Buprenodale multi-dose 0.3 mg.ml solution for injection for dogs, cats and horses

Main information

  • Trade name:
  • Buprenodale multi-dose 0.3 mg.ml solution for injection for dogs, cats and horses
  • Pharmaceutical form:
  • Solution for injection
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Buprenodale multi-dose 0.3 mg.ml solution for injection for dogs, cats and horses
    Netherlands
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • buprenorphine
  • Therapeutic area:
  • Cats Non Food, Dogs Non Food, Horses Non Food

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0475/001
  • Authorization date:
  • 31-07-2013
  • EU code:
  • UK/V/0475/001
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage, interactions, side effects

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SUMMARYOFPRODUCTCHARACTERISTICS

1. NAMEOFTHEVETERINARYMEDICINALPRODUCT

BuprenodaleMultidose,0.3mg/mlsolutionforinjectionfordogs,catsandhorses

2. QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmlcontains:

Activesubstance:

Buprenorphine0.3mg

Asbuprenorphinehydrochloride0.324mg

Excipients:

Chlorocresol 1.35mg

Forthefulllistofexcipients,seesection6.1.

3. PHARMACEUTICALFORM

Solutionforinjection.

Clear,colourlesssolution

4. CLINICALPARTICULARS

4.1Targetspecies

Dogs,catsandhorses.

4.2Indicationsforuse,specifyingthetargetspecies

Post-operativeanalgesiainthedogandcat.

Post-operativeanalgesia,incombinationwithsedation,inthehorse.

Potentiationofthesedativeeffectsofcentrallyactingagentsinthedogandhorse.

4.3Contraindications

Donotadministerbytheintrathecalorperiduralroute.

Donotusepre-operativelyforCaesareansection(seesection4.7).

Donotuseinknowncasesofhypersensitivitytotheactivesubstanceoranyofthe

excipients.

Pleaserefertosection4.11.

4.4Specialwarningsforeachtargetspecies

None.

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4.5Specialprecautionsforuse

i. Specialprecautionsforuseinanimals

Buprenorphinemayoccasionallycauserespiratorydepressionandaswithotheropioid

drugs,careshouldbetakenwhentreatinganimalswithimpairedrespiratoryfunctionor

animalsthatarereceivingdrugsthatcancauserespiratorydepression.

Incaseofrenal,cardiacorhepaticdysfunction,orshock,theremaybegreaterrisk

associatedwiththeuseoftheproduct.Thebenefit:riskratioforusingtheproduct

shouldbemadebytheattendingvet.Safetyhasnotbeenfullyevaluatedinclinically

compromisedcats.

Asbuprenorphineismetabolisedbytheliver,itsintensityanddurationofactionmaybe

affectedinanimalswithimpairedliverfunction.

Thesafetyofbuprenorphinehasnotbeendemonstratedinkittensorpuppieslessthan

7weeksofage,thereforeuseinsuchanimalsshouldbebasedonthebenefit:risk

assessmentoftheveterinarian.

Repeatadministrationearlierthantherecommendedrepeatintervalsuggestedin

Section4.9isnotrecommended.

Long-termsafetyofbuprenorphinehasnotbeeninvestigatedbeyond5consecutive

daysofadministrationincatsor4separateadministrationsonthreeconsecutivedays

inhorses.

Theeffectofanopioidonheadinjuryisdependentonthetypeandseverityoftheinjury

andtherespiratorysupportsupplied.Theproductshouldbeusedinaccordancewiththe

benefit:riskassessmentoftheattendingveterinarian.

Safetyhasnotbeenevaluatedinclinically-compromisedhorses.Inhorses,useof

opioidshasbeenassociatedwithexcitation,buteffectswithbuprenorphineareminimal

whenadministeredinconjunctionwithsedativesandtranquiliserssuchasdetomidine,

romifidine,xylazineandacepromazine.Inhorses,useofbuprenorphinewithouttheprior

useofasedativeagentcancauseexcitementandspontaneouslocomotoractivity.

Ataxiaisaknowneffectofdetomidineandsimilaragents;consequentlyitmaybeseen

afteradministrationofbuprenorphinewithsuchsubstances.Occasionally,ataxiamaybe

marked.Toensureataxichorsessedatedwithdetomidine/buprenorphinedonotlose

theirbalance,theyshouldnotbemovedorotherwisehandledinanywaythatwould

compromisetheirstability.

Buprenorphinemayreducegastrointestinalmotilityinhorses.

Thesafetyofbuprenorphinehasnotbeendemonstratedinhorsesyoungerthan

10monthsoldandweighinglessthan150kg;therefore,useinsuchanimalsshouldbe

basedontherisk:benefitassessmentoftheveterinarian.

ii. Specialprecautionstobetakenbythepersonadministeringtheveterinary

medicinalproducttoanimals

Asbuprenorphinehasopioid-likeactivity,careshouldbetakentoavoidaccidentalself-

injection.Incaseofaccidentalself-injectionoringestion,seekmedicaladvice

immediatelyandshowthepackageleafletorthelabeltothephysician.

Followingeyecontaminationorskincontact,washthoroughlywithcoldrunningwater.

Seekmedicaladviceifirritationpersists.

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4.6Adversereactions(frequencyandseriousness)

Salivation,bradycardia,hypothermia,agitation,dehydrationandmiosiscanoccurinthe

dog,andrarelyhypertensionandtachycardia.

Mydriasisandsignsofeuphoria(excessivepurring,pacing,rubbing)commonlyoccurin

catsandwillusuallyresolvewithin24hours.

Buprenorphinemayoccasionallycauserespiratorydepression;refertosection4.5i.

Inhorses,whenusedasdirectedinconjunctionwithsedativesortranquillisers,

excitationisminimalbutataxiamayoccasionallybemarked.Colicisrarelyreported.

4.7Useduringpregnancy,lactationorlay

Pregnancy:

Laboratorystudiesinratshavenotproducedanyevidenceofateratogeniceffect.

However,thesestudieshaveshownpost-implantationlossesandearlyfoetaldeaths.

Thesemayhaveresultedfromareductioninparentalbodyconditionduringgestation

andinpost-natalcareowingtosedationofthemothers.

Asreproductivestudieshavenotbeenconductedinthetargetspecies,useonly

accordingtothebenefit:riskassessmentbytheresponsibleveterinarian.

Theproductshouldnotbeusedpre-operativelyincasesofCaesareansection,dueto

theriskofrespiratorydepressionintheoffspringperiparturiently,andshouldonlybe

usedpost-operativelywithspecialcare(seebelow).

Lactation:

Studiesinlactatingratshaveshownthat,afterintramuscularadministrationof

buprenorphine,concentrationsofunchangedbuprenorphineinthemilkequalledor

exceededthatintheplasma.Asitislikelythatbuprenorphinewillbeexcretedinthemilk

ofotherspecies,useisnotrecommendedduringlactation.Useonlyaccordinglyto

benefit:riskassessmentbytheresponsibleveterinarian.

4.8Interactionwithothermedicinalproductsandotherformsofinteraction

Buprenorphinemaycausesomedrowsiness,whichmaybepotentiatedbyother

centrally-actingagents,includingtranquillisers,sedativesandhypnotics.

Thereisevidenceinhumanstoindicatethattherapeuticdosesofbuprenorphinedonot

reducetheanalgesicefficacyofstandarddosesofanopioidagonist,andthatwhen

buprenorphineisemployedwithinthenormaltherapeuticrange,standarddosesof

opioidagonistmaybeadministeredbeforetheeffectsoftheformerhaveendedwithout

compromisinganalgesia.However,itisrecommendedthatbuprenorphineisnotusedin

conjunctionwithmorphineorotheropioid-typeanalgesics,e.g.etorphine,fentanyl,

pethidine,methadone,papaveretumorbutorphanol.

Buprenorphinehasbeenusedwithacepromazine,alphaxalone/alphadalone,atropine,

detomidine,dexmedetomidine,halothane,isoflurane,ketamine,medetomidine,

propofol,romifidine,sevoflurane,thiopentoneandxylazine.

Whenusedincombinationwithsedatives,depressiveeffectsonheartrateand

respirationmaybeaugmented.

4.9Amountstobeadministeredandadministrationroute

Speciesand Post-OperativeAnalgesia Potentiationof

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route SedativeEffects

Dog:

Intramuscularor

intravenous

injection

10- 20μg/kg(0.3-0.6mlper10kg)

repeatedifnecessaryafter3-4hours

with10μg/kgor5-6hourswith20

μg/kgdoses 10- 20μg/kg

(0.3-0.6mlper10kg)

Cat:Intramuscular

orintravenous

Injection

10- 20μg/kg(0.3-0.6mlper10kg)

repeatedonceifnecessaryafter1 –2

hours --

Horse:

Intravenous

injection

10μg/kg(3.3mlper100kg)5minutes

afteradministrationofanivsedative.

Thedosemayberepeatedonce,if

necessary,afternotlessthan1-2

hours,incombinationwith

intravenoussedation,

5μg/kg(1.7mlper100

kg)5minutesafter

administrationofaniv

sedative,repeatedif

necessaryafter10

minutes.

Whenusedinhorses,anintravenoussedativemustbeadministeredwithinfiveminutes

priortoinjectionofbuprenorphine.

Indogs,sedativeeffectsarepresentby15minutesafteradministration.

Analgesicactivitymaynotdevelopfullyuntil30minutes.Toensurethatanalgesiais

presentduringsurgeryandimmediatelyonrecovery,theproductshouldbe

administeredpreoperativelyaspartofpremedication.

Whenadministeredforpotentiationofsedationoraspartofpremedication,thedoseof

othercentrally-actingagents,suchasacepromazineormedetomidine,shouldbe

reduced.Thereductionwilldependonthedegreeofsedationrequired,theindividual

animal,thetypeofotheragentsincludedinpremedicationandhowanaesthesiaistobe

inducedandmaintained.Itmayalsobepossibletoreducetheamountofinhalational

anaestheticused.

Animalsadministeredopioidspossessingsedativeandanalgesicpropertiesmayshow

variableresponses.Therefore,theresponseofindividualanimalsshouldbemonitored

andsubsequentdosesshouldbeadjustedaccordingly.Insomecases,repeatdoses

mayfailtoprovideadditionalanalgesia.Inthesecases,considerationshouldbegiven

tousingasuitableinjectableNSAID.

Anappropriatelygraduatedsyringemustbeusedtoallowaccuratedosing.

4.10Overdose(symptoms,emergencyprocedures,antidotes),ifnecessary

Incasesofoverdosage,supportivemeasuresshouldbeinstituted,and,ifappropriate,

naloxoneorrespiratorystimulantsmaybeused.

Whenadministeredatoverdosetodogs,buprenorphinemaycauselethargy.Atvery

highdoses,bradycardiaandmiosismaybeobserved.

Studiesinhorseswherebuprenorphinehasbeenadministeredwithsedativeshave

shownveryfeweffectsatuptofivetimestherecommendeddosage,butwhen

administeredonitsownitcancauseexcitement.

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Whenusedtoprovideanalgesiainhorses,sedationisrarelyseen,butmayoccurat

doselevelshigherthanthoserecommended.

Naloxonemaybeofbenefitinreversingreducedrespiratoryrateandrespiratory

stimulantssuchasDoxapramarealsoeffectiveinman.Becauseoftheprolonged

durationofeffectofbuprenorphineincomparisontosuchdrugs,theymayneedtobe

administeredrepeatedlyorbycontinuousinfusion.Volunteerstudiesinmanhave

indicatedthatopiateantagonistsmaynotfullyreversetheeffectsofbuprenorphine.

Intoxicologicalstudiesofbuprenorphinehydrochlorideindogs,biliaryhyperplasiawas

observedafteroraladministrationforoneyearatdoselevelsof3.5mg/kg/dayand

above.Biliaryhyperplasiawasnotobservedfollowingdailyintramuscularinjectionof

doselevelsupto2.5mg/kg/dayfor3months.Thisiswellinexcessofanyclinicaldose

regimeninthedog.

PleasealsorefertoSections4.5and4.6ofthisSPC.

4.11Withdrawalperiod

Theproductisnotauthorisedforuseinhorsesintendedforhumanconsumption.

5. PHARMACOLOGICALPROPERTIES

Pharmacotherapeuticgroup:Opioids,oripavinederivatives.

ATCVetCode:QN02AE01.

5.1Pharmacodynamicproperties

Insummarybuprenorphineisapotent,long-actinganalgesicactingatopiatereceptors

inthecentralnervoussystem.

Buprenorphinecanpotentiatetheeffectsofothercentrally-actingagents,butunlikemost

opiates,buprenorphinehas,atclinicaldoses,onlyalimitedsedativeeffectofitsown.

Buprenorphineexertsitsanalgesiceffectviahighaffinitybindingtovarioussubclasses

ofopiatereceptors,particularlyµ,inthecentralnervoussystem.Atclinicaldoselevels

foranalgesia,buprenorphinebindstoopiatereceptorswithhighaffinityandhigh

receptoravidity,suchthatitsdissociationfromthereceptorsiteisslow,as

demonstratedininvitrostudies.Thisuniquepropertyofbuprenorphinecouldaccountfor

itslongerdurationofactivitywhencomparedtomorphine.Incircumstanceswhere

excessiveopiateagonistisalreadyboundtoopiatereceptors,buprenorphinecanexert

anarcoticantagonisticactivityasaconsequenceofitshigh-affinityopiatereceptor

binding,suchthatanantagonisticeffectonmorphineequivalenttonaloxonehasbeen

demonstrated.

Buprenorphinehaslittleeffectongastro-intestinalmotility.

5.2Pharmacokineticparticulars

Buprenorphineisrapidlyabsorbedafterintramuscularinjectioninvariousanimal

speciesandman.Thesubstanceishighlylipophilicandthevolumeofdistributionin

bodycompartmentsislarge.

Pharmacologicaleffects(e.g.mydriasis)mayoccurwithinminutesofadministrationand

signsofsedationnormallyappearby15minutes.Analgesiceffectsindogsandcats

appeararound30minuteswithpeakeffectsusuallybeingobservedatabout1 –1.5

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hours.Inpain-freehorses,antinociceptiveeffectsappearduringthefirst15-30

minutes;peakantinociceptiveeffectsoccurbetween¾and6hoursafteradministration

Followingintravenousadministrationtodogsata20 μg/kgdose,themeanterminalhalf-

lifewas9hoursandthemeanclearancewas24ml/kg/min,however,thereis

considerableinter-dogvariabilityinpharmacokineticparameters.

Followingintramuscularadministrationtocats,themeanterminalhalf-lifewas6.3hours

andtheclearancewas23ml/kg/min;however,therewasconsiderableinter-cat

variabilityinpharmacokineticparameters.

Followingintravenousadministrationinhorses,buprenorphinehasameanresidence

timeofapproximately150minutes,avolumeofdistributionofapproximately2.5l/kg

andaclearancerateof10l/minute.

Combinedpharmacokineticandpharmacodynamicstudieshavedemonstrateda

markedhysteresisbetweenplasmaconcentrationandanalgesiceffect.Plasma

concentrationsofbuprenorphineshouldnotbeusedtoformulateindividualanimal

dosageregimens,whichshouldbedeterminedbymonitoringthepatient’sresponse.

Themajorrouteofexcretioninallspeciesexcepttherabbit(whereurinaryexcretion

predominates)isthefaeces.BuprenorphineundergoesN-dealkylationandglucuronide

conjugationbytheintestinalwallandtheliveranditsmetabolitesareexcretedviathe

bileintothegastro-intestinaltract.

Intissuedistributionstudiescarriedoutinratsandrhesusmonkeysthehighest

concentrationsofdrug-relatedmaterialwereobservedinliver,lungandbrain.Peak

levelsoccurredrapidlyanddeclinedtolowlevelsby24hoursafterdosing.

Proteinbindingstudiesinratshaveshownthatbuprenorphineishighlyboundtoplasma

proteins,principallytoalphaandbetaglobulins.

6. PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Chlorocresol

Glucosemonohydrate

Sodiumhydroxide(pHadjustment)

Hydrochloricacid,concentrated(pHadjustment)

Waterforinjection

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thisveterinarymedicinalproductmustnotbe

mixedwithotherveterinarymedicinalproducts.

6.3Shelflife

Shelf-lifeoftheveterinarymedicinalproductaspackagedforsale:2years.

Shelf-lifeafterfirstopeningthevial:28days.

6.4.Specialprecautionsforstorage

Thisveterinarymedicinalproductdoesnotrequireanyspecialstorageconditions.

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6.5Natureandcompositionofimmediatepackaging

Cardboardcartoncontaininga10mlclearTypeIglassvialwithaFluroTeccoated

bromobutylrubberstopperandaluminiumseal.

6.6Specialprecautionsforthedisposalofunusedveterinarymedicinal

productorwastematerialsderivedfromtheuseofsuchproducts

Anyunusedveterinarymedicinalproductorwastematerialsderivedfromsuch

veterinarymedicinalproductsshouldbedisposedofinaccordancewithlocal

requirements.

7. MARKETINGAUTHORISATIONHOLDER

DechraLimited

DechraHouse

JamageIndustrialEstate

TalkePits

Stoke-on-Trent

Staffordshire

ST71XW

UK

8. MARKETINGAUTHORISATIONNUMBER

Vm10434/4081

9. DATEOFFIRSTAUTHORISATION

10October2013

10.DATEOFREVISIONOFTHETEXT

October2013

Approved: 10/10/2013