Curam

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Amoxicillin sodium 1.06 g equivalent to amoxicillin 1 g - as part of a 5:1 mix;  ; Potassium clavulanate 238.3 mg equivalent to clavulanic acid 200 mg - as part of a 5:1 mix
Available from:
Novartis New Zealand Ltd
INN (International Name):
Amoxicillin sodium 1.06 g (=amoxicillin 1 g - as part of a 5:1 mix)
Dosage:
1000/200mg
Pharmaceutical form:
Powder for injection
Composition:
Active: Amoxicillin sodium 1.06 g equivalent to amoxicillin 1 g - as part of a 5:1 mix   Potassium clavulanate 238.3 mg equivalent to clavulanic acid 200 mg - as part of a 5:1 mix
Units in package:
Vial, glass, single dose, Type II, 20mL, 10 dose units
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Sandoz Industrial Products SA
Therapeutic indications:
Short term treatment of common bacterial infections such as: upper respiratory tract infections (including ENT): e.g. tonsillitis, sinusitis, otitis media; lower respiratory tract infections: e.g. acute exacerbations of chronic bronchitis, lobar and broncho-pneumonia; genito-urinary tract infections: e.g. cystitis, urethritis, pyelonephritis, female genital infections; skin and soft tissue infections; bone and joint infections: e.g. osteomyelitis; other infections: e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis, septicaemia, peritonitis, post-surgical infections. Prophylaxis against infection which may be associated with major surgical procedures such as gastro-intestinal, pelvic, head and neck, cardiac, renal, joint replacement and biliary tract surgery. Infections caused by amoxicillin susceptible organisms are amenable to amoxicillin/clavulanic acid treatment due to its amoxicillin content. Mixed infections caused by amoxicillin susceptible organisms in conjunction with amoxicillin/cl
Product summary:
Package - Contents - Shelf Life: Vial, glass, single dose, Type II, 20 ml - 1 dose units - 24 months from date of manufacture stored at or below 25°C 15 minutes reconstituted stored at or below 25°C. with water for injection - Vial, glass, single dose, Type II, 20 ml - 5 dose units - 24 months from date of manufacture stored at or below 25°C 15 minutes reconstituted stored at or below 25°C. with water for injection - Vial, glass, single dose, Type II, 20mL - 10 dose units - 24 months from date of manufacture stored at or below 25°C 15 minutes reconstituted stored at or below 25°C. with water for injection - Vial, glass, single dose, Type II, 20 ml - 20 dose units - 24 months from date of manufacture stored at or below 25°C 15 minutes reconstituted stored at or below 25°C. with water for injection - Vial, glass, single dose, Type II, 20 ml - 50 dose units - 24 months from date of manufacture stored at or below 25°C 15 minutes reconstituted stored at or below 25°C. with water for injection
Authorization number:
TT50-6268/2
Authorization date:
2002-08-26

NEWZEALAND DATASHEET

Curam

AmoxicillinSodiumPh Eurand PotassiumClavulanatePh Eur,powderfor

injection,500/100 mgand1000/200 mg(asamoxicillin/clavulanic acid)

Presentation

Curaminjectionisa white oralmostwhite crystalline powderasepticallyfilled into20 mlglassvials.

CuramInjection 500/100mg (600mg)containssterileAmoxicillinSodiumPhEurequivalentto

amoxicillin 500mgand sterile PotassiumClavulanatePh Eurequivalentto clavulanicacid100mg.

CuramInjection1000/200 mg(1.2g)containssterileAmoxicillinSodiumPh Eurequivalentto

amoxicillin 1000mgand sterile PotassiumClavulanatePh Eurequivalentto clavulanicacid200mg.

Uses

Actions

Curaminjectionisan antibioticasepticallycompoundedforparenteral administration fromamoxicillin

sodium-a beta-lactamantibacterialpenicillin and thepotassiumsaltofclavulanicacid-a beta-

lactamase inhibitor.Amoxicillin/clavulanicacidhasa notablybroad spectrumofactivityagainst

bacterialpathogensofclinical importanceto generalpracticeand secondary/tertiarycare.

Pharmacotherapeutic group

J01CR02-Combinationsofpenicillinsincluding beta-lactamase inhibitors

Mechanismofaction

RefertoAntibioticnature andmode ofaction.

Pharmacodynamic effects

RefertoAntibioticnature andmode ofaction.

Antibioticclass

Semi-syntheticpenicillin compounded with a beta-lactamase inhibitor.

Antibioticnatureandmodeofaction

Amoxicillinisan aminopenicillintype broad spectrumantibioticthatpossessesactivityagainstmany

Gram-positiveand Gram-negative aerobesand anaerobes.Amoxicillinisa bactericidal,cell-wall

activeagentthatinhibitsbacterialcellwallsynthesisbybindingto penicillin binding proteinsand

inhibitsthe cross-linking ofbacterial peptidoglycan.However,amoxicillinissusceptibleto degradation

bybeta-lactamasesso it'sintrinsicspectrumofactivityexcludesbacteria producing these enzymes.

Clavulanicacidisa beta-lactam,structurallyrelatedto the penicillins.Itpossessesthe abilityto

inactivate awide range ofbeta-lactamaseenzymescommonlyfound in micro-organismsresistantto

penicillinsand cephalosporins.In particular,ithasgood activityagainstthe clinicallyimportant

plasmid mediatedbeta-lactamasesfrequentlyresponsiblefortransferred drug resistance.Itis

generallylesseffective againstchromosomally-mediated type 1 beta-lactamases.When

appropriatelycombined withamoxicillin,clavulanicacid inhibitsthe degradation ofamoxicillin by

beta-lactamase enzymesand effectivelyextendsthe antibacterialspectrumofamoxicillin toinclude

manybacteria normallyresistantto amoxicillin,otherpenicillinsand cephalosporins.

Susceptibilitydata

The prevalence ofresistancemayvarygeographicallyand temporallyforselected species.Local

resistance informationisdesirable,particularlywhen treating severeinfections.Thefollowing

information onlyprovidesapproximate guidance on theprobabilitiesthatmicro-organismswill be

susceptible toamoxicillin/clavulanicacid.

Susceptible

Susceptible Gram-positive aerobesinclude:Bacillusanthracis[1];Corynebacteriumspp.;

Enterococcusfaecali's[1];Listeriamonocytogenes;Nocardia asteroides;Staphylococcusaureus[1];

Coagulase-negativestaphylococci[1](includingStaphylococcusepidermidis[1]);Streptococcusspp.;

Streptococcuspneumoniae;Group Astreptococci(includingStreptococcuspyogenes);Group B

streptococci(includingStreptococcusagalactiae);Viridansgroupstreptococci.

Susceptible Gram-positive anaerobesinclude:Clostridiumspp.;Peptococcusspp.;

Peptostreptococcusspp.

Susceptible Gram-negative aerobesinclude:Bordetella pertussis;Brucellaspp.;Gardnerella

vaginalis;Haemophilusinfluenzae[1];Helicobacterpylori;Legionellaspp.;Moraxella catarrhalis[1];

Neisseria gonorrhoeae[1];Neisseria meningitidis[1];Pasteurella multocida;Proteusmirabilis[1];

Proteusvulgaris[1];Salmonellaspp.[1];Vibrio cholerae;Yersinia enterocolitica[1].

Susceptible Gram-negative anaerobesinclude:Bacteroidesspp.[1](includingBacteroidesfragilis);

Fusobacteriumspp.[1].

Othersusceptible pathogensinclude:Borrelia burgdorferi;Chlamydiaespp.;Leptospira

icterohaemorrhagiae;Treponema pallidum.

Intermediate

Partiallysusceptible Gram-positive aerobesincludeEnterococcusfaecium[1].

Partiallysusceptible Gram-negative aerobesinclude:Escherichia coli[1];Klebsiellaspp.[1];Klebsiella

pneumoniae[1];Klebsiella oxytoca[1];Salmonella hadar[1];Salmonella typhimurium[1];Shigella

spp.[1].

Notes:

[1]somemembersofthesespeciesofbacteria produce beta-lactamase,renderingtheminsensitive

to amoxicillin alone.

Resistance

Although,amoxicillin/clavulanicacidmayexhibitin vitroactivityagainstmethicillin/oxacillin resistant

Staphylococcusaureus(MRSA)and coagulase-negative staphylococci (MRS)itisnotclinically

effective andisolatesshould thereforebe considered resistant.Rare beta-lactamase negative,

ampicillin resistant(BLNAR)strainsofH.influenzaeshould alsobe considered resistantto

amoxicillin/clavulanicacid despite the apparentin vitrosusceptibilityofsomeBLNAR strains.

ResistantGram-positiveaerobesincludeStaphylococcusaureus(MRSA)and Coagulase-negative

staphylococci(MRS).

ResistantGram-negativeaerobesinclude:Acinetobacterspp.;Citrobacterspp.;Enterobacterspp.;

Haemophilusinfluenzae(BLNAR);Morganella morganii;Providenciaspp.;Pseudomonas

aeruginosa;Serratiaspp.;Stenotrophomonasmaltophilia.

OtherresistantpathogensincludeMycoplasmaspp.andRickettsiaspp.

ClinicallyrelevantMIC ranges

Accordingto the USNationalCommitteeon Clinical LaboratoryStandards(NCCLS)in2001,the

following breakpointshave been definedforamoxicillin/clavulanicacid:

Enterobacteriaceae:NMT8/4mcg/mlsusceptible,16/8mcg/ml intermediate,NLT32/16mcg/ml

resistant;

Staphylococcusspp.andHaemophilusspp.:NMT4/2mcg/mlsusceptible,NLT8/4mcg/mlresistant;

Streptococcuspneumoniae:NMT2/1mcg/ml susceptible,4/2mcg/mlintermediate,NLT8/4mcg/ml

resistant;

Anaerobicbacteria:NMT4/2mcg/mlsusceptible,8/4mcg/mlintermediate,NLT16/8mcg/ml

resistant.

No NCCLSbreakpointisstipulatedforVibrio cholerae,however,ampicillin susceptibility(NMT8

mcg/mlsusceptible,16mcg/mlintermediate,NLT32mcg/ml resistant)isrepresentativefor

amoxicillin/clavulanicacid.

ForEnterococcusspp.penicillin and ampicillin susceptibility(NMT8mcg/ml susceptible,NLT16

mcg/mlresistant)maybe used to predictthe susceptibilityto amoxicillin/clavulanicacid.

Pharmacokinetics

Absorption

Amoxicillinand clavulanicacidare notlipophilic.The sodiumsaltofamoxicillin and the potassiumsalt

ofclavulanicacidfullydissociate inaqueoussolution atphysiologicalpH.

Mean pharmacokineticparametersofamoxicillin and clavulanicacidwere measured after

administration ofamoxicillin/clavulanicacidinjectionintwo differentdosesto healthyvolunteers.

Following a 600mg bolusinjectioncontaining amoxicillin 500 mgand clavulanicacid 100mg:the

mean peakplasmaconcentrationswere 32.2 mcg/mlforamoxicillin and 10.5mcg/mlforclavulanic

acid;themean halfliveswere 1.07 hoursforamoxicillinand 1.12 hoursforclavulanicacid;themean

AUCvalueswere 25.5 h.mg/lforamoxicillin and 9.2 h.mg/lforclavulanicacid;the urinaryrecovery

ratesin 0 to6 hourswere 66.5% foramoxicillinand 46.0%forclavulanicacid.

Following a 1200mg bolusinjectioncontaining amoxicillin 1000mgand clavulanicacid 200mg:the

mean peakplasmaconcentrationswere 105.4 mcg/mlforamoxicillinand 28.5 mcg/mlforclavulanic

acid;themean halfliveswere 0.9 hoursforamoxicillinand 0.9 hoursforclavulanicacid;themean

AUCvalueswere 76.3 h.mg/lforamoxicillin and 27.9 h.mg/lforclavulanicacid;the urinaryrecovery

ratesin 0 to6 hourswere 77.4% foramoxicillinand 63.8%forclavulanicacid.

Distribution

Intravenousadministration ofthe prescribed dose ofamoxicillin/clavulanicacid providestherapeutic

levelsofboth constituentsin thetissuesand interstitialfluidsincluding gall bladder,skin,abdominal,

adipose and muscle tissues,synovialand peritonealfluids,bile and pus.Neitheramoxicillin nor

clavulanicacidishighlybound toplasma proteinsand studiesdemonstrate thatabout13%to 25% of

the totalplasma drugcontentofeachcompound bindsto protein.Fromanimalstudiesthereisno

evidence to suggestthateithercompound accumulatesin anyorgan.

Lowlevelsofamoxicillin and residuallevelsofclavulanicacidare detectablein breastmilk.Withthe

exception ofthe riskofsensitisation associated with thisexcretion,there are no known detrimental

effectsforthe breastfed infant.

While amoxicillinand clavulanicacid crossthe placenta,no adverse effectshave been observed in

animal reproductionstudies.

Biotransformation

Amoxicillinispartlymetabolised with between 10 and 25% oftheinitial dose foundinthe urine asthe

inactive penicilloicacid.Clavulanicacidisextensivelymetabolised.Theinactivemetabolites2,5-

dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylicacid and 1-amino-4-hydroxy-butan-2-one

are eliminated byurinaryand biliaryexcretion.Approximately27% ofaparenterallyadministered

dose ofclavulanicacidiscompletelymetabolisedin vivoto carbon dioxide and eliminatedin expired

airand water.

Elimination

Renalexcretionisthemajorelimination pathwayforamoxicillin,while clavulanate iseliminated by

both renaland non-renalmechanisms.Approximately60 to 70% ofthe amoxicillin and approximately

40 to 65% ofthe clavulanicacidcontentare excreted unchanged in urine during thefirst6 hoursafter

administration ofa singlebolusintravenousinjection ofamoxicillin/clavulanicacid 600mg or1.2 g.

Indications

Shorttermtreatmentofcommon bacterial infectionssuch as:upperrespiratorytractinfections

(including ENT):e.g.tonsillitis,sinusitis,otitismedia;lowerrespiratorytractinfections:e.g.acute

exacerbationsofchronicbronchitis,lobarand broncho-pneumonia;genito-urinarytractinfections:

e.g.cystitis,urethritis,pyelonephritis,female genital infections;skin and softtissue infections;bone

and jointinfections:e.g.osteomyelitis;otherinfections:e.g.septicabortion,puerperalsepsis,intra-

abdominalsepsis,septicaemia,peritonitis,post-surgicalinfections.

Prophylaxisagainstinfection whichmaybe associated withmajorsurgicalproceduressuch as

gastro-intestinal,pelvic,head and neck,cardiac,renal,jointreplacementand biliarytractsurgery.

Infectionscaused byamoxicillin susceptible organismsare amenableto amoxicillin/clavulanicacid

treatmentduetoitsamoxicillin content.Mixedinfectionscausedbyamoxicillin susceptible organisms

in conjunction with amoxicillin/clavulanicacid susceptible beta-lactamase-producingorganismsmay

thereforebe treated byamoxicillin/clavulanicacid.

Dosageandadministration

Dosage

Each 30mg amoxicillin/clavulanicacid provides5mgclavulanicacidwith 25mgamoxicillin.

Children 0 to 3 months

30 mg/kg amoxicillin/clavulanicacid every12 hoursininfants<4 kg and30 mg/kg

amoxicillin/clavulanicacid every8hoursininfants>4kg.

Children 3monthsto 12 years

Usually30mg/kg amoxicillin/clavulanicacidgiven 8hourly.Inmore seriousinfections,increase the

dosing frequencyto 6 hourlyintervals.

Adultsand children 40 kg and over

Usually1.2 ggiven 8hourly.Inmore seriousinfections,increase the dosingfrequencyto6 hourly

intervals.

Surgical prophylaxis

Surgical prophylaxiswith amoxicillin/clavulanicacidshould aimto protectthe patientforthe period of

riskofinfection.Accordingly,proceduresin adultslastingforlessthan 1 hourare successfully

covered by1.2 g amoxicillin/clavulanicacidintravenousgiven atinduction ofanaesthesia.Longer

operationsrequire subsequentdosesof1.2 g amoxicillin/clavulanicacidIV(up to4 dosesin 24

hours),and thisregimecan be continuedforseveraldaysifthe procedure hassignificantlyincreased

the riskofinfection.Clearclinical signsofinfection atoperation willrequire a normal course ofIVor

oralamoxicillin/clavulanicacidtherapypost-operatively.

Renalimpairment

Intravenousdosing adjustmentsare based on the maximumrecommendedlevel ofamoxicillin.

Adults

Mildimpairment(creatinineclearance>30ml/min)requiresno change in dosage.Formoderate

impairment(creatinine clearance 10to 30ml/min)give1.2 g IVstatfollowed by600 mgIV12 hourly.

Forsevereimpairment(creatinine clearance <10ml/min)give 1.2 gIVstatfollowed by600mg IV24

hourly.Dialysisdecreasesserumconcentrationsofamoxicillin/clavulanicacid.Anadditional 600mg

IVdose mayneed to be supplemented atthe end ofdialysis

Children

Mild impairment(creatinine clearance >30 ml/min)requiresnochangeindosage.Formoderate

impairment(creatinine clearance 10to 30ml/min)give30 mg/kg 12 hourly.Forsevereimpairment

(creatinine clearance <10ml/min)give 30mg/kg every24 hours.Dialysisdecreasesserum

concentrationsofamoxicillin/clavulanicacid.An additional15mg/kgmayneed to be supplemented at

theend ofdialysis,then 30mg/kg/day.

Hepatic impairment

Dosewith caution;monitorhepaticfunction atregularintervalsforboth adultsand children.There are

asyetinsufficientdata on whichto base a dosage recommendation.

Elderly

No adjustmentneeded,dose asforadults.Ifthereisevidence ofrenalimpairment,dose should be

adjusted asforrenallyimpairedadults(see above).

Administration

Curaminjectionmaybe administered eitherbyintravenousinjection orbyintermittentinfusion.Itis

notsuitableforintramuscularadministration.Each1.2gvialcontainsapproximately1.0mmol

potassiumand 3.1mmol sodium.

To reconstitute the 600mgvial,dissolve contentsinWaterforInjectionsBP10mlto give afinal

volume of10.5ml.

To reconstitutethe 1.2 gvial,dissolve contentsinWaterforInjectionsBP20 mlto give afinalvolume

of20.9 ml.

Curaminjection should be givenbyslowintravenousinjection overaperiod of3to 4minutesand

within20 minutesofreconstitution.Itmaybe injecteddirectlyinto the veinorviaadrip tube.

To prepare amoxicillin/clavulanateforintravenousinfusion,add withoutdelay600mgreconstituted

solution to50mlinfusionfluid or1.2 g reconstituted solutionto 100mlinfusionfluid (e.g.using a

mini-bagorin-line burette).Infuse over30 to40minutesand complete within thetimesstated.

Satisfactoryantibioticconcentrationsare retained at5°C and atroomtemperature (25°C)in the

recommended volumesofthe following infusion fluids.Ifreconstitutedandmaintained atroom

temperature,infusionsshould be completed withinthe time stated.

Amoxicillin/clavulanicacidintravenousinfusionisstablefor4 hoursat25°Cwhen prepared in the

following diluents:WaterforInjectionsBP;SodiumChloride IntravenousinfusionBP(0.9% w/v);

SodiumLactate Intravenousinfusion BP(M/6).

Amoxicillin/clavulanicacidintravenousinfusionisstablefor3 hoursat25°Cwhen prepared in the

following diluents:Compound SodiumChloride Injection BPC 1959 (Ringer's);Compound Sodium

Lactate IntravenousInfusion BP(Ringer-Lactate:Hartmann's);PotassiumChloride and Sodium

ChlorideIntravenousInfusion BP.

Forstorage at5°C,thereconstituted solution should beadded to pre-refrigeratedinfusion bagswhich

maybe storedforupto 8 hours.Thereafter,theinfusion should be administeredimmediatelyafter

reaching roomtemperature.Amoxicillin/clavulanicacidintravenousinfusionisstablefor8hoursat

5°C when prepared in thefollowing diluents:WaterforInjectionsBP;SodiumChloride Intravenous

infusion BP(0.9% w/v).

Amoxicillin/clavulanicacidinjection islessstable in infusionscontaining glucose,dextran or

bicarbonate.Reconstituted solution should,therefore,notbe added to such infusionsbutmaybe

injected intothe driptubing overa period of3to 4minutes.

Anyresidualantibioticsolutionsshould be discarded.Curaminjectionvialsare notsuitableformulti-

dose use.

Amoxicillin/clavulanicacidinjection should notbemixed with blood products,otherproteinaceous

fluidssuch asprotein hydrolysatesorwith intravenouslipidemulsions.

Contraindications

Hypersensitivityto one oftheconstituentsofthemedicine.

Hypersensitivityto otherbeta-lactamantibioticssuch aspenicillinsand cephalosporins.

Previoushistoryofjaundice orhepaticdysfunction associated with amoxicillin/clavulanicacid.

Warningsandprecautions

Beforeinitiating amoxicillin/clavulanicacid therapyitisimperativeto determineifthe patientis

hypersensitiveto penicillins,cephalosporinsorotherallergens.Seriousand occasionallyfatal cases

ofhypersensitivity(anaphylactoid reactions)have beenreported inpatientsreceiving penicillin

therapy.These reactionsare morelikelyto occurinindividualswith a historyofpenicillin

hypersensitivity.Ifan allergicreaction occurs,discontinue amoxicillin/clavulanicacidimmediatelyand

replace with an appropriate alternativetherapy.Seriousanaphylactoidreactionsrequireimmediate

emergencytreatmentwith adrenaline orepinephrine.Oxygen,intravenoussteroidsand airway

managementincludingintubationmayalso be required.Thereiscross-resistance and cross-

hypersensitivitywith the otherpenicillinsand sometimesalso with cephalosporins.

Avoid amoxicillin/clavulanicacidifinfectiousmononucleosisissuspected since the incidence ofa

morbilliformrash hasbeen associated with thisconditionfollowing amoxicillin treatment.

In general,amoxicillin/clavulanicacidiswelltolerated and possessesthe characteristiclowtoxicityof

the penicillin group ofantibiotics.Periodicassessmentoforgan systemfunctions,including renal,

hepaticand haematopoieticfunctionisadvisable during prolonged therapy.

Aswith otherbroad spectrumantibiotics,superinfectionsdue to non-susceptiblemicro-organisms

mayoccur,particularlyinpatientswith chronicdisordersand/orimpairedimmune defence

mechanisms.Mucocutaneouscandida infectionshavebeen reported.

Prolonged use mayalso occasionallyresultinthe overgrowth ofnon-susceptibleorganismsinthe

intestinaltract.Ifsevere diarrhoea occurs,thediagnosisofpseudomembranouscolitisshould be

considered.In thiscase,appropriatemeasuresshould be taken.Likewise,appropriatemeasures

should be taken inthe eventofhaemorrhagiccolitis.

During high-dose therapy,maintaining adequatefluidintake and urinaryoutputisnecessaryto

minimise the riskofamoxicillin crystalluria.Bladdercathetersshould be checked regularlyforpatency

sincesome medicines,includingamoxicillin,mayprecipitateinthe urine atroomtemperatureifthey

are presentin highconcentrations.

In patientswithmoderate orsevere renalimpairment,the dosage should be adjusted according to

the degree ofimpairment(refertoDosage and administration).

Convulsionsmayoccurin patientswith impaired renalfunction orinthose receivinghigh doses.

Amoxicillin/clavulanicacid should be administered withcautionto patientspresenting hepatic

dysfunction.Liverfunction should also bemonitored regularly.Currently,there isinsufficient

informationtomakea dosage recommendation.

Hepatitisand cholestaticjaundice associated with amoxicillin/clavulanicacid and otherbeta-lactam

antibioticshave been reported rarely.Hepaticeffectsoccurpredominantlyinmalesand elderly

patients,particularlythose over65 yearsofage.These side-effectsareveryrarelyreportedin

children.The incidence appearsto increase with treatmentcoursesexceeding 14 days.Signsand

symptomsusuallyoccurduringorshortlyaftertreatment,butinsome casesmaynotbecome

apparentuntilseveralweeksaftertreatmentcessation.Hepaticeffectsare usuallytransientand

reversible.However,theymaybe severeand inextremelyrarecases,a fataloutcome hasbeen

reported.These havemostlyoccurredin patientswitha seriousunderlying disease,orpatientstaking

potentiallyhepatotoxicagentsinaddition toamoxicillin/clavulanicacid.

Prolongation ofprothrombintime hasbeen reported rarely.Ifanticoagulantsare prescribed

concomitantly,itmaybenecessaryto monitorthepatient.

Ifthe parenteral administration ofhigh dosesisnecessary,the sodiumcontentmustbe considered

forpatientson a sodium-restricted diet.

Theoccurrenceattreatmentinitiationofafeverishgeneralisederythemaassociatedwithpustule

maybeasymptomofacutegeneralisedexanthemouspustulosis(AGEP).Thisreactionrequires

Curamdiscontinuation andisa contraindication tosubsequentadministration ofamoxicillin.

The presence ofclavulanicacidmaycausea non-specificbinding ofIgGand albumin byred cell

membranesleadingto afalse positive Coombstest.

Pregnancy andlactation

Useinpregnancy

Assigned CategoryB1 bythe Australian Drug Evaluation Committee.Thiscategoryincludes

medicineswhich have been taken byonlyalimited numberofpregnantwomen and women of

childbearing age,withoutan increase inthefrequencyofmalformation orotherdirectorindirect

harmful effectson the humanfoetushaving been observed.

Reproduction studiesin animals(miceand ratsatdosesup to 10 timesthe human dose)with orally

and parenterallyadministered amoxicillin/clavulanicacid have shown no teratogeniceffects.Ina

single studyin womenpresenting preterm,premature rupture ofthefoetalmembrane (pPROM),it

wasreported thatprophylactictreatmentwith amoxicillin/clavulanicacidmaybeassociated with an

increased riskofnecrotising enterocolitisin neonates.Aswith allmedicines,use should be avoided

in pregnancy,unlessconsidered essentialbythephysician.

Useinlactation

Administration ofamoxicillin/clavulanicacidinjectionispermitted duringlactation.Apartfromtherisk

ofsensitisation,associated with the excretion oftrace quantitiesin breastmilk,there are noknown

effectspotentiallydetrimental tothe breastfedinfant.

Effectsonability todrive anduse machines

Thismedicineispresumed tobe safe orunlikelyto produce an effect.

Adverse effects

Datafromlarge clinical trialswere used to determinethe incidence ofverycommontorare adverse

effects.Theincidencesofall otheradverse effectsoccurring below1 in10,000were mainly

determined frompost-marketing data and reflectthe reporting rateratherthan thetrueincidence.

Common (incidencefrom1in100to 1in 10)

Gastrointestinaltract

Lowergastro-intestinalirritationreactionssuch asdiarrhoea and pruritusanihave been observed.

These side-effectsare generallyofamildand transitorynature.

Infectionsand infestations

Mucocutaneouscandidiasis.

Skin andsubcutaneous tissues

Allergicskin reactionsoccursignificantlymoreoftenthan with otherpenicillinsand generallyare

maculopapularin nature.Ina smallmajorityofcases,"fifth dayrash"(amorbilliformexanthema)is

reported.Thisisdependentonthe size ofthe dose and the patient'scondition.

Uncommon(incidence from1 in1000 to1 in100)

Gastrointestinaltract

Indigestion,nausea andvomiting.

Hepatobiliary tract

Amoderate rise inASTand/orALTvalueshasbeen noted inpatientstreated with beta-lactam

antibiotics,butthe significance ofthesefindingsisunknown.

Nervous system

Dizziness,headache.

Skin andsubcutaneoustissues

TypicaltypeIallergicreactionssuch asskin rash,pruritis,urticaria and purpura;angio-oedema and

anaphylaxiscan occurlessfrequently.

Rare (incidence from1 in10,000 to1 in1,000)

Blood andlymphaticsystem

Abnormalitiesofthe blood count,usuallyreversible such asleucopenia (including neutropenia)and

thrombocytopenia.

Cardiovascular system

In rare cases,allergiescan resultin anaphylacticshock.

Skin andsubcutaneoustissues

Erythema multiforme.

Vascular

Thrombophlebitisatthe siteofinjection.

Very rare (incidencebelow1 in10,000)

Blood andlymphaticsystem

Reversibleagranulocytosisand haemolyticanaemia.Prolongation ofbleeding and prothrombin time

(refer toWarningsand precautions).

Gastrointestinaltract

Antibiotic-associated colitis(including pseudomembranouscolitisand haemorrhagiccolitis)occur,

although atalowerincidence than orallyadministeredamoxicillin/clavulanicacid.

Blackhairytongue.Superficialtooth discolouration hasbeen reported inchildren.Good oral hygiene

mayhelpto preventtooth discolouration asitcan usuallyberemoved bybrushing.

Hepatobiliarytract

Hepatitisand cholestaticjaundice associated with amoxicillin/clavulanicacid and otherbeta-lactam

antibioticshave been reported rarely.Hepaticeffectsoccurpredominantlyinmalesand elderly

patients,particularlythose over65 yearsofage.These side-effectsareveryrarelyreportedin

children.The incidence appearsto increase with treatmentcoursesexceeding 14 days.Signsand

symptomsusuallyoccurduringorshortlyaftertreatment,butinsome casesmaynotbecome

apparentuntilseveralweeksaftertreatmentcessation.Hepaticeffectsare usuallytransientand

reversible.However,theymaybe severeand inextremelyrarecases,a fataloutcome hasbeen

reported.These havemostlyoccurredin patientswitha seriousunderlying disease,orpatientstaking

potentiallyhepatotoxicagentsinaddition toamoxicillin/clavulanicacid(refer toWarningsand

precautions).

Immunesystem disorders

Angioneuroticoedema,anaphylaxis,serumsickness-like syndrome,hypersensitivityvasculitis.

Nervous system

Reversiblehyperactivityand convulsions.Convulsionsmayoccurin patientswithimpaired renal

functionorin those receiving high doses(refer toWarningsand precautions).

Skin andsubcutaneoustissues

Stevens-Johnson syndrome,toxicepidermal necrolysis,bullousexfoliative dermatitis,acute

generalised exanthematouspustulosis(AGEP).The appearance ofskinhypersensitivityreactions

warrantsdiscontinuation ofamoxicillin/clavulanicacidtreatment(refertoWarningsand precautions).

Urogenitaltract

Interstitialnephritisand crystalluria (refertoOverdosage)

Interactions

Othermedicines

Amoxicillin/clavulanicacidinjectionmustnotbe administered concomitantlywith bacteriostatic

agents,such astetracyclines,macrolidesand chloramphenicol,particularlyinacute infections.

Anumberofagentscaninhibitthe renaltubularsecretion ofamoxicillin butnotclavulanicacid.

Inhibitorsinclude probenecid,phenylbutazone,oxyphenbutazone and to a lesserextent,

acetylsalicylicacid,indomethacin and sulfinpyrazone.Asinhibition ofrenaltubularsecretion prolongs

the half-lifeand increasesplasmalevelsofamoxicillinonly,concomitantuse ofprobenecidisnot

recommended.

Concomitantadministration with aminoglycosidesispossible to providesynergisticactivitybutrefer

toPharmaceuticalprecautions.

Concomitantuse ofamoxicillin and oral contraceptivesisassociated with theincidence of

breakthrough bleeding and possiblyreduced activityofthe oralcontraceptives.Amoxicillin/clavulanic

acidmayaffectthe gutflora,leadingtoloweroestrogen reabsorption and reduced efficacyof

combined oral contraceptives.

Concomitantuse ofallopurinolduring treatmentwith amoxicillincan increase the riskofallergicskin

reactions.There areno data onthe concomitantuse ofamoxicillin/clavulanicacid and allopurinol.

Amoxicillincan partiallyeradicate the gastrointestinalflora and therefore potentiallyincrease the

absorption ofconcomitantlyadministered digoxin.

Concurrentadministration ofamoxicillin/clavulanicacid anddisulfiramispoorlytolerated.Therefore,

amoxicillin/clavulanicacidinjection should notbe used concomitantlywith disulfiram.

Laboratory diagnostic tests

Non-enzymaticmethodsforglucosedetermination inurine maygivefalse-positiveresults.

Clavulanicacidmaycause anon-specificbindingofIgGandalbuminbyredcellmembranesleading

to afalse positiveCoombstest(refertoWarningsand precautions).

Overdosage

Drug dependency,addiction and recreationalabuse havenotbeen reported asproblems.

Signsand symptoms

Convulsionscan occurfollowing parenteraladministration ofan overdose,particularlyin patientswith

renaldysfunction.Thisisalso possible afterintrathecaladministration.Gastrointestinalsymptoms

and disturbance offluidand electrolyte balancesmaybe evident.

Complicationsfromamoxicillin crystalluriamaypresentin high doses(refertoWarningsand

precautions).Amoxicillin hasbeen reported to precipitate inbladdercathetersafterintravenous

administration oflarge doses.Aregularcheckofpatencyshould bemaintained.

Management

Convulsionscan be treatedwith diazepam.Amoxicillinand clavulanicacidcan be removedfromthe

circulation byhaemodialysis.Treatothersymptomssymptomatically.Gastrointestinalsymptomsmay

be treated symptomaticallybyattendingto thewaterand electrolyte balance.Aprospectivestudyof

51 paediatricpatientsata poison controlcentre suggested thatoverdosageslessthan 250 mg/kg of

amoxicillin are notassociated with significantclinicalsymptomsand do notrequiregastricemptying.

Pharmaceuticalprecautions

Instructionsforuse/handling

Aseptictechniquesin reconstitution andimmediateuseofthe solution arerecommended.Aseptic

techniquesare especiallyimportantifthe solutionisnotused immediately.Anyunused solution

should be discarded.

WaterforInjectionsBPisthe normaldiluent.RefertoDosage and administrationforthe instructions

forreconstitution.Atransientpinkcolourationmaydevelop during reconstitution.Reconstituted

solutionsare normallycolourlessora pale strawcolour.The stabilityofamoxicillin/clavulanicacid

intravenoussolutionsisconcentration dependent.Inthe eventthatthe use ofmoreconcentrated

solutionsisrequired,the stabilityperiod should be adjusted accordingly.

Incompatibilities

Reconstituted solutionsofamoxicillin/clavulanicacidmustnotbe directlymixed withaminoacid

solutions,lipidemulsions,blood,protein hydrolysatesand solutionscontainingglucose,dextran or

bicarbonate (refertoDosage and administration).

Amoxicillininactivatesaminoglycosidesin solution so avoidmixingthese agentsduring preparation

and administration.

Individualvialsmayappearturbid when the reconstituted contentsare mixedwith lignocaineor

lidocaine solutions.Turbidsolutionsshould be discarded.

Shelflife

Unopenedcontainer:

36 months.

After container firstopened:

Notapplicable.

Afterdilutionorreconstitution:

The productshould be used immediately;within 15minutesasa solutionforinjection and within 60

minutesasa solutionforinfusion.

Specialprecautions forstorage

Store atorbelow25°C.Protectfromlight.

Medicine classification

Prescription Medicine.

Package quantities

Packsof10vials.

Further information

Listofexcipients

Nil.

Name andaddress

NovartisNewZealand Limited

Private Bag 65904 MairangiBay

AUCKLAND0754

Telephone:0800 354 335

Dateofpreparation

10 October2012

Document Outline

Similar products

Search alerts related to this product

Share this information