ATOPICA 25 mg

Main information

  • Trade name:
  • ATOPICA 25 mg
  • Pharmaceutical form:
  • Capsule, soft
  • Medicine domain:
  • Animals
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ATOPICA 25 mg
    United Kingdom
  • Language:
  • English

Therapeutic information

  • Therapeutic group:
  • ciclosporin
  • Therapeutic area:
  • Dogs

Other information

Status

  • Source:
  • HMA - Europe
  • Authorization number:
  • FR/V/0137/002
  • Authorization date:
  • 26-07-2007
  • EU code:
  • FR/V/0137/002
  • Last update:
  • 09-08-2016

Summary of Product characteristics: dosage,interactions,side effects

ATOPICA25mgSPC. [updateofADRsection,January2013]

1. NAMEOFTHEVETERINARYMEDICINALPRODUCT

ATOPICA25mgsoftcapsulesfordogs

2. QUALITATIVEANDQUANTITATIVECOMPOSITION

Activesubstance:

Ciclosporin 25.00mg

Excipient(s):

-tocopherol(E-307) 0.25mg

Ironoxideblack(E-172)0.105mg

Titaniumdioxide(E-171)2.12mg

Carminicacid(E-120)<1.00

g

Forafulllistofexcipients,seesection6.1.

3. PHARMACEUTICALFORM

Softcapsule

Blue-greyovalcapsulesbearingthefollowingimprint:NVR25mg.

4. CLINICALPARTICULARS

4.1Targetspecies

Dogs(weighingfrom4to7.5kg)

4.2Indicationsforuse,specifyingthetargetspecies

Treatmentofchronicmanifestationsofatopicdermatitisindogs.

4.3Contraindications

Donotuseincasesofhypersensitivitytociclosporinoroneoftheexcipients.

Forallcapsulestrengths,donotuseindogslessthansixmonthsofageorlessthan2kgin

weight.

Donotuseincaseswithahistoryofmalignantdisordersorprogressivemalignantdisorders.

Donotvaccinatewithalivevaccineduringtreatmentorwithinatwo-weekintervalbeforeor

aftertreatment.(seealsosections4.5“Specialprecautionsforuse”and4.8“Interactionwith

othermedicinalproducts”).

4.4Specialwarnings

None.

4.5Specialprecautionsforuse

i)Specialprecautionsforuseinanimals

Clinicalsignsofatopicdermatitissuchaspruritusandskininflammationarenotspecificfor

thisdiseaseandthereforeothercausesofdermatitissuchasectoparasiticinfestations,other

allergieswhichcausedermatologicalsigns(e.g.fleaallergicdermatitisorfoodallergy)or

bacterialandfungalinfectionsshouldberuledoutbeforetreatmentisstarted.Itisgood

practicetotreatfleainfestationsbeforeandduringtreatmentofatopicdermatitis.

Itisrecommendedtoclearbacterialandfungalinfectionsbeforeadministeringtheveterinary

medicinalproduct.However,infectionsoccurringduringtreatmentarenotnecessarilya

reasonfordrugwithdrawal,unlesstheinfectionissevere.

Acompleteclinicalexaminationshouldbeperformedbeforetreatment.Asciclosporininhibits

T-lymphocytesandthoughitdoesnotinducetumors,itmayleadtoincreasedincidencesof

clinicallyapparentmalignancy.Lymphadenopathyobservedontreatmentwithciclosporin

shouldberegularlymonitored.

Inlaboratoryanimals,ciclosporinisliabletoaffectthecirculatinglevelsofinsulinandtocause

anincreaseinglycaemia.Inthepresenceofsuggestivesignsofdiabetesmellitus,theeffect

oftreatmentonglycaemiamustbemonitored.Ifsignsofdiabetesmellitusareobserved

followingtheuseoftheproduct,e.g.polyuriaorpolydipsia,thedoseshouldbetaperedor

discontinuedandveterinarycaresought.Theuseofciclosporinisnotrecommendedin

diabeticdogs.

Closelymonitorcreatininelevelsindogswithsevererenalinsufficiency.

Particularattentionmustbepaidtovaccination.Treatmentwiththeveterinarymedicinal

productmayinterferewithvaccinationefficacy.Inthecaseofinactivatedvaccines,itisnot

recommendedtovaccinateduringtreatmentorwithinatwo-weekintervalbeforeorafter

administrationoftheproduct .Forlivevaccinesseealsosection4.3“Contraindications”.

Itisnotrecommendedtouseotherimmunosuppressiveagentsconcomitantly.

ii)Specialprecautionstobetakenbythepersonadministeringtheveterinary

medicinalproducttoanimals

Washhandsafteradministration.

Inthecaseofaccidentalingestionofthecapsuleoritscontents,seekmedicaladvice

immediatelyandshowthepackageleafletorthelabeltothephysician.

4.6Adversereactions(frequencyandseriousness)

Theoccurrenceofadversereactionsisuncommon.Themostfrequentlyobserved

undesirableeffectsaregastrointestinaldisturbancessuchasvomiting,mucoidorsoftfaeces

anddiarrhoea.Theyaremildandtransientandgenerallydonotrequirethecessationofthe

treatment.

Otherundesirableeffectsmaybeobservedinfrequently:lethargyorhyperactivityanorexia,

mildtomoderategingivalhyperplasia,skinreactionssuchasverruciformlesionsorchange

ofhaircoat,redandswollenpinnae,muscleweaknessormusclecramps.Theseeffects

generallyresolvespontaneouslyaftertreatmentisstopped.

Veryrarelydiabetesmellitushasbeenobserved,reportedmainlyinWestHighlandWhite

Terriers.

Asforthesubjectofmalignancy,pleaseseesections4.3“Contraindications”and4.5“Special

precautionsforuse”.

4.7Useduringpregnancy,lactationorlay

Inlaboratoryanimals,atdoseswhichinducematernaltoxicity(ratsat30mg/kgbwand

rabbitsat100mg/kgbw)ciclosporinwasembryo-andfetotoxic,asindicatedbyincreased

pre-andpostnatalmortalityandreducedfoetalweighttogetherwithskeletalretardations.In

thewell-tolerateddoserange(ratsatupto17mg/kgbwandrabbitsatupto30mg/kgbw)

ciclosporinwaswithoutembryolethalorteratogeniceffects.Thesafetyofthedrughasneither

beenstudiedinbreedingmaledogsnorinpregnantorlactatingfemaledogs.Intheabsence

ofsuchstudiesinthedog,itisrecommendedtousethedruginbreedingdogsonlyupona

positiverisk/benefitassessmentbytheveterinarian.Ciclosporinpassestheplacentabarrier

andisexcretedviamilk.Thereforethetreatmentoflactatingbitchesisnotrecommended.

4.8Interactionwithothermedicinalproductsandotherformsofinteraction

Varioussubstancesareknowntocompetitivelyinhibitorinducetheenzymesinvolvedinthe

metabolismofciclosporin,inparticularcytochromeP450(CYP3A4).Incertainclinically

justifiedcases,anadjustmentofthedosageoftheveterinarymedicinalproductmaybe

required.Ketoconazoleat5-10mg/kgisknowntoincreasethebloodconcentrationof

ciclosporinindogsuptofive-fold,whichisconsideredtobeclinicallyrelevant.During

concomitantuseofketoconazoleandciclosporintheveterinarianshouldconsiderasa

practicalmeasuretodoublethetreatmentintervalifthedogisonadailytreatmentregime.

Macrolidessuchaserythromycinmayincreasetheplasmalevelsofciclosporinuptotwofold.

Certain inducers of cytochrome P450, anticonvulsants and antibiotics (e.g.

trimethoprim/sulfadimidine)maylowertheplasmaconcentrationofciclosporin.

CiclosporinisasubstrateandaninhibitoroftheMDR1P-glycoproteintransporter.Therefore,

theco-administrationofciclosporinwithP-glycoproteinsubstratessuchasmacrocyclic

lactones(e.g.ivermectinandmilbemycin)coulddecreasetheeffluxofsuchdrugsfrom

blood-brainbarriercells,potentiallyresultinginsignsofCNStoxicity.

Ciclosporincanincreasethenephrotoxicityofaminoglycosideantibioticsandtrimethoprim.

Theconcomitantuseofciclosporinisnotrecommendedwiththeseactiveingredients.

Particularattentionmustbepaidtovaccination(seesections4.3“Contraindications”and4.5

“Specialprecautionsforuse”).

4.9Amountstobeadministeredandadministrationroute

Themeanrecommendeddoseofciclosporinis5mg/kgbodyweightaccordingtothe

followingscheme.

–Foradogweighing4to<7.5kgonecapsuleoftheveterinarymedicinalproduct

Theveterinarymedicinalproductwillinitiallybegivendailyuntilasatisfactoryclinical

improvementisseen.Thiswillgenerallybethecasewithin4weeks.Ifnoresponseis

obtainedwithinthefirst8weeks,thetreatmentshouldbestopped.

Oncetheclinicalsignsofatopicdermatitisaresatisfactorilycontrolled,thepreparationcan

thenbegiveneveryotherdayasamaintenancedose.Theveterinarianshouldperforma

clinicalassessmentatregularintervalsandadjustthefrequencyofadministrationtothe

clinicalresponseobtained.

Insomecaseswheretheclinicalsignsarecontrolledwithevery-other-daydosing,the

veterinariancandecidetogivetheveterinarymedicinalproductevery3to4days.

Adjuncttreatment(e.g.medicatedshampoos,fattyacids)maybeconsideredbeforereducing

thedosinginterval.

Treatmentmaybestoppedwhentheclinicalsignsarecontrolled.Uponrecurrenceofclinical

signs,treatmentshouldberesumedatdailydosing,andincertaincasesrepeatedtreatment

coursesmayberequired.

Theveterinarymedicinalproductshouldbegivenatleast2hoursbeforeorafterfeeding.

Insertthecapsuledirectlyintothedog’smouth.

4.10Overdose(symptoms,emergencyprocedures,antidotes),ifnecessary

Noundesirableeffectsbeyondthosethatwereseenunderrecommendedtreatmenthave

beenobservedinthedogwithasingleoraldoseofupto6timesofwhatisrecommended.

Inadditiontowhatwasseenunderrecommendeddosage,thefollowingadversereactions

wereseenincaseofoverdosefor3monthsormoreat4timesthemeanrecommended

dosage:hyperkeratoticareasespeciallyonthepinnae,callous-likelesionsofthefootpads,

weightlossorreducedweightgain,hypertrichosis,increasederythrocytesedimentationrate,

decreasedeosinophilvalues.Frequencyandseverityofthesesignsaredosedependent.

Thereisnospecificantidoteandincaseofsignsofoverdosethedogshouldbetreated

symptomatically.Thesignsarereversiblewithin2monthsfollowingcessationoftreatment.

4.11Withdrawalperiod(s)

Notapplicable.

5. PHARMACOLOGICALPROPERTIES

Pharmacotherapeuticgroup:Selectiveimmunosuppressiveagents

ATCvetcode:QL04AD01.

5.1Pharmacodynamicproperties

Ciclosporin(alsoknownascyclosporin,cyclosporine,cyclosporineA,CsA)isaselective

immunosuppressor.Itisacyclicpolypeptideconsistingof11aminoacids,hasamolecular

weightof1203daltonsandactsspecificallyandreversiblyonTlymphocytes.

Ciclosporinexertsanti-inflammatoryandantipruriticeffectsinthetreatmentofatopic

dermatitis.CiclosporinhasbeenshowntopreferentiallyinhibittheactivationofT-lymphocytes

onantigenicstimulationbyimpairingtheproductionofIL-2andotherT-cellderivedcytokines.

Ciclosporinalsohasthecapacitytoinhibittheantigen-presentingfunctionontheskinimmune

system.Itlikewiseblockstherecruitmentandactivationofeosinophils,theproductionof

cytokinesbykeratinocytes,thefunctionsofLangerhanscells,thedegranulationofmastcells

andthereforethereleaseofhistamineandpro-inflammatorycytokines.

Ciclosporindoesnotdepresshaematopoiesisandhasnoeffectonthefunctionofphagocytic

cells.

5.2Pharmacokineticparticulars

Absorption

Thebioavailabilityofciclosporinisabout35%.Thepeakplasmaconcentrationisreached

within1to2hours.Thebioavailabilityisbetterandlesssubjecttoindividualvariationsif

ciclosporinisadministeredtofastedanimalsratherthanatmealtimes.

Distribution

Indogs,thevolumeofdistributionisabout7.8L/kg.Ciclosporiniswidelydistributedtoall

tissues.Followingrepeateddailyadministrationtodogsciclosporinconcentrationintheskin

isseveraltimeshigherthaninblood.

Metabolism

CiclosporinismetabolisedmainlyintheliverbycytochromeP450(CYP3A4),butalsointhe

intestine.Metabolismtakesplaceessentiallyintheformofhydroxylationanddemethylation,

leadingtometaboliteswithlittleornoactivity.Unchangedciclosporinrepresentsabout25%of

circulatingbloodconcentrationsinthecourseofthefirst24hours.

Elimination

Eliminationismainlyviathefaeces.Only10%isexcretedintheurine,mostlyintheformof

metabolites.Nosignificantaccumulationwasobservedinbloodofdogstreatedforoneyear.

6. PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Carminicacid(E_120)

Cornoil-mono-di-triglycerides

Ethanol(E-1510)

Gelatine(E-441)

Glycerol(E-422)

Ironoxideblack(E-172)

Macrogolglycerolhydroxystearate

Propyleneglycol(E-1520)

Titaniumdioxide(E-171)

-Tocopherol(E-307)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4.Specialprecautionsforstorage

Donotstoreabove25

C.Keepthemedicinalproductintheblisterpack.Keeptheblister

packintheoutercarton.

6.5Natureandcompositionofimmediatepackaging

Boxcontaining15capsulesin3aluminium/aluminiumblisterpacks

Boxcontaining30capsulesin6aluminium/aluminiumblisterpacks

Boxcontaining60capsulesin12aluminium/aluminiumblisterpacks

Notallpacksizesmaybemarketed.

6.6Specialprecautionsforthedisposalofunusedveterinarymedicinalproductor

wastematerialsderivedfromtheuseofsuchproducts

Anyunusedveterinarymedicinalproductorwastematerialderivedfromsuchveterinary

medicinalproductsshouldbedisposedofinaccordancewithnationalrequirements.

7. MARKETINGAUTHORISATIONHOLDER

NovartisSanteAnimaleS.A.S.

14,bdRichelieu

F-92500Rueil-Malmaison

France

8. MARKETINGAUTHORISATIONNUMBER(S)

Boxcontaining3blisterpacks:---

Boxcontaining6blisterpacks:---

Boxcontaining12blisterpacks:---

9. DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

12.08.2002/July2007

10.DATEOFREVISIONOFTHETEXT

May2008

PROHIBITIONOFSALE,SUPPLYAND/ORUSE

Notapplicable.

10-7-2018

Verkazia (Santen Oy)

Verkazia (Santen Oy)

Verkazia (Active substance: ciclosporin) - Centralised - Authorisation - Commission Decision (2018)4469 of Tue, 10 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4411

Europe -DG Health and Food Safety

1-6-2018

Withdrawn application:  Restaysis, ciclosporin, Initial authorisation

Withdrawn application: Restaysis, ciclosporin, Initial authorisation

Europe - EMA - European Medicines Agency