Combisyn Injection

Main information

  • Trade name:
  • Noroclav inyectable
  • Pharmaceutical form:
  • Suspension for injection
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Noroclav inyectable
    Spain
  • Language:
  • English

Therapeutic information

  • Therapeutic area:
  • Cattle

Other information

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0200/001
  • Authorization date:
  • 17-08-2011
  • EU code:
  • UK/V/0200/001
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage,interactions,side effects

Revised:August2011

AN:00927/2010

Page1of7

SUMMARYOFPRODUCTCHARACTERISTICS

1. NAMEOFTHEVETERINARYMEDICINALPRODUCT

CombisynSuspensionforInjection(UnitedKingdom)

NoroclavSuspensionforInjection(France)

NoroclavSuspensionforInjection(Portugal)

Noroclav175mgSuspensionforInjection(Spain)

NoroclavInjection(Belgium,Italy)

2. QUALITATIVEANDQUANTITATIVECOMPOSITION

Each1mlsupplies:

ActiveSubstance:

Amoxicillin(asAmoxicillintrihydrate) 140mg

Clavulanicacid(asPotassiumclavulanate) 35mg

Excipients:

Butylatedhydroxyanisole(E320)0.08mg

Butylatedhydroxytoluene(E321)0.08mg

Forafulllistofexcipients,seesection6.1

3. PHARMACEUTICALFORM

Suspensionforinjection.

Anoff-whitetocreamoilysuspension.

4. CLINICALPARTICULARS

4.1Targetspecies

CattleandDogs.

4.2Indicationsforuse,specifyingthetargetspecies

InCattle:

TreatmentofrespiratoryinfectionsduetoPasteurellamultocidaand

Mannheimiahaemolytica.

InDogs:

Respiratorytractinfections,urinarytractinfections,skinandsofttissue

infections(e.g.abscesses,pyoderma,analsacculitisandgingivitis

Revised:August2011

AN:00927/2010

Page2of7

4.3Contraindications

Donotuseinanimalswithknownhypersensitivitytopenicillinorother

substancesofthebeta-lactamgroup.

Donotuseinanimalswithseriousdysfunctionofkidneysaccompaniedby

anuriaoroliguria.

Donotuseinrabbits,guineapigs,hamstersorgerbils.

Theuseoftheproductiscontraindicatedwhereresistancetothecombination

ofpenicillinsorothersubstancesofthebeta-lactamgroupisknowntooccur.

4.4SpecialWarningsforeachtargetspecies

None.

4.5Specialprecautionsforuse

i. Specialprecautionsforuseinanimals

Thisproductdoesnotcontainanantimicrobialpreservative.

Clavulanicacidismoisturesensitive.Itisveryimportanttherefore,thata

completelydryneedleandsyringeisusedwhenextractingsuspensionfor

injectioninordertoavoidcontaminatingtheremainingcontentsofthevial

withdropsofwater.

Contaminationwillresultinobviousbeadsofdark,browndiscolouration

correspondingtotheintroducedwaterdroplets.Suspensionaffectedin

thiswayshouldnotbeusedasitmayhavesignificantlyreducedpotency.

Shakebeforeuse.

Incaseoftheoccurrenceofallergicreaction,thetreatmentshouldbe

withdrawn.

Inappropriateuseoftheproductmayincreasetheprevalenceofbacteria

resistanttoamoxycillin/clavulanicacid.

Inanimalswithhepaticandrenalfailurethedosingregimeshouldbe

carefullyevaluated.

Cautionisadvisedintheuseofsmallherbivoresotherthanthosein4.3.

Useoftheproductshouldbebasedonsusceptibilitytestingandtakeinto

accountofficialandlocalantimicrobialpolicies.

Revised:August2011

AN:00927/2010

Page3of7

Narrowspectrumantibacterialtherapyshouldbeusedforfirstline

treatmentwheresusceptibilitytestingsuggeststhelikelyefficacyofthis

approach.

ii.Specialprecautionstobetakenbythepersonadministeringtheveterinary

medicinalproducttoanimals

Penicillinsandcephalosporinsmaycausehypersensitivity(allergy)

followinginjection,inhalation,ingestionorskincontact.Hypersensitivity

topenicillinsmayleadtocross-reactionstocephalosporinsandvice

versa.Allergicreactionstothesesubstancesmayoccasionallybe

serious.

Donothandlethisproductifyouknowyouaresensitised,orifyouhave

beenadvisednottoworkwithsuchpreparations.

Incaseofcontactwitheyes,rinseimmediatelywithplentyofwater.

Handlethisproductwithgreatcaretoavoidexposure,takingall

recommendedprecautions.

Ifyoudevelopsymptomsfollowingexposuresuchasaskinrash,you

shouldseekmedicaladviceandshowthedoctorthiswarning.Swellingof

theface,lipsoreyesordifficultywithbreathingaremoreserious

symptomsandrequireurgentmedicalattention.

Washhandsafteruse.

4.6Adversereactions(frequencyandseriousness)

Diarrhoea,vomitingandsweatingmayrarelyoccurafteradministrationofthe

product.Useoftheproductmayoccasionallyresultinpainoritchingon

injectionand/orlocaltissuereaction.

Hypersensitivityreactionsunrelatedtodosecanoccurwiththeseagents.

Allergicreactions(e.g.,skinreactions,anaphylaxis)mayoccasionallyoccur.

Localtissuereactionsatthesiteofinjectionmayoccurfollowingadministration.

Thesereactionsaregenerallyofmildtomoderateswellingand/orhardness

andcanpersistforupto2weeksfollowingadministrationattherecommended

doserateintherumporlegmusclesand4daysafteradministrationatthe

recommendeddoserateintheneckmuscles.Painoninjectionmay

occasionallyoccur.

4.7Useduringpregnancy,lactationorlay

Studiesinlaboratoryanimalshavenotproducedanyevidenceofteratogenic

effects.

Thesafetyoftheproducthasnotbeenassessedinpregnantandlactating

cowsorbitches.

Revised:August2011

AN:00927/2010

Page4of7

Useonlyaccordingtothebenefit/riskassessmentbytheresponsibleveterinary

surgeon.

4.8Interactionwithothermedicinalproductsandotherformsofinteraction

Thebactericidaleffectofamoxicillinisneutralizedbysimultaneoususeof

bacteriostaticactingpharmaceuticals(macrolides,sulfonamidesand

tetracyclines).

Thepotentialforallergiccross-reactivitywithotherpenicillinsshouldbe

considered.Penicillinsmayincreasetheeffectsofaminoglycosides.

4.9Amountstobeadministeredandadministrationroute

Theproductisindicatedforintramuscularadministrationtocattleand

subcutaneousadministrationtodogs.

Therecommendeddosagerateof8.75mg/kgbodyweight[7mg/kgbodyweight

amoxicillinand1.75mg/kg/bodyweightofclavulanicacid](1mlper20kg

bodyweight)oncedailyfor3-5days.Shakethevialwellbeforeuse.Usea

completelydrysterileneedleandsyringe.Swabtheseptumbeforeremoving

eachdose.

InCattle,themaximumvolumeadministeredatthesiteofinjectionshouldnot

exceed10ml.

Seealsosection4.5(i)

4.10Overdose(symptoms,emergencyprocedures,antidotes),ifnecessary

InCattle,theproductiswelltoleratedupto2timestherecommendeddose

administeredforupto5days.

Studiesincattleatthenormaldoserateandtwicethenormaldoseratehave

showntransientanddosedependentmuscledamageattheinjectionsite

resultinginincreasedCreatinekinaseandAspartateAminotransferaselevels.

Injectionsitereactionstendedtobedosedependentandwerefullyresolvedby

2weeksafteradministrationtothelegandrumpand4daysafter

administrationtotheneckevenattwicetherecommendeddoserate.Noother

clinicallysignificantabnormalitiesweredetected.

Theproductiswelltoleratedupto3timestherecommendeddoserate

administeredforupto6daysfordogshowever,indogs,reactionsatthe

injectionsitemayoccurat3timestherecommendeddoserateresolvingafter2

weeks.

4.11Withdrawalperiod

Meatandoffal:42days.

Milk60hours[5milkings]

Revised:August2011

AN:00927/2010

Page5of7

5. PHARMACOLOGICALPROPERTIES

Pharmacotherapeuticgroup:Antimicrobial

ATCVetCode:QJ01CR02

5.1Pharmacodynamicproperties

ModeofAction

Amoxicillinisabeta-lactamantibioticanditsstructurecontainsthebeta-lactam

ringandthiazolidineringcommontoallpenicillins.Amoxicillinshowsactivity

againstsusceptibleGrampositivebacteriaandGramnegativebacteria.

Beta-lactamantibioticspreventthebacterialcellwallfromformingbyinterfering

withthefinalstageofpeptidoglycansynthesis.Theyinhibittheactivityof

transpeptidaseenzymes,whichcatalysecross-linkageoftheglycopeptide

polymerunitsthatformthecellwall.Theyexertabactericidalactionbutcause

lysisofgrowingcellsonly.

Clavulanicacidisoneofthenaturallyoccurringmetabolitesofthe

streptomyceteStreptomycesclavuligerus.Ithasstructuralsimilaritytothe

penicillinnucleus,includingpossessionofabeta-lactamring.Clavulanicacid

isabeta-lactamaseinhibitoractinginitiallycompetitivelybutultimately

irreversibly.

Clavulanicacidwillpenetratethebacterialcellwallbindingtobothextracellular

andintracellularbeta-lactamases.

Amoxicillinissusceptibletobreakdownbyß-lactamasesproducedbysome

bacterialspecies,andthereforecombinationwithaneffectiveß-lactamase

inhibitor(clavulanicacid)extendstherangeofbacteriaagainstwhichitisactive

toincludeß-lactamaseproducingspecies.

Invitropotentiatedamoxicillinisactiveagainstawiderangeofclinically

importantbacteriaincludingPasteurellamultocidaandMannheimia

haemolytica.

Anotherpossiblemodeofresistancetobeta-lactamantibioticscanbe

associatedwithchromosomalmutationsinbacteriaresultinginmodificationof

thepenicillinbindingproteins(PBPs)ormodificationofthecellularpermeability

to 

-lactamantibioticsbytheirnaturesuchchromosomalmutationstendtobe

relativelyslowindevelopmentprimarilybyverticaltransmission.Atrendin

resistanceofE.coliisreported.

ThetablebelowshowstheMIC

50 andMIC

values(expressedas

concentrationsofAmoxicillin/ClavulanicAcid)againstbacterialpathogensin

Dogs,determinedin-vitro.

Revised:August2011

AN:00927/2010

Page6of7

MinimumInhibitoryConcentrations(<IC)vis-á-viscombinationAmoxicillin/

ClavulanicAcidagainstbacterialpathogensinDogs:

Pathogen MIC

50 MIC

90 Minimum Maximum

Staphylococcus

intermedius ≤0.5/0.25≤0.5/0.25≤0.5/0.25 2/1

B-haemolytic

Streptococcus ≤0.5/0.25≤0.5/0.25≤0.5/0.25≤0.5/0.25

Staphylococcusaureus 2/1 2/1 ≤0.5/0.25 2/1

Escherichiacoli 4/2 8/4 1/0.5 64/32

Pasteurellamultocida ≤0.5/0.25≤0.5/0.25≤0.5/0.25 1/0.5

ThefollowingAmoxicillinbreakpointsareused:≤2μg/ml(Susceptible)and

>8μg/ml(Resistant).

5.2Pharmacokineticproperties

Afterintramuscularadministrationtocattleandsubcutaneousadministrationto

dogs,amoxicillinandclavulanicacidarewellabsorbedanddistributedinthe

tissues.Theprinciplerouteofeliminationofamoxicllinandclavulanicacidisin

theurine.

Afterintramuscularadministrationoftheproducttocattleattherecommended

doseoncedailyforfiveconsecutivedays,thefollowingparameterswere

observed:

Cmaxof1.69µg/ml,Tmaxof2.67h,AUCof30.59µg/ml.handt½of15.22hfor

amoxicillinandCmaxof0.94µg/ml,Tmaxof1.3h,AUCof3.123µg/ml.hand

t½of1.71hforclavulanicacid.

Aftersubcutaneousadministrationofthemaximumrecommendeddoseto

dogs,thefollowingparameterswereobserved:Cmaxof8.66μg/ml,Tmaxof

1.78handAUCof50.98μg/ml.hforamoxicillin.

6. PHARMACEUTICALPARTICULARS

6.1Listofexcipients

PropyleneGlycolDicaprylate/Dicaprate

Butylatedhydroxyanisole

Butylatedhydroxytoluene

6.2Incompatibilities

Donotmixwithotherveterinarymedicinalproducts.

6.3Shelflife

Shelf-lifeoftheveterinarymedicinalproductaspackagedforsale:1year

Shelf-lifeafterfirstopeningtheimmediatepackaging:28days

Revised:August2011

AN:00927/2010

Page7of7

6.4Specialprecautionsforstorage

Donotstoreabove25ºC.

Onceavialhasbeenbroachedthecontentsshouldbeusedwithin28days.

Discardunusedmaterial.

6.5Natureandcompositionofimmediatepackaging

TheproductwillbesuppliedinclearcolourlesstypeIIglassvialsof50mland

100ml,completewithnitrylbungsandaluminiumcaps.

6.6Specialprecautionsforthedisposalofunusedveterinarymedicinal

productorwastematerialsderivedfromtheuseofsuchproducts

Anyunusedveterinarymedicinalproductorwastematerialsderivedfromsuch

veterinarymedicinalproductsshouldbedisposedofinaccordancewithlocal

requirements.

7. MARKETINGAUTHORISATIONHOLDER

NorbrookLaboratoriesLimited

StationWorks

Newry

Co.Down,BT356JP

NorthernIreland

8. MARKETINGAUTHORISATIONNUMBER(S)

ManA:2000

Vm: 02000/4226

9. DATEOFFIRSTAUTHORISATION

Date:13 th January2003

10.DATEOFREVISIONOFTHETEXT

Date:August2011

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