Tilmodil 300 mg/ ml, soultion for injection

Main information

  • Trade name:
  • Tilmodil
  • Pharmaceutical form:
  • Solution for injection
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Tilmodil
    Germany
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • tilmicosin
  • Therapeutic area:
  • Cattle, Sheep

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0348/001
  • Authorization date:
  • 26-01-2011
  • EU code:
  • UK/V/0348/001
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage, interactions, side effects

1.NAMEoftheveterinarymedicinalproduct:

TILMODIL300mg/mlSolutionforInjectionforcattleandsheep

2.QUALITATIVEandQUANTITATIVECOMPOSITION:

Activeingredient:Tilmicosin300 mg/ml

Excipient:Propyleneglycol250 mg/ml

Forafulllistofexcipients,seesection6.1.

3.PHARMACEUTICALFORM:

Solutionforinjection.

Clear,yellowishtobrown-yellowishsolution(pH=6).

4.CLINICALPARTICULARS:

4.1.Targetspecies:

Cattleandsheep.

4.2.Indicationsforuse:

TILMODILisindicatedforthetreatmentofpneumoniaincattleandsheep,associatedwithMannheimia

haemolytica,Pasteurellamultocidaandothermicroorganismssensitivetotilmicosin,andforthe

treatmentofovinemastitisassociatedwithStaphylococcusaureusandMycoplasmaagalactiae.

Forthetreatmentofinterdigitalnecrobacillosisincattle(bovinepododermatitis,foulinthefoot)and

ovinefootrot.

4.3.Contra-indications:

Donotadministerintravenously.

Donotadministertopigs.

Donotadministertohorses.

Donotadministertogoats.

4.4.Specialwarningsforeachtargetspecies:

Sheep:Donotinjectlambsweighinglessthan15kg,sincethereisarealriskofoverdosetoxicity.

Accurateweighingoflambsisimportanttoavoidoverdosage.Theuseofa2mlorsmallersyringewill

facilitateaccuratedosing.

4.5Specialprecautionsforuse:

i)Specialprecautionsforuseinanimals:

Official,nationalandregionalantimicrobialpoliciesshouldbetakenintoaccountwhentheproductis

used.

ii)Specialprecautionstobetakenbythepersonadministeringthemedicinalproducttoanimals:

OperatorSafetyWarnings:

Injectionofthisdruginhumanscanbelethal–Exerciseextremecautiontoavoidaccidentalself-

injectionandfollowtheadministrationinstructionsandtheguidancebelowprecisely

Thisproductshouldonlybeadministeredbyaveterinarysurgeon.

NevercarryasyringeloadedwithTilmodilwiththeneedleattached.Theneedleshouldbe

connectedtothesyringeonlywhenfillingthesyringeoradministeringtheinjection.Keepthe

syringeandneedleseparateatallothertimes.

Donotuseautomaticinjectionequipment.

Ensurethatanimalsareproperlyrestrained,includingthoseinthevicinity.

DonotworkalonewhenusingTilmodil.

IncaseofhumaninjectionSEEKIMMEDIATEMEDICALATTENTIONandtakethevialorthe

packageinsertwithyou.Applyacoldpack(noticedirectly)totheinjectionsite.

Additionaloperatorsafetywarnings:

Avoidcontactwitheyes.

Maycausesensitisationbyskincontact.Washhandsafteruse.

NOTETOTHEPHYSICIAN

Injectionoftilmicosininhumanshasbeenassociatedwithfatalities.

Thecardiovascularsystemisthetargetoftoxicity,andthistoxicitymaybeduetocalciumchannel

blockade.Administrationofintravenouscalciumchlorideshouldonlybeconsideredifthereis

positiveconfirmationofexposuretotilmicosin.

Indogstudies,tilmicosininducedanegativeinotropiceffectwithconsequenttachycardia,anda

reductioninsystemicarterialbloodpressureandarterialpulsepressure.

Donotgiveadrenalinorbeta-adrenergicantagonistssuchaspropranolol.

Inpigs,tilmicosin-inducedlethalityispotentiatedbyadrenaline.

Indogs,treatmentwithintravenouscalciumchlorideshowedapositiveeffectontheleftventricular

inotropicstateandsomeimprovementsinvascularbloodpressureandtachycardia.

Pre-clinicaldataandanisolatedclinicalreportsuggestthatcalciumchlorideinfusionmayhelpto

reversetilmicosin-inducedchangesinbloodpressureandheartrateinhumans.

Administrationofdobutamineshouldalsobeconsideredduetoitspositiveinotropiceffectsalthough

itdoesnotinfluencetachycardia.

Astilmicosinpersistsintissuesforseveraldays,thecardiovascularsystemshouldbeclosely

monitoredandsupportivetreatmentprovided.

Physicianstreatingpatientsexposedtothiscompoundareadvisedtodiscussclinicalmanagementwith

theNationalPoisonInformationServiceon: [Tocompletewithemergencytelephonenumberof

NationalPoisonInformationService(s).]

UK:08448920111;Ireland:018379964;Germany:03019240;Belgium,Luxembourg:070245

245;TheNetherlands:0302748888;Denmark:035315555

4.6Adversereactions(frequencyandseriousness):

Occasionally,asoftdiffuseswellingmayoccurattheinjectionsitebutthisdisappearswithinfivetoeight

days.

Deathsofcattlehavebeenobservedfollowingasingleintravenousdoseof5mg/kg,andfollowingthe

subcutaneousinjectionofdosesof150mg/kgat72hourintervals.Inpigs,intramuscularinjectionat

20mg/kghascauseddeaths.Sheephavediedfollowingasingleintravenousinjectionof7.5mg/kg.

4.7 Useduringpregnancy,lactationorlay:

Seesection4.11.

4.8 Interactionwithothermedicinalproductsandotherformsofinteraction:

Interactionsbetweenmacrolidesandionophoreshavebeenobservedinsomespecies.

4.9 Amounttobeadministeredandadministrationroute:

Asinglesubcutaneousinjectionof0.5or1mlTilmodilper30kgbodyweightincattleandsheep(eq.to

5or10mgtilmicosinperkg,respectively).

Cattle

Forpneumoniaincattle,use10mg/kgbodyweight.

Forinterdigitalnecrobacillosisincattle,use5mg/kgbodyweight.

Withdrawtherequireddosefromthevialandremovethesyringefromtheneedle.Ifagroupofanimalsis

tobetreated,leavetheneedleinthevialasadraw-offneedleforsubsequentdoses.Restraintheanimal

andinsertaseparateneedlesubcutaneouslyintotheinjectionsite.Injectioninafoldofskinovertherib

cagebehindtheshoulderissuggested.Connectthesyringetotheneedleandinjectintothebaseofthe

skinfold.Donotinjectmorethan20mlperinjectionsite.

Sheep

Withdrawtherequireddosefromthevialandremovethesyringefromtheneedle,leavingtheneedlein

thevial.Restrainthesheepwhilstleaningovertheanimalandinsertaseparateneedlesubcutaneously

intotheinjectionsite,whichshouldbeinafoldofskinovertheribcagebehindtheshoulder.Connect

thesyringetotheneedleandinjectintothebaseoftheskinfold.Usethesamedraw-offneedleforthe

wholegrouptobetreated.

Forpneumoniaandmastitisinsheep,use10mg/kgbodyweight.Donotinjectlambsweighinglessthan

15kg,sincethereisarealriskofoverdosagetoxicity.

Forthetreatmentoffootrot,use5mg/kgbodyweight.Duetothepotentialofinaccuratedosingleading

tooverdosing,thisproductshouldnotbeusedtotreatfootrotinsheepweighinglessthan30kg.

Accurateweighingoflambsisimportanttoavoidoverdosage.Theuseofa2mlorsmallersyringewill

facilitateaccuratedosing.

Avoidintroductionofcontaminationintobottleduringuse.Shouldanygrowthordiscolourationoccur

theproductshouldbediscarded.

Donotbroachthevialmorethan25times.

Ifnoimprovementisnotedwithin48hours,thediagnosisshouldbeconfirmed.

4.10. Overdose(symptoms,emergencyprocedures,antidotes),ifnecessary:

Theacutemanifestationsofmultipleinjectionsoflargesubcutaneousdoses(150mg/kg)incattle

includedmoderateelectrocardiographicchangesaccompaniedbymildfocalmyocardialnecrosis,marked

injectionsiteoedema,anddeath.

Singlesubcutaneousinjectionsof30mg/kginsheepproducedincreasedrespirationrate,andathigher

levels(150mg/kg)ataxia,lethargyanddroopingofthehead.

4.11. Withdrawalperiods:

Cattletissues60days

Sheeptissues:42days.

Sheepmilk:15days(360hours).

Donotuseincattleproducingmilkforhumanconsumption.

Donotuseinpregnantdairyheifersordrydairycowswithin60daysofcalving.

5)PHARMACOLOGICALPROPERTIES:

Pharmcotherapeuticgroup:Antibacterialsforsystemicuse,macrolides,tilmicosin.

ATCvetcode:QJ01FA91

5.1.Pharmacodynamicproperties:

Tilmicosinisasemi-syntheticantibioticofthemacrolidegroup,andisbelievedtoaffectbacterialprotein

synthesis.Itisbacteriostaticbutathighconcentrationsitmaybebactericidal.

Tilmicosinhasanin-vitroantibacterialspectrumthatispredominantlyGram-positivewithactivity

againstcertainGram-negativemicro-organisms.ThespectrumincludesMannheimia,Pasteurella,

Actinobacillus(Haemophilus),Actinomyces(Corynebacterium),Fusobacterium,Dichelobacter,

Staphylococcus,andMycoplasmaorganismsofbovine,porcine,ovineandavianorigin.

Followingoralorparenteraladministrationoftilmicosinthemaintargetorganfortoxicityistheheart.

Theprimarycardiaceffectsareincreasedheartrate(tachycardia)anddecreasedcontractility(negative

inotrophy).Cardiovasculartoxicitymaybeduetocalciumchannelblockade.

Indogs,CaCl

2 treatmentshowedapositiveeffectontheleftventricularinotrophicstateaftertilmicosin

administrationandsomechangesinvascularbloodpressureandheartrate.

Dobutaminepartiallyoffsetthenegativeinotropiceffectsinducedbytilmicosinindogs.Betaadrenergic

antagonistssuchaspropanololexacerbatedthenegativeinotrophyoftilmicosinindogs.

Inpigs,intramuscularinjectionof10mgtilmicosin/kgcausedincreasedrespiration,emesisand

convulsions;20mg/kgresultedinmortalityin3of4pigs,and30mg/kgcausedthedeathofall4pigs

tested.Intravenousinjectionof4.5to5.6mgtilmicosin/kgfollowedbyintravenousinjectionof1ml

epinephrine(1/1000)2to6timesresultedindeathofall6injectedpigs.Pigsgiven4.5to5.6mg

tilmicosin/kgintravenouslywithnoepinephrineallsurvived.Theseresultssuggestthatintravenous

epinephrinemaybecontraindicated.

5.2.Pharmacokineticparticulars:

Absorption:Whenadministeredasrecommendedtocalvesandsheepbysubcutaneousinjectionoverthe

dorso-lateralchest,themainparametersare:

Doserate(tilmicosin) T

Cattle:

Neonatalcalves

Feedlotcattle

10mg/kgb.w.

10mg/kgb.w.

1hour

1hour

1.55µg/ml

0.97µg/ml

Sheep:

40kganimals

28-50kganimals

10mg/kgb.w.

10mg/kgb.w.

8hours

8hours

0.44µg/ml

1.18µg/ml

Distribution:Followingsubcutaneousinjection,tilmicosinisdistributedthroughoutthebody,but

especiallyhighlevelsarefoundinthelung.Incalves,lungconcentrationsoftilmicosinremainabovethe

of3.12µg/mlforMannheimiahaemolyticaforatleast72hoursafterinjection.Inlambs,lung

concentrationwasfoundtobeapproximately3.7µg/mlthreedaysafterasinglesubcutaneousinjectionof

10mg/kg.Inlactatingewes,milklevelsremainedabovetheMIC

of<1

g/mlforStaphylococcus

aureusforatleast72hoursafterinjection.

Biotransformation:Severalmetabolitesareformed,thepredominantonebeingidentifiedasT1(N-

demethyltilmicosin).Howeverthebulkofthetilmicosinisexcretedunchanged.

Elimination:Followingsubcutaneousinjection,tilmicosinisexcretedmainlyviathebileintothefaeces,

butasmallproportionisexcretedviatheurine.Thehalf-lifefollowingsubcutaneousinjectionincattleis

2-3days.

6.PHARMACEUTICALPARTICULARS

6.1.Listofexcipients:

Propyleneglycol

Phosphoricacid(forpHadjustment)

WaterforInjection

6.2.Incompatibilities:

Intheabsenceofcompatibilitystudies,thisveterinarymedicinalproductmustnotbemixedwithother

veterinarymedicinalproducts.

6.3.Shelf-life:

Shelf-lifeoftheveterinarymedicinalproductaspackagedforsale:3years.

Shelf-lifeafterfirstopeningtheimmediatepackaging:28days.

6.4.Specialprecautionsforstorage:

Donotstoreabove25°C.Protectfromlight.

Onceopenedusetheremainingsolutionwithin28 days.Discardunusedmaterial.

6.5.Natureandcompositionofimmediatepackaging:

Cardboardboxwith1or12multi-doseambercoloured,glassvials(typeII)of50or100mlwith

bromobutyl,teflon-coatedstoppersandanaluminiumcap.

Notallpacksizesmaybemarketed.

6.6.Specialprecautionsforthedisposalofunusedveterinarymedicinalproduct

orwastematerialsderivedfromtheuseofsuchproducts:

Anyunusedveterinarymedicinalproductorwastematerialsderivedfromsuchveterinarymedicinal

productsshouldbedisposedofinaccordancewithlocalrequirements.

7.MARKETINGAUTHORISATIONHOLDER

EMDOKAbvba,JohnLijsenstraat,16,B-2321Hoogstraten,Belgium.

8.MARKETINGAUTHORISATIONNUMBER:

9.DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION:

10.DATEOFREVISIONOFTEXT:

PROHIBITIONOFSALE,SUPPLYAND/ORUSE:

[TobecompletedinaccordancewithnationalrequirementsafterconclusionoftheDCphase,e.g.:]

<Prescriptiononlymedicine.>

<Forusebyveterinarysurgeonsonly.>