Epityl 60 mg Chewable Tablets

Main information

  • Trade name:
  • Epityl 60 mg Chewable Tablets
  • Pharmaceutical form:
  • Chewable tablet
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • Epityl 60 mg Chewable Tablets
    Spain
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • Phenobarbital
  • Therapeutic area:
  • Dogs

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • UK/V/0438/001
  • Authorization date:
  • 24-04-2013
  • EU code:
  • UK/V/0438/001
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage, interactions, side effects

Issued:September2013

AN.01713/2011

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SUMMARYOFPRODUCTCHARACTERISTICS

1. NAMEOFTHEVETERINARYMEDICINALPRODUCT

Epityl60mgFlavouredTabletsforDogs

Epitylvet60mgTabletsforDogs(SEandFI)

Epityl60mgTabletsforDogs(FR)

2. QUALITATIVEANDQUANTITATIVECOMPOSITION

Activeingredient:

Eachtabletcontains:

Phenobarbital60mg

Forafulllistofexcipients,seesection6.1

3. PHARMACEUTICALFORM

Tablet

White,circulartabletwithcrossbreaklineononeside.

Thetabletscanbedividedintoequalhalvesorquarters.

4. CLINICALPARTICULARS

4.1 Targetspecies

Dog

4.2 Indicationsforuse,specifyingthetargetspecies

Phenobarbitalisanantiepilepticagentforthepreventionofseizuresduetogeneralized

epilepsyindogs.

4.3 Contra-indications

Donotuseincaseofhypersensitivitytobarbituates.

Donotuseinanimalswithseriousimpairedhepaticfunction.

Donotuseinanimalswithseriousrenalorcardiovasculardisorders.

Donotuseindogsweighinglessthan6kgbodyweight.

4.4 Specialwarningsforeachtargetspecies

Thedecisiontostartantiepilepticdrugtherapywithphenobarbitalshouldbeevaluated

foreachindividualcaseanddependsonnumber,frequency,durationandseverityof

seizuresindogs.

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Administrationoftabletsshouldoccuratthesametime(s)eachday,andshouldbeco-

ordinatedwithfeedingtimesinaconsistentmanner.Withdrawalortransitionfromother

typesofantieleptictherapyshouldbemadegraduallytoavoidprecipitatinganincrease

inthefrequencyofseizures.

4.5 Specialprecautionsforuse

Specialprecautionsforuseinanimals

Cautionisrecommendedinanimalswithimpairedhepaticandrenalfunction,

hypovolemia,anemiaandcardiacorrespiratorydysfunction.Thechanceofhepatotoxic

sideeffectscanbediminishedordelayedusinganeffectivedosethatisaslowas

possible.Monitoringofhepaticparametersisrecommendedincaseofaprolonged

therapy.

Itisrecommendedtoassesstheclinicalpathologyofthepatient2-3weeksafterstartof

treatmentandafterwardsevery4-6months,e.g.measurementofhepaticenzymesand

serumbileacids.Itisimportanttoknowthattheeffectsofhypoxiaetc.docause

increasedlevelsofhepaticenzymesafteraseizure.Phenobarbitalmayincreasethe

activityofserumalkalinephosphataseandtransaminases.Thesemaydemonstrate

non-pathologicalchanges,butcouldalsorepresenthepatotoxicity,liverfunctiontests

arerecommended.Increasedliverenzymevaluesmaynotalwaysrequireadose

reductionofphenobarbitaliftheserumbileacidsareinthenormalrange.

Instabilizedepilepticpatients,itisnotrecommendedtoswitchfromotherphenobarbital

formulatorstoEpityl60mgtablets.However,ifthiscannotbeavoidedthenadditional

cautionshouldbetaken.Thisincludesmorefrequentplasmaconcentrationsamplingto

ensurethattherapeuticlevelsaremaintained.Monitoringforincreasedsideeffectsand

forhepaticdysfunctionshouldbeconductedmoreregularlyuntilstabilisationis

confirmed.Withdrawaloftherapywithphenobarbitalformulationsshouldbemade

graduallytoavoidprecipitatinganincreaseinthefrequencyofseizures.

Specialprecautionstobetakenbythepersonadministeringtheveterinary

medicinalproducttoanimals

Peoplewithknownhypersensitivitytobarbituratesshouldavoidcontactwiththe

veterinarymedicinalproduct.Washhandsthoroughlyafteruse.

Takeutmostcarethatchildrendonotcomeincontactwiththeproduct.Childrenare

particularlyatriskofintoxicationwhichmayprovefatal.Incaseofaccidentalingestion,

seekmedicalattentionimmediatelyandshowthepackageleafletorthelabeltothe

physician.Ifpossible,thephysicianshouldbeinformedaboutthetimeandamountof

ingestion,asthisinformationmayhelptoensurethatappropriatetreatmentisgiven.

Eachtimeanunusedpart-tabletisstoreduntilnextuse,itshouldbereturnedeitherto

theopenblisterspaceandinsertedbackintothecardboardboxorplacedbackintothe

containerandkeptinasafeplaceoutofthereachandsightofchildrenasitposesa

healthrisktosmallchildrenduetoaccidentalingestion.

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4.6 Adversereactions(frequencyandseriousness)

Duringstartoftherapyataxia,andsedationcanoccurbuttheseeffectsareusually

transitoryanddisappearinmost,butnotall,patientswithcontinuedmedication.Some

animalscandemonstrateaparadoxicalhyperexcitability,particularlyafterfirststarting

therapy.Asthishyperexcitabilityisnotlinkedtooverdosage,noreductionofdosageis

needed.Polyuria,polydipsiaandpolyphagiacanoccurataverageorhighertherapeutic

activeserumconcentrations;theseeffectscanbediminishedbylimitingintakeoffood.

Sedationandataxiaoftenbecomesignificantconcernsasserumlevelsreachthehigher

endsofthetherapeuticrange.Highplasmaconcentrationsmaybeassociatedwith

hepatotoxicity.Phenobarbitalcanhavedeleteriouseffectsonstemcellsfrombone

marrow.Consequencesareimmunotoxicpancytopeniaand/orneutropenia.These

reactionsdisappearafterthetreatment’swithdrawal.Treatingdogswithphenobarbital

maylowertheirTT4orFT4serumlevels,howeverthismaynotbeanindicationof

hypothyroidism.Treatmentwiththyroidhormonereplacementshouldonlybestartedif

thereareclinicalsignsofthedisease.

Ifadverseeffectsaresevere,thedecreaseintheadministereddoseisrecommended.

4.7 Useduringpregnancy,lactationorlay

Phenobarbitalcrossestheplacentalbarrierandathigherdoses(reversible)withdrawal

symptomsinnewbornscannotbeexcluded.Studiesinlaboratoryanimalshaveshown

evidenceofactionofphenobarbitalonprenatalgrowth,especiallyconcerningsexual

development.Neonatalbleedingtendencieshavebeenassociatedwithphenobarbital

treatmentduringpregnancy.AdministrationofVitaminKtothedamfor10daysbefore

parturitionmayhelptominimizetheseeffectsonthefetus.

Thesafetyoftheproducthasnotbeenestablishedduringpregnancyofdogs.The

benefitsoftreatmentmaybegreaterthanthepotentialrisksassociatedwithepileptic

seizuresonthefetus(hypoxiaandacidosis).Therefore,incaseofpregnancy,

terminationofantiepileptictreatmentisnotrecommended;however,thedoseshouldbe

aslowaspossible.

Phenobarbitalisexcretedinsmallamountsinbreastmilkandduringnursing,pups

shouldbemonitoredcarefullyforundesiredsedativeeffects.Weaningearlymaybean

option.Ifsomnolence/sedativeeffects(thatcouldinterferewithsuckling)appearin

nursingnewborns,anartificialsucklingmethodshouldbechosen.

Useduringpregnancyandlactationonlyaccordingtothebenefit/riskassessmentbythe

responsibleveterinarian.

4.8 Interactionwithothermedicinalproductsandotherformsofinteraction

Atherapeuticdoseofphenobarbitalforantiepileptictherapycansignificantlyinduce

plasmaproteins,(suchas α1acidglycoprotein,AGP),whichbinddrugs.Phenobarbital

mayreducetheactivityofsomedrugsbyincreasingtherateofmetabolismthrough

inductionofdrug-metabolisingenzymesinlivermicrosomes.Thereforespecial

attentionmustbepaidtothepharmacokineticsanddosesofdrugssimultaneously

administered.Theplasmaticconcentrationofarangeofdrugs(forexample

cyclosporine,thyroidhormonesandtheophylline)isdecreasedinthecaseofconcurrent

administrationofphenobarbital.Concurrentusewithotherdrugshavingacentral

depressiveaction(likenarcoticanalgesics,morphinicderivates,phenothiazines,

antihistamines,clomipramineandchloramphenicol)canincreasetheeffectof

phenobarbital.

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Cimetidineandketoconazoleareinhibitorsofhepaticenzymes:concurrentusewith

phenobarbitalcaninduceanincreaseofserumconcentrationofphenobarbital.

Phenobarbitalmaydecreasetheabsorptionofgriseofulvin.Concurrentusewith

potassiumbromideincreasestheriskofpancreatitis.Useofphenobarbitaltabletsin

conjunctionwithprimidoneisnotrecommendedasprimidoneispredominantly

metabolizedtophenobarbital.

Thefollowingdrugscandecreasetheconvulsivethreshold:quinolones,highdosesof β-

lactamantibiotic,theophyllin,aminophyllin,cyclosporineandpropofolforexample).

Medicationswhichmayaltertheseizurethresholdshouldonlybeusedifreally

necessaryandwhennosaferalternativeexists.

Thefollowingdrugscandecreasetheco nvulsivethreshold:quinolones,highdosesofβ-

lactamantibiotic,theophyllin,aminophyllin,cyclosporineandpropofolforexample).

Medicationswhichmayaltertheseizurethresholdshouldonlybeusedifreally

necessaryandwhennosaferalternativeexists

4.9 Amountstobeadministeredandadministrationroute

Fororaladministration.Therequireddosagewilldiffertosomeextentbetween

individualsandwiththenatureandseverityofthedisorder.

Dogsshouldbedosedorally,startingwithadoseof2-5mgperkgbodyweightperday.

Thedoseshouldbedividedandadministeredtwicedaily.

Steadystateserumconcentrationsarenotreacheduntil1-2weeksaftertreatmentis

initiated.Thefulleffectofthemedicationdoesnotappearfortwoweeksanddoses

shouldnotbeincreasedduringthistime.

Tabletsmustbegivenatthesametimeeachdaytooptimizetreatmentsuccess.

Ifseizuresarenotbeingcontrolled,thedosagemaybeincreasedby20%atatime,with

associatedmonitoringofserumphenobarbitallevels.Thephenobarbitalserum

concentrationmaybecheckedaftersteadystatehasbeenachieved,andifitisless

than15µg/mlthedosemaybeadjustedaccordingly.Ifseizuresrecurthedosemaybe

raiseduptoamaximumserumconcentrationof45µg/ml.Highplasmaconcentrations

maybeassociatedwithhepatotoxicity.Bloodsamplescouldbetakenatthesametime

toallowplasmaphenobarbitalconcentrationtobedeterminedpreferablyduringtrough

levels,shortlybeforethenextdoseofphenobarbitalisdue.

Plasmaconcentrationsshouldbeinterpretedinconjunctionwiththeobservedresponse

totherapyandafullclinicalassessmentincludingmonitoringforevidenceoftoxic

effectsineachanimal.

Clinicaldatasuggeststhatconsiderablevariationinplasmaconcentrationsof

phenobarbitalmaybeobservedinsomeanimals.Thisvariationmayresultinananimal

withatroughplasmaconcentrationofphenobarbitalbelowthetypicalminimum

therapeuticlevel(15µg/ml)andapeakplasmaconcentrationapproachingthe

maximumlevel(45µg/ml).Iftheseizurecontrolisinadequateinsuchanimals,care

shouldbetakenwhenincreasingthedoseastoxiclevelsmaybereachedor

exceeded.Peakandtroughplasmaconcentrationsofphenobarbitalmayneedtobe

measuredinsuchanimals.(Peakplasmaconcentrationsarereachedwithin

approximately3hoursafteradministration).

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Iftheseizuresarenotbeingsatisfactorilycontrolledandifthemaximumplasma

concentrationofphenobarbitalisabout40µg/ml,thenthediagnosisshouldbe

reconsideredand/orasecondantiepilepticproduct(suchasbromides)shouldbe

addedtothetreatmentprotocol.

Tabletscanbedividedintoequalhalvesorquarterstoensureaccuratedosing.

Tobreakacrossscoredtabletintoquarters,placethetabletonanevensurfacewiththe

scoredsideupandapplypressureonthemiddlewithyourthumb.

Tobreakatabletintotwohalves,placethetabletonanevensurfacewiththescored

sideup,holdonehalfofthetabletandpressdownontheotherhalf.

4.10Overdose(symptoms,emergencyprocedures,antidotes),ifnecessary

Symptomsofoverdoseare:

-depressionofthecentralnervoussystemdemonstratedbysignsrangingfromsleepto

coma,

-respiratoryproblems,

-cardiovascularproblems,hypotensionandshockleadingtorenalfailureanddeath.

Incaseofoverdoseremoveingestedproductfromthestomach,andgiverespiratory

andcardiovascularsupportasnecessary.

Thereisnospecificantidote,butCNSstimulants,(likeDoxapram)maystimulatethe

respiratorycentre.

4.11Withdrawalperiod(s)

Notapplicable.

5. PHARMACOLOGICALPROPERTIES

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Pharmacotherapeuticgroup:Antiepileptics/barbituratesandderivates

ATCVetCode:QN03AA02

5.1 Pharmacodynamicproperties

Theantiepilepticeffectsofphenobarbitalareprobablytheresultofatleasttwo

mechanisms:Decreasedmonosynaptictransmission,whichpresumablyresultsin

reducedneuronalexcitabilityandanincreaseinthemotorcortex'sthresholdfor

electricalstimulation.

5.2 Pharmacokineticparticulars

Afteroraladministrationofphenobarbitaltodogs,thedrugisrapidlyabsorbedand

maximalplasmaconcentrationsarereachedwithin3hours.Bioavailabilityisbetween

86%-96%.About45%oftheplasmaconcentrationisproteinbound.Metabolismisby

aromatichydroxylationofthephenylgroupintheparaposition,andaboutonethirdof

thedrugisexcretedunchangedintheurine.Eliminationhalf-livesvaryconsiderably

betweenindividualsandrangefromabout40-90hours.Steadystateserum

concentrationsarenotreacheduntil1-2weeksaftertreatmentisinitiated.

Afteroraladministrationoftheproductto16beagledogstwicedaily,at12hours

intervals,for14days,atadoserateof0.5tabletperdog,whichequatedto4-5mg/kg

bodyweight,maximumplasmaconcentrationsreachedwithin3hoursvariedfrom32.30

to47.64µg/mlandminimumplasmaconcentrationsvariedfrom12.94to21.05µg/ml.

6. PHARMACEUTICALPARTICULARS

6.1 Listofexcipients

Lactosemonohydrate

Microcrystallinecellulose

Magnesiumstearate

Maizestarch

Talc

Grilledmeatflavour

6.2 Incompatibilities

Noneknown

6.3 Shelflife

Shelflifeoftheveterinarymedicinalproductaspackagedforsale: 3years

Shelflifeofdividedtablets: 2days

6.4. Specialprecautionsforstorage

Thisveterinarymedicinalproductdoesnotrequireanyspecialstorageconditions.

Dividedtabletsshouldbestoredintheoriginalpack.Anydividedtabletportions

remainingafter2daysshouldbediscarded.Keeptheblisterintheoutercarton.

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6.5 Natureandcompositionofimmediatepackaging

Blisterstrips(PVC/Aluminium)containing10tabletsincartonsof10,20,30,40,50,60,

70,80,90,100,500and1000tablets.

WhiteHDPEcontainerswithapolypropylenechildresistantcapcontaining100or500

tablets.

Notallpacksizesmaybemarketed.

6.6 Specialprecautionsforthedisposalofunusedveterinarymedicinal

productorwastematerialsderivedfromtheuseofsuchproducts

Anyunusedveterinarymedicinalproductorwastematerialderivedfromsuchveterinary

medicinalproductsshouldbedisposedofinaccordancewithlocalrequirements.

7. MARKETINGAUTHORISATIONHOLDER

ChanellePharmaceuticalsManufacturingLtd

Loughrea

Co.Galway

Ireland

8. MARKETINGAUTHORISATIONNUMBER

Vm08749/4034

9. DATEOFFIRSTAUTHORISATION

19September2013

10. DATEOFREVISIONOFTHETEXT

September2013

APPROVED 19/09/13