Transcription

ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS1

1.NAME OF THE VETERINARY MEDICINAL PRODUCTApoquel 3.6 mg film-coated tablets for dogsApoquel 5.4 mg film-coated tablets for dogsApoquel 16 mg film-coated tablets for dogs2.QUALITATIVE AND QUANTITATIVE COMPOSITIONActive substance:Each film-coated tablet contains:Apoquel 3.6 mg:Apoquel 5.4 mg:Apoquel 16 mg:3.6 mg oclacitinib (as oclacitinib maleate)5.4 mg oclacitinib (as oclacitinib maleate)16 mg oclacitinib (as oclacitinib maleate)For the full list of excipients, see section 6.1.3.PHARMACEUTICAL FORMFilm-coated tablets.White to off-white, oblong shaped film-coated tablets with a score-line on both sides and marked withthe letters "AQ" and "S", "M" or "L" on both sides. The letters "S", "M" and "L" refer to the differentstrengths of tablets: "S" is on the 3.6 mg tablets, "M" on the 5.4 mg tablets, and "L" on the 16 mgtablets.The tablets can be divided into equal halves.4.CLINICAL PARTICULARS4.1Target speciesDogs4.2Indications for use, specifying the target speciesTreatment of pruritus associated with allergic dermatitis in dogs.Treatment of clinical manifestations of atopic dermatitis in dogs.4.3ContraindicationsDo not use in cases of hypersensitivity to the active substance or to any of the excipients.Do not use in dogs less than 12 months of age or less than 3 kg bodyweight.Do not use in dogs with evidence of immune suppression, such as hyperadrenocorticism, or withevidence of progressive malignant neoplasia as the active substance has not been evaluated in thesecases.4.4Special warnings for each target speciesNone.2

4.5Special precautions for useSpecial precautions for use in animals:Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbateneoplastic conditions. Dogs receiving Apoquel tablets should therefore be monitored for thedevelopment of infections and neoplasia.When treating pruritus associated with allergic dermatitis with oclacitinib, investigate and treat anyunderlying causes (e.g. flea allergic dermatitis, contact dermatitis, food hypersensitivity). Furthermore,in cases of allergic dermatitis and atopic dermatitis, it is recommended to investigate and treatcomplicating factors, such as bacterial, fungal or parasitic infections/infestations (e.g. flea and mange).Given the potential for effects on certain clinicopathological parameters (see section 4.6), periodicmonitoring with complete blood counts and serum biochemistry is recommended when dogs are onlong-term treatment.Special precautions to be taken by the person administering the veterinary medicinal product toanimals:Wash hands after administration.In case of accidental ingestion, seek medical advice immediately and show the package leaflet or thelabel to the physician.4.6Adverse reactions (frequency and seriousness)The common adverse reactions seen up to day 16 of the field trials are listed in the following table:DiarrhoeaVomitingAnorexiaNew cutaneous orsubcutaneous lumpsLethargyPolydipsiaAdverse reactions observed in atopicdermatitis study up to day 16Apoquel (n 152)Placebo(n Adverse reactions observed inpruritus study up to day 7ApoquelPlacebo(n 216)(n r day 16, the following adverse reactions have been observed:pyoderma and non-specified dermal lumps have been observed very commonly;otitis, vomiting, diarrhoea, histiocytoma, cystitis, yeast skin infections, pododermatitis, lipoma,polydipsia, lymphadenopathy, nausea, increased appetite and aggression have been observedcommonly.Treatment-related clinical pathology changes were restricted to an increase in mean serum cholesteroland a decrease in mean leukocyte count, however, all mean values remained within the laboratoryreference range. The decrease in mean leukocyte count observed in oclacitinib-treated dogs was notprogressive, and affected all white blood cell counts (neutrophil, eosinophil and monocyte counts)except lymphocyte counts. Neither of these clinical pathology changes appeared clinically significant.The development of papillomas was noted in a number of dogs in a laboratory study.Anaemia and lymphoma have been reported very rarely in spontaneous reports.Regarding susceptibility to infection and neoplastic conditions, see section 4.5.The frequency of adverse reactions is defined using the following convention:- very common (more than 1 in 10 animals treated displaying adverse reaction(s))3

- common (more than 1 but less than 10 animals in 100 animals treated)- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)- rare (more than 1 but less than 10 animals in 10,000 animals treated)- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).4.7Use during pregnancy, lactation or layThe safety of the veterinary medicinal product has not been established during pregnancy andlactation, or in breeding male dogs, therefore its use is not recommended during pregnancy, lactationor in dogs intended for breeding.4.8Interaction with other medicinal products and other forms of interactionNo drug interactions were observed in field studies where oclacitinib was administered concomitantlywith veterinary medicinal products such as endo- and ectoparasiticides, antimicrobials and antiinflammatories.The impact of oclacitinib administration on vaccination with modified live vaccines, canineparvovirus (CPV), canine distemper virus (CDV) and canine parainfluenza (CPI) and inactivatedrabies vaccine (RV), on 16 week old vaccine naïve puppies has been studied. An adequate immuneresponse (serology) to CDV and CPV vaccination was achieved when puppies were administeredoclacitinib at 1.8 mg/kg bodyweight (bw) twice daily for 84 days. However, the findings of this studyindicated a reduction in serological response to vaccination with CPI and RV in puppies being treatedwith oclacitinib compared to untreated controls. The clinical relevance of these observed effects foranimals vaccinated while being administered oclacitinib (in accordance with the recommended dosingregimen) is unclear.4.9Amounts to be administered and administration routeFor oral use.Dosage and treatment schedule:The recommended initial dose is 0.4 to 0.6 mg oclacitinib/kg bodyweight, administered orally, twicedaily for up to 14 days.For maintenance therapy, the same dose (0.4 to 0.6 mg oclacitinib/kg bodyweight) should then beadministered only once a day. The requirement for long-term maintenance therapy should be based onan individual benefit-risk assessment.These tablets can be administered with or without food.The dosing table below shows the number of tablets required. The tablets are breakable along thescore line.4

Bodyweight (kg)of gth and number of tablets to be administered:Apoquel 3.6 mg tablets½Apoquel 5.4 mg tabletsApoquel 16 mg tablets½112½11½24.10 Overdose (symptoms, emergency procedures, antidotes), if necessaryOclacitinib tablets were administered to healthy, one year old Beagle dogs twice daily for 6 weeks,followed by once per day for 20 weeks, at 0.6 mg/kg bw, 1.8 mg/kg bw and 3.0 mg/kg bw for a totalof 26 weeks.Clinical observations that were considered likely to be related to oclacitinib treatment included:alopecia (local), papilloma, dermatitis, erythema, abrasions and scabbing/crusts, interdigital "cysts",and oedema of the feet.Dermatitis lesions were mostly secondary to the development of interdigital furunculosis on one ormore feet during the study, with the number and frequency of observations increasing with increasingdose. Lymphadenopathy of peripheral nodes was noted in all groups, increasing in frequency withincreasing dose, and was frequently associated with interdigital furunculosis.Papilloma was considered treatment related, but not dose related.There is no specific antidote and in case of signs of overdose the dog should be treatedsymptomatically.4.11 Withdrawal period(s)Not applicable.5.PHARMACOLOGICAL PROPERTIESPharmacotherapeutic group: Agents for dermatitis, excluding corticosteroids.ATC vet code: QD11AH90.5.1Pharmacodynamic propertiesOclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokinesdependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that areproinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exerteffects on other cytokines (for example, those involved in host defence or haematopoiesis) with thepotential for unwanted effects.5

5.2Pharmacokinetic particularsFollowing oral administration in dogs, oclacitinib maleate is rapidly and well absorbed, with a time topeak plasma concentration (tmax) of less than 1 hour. The absolute bioavailability of oclacitinib maleatewas 89%. The prandial state of the dog does not significantly affect the rate or extent of its absorption.Total body oclacitinib clearance from plasma was low – 316 ml/h/kg bodyweight (5.3 ml/min/kgbodyweight), and the apparent volume of distribution at steady-state was 942 ml/kg bodyweight.Following intravenous and oral administration, the terminal t1/2s were similar at 3.5 and 4.1 hoursrespectively. Oclacitinib exhibits low protein binding with 66.3% to 69.7% bound in fortified canineplasma at nominal concentrations ranging from 10 to 1,000 ng/ml.Oclacitinib is metabolised in the dog to multiple metabolites. One major oxidative metabolite wasidentified in plasma and urine.Overall the major clearance route is metabolism, with minor contributions from renal and biliaryelimination. Inhibition of canine cytochrome P450s is minimal with IC50s 50-fold greater than theobserved mean Cmax (333 ng/ml or 0.997 µM) following 0.6 mg/kg bw oral administration in the targetanimal safety study. Therefore, the risk of metabolic drug-drug interactions due to oclacitinibinhibition is very low. No accumulation was observed in the blood of dogs treated for 6 months withoclacitinib.6.PHARMACEUTICAL PARTICULARS6.1List of excipientsTablet core:Cellulose, microcrystallineLactose monohydrateMagnesium stearateSodium starch glycolateTablet coating:Lactose monohydrateHypromellose (E464)Titanium dioxide (E171)Macrogol 400 (E1521)6.2Major incompatibilitiesNot applicable.6.3Shelf lifeShelf life of the veterinary medicinal product as packaged for sale in blisters: 2 years.Shelf life of the veterinary medicinal product as packaged for sale in bottles: 18 months.Any remaining half tablets should be discarded after 3 days.6.4Special precautions for storageStore below 25 C.Any remaining half tablet should be placed back in the opened blister and stored in the original cardboardcarton, or in the HDPE bottle (for a maximum of 3 days).6

6.5Nature and composition of immediate packagingAll tablets strengths are packaged in either aluminium/PVC/Aclar or aluminium/PVC/PVDC blisters(each strip containing 10 film-coated tablets) packed into an outer cardboard box, or white HDPEplastic bottle with child resistant closure. Pack sizes of 20, 50 or 100 tablets.Not all pack sizes may be marketed.6.6Special precautions for the disposal of unused veterinary medicinal product or wastematerials derived from the use of such productsAny unused veterinary medicinal product or waste materials derived from such veterinary medicinalproducts should be disposed of in accordance with local requirements.7.MARKETING AUTHORISATION HOLDERZoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUM8.MARKETING AUTHORISATION NUMBER(S)EU/2/13/154/001 (2 x 10 tablets, 3.6 mg)EU/2/13/154/007 (5 x 10 tablets, 3.6 mg)EU/2/13/154/002 (10 x 10 tablets, 3.6 mg)EU/2/13/154/010 (20 tablets, 3.6 mg)EU/2/13/154/011 (50 tablets, 3.6 mg)EU/2/13/154/012 (100 tablets, 3.6 mg)EU/2/13/154/003 (2 x 10 tablets, 5.4 mg)EU/2/13/154/008 (5 x 10 tablets, 5.4 mg)EU/2/13/154/004 (10 x 10 tablets, 5.4 mg)EU/2/13/154/013 (20 tablets, 5.4 mg)EU/2/13/154/014 (50 tablets, 5.4 mg)EU/2/13/154/015 (100 tablets, 5.4 mg)EU/2/13/154/005 (2 x 10 tablets, 16 mg)EU/2/13/154/009 (5 x 10 tablets, 16 mg)EU/2/13/154/006 (10 x 10 tablets, 16 mg)EU/2/13/154/016 (20 tablets, 16 mg)EU/2/13/154/017 (50 tablets, 16 mg)EU/2/13/154/018 (100 tablets, 16 mg)EU/2/13/154/019 (2 x 10 tablets, 3.6 mg)EU/2/13/154/020 (5 x 10 tablets, 3.6 mg)EU/2/13/154/021 (10 x 10 tablets, 3.6 mg)EU/2/13/154/022 (2 x 10 tablets, 5.4 mg)EU/2/13/154/023 (5 x 10 tablets, 5.4 mg)EU/2/13/154/024 (10 x 10 tablets, 5.4 mg)EU/2/13/154/025 (2 x 10 tablets, 16 mg)EU/2/13/154/026 (5 x 10 tablets, 16 mg)EU/2/13/154/027 (10 x 10 tablets, 16 mg)9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATIONDate of first authorisation: 12/09/2013.Date of last renewal: 26/07/2018.7

10.DATE OF REVISION OF THE TEXTDetailed information on this veterinary medicinal product is available on the website of the EuropeanMedicines Agency (http://www.ema.europa.eu/).PROHIBITION OF SALE, SUPPLY AND/OR USENot applicable.8

ANNEX IIA.MANUFACTURERS RESPONSIBLE FOR BATCH RELEASEB.CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USEC.STATEMENT OF THE MRLs9

A.MANUFACTURERS RESPONSIBLE FOR BATCH RELEASEName and address of the manufacturers responsible for batch releasePfizer Italia S.R.L.Via del Commercio 25/2763100 Marino Del Tronto (AP)ITALYorZoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUMThe printed package leaflet of the medicinal product must state the name and address of themanufacturer responsible for the release of the concerned batch.B.CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USEVeterinary medicinal product subject to prescription.C.STATEMENT OF THE MRLsNot applicable.10

ANNEX IIILABELLING AND PACKAGE LEAFLET11

A. LABELLING12

PARTICULARS TO APPEAR ON THE OUTER PACKAGECARDBOARD CARTON for Blister1.NAME OF THE VETERINARY MEDICINAL PRODUCTApoquel 3.6 mg film-coated tablets for dogsApoquel 5.4 mg film-coated tablets for dogsApoquel 16 mg film-coated tablets for dogsoclacitinib2.STATEMENT OF ACTIVE SUBSTANCES3.6 mg oclacitinib per tablet (as oclacitinib maleate).5.4 mg oclacitinib per tablet (as oclacitinib maleate).16 mg oclacitinib per tablet (as oclacitinib maleate).3.PHARMACEUTICAL FORMFilm-coated tablets4.PACKAGE SIZE20 tablets50 tablets100 tablets5.TARGET SPECIESDogs6.INDICATION(S)7.METHOD AND ROUTE(S) OF ADMINISTRATIONRead the package leaflet before use.Oral use.8.WITHDRAWAL PERIOD(S)9.SPECIAL WARNING(S), IF NECESSARYRead the package leaflet before use.13

10.EXPIRY DATEEXP {month/year}11.SPECIAL STORAGE CONDITIONSStore below 25 C.Any remaining half tablet should be stored in the blister and discarded if not used within 3 days.12.SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS ORWASTE MATERIALS, IF ANYDisposal: read the package leaflet.13.THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS ORRESTRICTIONS REGARDING SUPPLY AND USE, IF APPLICABLEFor animal treatment only. To be supplied only on veterinary prescription.14.THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”Keep out of the sight and reach of children.15.NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDERZoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUM16.MARKETING AUTHORISATION NUMBER(S)EU/2/13/154/001 (2 x 10 tablets, 3.6 mg)EU/2/13/154/007 (5 x 10 tablets, 3.6 mg)EU/2/13/154/002 (10 x 10 tablets, 3.6 mg)EU/2/13/154/003 (2 x 10 tablets, 5.4 mg)EU/2/13/154/008 (5 x 10 tablets, 5.4 mg)EU/2/13/154/004 (10 x 10 tablets, 5.4 mg)EU/2/13/154/005 (2 x 10 tablets, 16 mg)EU/2/13/154/009 (5 x 10 tablets, 16 mg)EU/2/13/154/006 (10 x 10 tablets, 16 mg)EU/2/13/154/019 (2 x 10 tablets, 3.6 mg)EU/2/13/154/020 (5 x 10 tablets, 3.6 mg)EU/2/13/154/021 (10 x 10 tablets, 3.6 mg)EU/2/13/154/022 (2 x 10 tablets, 5.4 mg)EU/2/13/154/023 (5 x 10 tablets, 5.4 mg)EU/2/13/154/024 (10 x 10 tablets, 5.4 mg)EU/2/13/154/025 (2 x 10 tablets, 16 mg)EU/2/13/154/026 (5 x 10 tablets, 16 mg)EU/2/13/154/027 (10 x 10 tablets, 16 mg)14

17.MANUFACTURER’S BATCH NUMBERLot {number}15

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPSBLISTER1.NAME OF THE VETERINARY MEDICINAL PRODUCTApoquel 3.6 mg tablets for dogs.Apoquel 5.4 mg tablets for dogs.Apoquel 16 mg tablets for dogs.oclacitinib2.NAME OF THE MARKETING AUTHORISATION HOLDERZoetis3.EXPIRY DATEEXP {month/year}4.BATCH NUMBERLot {number}5.THE WORDS “FOR ANIMAL TREATMENT ONLY”For animal treatment only.16

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGELABEL for Bottle1.NAME OF THE VETERINARY MEDICINAL PRODUCTApoquel 3.6 mg film-coated tablets for dogsApoquel 5.4 mg film-coated tablets for dogsApoquel 16 mg film-coated tablets for dogsoclacitinib2.STATEMENT OF ACTIVE SUBSTANCES3.6 mg oclacitinib per tablet (as oclacitinib maleate).5.4 mg oclacitinib per tablet (as oclacitinib maleate).16 mg oclacitinib per tablet (as oclacitinib maleate).3.PHARMACEUTICAL FORMFilm-coated tablets4.PACKAGE SIZE20 tablets50 tablets100 tablets5.TARGET SPECIESDogs6.INDICATION(S)7.METHOD AND ROUTE(S) OF ADMINISTRATIONRead the package leaflet before use.Oral use.8.WITHDRAWAL PERIOD(S)9.SPECIAL WARNING(S), IF NECESSARYRead the package leaflet before use.17

10.EXPIRY DATEEXP {month/year}11.SPECIAL STORAGE CONDITIONSStore below 25 C.Any remaining half tablet should be stored in the bottle and discarded if not used within 3 days.12.SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS ORWASTE MATERIALS, IF ANYDisposal: read the package leaflet.13.THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS ORRESTRICTIONS REGARDING SUPPLY AND USE, IF APPLICABLEFor animal treatment only. To be supplied only on veterinary prescription.14.THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”Keep out of the sight and reach of children.15.NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDERZoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUM16.MARKETING AUTHORISATION NUMBER(S)EU/2/13/154/010 (20 tablets, 3.6 mg)EU/2/13/154/011 (50 tablets, 3.6 mg)EU/2/13/154/012 (100 tablets, 3.6 mg)EU/2/13/154/013 (20 tablets, 5.4 mg)EU/2/13/154/014 (50 tablets, 5.4 mg)EU/2/13/154/015 (100 tablets, 5.4 mg)EU/2/13/154/016 (20 tablets, 16 mg)EU/2/13/154/017 (50 tablets, 16 mg)EU/2/13/154/018 (100 tablets, 16 mg)17.MANUFACTURER’S BATCH NUMBERLot {number}18

B. PACKAGE LEAFLET19

PACKAGE LEAFLET:Apoquel 3.6 mg film-coated tablets for dogsApoquel 5.4 mg film-coated tablets for dogsApoquel 16 mg film-coated tablets for dogs1.NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OFTHE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCHRELEASE, IF DIFFERENTMarketing authorisation holder:Zoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUMManufacturer responsible for batch release:Pfizer Italia S.R.L.Via del Commercio 25/2763100 Marino Del Tronto (AP)ITALYorZoetis Belgium SARue Laid Burniat 11348 Louvain-la-NeuveBELGIUM2.NAME OF THE VETERINARY MEDICINAL PRODUCTApoquel 3.6 mg film-coated tablets for dogsApoquel 5.4 mg film-coated tablets for dogsApoquel 16 mg film-coated tablets for dogsoclacitinib3.STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)Each film-coated tablet contains 3.6 mg, 5.4 mg or 16 mg oclacitinib (as oclacitinib maleate).White to off-white, oblong shaped film-coated tablets with a score-line on both sides and marked withthe letters "AQ" and "S", "M" or "L" on both sides. The letters "S", "M" and "L" refer to the differentstrengths of tablets: "S" is on the 3.6 mg tablets, "M" on the 5.4 mg tablets, and "L" on the 16 mgtablets.The tablets can be divided into equal halves.4.INDICATION(S)Treatment of pruritus associated with allergic dermatitis in dogs.Treatment of clinical manifestations of atopic dermatitis in dogs.20

5.CONTRAINDICATIONSDo not use in cases of hypersensitivity to oclacitinib or to any of the excipients.Do not use in dogs less than 12 months of age or less than 3 kg bodyweight.Do not use in dogs with evidence of immune suppression such as hyperadrenocorticisim or with