Closiver

Main information

  • Trade name:
  • Closiver Solution for Injection for Sheep
  • Pharmaceutical form:
  • Solution for injection
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Closiver Solution for Injection for Sheep
    Ireland
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • ivermectin, combinations
  • Therapeutic area:
  • Sheep

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0277/002
  • Authorization date:
  • 26-05-2011
  • EU code:
  • UK/V/0277/002
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage, interactions, side effects

Revised:May2011

AN:00041/2011

SUMMARYOFPRODUCTCHARACTERISTICS

1. NAMEOFTHEVETERINARYMEDICINALPRODUCT

ClosiverSolutionforInjectionforSheep(UK&IE)

ClosamectinSolutionforInjectionforSheep(AT,BE,CZ,IT,ES&SK)

OestrocurSolutionforInjectionforSheep(FR)

ClosamectinFFSolutionforInjectionforSheep(PT)

2. QUALITATIVEANDQUANTITATIVECOMPOSITION

ActiveSubstance(s)

Ivermectin 5mg/ml

Closantel(asclosantelsodiumdihydrate) 125mg/ml

OtherSubstances

Containssodiumformaldehydesulphoxylate5mg/ml(asantioxidant)

ForafulllistofexcipientsseeSection6.1

3. PHARMACEUTICALFORM

Solutionforinjection.

Aclearambersolution.

4. CLINICALPARTICULARS

4.1 TargetSpecies:

Sheep.

4.2 IndicationsforUse(SpecifyingtheTargetSpecies):

Forthetreatmentofmixedtrematode(fluke)andnematodeorarthropod

infestationsduetogastrointestinalroundworms,trematodes,lungworms,nasalbots

andmitesofsheep.

Gastrointestinalroundworms

Ostertagiacircumcincta(includinginhibitedL4),Ostertagiatrifurcata(adultandL4),

Haemonchuscontortus(includinginhibitedL4),Trichostrongylusaxei(adult),

Trichostrongyluscolubriformis(adultandL4),T.vitrinus(adult)Cooperiacurticei

(adultandL4),Oesophagostomumcolumbianum(adultandL4),O.venulosum

(adult)Chabertiaovina(adultandL4)Nematodirusfilicollis(adultandL4),Trichuris

ovis(adult).

[L4=fourthstagelarave]

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AN:00041/2011

Lungworms

Dictyocaulusfilaria(adultand4 th stagelarvae)

Protostrongylusrufescens(adult)

LiverFluke(Adultsand7weeksimmature)

Fasciolagigantica,Fasciolahepatica

NasalBots

Oestrusovis

MangeMites

Psoroptesovis(Treatmentrequireasecondinjectionofanivermectin-onlyproduct

7dayslater.Seesections4.4and4.9)

Benzimidazole –resistantstrainsofHaemonchuscontortusandOstertagia

circumcinctaarealsocontrolled.

4.3 Contraindications:

Donotuseintravenouslyorintramuscularly.Avermectinsmaynotbewelltolerated

inallnon-targetspecies(casesofintolerancewithfataloutcomearereportedin

dogs –especiallyCollies,OldEnglishSheepdogsandrelatedbreedsorcrosses,

andalsointurtles/tortoises).

Donotuseincasesofknownhypersensitivitytotheactivesubstancesortoany

otherexcipients.

4.4 SpecialWarningsforEachTargetSpecies:

Careshouldbetakentoavoidthefollowingpracticesbecausetheyincreasethe

riskofdevelopmentofresistanceandcouldultimatelyresultinineffectivetherapy:

Toofrequentandrepeateduseofanthelminticsfromthesameclass,overan

extendedperiodoftime.

Underdosingwhichmaybeduetounderestimationofbodyweight,

misadministrationoftheproduct,orlackofcalibrationofthedosingdevice.

Suspectedclinicalcasesofresistancetoanthelminticsshouldbefurther

investigatedusingappropriatetests(e.g.FaecalEggCountReductionTest).

Wheretheresultsofthetestsstronglysuggestresistancetoaparticular

anthelmintic,ananthelminticbelongingtoanotherpharmacologicalclassand

havingadifferentmodeofactionshouldbeused.

ResistancetoivermectinandclosantelhasbeenreportedinHaemonchuscontortus

insheep.Thereforetheuseofthisproductshouldbebasedonlocal

epidemiologicalinformationaboutthesusceptibilityoftheHaemonchuscontortus

andrecommendationsonhowtolimitfurtherselectionforresistanceto

anthelmintics.

Insheeptreatmentofpsoropticmange(sheepscab)withoneinjectionofthis

productwillnotbeeffectiveineliminatingallthemites.Asuitableivermectin –only

Revised:May2011

AN:00041/2011

injectableproductmustbeadministeredsevendaysafterthetreatmentwiththis

producttotreatclinicalsignsandtoeliminatethemites.

Sheepscab(Psoroptesovis)isanextremelycontagiousexternalparasiteofsheep.

Toensurecompletecontrolgreatcaremustbetakentoavoidre-infestation,as

mitesmaybeviableforupto15daysoffthesheep.Itisimportantthatallsheep

whichhavebeenincontactwithinfectedsheeparetreatedwithanappropriate

product.Contactbetweentreated,infectedanduntreatedflocksmustbeavoided

untilatleastsevendaysaftertreatment.

4.5 SpecialPrecautionsforUse:

i. Specialprecautionsforuseinanimals

None

ii. Specialprecautionstobetakenbythepersonadministeringtheveterinary

medicinalproducttoanimals

Donotsmoke,eatordrinkwhilehandlingtheproduct.

Directcontactoftheproductwiththeskinshouldbekepttoaminimum.Wash

handsafteruse.Takecaretoavoidself-injection.Inadvertentself-injection

mayresultinlocalirritationand/orpainattheinjectionsite.

4.6 AdverseReactions(FrequencyandSeriousness):

Transitoryswellinghasoccasionallybeenobservedattheinjectionsite.

Occasionallythisswellingisaccompaniedbypainanddiscomfort.Thisswelling

resolvescompletelywithin14daysfollowingtreatment.

4.7 UseDuringPregnancy,LactationorLay:

ClosiverInjectioncanbeadministeredtosheepatanystageofpregnancyor

lactationprovidedthatthemilkisnotintendedforhumanconsumption.(See

section4.11).

4.8 InteractionswithOtherMedicamentsandOtherFormsofInteraction:

Donotadministerconcomitantlywithchlorinatedcompounds.TheeffectofGABA

agonistsareincreasedbyivermectin.

Pleaserefertosection4.3oftheSPC.

4.9 AmountstobeAdministeredandAdministrationRoute:

ClosiverInjectionshouldbeadministeredatadosagerateof200

givermectinper

kgbodyweightand5mgclosantelperkgbodyweight(1mlper25kg).Itshould

onlybeinjectedsubcutaneouslyintotheneck.Asterile16-gauge,one-inchneedle

isrecommended.

ForthetreatmentandcontrolofsheepscabaninjectionofClosiverInjectionfor

Sheepmaybeadministeredbutmustbefollowedwithasecondinjectionofan

ivermectinonlyproductsevendaysaftertheinitialinjectiontotreatclinicalsignsof

Revised:May2011

AN:00041/2011

scabandtoeliminatemites.Thisinjectionshouldbeadministeredattheotherside

oftheneck.

Thisproductdoesnotcontainanantimicrobialpreservative.Swabseptumbefore

removingeachdose.Useadrysterileneedleandsyringe.For250mland500ml

packsizes,useofamultipledosesyringeisrecommended.Torefillthesyringe,

useofadraw-offneedleisrecommendedtoavoidexcessivebroachingofthe

stopper.

Donotexceed40broachingspervial.Ifmorethan40broachingsarerequired,use

ofadrawoffneedleisrecommended.

Thetimingfortreatmentshouldbebasedonepidemiologicalfactorsandshouldbe

customisedforeachindividualfarm.Aswithotheranthelmintics,veterinaryadvice

shouldbesoughtonappropriatedosingprogrammesandstockmanagementto

achieveadequateparasitecontrolandreducethelikelihoodofresistance

developing.

Toensureadministrationofacorrectdose,bodyweightshouldbedeterminedas

accuratelyaspossible;accuracyofthedosingdeviceshouldbechecked.

Ifanimalsaretobetreatedcollectivelyratherthanindividuallytheyshouldbe

groupedaccordingtotheirbodyweightanddosedaccordingly,inordertoavoid

under-orover-dosing.

4.10Overdose(Symptoms,EmergencyProceduresandAntidotes)(ifnecessary):

Doselevelsupto4.0mg/kgivermectin(20timestherecommendeddosage)

administeredsubcutaneously,resultinataxiaanddepressioninsheep.

Closantellikeothersalicylanilidesisapotentuncouplerofoxidativephosphorylation

andthesafetyindexisnotashighasisthecaseofmanyotheranthelmintics.

Howeverwhereusedasdirectedthereareunlikelytobeanyuntowardeffects.

Signsofoverdosagecanincludelossofappetite,decreasedvision,loosefaeces

andincreasedfrequencyofdefaecation.Highdosesmaycauseblindness,

hyperventilation,hyperthermia,generalweakness,inco-ordination,convulsions,

tachycardiaandinextremecasesdeath.Thelethaldose(LD

)ofclosantelin

sheep,afterasingleintramusculardose,washigherthan40mg/kg.Moreover,

somestudiesconductedinsheepreportedsignsofoverdosewithdosesofaround

4timesthetherapeuticdose(bothinjectableandoral).Treatmentofoverdosageis

symptomaticasnoantidotehasbeenidentified.

4.11WithdrawalPeriod:

Meatandoffal: 28days

Milk:Notpermittedforuseinanimalsproducingmilkforhumanconsumption,

includingpregnantanimalsintendedtoproducemilkforhumanconsumption.

Revised:May2011

AN:00041/2011

5. PHARMACOLOGICALPROPERTIES

ATCvetcode:QP54AA51

Pharmacotherapeuticgroup:Endectocides

5.1 PharmacodynamicProperties:

Ivermectinisanendectocidewithactivityagainstawiderangeofinternaland

externalparasites.Ivermectinisamacrocyliclactoneandactsbyinhibitingnerve

impulses.Itbindsselectivelyandwithhighaffinitytoglutamate-gatedchlorideion

channelswhichoccurininvertebratenerveandmusclecells.Thisleadstoan

increaseinthepermeabilityofthecellmembranetochlorideionswith

hyperpolarizationofthenerveormusclecell,resultinginparalysisanddeathofthe

relevantparasites.Compoundsofthisclassmayalsointeractwithotherligand-

gatedchloridechannels,suchasthosegatedbytheneurotransmittergamma-

aminobutyricacid(GABA).Themarginofsafetyforcompoundsofthisclassis

attributabletothefactthatmammalsdonothaveglutamate-gatedchloride

channels.Themacrocyliclactoneshavealowaffinityforothermammalianligand-

gatedchloridechannelsandtheydonotreadilycrosstheblood-brainbarrier.

Closantelisamemberofthesalicylanilideclassofanthelmintics.Salicylanilides

arehydrogen(proton)ionophores(referredtoasoxidativephosphorylase

uncouplers.)

Thechemicalstructureofsalicylanilidesillustratethepossessionofadetachable

proton.Thistypeofmoleculeislipophilicandisknowntoshuttleprotonsacross

membranes,inparticulartheinnermitochondrialmembrane.Closantelactsby

uncouplingoxidativephosphorylation.

Closantelisaparasiticidewithflukicideactivityandefficacyagainstcertainother

helminthsandarthropods.

5.2 PharmacokineticProperties:

AftersubcutaneousadministrationofClosiverInjectiontosheepatadoserateof

givermectinperkgand5mgclosantelperkgthefollowingparameterswere

observed:IvermectinCmaxof24.52ng/mlandAUCof2082.93ng.h/ml;

ClosantelCmaxof70.4

g/mlandAUCof41043

g.h/ml.

Ivermectinbindsextensivelytoplasmaproteins.Duetoitshighlipophilicnature,

ivermectinisextensivelydistributed.Ittendstoaccumulateinfattissue,whichacts

asadrugreservoirandthehighestlevelsofivermectinarefoundinliverandfat.

Ivermectinisonlypartiallymetabolised.Ivermectinismainlyeliminatedinthe

faecesasunaltereddrugandfaecalexcretionaccountsfor90%ofthedose

administeredwith<2%ofthedoseexcretedinurine.Ivermectinisalsoexcretedby

themammarygland.

Salicylanilidesarepoorlymetabolisedandareexcretedmainlyunchanged.The

mainexcretionrouteisthefaecesviathebile.Closantelisextensivelyboundto

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plasmaproteins,almostexclusivelytoalbumin.Thedistributiontotissuesispoor.

Closantelhasalongeliminationhalf-life.

6. PHARMACEUTICALPARTICULARS

6.1 ListofExcipients:

PovidoneK12

SodiumFormaldehydeSulphoxylate

Macrogol200

GlycerolFormal

6.2 MajorIncompatibilities:

Intheabsenceofcompatibilitystudies,thisveterinarymedicinalproductmustnot

bemixedwithotherveterinarymedicinalproducts.

6.3 Shelf-Life:

Shelf-lifeoftheveterinaryproductaspackagedforsale:18months.

Shelf-lifeafterfirstopeningofimmediatepackaging:28days.

6.4 SpecialPrecautionsforStorage:

Donotstoreabove25°C.

Protectfromlight.

Discardunusedmaterial.

6.5 NatureandCompositionofImmediatePackaging:

100ml,250mland500mlTypeIglassmultidosevialsandaluminiumcaps

completewithbromobutylbungsandaluminiumseals.

Notallpacksizesmaybemarketed.

6.6 SpecialPrecautionsfortheDisposalofUnusedVeterinaryMedicinalProduct

orWasteMaterialsDerivedfromtheUseofSuchProducts,ifappropriate:

EXTREMELYDANGEROUSTOFISHANDAQUATICLIFE.Donotcontaminate

surfacewatersorditcheswiththeproductorusedcontainer.Anyunusedproduct

orwastematerialsderivedfromsuchveterinarymedicinalproductsshouldbe

disposedofinaccordancewithlocalrequirements.

Revised:May2011

AN:00041/2011

7. MARKETINGAUTHORISATIONHOLDER

NorbrookLaboratoriesLimited

StationWorks

CamloughRoad

Newry

CoDown,BT356JP

NorthernIreland

8 MARKETINGAUTHORISATIONNUMBER

Vm 02000/4298

9. DATEOFFIRSTAUTHORISATION

01October2010

10. DATEOFREVISIONOFTHETEXT

May2011