterialpneumonia,infectedbronchiectasis,lung

abscessandpost-operativechestinfections.

UrinaryTractInfectionssuchasacuteandchronicpyelonephritis,cystitisandasymptomaticbacteriuria.

SoftTissueInfectionssuchascellulitis,peritonitisandwoundinfections.

BoneandJointInfectionssuchasosteomyelitis,septicarthritis.

ObstetricandGynaecologicalInfectionssuchaspelvicinflammatorydisease.

Gonorrhoeaparticularlywhenpenicillinhasfailedorisunsuitable.

OtherBacterialInfections,meningitisandothersensitiveinfectionssuitableofparenteralantibiotictherapy.

Prophylaxis:

TheadministrationofClaforanprophylacticallymayreducetheincidenceofcertainpost-operativeinfectionsin

patientsundergoingsurgicalproceduresthatareclassifiedascontaminatedorpotentiallycontaminatedorinclean

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Protectionisbestensuredbyachievingadequatelocaltissueconcentrationsatthetimecontaminationislikelytooccur.

Claforanshouldthereforebeadministeredimmediatelypriortosurgeryandifnecessarycontinuedintheimmediate

post-operativeperiod.

Administrationshouldusuallybestoppedwithin24hourssincecontinuinguseofanyantibioticinthemajorityof

surgicalproceduresdoesnotreducetheincidenceofsubsequentinfection.

Claforanmayalsobeusedprophylacticallyalongwithorallyadministerednon-absorbableantibioticstoreducethe

incidenceofinfectionamongselectedpatientsundergoingintensivetherapy,whosedurationofstayinIntensiveCare

Unitisanticipatedtoexceed48hours.

Bacteriology:

ThefollowingorganismshaveshowninvitrosensitivitytoClaforan.

GramPositive

Staphylococci,includingcoagulase-positive,coagulase-negativeandpenicillinaseproducingstrains.

Beta-haemolyticandotherstreptococcisuchasStreptococcusmitis(viridans)(manystrainsofenterococci,e.g.

Streptococcusfaecalis,arerelativelyresistant).

Streptococcus(Diplococcus)pneumonia.

Clostridiumspp.

GramNegative

Escherichiacoli.

Haemophiliusinfluenzaeincludingampicillinresistantstrains.

Klebsiellaspp.

Proteusspp.(bothindolepositiveandindolenegative).

Enterobacterspp.

Neisseriaspp.(includingB-lactamaseproducingstrainsofN.gonorrhoea).

Salmonellaspp.(includingSal.Typhi).

Shigellaspp.

Providenciaspp.

Serratiaspp.

Citrobacterspp.

ClaforanhasfrequentlyexhibitedusefulinvitroactivityagainstPseudomonasandBacteroidesspeciesalthoughsome

strainsofBacteroidesfragilisareresistant.

ThereisinvitroevidenceofsynergybetweenClaforanandaminoglycosideantibioticssuchasgentamicinagainstsome

speciesofGram-NegativebacteriaincludingsomestrainsofPseudomonas.Noinvitroantagonismhasbeennoted.In

severeinfectionscausebyPseudomonasspp.theadditionofanaminoglycosideantibioticmaybeindicated.

4.2Posologyandmethodofadministration

Dosage:

Claforanmaybeadministeredintravenouslyorbybolusinjectionorinfusionorintramuscularly.Thedosage,route

andfrequencyofadministrationshouldbedeterminedbytheseverityofinfection,thesensitivityofcausativeorganism

andconditionofthepatient.

Therapymaybeinitiatedbeforetheresultsofsensitivitytestsareknown.

Adults:Therecommendeddosageformildtomoderateinfectionsis1g12hourly.However,dosagemaybevaried

accordingtotheseverityoftheinfection,sensitivityofcausativeorganismsandconditionofthepatient.Therapymay

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Insevereinfectionsdosagemaybeincreasedupto12gdailygivenin3or4ordivideddoses.Forinfectionscausedby

sensitivePseudomonasspp.dailydosesofgreaterthan6gwillusuallyberequired.

DosageinGonorrhoea:Asingleinjectionof1gmaybeadministeredintramuscularlyorintravenously.

Children:Theusualdosagerangeis100-150mg/kg/dayin2to4divideddoses.However,inverysevereinfections

dosesofupto200mg/kg/daymayberequired.

Neonates:Therecommendeddosageis50mg/kg/dayin2to4divideddoses.Insevereinfections150-200mg/kg/day,

individeddoses,havebeengiven.

DosageinRenalImpairment:

Becauseofextra-renalelimination,itisonlynecessarytoreducethedosageofClaforaninsevererenalfailure

(GFR<5ml/min=serumcreatinineapproximately751micromol/1).Afteraninitialloadingdoseof1g,dailydose

shouldbehalvedwithoutchangeinthefrequencyofdosing,i.e.1gin12hourlybecomes0.5g12hourly,1g8hourly

becomes0.5g8hourly,2g8hourlybecomes1g8hourlyetc.Asinallotherpatients,dosagemayrequirefurther

adjustmentaccordingtothecourseoftheinfectionandthegeneralconditionofthepatient.

ADMINISTRATION:

IntravenousandIntramuscularadministration:

ReconstituteClaforanwithWaterforInjectionasgivenintheDilutionTable.Shakewelluntildissolvedandthen

withdrawtheentirecontentsofthevialintothesyringeanduseimmediately.

DilutionTable:

IntravenousInjection:

Claforanmaybeadministeredbyintravenousinfusion.1-2garedissolvedin40-100mlofWaterforInjectionorinthe

infusionfluidslistedunder"PharmaceuticalParticulars".Thepreparedinfusionmaybeadministeredover20-60

minutes.Toproduceaninfusionusingvialswithaninfusionconnector,removethesafetycapanddirectlyconnectthe

infusionbag.Theneedleintheclosurewillautomaticallypiercethevialstopper.Pressingtheinfusionbagwill

transfersolventintothevial.Reconstitutebyshakingthevialandfinally,transferthereconstitutedsolutionbacktothe

infusionbagreadyforuse.

4.3Contraindications

Knownorsuspectedallergytocephalosporins.

4.4Specialwarningsandprecautionsforuse

Preliminaryenquiryaboutallergytopenicillinandotherbeta-lactamantibioticsisnecessarybeforeprescribing

cephalosporinssincecrossallergyoccursin5-10%ofcases.

Hypersensitivityreactions(anaphylaxis)occurringwiththetwotypesofantibioticscanbeseriousandoccasionally

fatal.Hypersensitivityrequiresthattreatmentbestopped.

VialSize Diluenttobeadded

500mg 2ml

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MethodofAdministration".

Aswithotherantibiotics,theuseofClaforan,especiallyifprolonged,mayresultinovergrowthofnon-susceptible

organisms.Repeatedevaluationoftheconditionofthepatientisessential.Ifsuperinfectionoccursduringtherapy,

appropriatemeasuresshouldbetaken.

ClaforanreconstitutedwithLignocainemustneverbeused:

Bytheintravenousroute

Ininfantsunder30months

Insubjectswithaprevioushistoryofhypersensitivitytothisproduct

Inpatientswhohaveanunpacedheartblock

Inpatientswithsevereheartfailure.

ThesodiumcontentofClaforan(2.09mmol/g)shouldbetakenintoaccountwhenprescribingtopatientsrequiring

sodiumrestriction.

Claforanmaypredisposepatientstopseudo-membranouscolitis.Althoughanyantibioticmaypredisposetopseudo-

membranouscolitis,theriskishigherwithbroadspectrumdrugs,suchascephalosporins.

Thissideeffect,whichmayoccurmorefrequentlyinpatientsreceivinghigherdosesforprolongedperiods,shouldbe

consideredaspotentiallyserious.ThepresenceofC.Difficileshouldbeinvestigated,andtreatmentwithClaforan

stoppedincasesofsuspectedcolitis.

Thediagnosisshouldbeconfirmedbysigmoidoscopyandspecificantibiotictherapy(e.g.oralvancomycinor

Metronidazole)initiatedifconsideredclinicallynecessary.Theadministrationofproductswhichcausefaecalstasis

shouldbeavoided.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Cephalosporinantibioticsathighdosageshouldbegivenwithcautiontopatientsreceivingaminoglycosideantibiotics

orpotentdiureticssuchasfrusemideasthesecombinationsaresuspectedtoadverselyaffectrenalfunction.

However,attherecommendeddoses,enhancementofnephrotoxicityisunlikelytobeaproblemwithClaforan.

ProbenecidinterfereswithrenaltubulartransferofClaforan,delayingitsexcretionandincreasingtheplasma

concentration.

InterferencewithLaboratoryTests:

ApositiveCoombstestmaybeseenduringtreatmentwithCephalosporins.Thisphenomenonmayoccurduring

treatmentwithClaforan.

Afalsepositivereactiontoglucosemayoccurwithreducingsubstancesbutnotwiththeuseofspecificglucose

oxidosemethods.

4.6Pregnancyandlactation

Pregnancy:ItisknownthatClaforancrossestheplacentalbarrier.Althoughstudiesinanimalshavenotshownan

adverseeffectonthedevelopingfoetus,thesafetyofClaforaninhumanpregnancyhasnotbeenestablished.

Consequently,Claforanshouldnotbeadministeredduringpregnancyespeciallyduringthefirsttrimester,without

carefullyweighingtheexpectedbenefitagainstpossiblerisks.

Lactation:Claforanisexcretedinthemilk.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

AdversereactionstoClaforanhaveoccurredrelativelyinfrequentlyandhavegenerallybeenmildandtransient.

Effectsreportedincludecandidiasis,nausea,vomiting,abdominalpain,diarrhoea(diarrhoeamaysometimesbea

symptomofpseudomembranouscolitis(seewarnings)),transientrisesinlivertransaminases,alkalinephosphatase

and/orbilirubin.

AswithotherCephalosporins,changesinrenalfunctionhavebeenobservedwithhighdosesofClaforan,particularly

whenco-prescribedwithaminoglycosides.Rarecasesofinterstitialnephritishavebeenreportedinpatientstreatedwith

Claforan.

AdministrationofhighdosesofCephalosporins,particularlyinpatientswithrenalinsufficiency,mayresultin

encephalopathy(e.g.impairmentofconsciousness,abnormalmovementsandconvulsions).

Hypersensitivityreactionshavebeenreported.Theseincludeskinrashes,pruritusandlessfrequentlyurticaria,drug

feverandveryrarelyanaphylaxis(e.g.angioedema&bronchospasmpossiblyculminatinginshock).

Aswithothercephalosporins,occasionalcasesofbullousreactionssuchasStevensJohnsonSyndrome,toxic

epidermalnecrolysisanderythemamultiformehavealsobeenreported.

Aswithotherbeta-lactamantibiotics,granulocytopeniaandmorerarelyagranulocytosismaydevelopduringtreatment

withClaforan,particularlyifgivenoverlongperiods.Afewcasesofeosinophiliaandneutropeniahavebeen

observed,reversiblewhentreatmentisceased.Somecasesofrapidlyreversibleeosinophiliaandthrombocytopeniaon

stoppingtreatmenthavebeenreported.Rarecasesofhaemolyticanaemiahavebeenreported.Forcasesoftreatment

lastinglongerthan10days,bloodcountshouldthereforebemonitored.

Transientpainmaybeexperiencedatthesiteofinjection.Thisismorelikelytooccurwithhigherdoses.Occasionally,

phlebitishasbeenreportedinpatientsreceivingintravenousClaforan.However,thishasrarelybeenacausefor

discontinuationsoftreatment.

Averysmallnumberofcasesofarrhythmiashaveoccurredfollowingrapidbolusinfusionthroughacentralvenous

catheter.

Thefollowingsymptomshaveoccurredafterseveralweeksoftreatmentforborreliosis:skinrash,itching,fever,

leucopenia,increasesinliverenzymes,difficultyofbreathing,jointdiscomfort.Tosomeextentthesemanifestations

areconsistentwiththesymptomsoftheunderlyingdisease,forwhichthepatientisbeingtreated.

4.9Overdose

SerumlevelsofClaforanmaybereducedbyperitonealdialysisorhaemodialysis.Inthecaseofoverdosage,

particularlyinrenalinsufficiencythereisariskofreversibleencephalopathy.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Claforanisabroadspectrumbactericidalcephalosporinantibiotic.Claforanisexceptionallyactiveinvitroagainst

Gram-negativeorganismssensitiveorresistanttofirstorsecondgenerationcephalosporins.Itissimilartoother

cephalosporinsinactivityagainstGram-positivebacteria.

5.2Pharmacokineticproperties

Pharmacokinetics:Aftera1000mgintravenousbolus,meanpeakplasmaconcentrationsofcefotaximeusuallyrange

between81and102µg/ml.Dosesof500mgand2000mgproduceplasmaconcentrationsof38and200µg/ml,

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for10or14days.

Theapparentvolumeofdistributionatsteady-stateofcefotaximeis21.6L/1.73m 2

after1gintravenous30minute

infusion.

Concentrationsofcefotaxime(usuallydeterminedbynon-selectiveassay)havebeenstudiedinawiderangeofhuman

bodytissuesandfluids.Cerebrospinalfluidconcentrationsarelowwhenthemeningesarenotinflamed,butare

between3and30µg/mlinchildrenwithmeningitis.

Cefotaximeusuallypassestheblood-brainbarrierinlevelsabovetheMICofcommonsensitivepathogenswhenthe

meningesareinflamed.Concentrations(0.2-5.4µg/ml),inhibitoryformostGram-negativebacteria,areattainedin

purulentsputum,bronchialsecretionsandpleuralfluidafterdosesof1or2g.Concentrationslikelytobeeffective

againstmostsensitiveorganismsaresimilarlyattainedinfemalereproductiveorgans,otitismediaeffusions,prostatic

tissue,interstitialfluid,renaltissue,peritonealfluidandgallbladderwall,afterusualtherapeuticdoses.High

concentrationsofcefotaximeanddesacetyl-cefotaximeareattainedinbile.

Cefotaximeispartiallymetabolisedpriortoexcretion.Theprinciplemetaboliteisthemicrobiologicallyactiveproduct,

desacetyl-cefotaxime.Mostofadoseofcefotaximeisexcretedintheurineabout60%asunchangeddrugandafurther

24%asdesacetyl-cefotaxime.Plasmaclearanceisreportedtobebetween260and390ml/minuteandrenalclearance

145to217ml/minute.

Afterintravenousadministrationofcefotaximetohealthyadults,theeliminationhalf-lifeoftheparentcompoundis0.9

to1.14hoursandthatofthedesacetylmetabolite,about1.3hours.

Inneonatesthepharmacokineticsareinfluencedbygestationalandchronologicalage,thehalf-lifebeingprolongedin

prematureandlowbirthweightneonatesofthesameage.

Insevererenaldysfunctiontheeliminationhalf-lifeofcefotaximeitselfisincreasedminimallytoabout2.5hours,

whereasthatofdesacetyl-cefotaximeisincreasedtoabout10hours.Totalurinaryrecoveryofcefotaximeandits

principalmetabolitedecreaseswithreductioninrenalfunction.

5.3Preclinicalsafetydata

Notapplicable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

None

6.2Incompatibilities

Prolongeduseofananti-infectivemayresultinthedevelopmentofsuperinfectionduetoorganismsresistanttothat

anti-infective.

Aminoglycosidesareincompatiblewithcephalosporinsinparenteralmixtures.

6.3ShelfLife

Unopened:2years

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6.4Specialprecautionsforstorage

Unopened:Donotstoreabove25°C.Keepthevialintheoutercarton.

Injection:Useimmediatelyafterreconstitution.

Infusion:Somereconstitutedormixedsolutionswillretainsatisfactorypotencyforupto24hoursrefrigerated

(at2-8°C)–SeeSection6.6.forfurtherinformation.

After24hoursanyunusedsolutionshouldbediscarded.

Fromamicrobiologicalpointofview,theproductshouldbeusedimmediately.Ifnotusedimmediately,in–usestorage

timesandconditionspriortousearetheresponsibilityoftheuserandwouldnormallynotbelongerthan24hoursat

2-8°C,unlessreconstitution/dilutionhastakenplaceincontrolledandvalidatedasepticconditions.

6.5Natureandcontentsofcontainer

ClaforanissuppliedintypeIIIcolourlessglassvials,closedwithagreyelastomerstoppersealedwitheitheran

aluminiumcapfittedwithadetachablefliptop,oraninfusionconnectorclosure.

Thebottlesareboxedindividuallyandinpacksof10,25or50.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forsingleuseonly.Discardanyunusedcontents.

WhendissolvedinWaterforInjections,astraw-colouredsolutionisformedwhichissuitableforintravenousor

intramuscularinjection.

ReconstitutedSolution:Whilstitispreferabletouseonlyfreshlypreparedsolutionsforbothintravenousand

intramuscularinjection,Claforaniscompatiblewithseveralcommonlyusedintravenousinfusionfluidsandwillretain

satisfactorypotencyforupto24hoursrefrigerated(2-8°C)inthefollowing:

WaterforInjections

SodiumChlorideInjection

5%DextroseInjection

DextroseandSodiumChlorideInjection

CompoundSodiumLactateInjection(Ringer-lactateInjection)

Claforanisalsocompatiblewith1%lignocaine,howeverfreshlypreparedsolutionsshouldbeused.

Claforanisalsocompatiblewithmetronidazoleinfusion(500mg/100ml)andbothwillmaintainpotencywhen

refrigerated(2-8°C)forupto24hours.

Someincreaseincolourofpreparedsolutionsmayoccuronstorage.

However,providedtherecommendedstorageconditionsareobserved,thisdoesnotindicatechangeinpotencyor

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7MARKETINGAUTHORISATIONHOLDER

sanofi-aventisIrelandLtd

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA540/37/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13 th

May1981

Dateoflastrenewal:18 th

December2004

10DATEOFREVISIONOFTHETEXT

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