ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel 3.6 mg film-coated tablets for dogs

Apoquel 5.4 mg film-coated tablets for dogs

Apoquel 16 mg film-coated tablets for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains:

Active substance:

3.6 mg oclacitinib (as oclacitinib maleate).

5.4 mg oclacitinib (as oclacitinib maleate).

16 mg oclacitinib (as oclacitinib maleate).

Excipients:

Qualitative composition of excipients and other constituents

Tablet core:

Cellulose, microcrystalline

Lactose monohydrate

Magnesium stearate

Sodium starch glycolate

Tablet coating:

Lactose monohydrate

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 400 (E1521)

White to off-white, oblong shaped film-coated tablets with a score-line on both sides and marked with the letters "AQ" and "S", "M" or "L" on both sides. The letters "S", "M" and "L" refer to the different strengths of tablets: "S" is on the 3.6 mg tablets, "M" on the 5.4 mg tablets, and "L" on the 16 mg tablets.

The tablets can be divided into equal halves.

3. CLINICAL INFORMATION

3.1 Target species

Dogs.

3.2 Indications for use for each target species

Treatment of pruritus associated with allergic dermatitis in dogs.

Treatment of clinical manifestations of atopic dermatitis in dogs.

3.3 Contraindications

Do 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 with evidence of progressive malignant neoplasia as the active substance has not been evaluated in these cases.

3.4 Special warnings

None.

3.5 Special precautions for use

Special precautions for safe use in the target species:

Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbate neoplastic conditions. Dogs receiving the veterinary medicinal product should therefore be monitored for the development of infections and neoplasia.

When treating pruritus associated with allergic dermatitis with oclacitinib, investigate and treat any underlying 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 treat complicating 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 3.6 "Adverse events"), periodic monitoring with complete blood counts and serum biochemistry is recommended when dogs are on long-term treatment.

Special precautions to be taken by the person administering the veterinary medicinal product to animals:

Wash hands after administration.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Special precautions for the protection of the environment:

Not applicable.

3.6 Adverse events

Dogs:

Very common (>1 animal / 10 animals treated):	pyoderma, skin lump, papilloma
Common (1 to 10 animals / 100 animals treated):	lethargy, lipoma, polydipsia, increased appetite nausea, vomiting, diarrhoea, anorexia histiocytoma, fungal skin infection, pododermatitis otitis lymphadenopathy cystitis aggression
Very rare (<1 animal / 10,000 animals treated, including isolated reports):	anaemia, lymphoma, convulsion

Treatment-related clinical pathology changes were restricted to an increase in mean serum cholesterol and a decrease in mean leukocyte count, however, all mean values remained within the laboratory reference range. The decrease in mean leukocyte count observed in oclacitinib-treated dogs was not progressive, and affected all white blood cell counts (neutrophil, eosinophil and monocyte counts) except lymphocyte counts. Neither of these clinical pathology changes appeared clinically significant.

Regarding susceptibility to infection and neoplastic conditions, see section 3.5 "Special precautions for use".

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See also the last section of the package leaflet for respective contact details.

3.7 Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has not been established during pregnancy and lactation, or in breeding male dogs, therefore its use is not recommended during pregnancy, lactation or in dogs intended for breeding.

3.8 Interaction with other medicinal products and other forms of interaction

No drug interactions were observed in field studies where oclacitinib was administered concomitantly with veterinary medicinal products such as endo- and ectoparasiticides, antimicrobials and antiinflammatories.

The impact of oclacitinib administration on vaccination with modified live vaccines, canine parvovirus

(CPV), canine distemper virus (CDV) and canine parainfluenza (CPI) and inactivated rabies vaccine

(RV), on 16 week old vaccine naive puppies has been studied. An adequate immune response

(serology) to CDV and CPV vaccination was achieved when puppies were administered oclacitinib at 1.8 mg/kg bodyweight (bw) twice daily for 84 days. However, the findings of this study indicated a reduction in serological response to vaccination with CPI and RV in puppies being treated with oclacitinib compared to untreated controls. The clinical relevance of these observed effects for animals vaccinated while being administered oclacitinib (in accordance with the recommended dosing regimen) is unclear.

3.9 Administration routes and dosage

For oral use.

The recommended initial dose is 0.4 to 0.6 mg oclacitinib/kg bodyweight, administered orally, twice daily for up to 14 days.

For maintenance therapy, the same dose (0.4 to 0.6 mg oclacitinib/kg bodyweight) should then be administered only once a day. The requirement for long-term maintenance therapy should be based on an 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 the score line.

Bodyweight (kg) of dog	Strength and number of tablets to be administered:
	Apoquel 3.6 mg tablets	Apoquel 5.4 mg tablets	Apoquel 16 mg tablets
3.0–4.4	½
4.5–5.9		½
6.0–8.9	1
9.0–13.4		1
13.5–19.9			½
20.0–26.9		2
27.0–39.9			1
40.0–54.9			1½
55.0–80.0			2

3.10 Symptoms of overdose (and where applicable, emergency procedures and antidotes)

Oclacitinib 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 total of 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 or more feet during the study, with the number and frequency of observations increasing with increasing dose. Lymphadenopathy of peripheral nodes was noted in all groups, increasing in frequency with increasing 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 treated symptomatically.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

3.12 Withdrawal periods

Not applicable.

4. PHARMACOLOGICAL INFORMATION

4.1 ATCvet code: QD11AH90.

4.2 Pharmacodynamics

Oclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokines dependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that are proinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exert effects on other cytokines (for example, those involved in host defence or haematopoiesis) with the potential for unwanted effects.

4.3 Pharmacokinetics

Following oral administration in dogs, oclacitinib maleate is rapidly and well absorbed, with a time to peak plasma concentration (t_max) of less than 1 hour. The absolute bioavailability of oclacitinib maleate was 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/kg bodyweight), and the apparent volume of distribution at steady-state was 942 ml/kg bodyweight. Following intravenous and oral administration, the terminal t_1/2s were similar at 3.5 and 4.1 hours respectively. Oclacitinib exhibits low protein binding with 66.3% to 69.7% bound in fortified canine plasma at nominal concentrations ranging from 10 to 1,000 ng/ml.

Oclacitinib is metabolised in the dog to multiple metabolites. One major oxidative metabolite was identified in plasma and urine.

Overall the major clearance route is metabolism, with minor contributions from renal and biliary elimination. Inhibition of canine cytochrome P450s is minimal with IC₅₀s 50-fold greater than the observed mean C_max (333 ng/ml or 0.997 µM) following 0.6 mg/kg bw oral administration in the target animal safety study. Therefore, the risk of metabolic drug-drug interactions due to oclacitinib inhibition is very low. No accumulation was observed in the blood of dogs treated for 6 months with oclacitinib.

5. PHARMACEUTICAL PARTICULARS

5.1 Major incompatibilities

Not applicable.

5.2 Shelf life

Shelf 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.

5.3 Special precautions for storage

Store below 25 °C.

Any remaining half tablet should be placed back in the opened blister and stored in the original cardboard carton, or in the HDPE bottle (for a maximum of 3 days).

5.4 Nature and composition of immediate packaging

All 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 HDPE plastic bottle with child resistant closure. Pack sizes of 20, 50 or 100 tablets.

Not all pack sizes may be marketed.

5.5 Special precautions for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products

Medicines should not be disposed of via wastewater or household waste.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

6. NAME OF THE MARKETING AUTHORISATION HOLDER

Zoetis Belgium

7. 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)

8. DATE OF FIRST AUTHORISATION

Date of first authorisation: 12/09/2013.

9. DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

10. CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription.

Detailed information on this veterinary medicinal product is available in the Union Product Database.

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel 3.6 mg chewable tablets for dogs

Apoquel 5.4 mg chewable tablets for dogs

Apoquel 16 mg chewable tablets for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each chewable tablet contains:

Active substance:

3.6 mg oclacitinib (as oclacitinib maleate).

5.4 mg oclacitinib (as oclacitinib maleate).

16 mg oclacitinib (as oclacitinib maleate).

Excipients:

Qualitative composition of excipients and other constituents

Pork liver powder

Crospovidone (type A)

Sodium starch glycolate (type A)

Glycerol monostearate 40-55 (type II)

Macrogol 3350

Glycerol

Sodium chloride

Xanthan gum

Brewer’s yeast dried

Silica colloidal anhydrous

Magnesium stearate

Light to dark brown pentagon shaped mottled chewable tablets with score lines on both sides. The tablets are debossed with the corresponding strength (“S S” for 3.6 mg, “M M” for 5.4 mg and “L L” for 16 mg).

The tablets can be divided into equal halves.

3. CLINICAL INFORMATION

3.1 Target species

Dogs.

3.2 Indications for use for each target species

Treatment of pruritus associated with allergic dermatitis in dogs.

Treatment of clinical manifestations of atopic dermatitis in dogs.

3.3 Contraindications

Do 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 with evidence of progressive malignant neoplasia as the active substance has not been evaluated in these cases.

3.4 Special warnings

None.

3.5 Special precautions for use

Special precautions for safe use in the target species:

Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbate neoplastic conditions. Dogs receiving the veterinary medicinal product should therefore be monitored for the development of infections and neoplasia.

When treating pruritus associated with allergic dermatitis with oclacitinib, investigate and treat any underlying 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 treat complicating 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 3.6 “Adverse events”), periodic monitoring with complete blood counts and serum biochemistry is recommended when dogs are on long-term treatment.

The tablets are flavoured. In order to avoid accidental ingestion, store tablets in a safe place out of reach of animals.

Special precautions to be taken by the person administering the veterinary medicinal product to animals:

Wash hands after administration.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Ingestion of this product may be harmful for children. To avoid accidental ingestion, administer the tablet(s) to the dog immediately after removal from the blister packaging.

Special precautions for the protection of the environment:

Not applicable.

3.6 Adverse events

Dogs:

Very common (>1 animal / 10 animals treated):	pyoderma, skin lump, papilloma
Common (1 to 10 animals / 100 animals treated):	lethargy, lipoma, polydipsia, increased appetite nausea, vomiting, diarrhoea, anorexia histiocytoma, fungal skin infection, pododermatitis otitis lymphadenopathy cystitis aggression
Very rare (<1 animal / 10,000 animals treated, including isolated reports):	anaemia, lymphoma, convulsion

Treatment-related clinical pathology changes were restricted to an increase in mean serum cholesterol and a decrease in mean leukocyte count, however, all mean values remained within the laboratory reference range. The decrease in mean leukocyte count observed in oclacitinib-treated dogs was not progressive, and affected all white blood cell counts (neutrophil, eosinophil and monocyte counts) except lymphocyte counts. Neither of these clinical pathology changes appeared clinically significant.

Regarding susceptibility to infection and neoplastic conditions, see section 3.5 “Special precautions for use”.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See also the last section of the package leaflet for respective contact details.

3.7 Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has not been established during pregnancy and lactation, or in breeding male dogs, therefore its use is not recommended during pregnancy, lactation or in dogs intended for breeding.

3.8 Interaction with other medicinal products and other forms of interaction

No drug interactions were observed in field studies where oclacitinib was administered concomitantly with veterinary medicinal products such as endo- and ectoparasiticides, antimicrobials and antiinflammatories.

The impact of oclacitinib administration on vaccination with modified live vaccines, canine parvovirus

(CPV), canine distemper virus (CDV) and canine parainfluenza (CPI) and inactivated rabies vaccine

(RV), on 16 week old vaccine naive puppies has been studied. An adequate immune response

(serology) to CDV and CPV vaccination was achieved when puppies were administered oclacitinib at 1.8 mg/kg bodyweight (bw) twice daily for 84 days. However, the findings of this study indicated a reduction in serological response to vaccination with CPI and RV in puppies being treated with oclacitinib compared to untreated controls. The clinical relevance of these observed effects for animals vaccinated while being administered oclacitinib (in accordance with the recommended dosing regimen) is unclear.

3.9 Administration routes and dosage

For oral use.

The recommended initial dose is 0.4 to 0.6 mg oclacitinib/kg bodyweight, administered orally, twice daily for up to 14 days.

For maintenance therapy, the same dose (0.4 to 0.6 mg oclacitinib/kg bodyweight) should then be administered only once a day. The requirement for long-term maintenance therapy should be based on an individual benefit-risk assessment.

Apoquel tablets are chewable, palatable and readily consumed by the majority of dogs.

These tablets can be administered with or without food.

The dosing table below shows the number of tablets required. The tablets are breakable along the score line.

Bodyweight (kg) of dog	Strength and number of tablets to be administered:
	Apoquel 3.6 mg tablets	Apoquel 5.4 mg tablets	Apoquel 16 mg tablets
3.0–4.4	½
4.5–5.9		½
6.0–8.9	1
9.0–13.4		1
13.5–19.9			½
20.0–26.9		2
27.0–39.9			1
40.0–54.9			1½
55.0–80.0			2

3.10 Symptoms of overdose (and where applicable, emergency procedures and antidotes)

Oclacitinib 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 total of 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 or more feet during the study, with the number and frequency of observations increasing with increasing dose. Lymphadenopathy of peripheral nodes was noted in all groups, increasing in frequency with increasing 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 treated symptomatically.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

3.12 Withdrawal periods

Not applicable.

4. PHARMACOLOGICAL INFORMATION

4.1 ATCvet code: QD11AH90.

4.2 Pharmacodynamics

Oclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokines dependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that are proinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exert effects on other cytokines (for example, those involved in host defence or haematopoiesis) with the potential for unwanted effects.

4.3 Pharmacokinetics

Following oral administration in dogs at a dose ranging from 0.55 to 0.9 mg oclacitinib/kg bodyweight, the observed mean C_max was 352 ng/ml (ranging from 207 to 860 ng/ml), which occurred at approximately 1.7 hours (t_max) post dosing. The half-life (t_1/2) is 4.8 hours in plasma.

Total body oclacitinib clearance from plasma was low – 316 ml/h/kg bodyweight (5.3 ml/min/kg bodyweight), and the apparent volume of distribution at steady-state was 942 ml/kg bodyweight. Oclacitinib exhibits low protein binding with 66.3% to 69.7% bound in fortified canine plasma at nominal concentrations ranging from 10 to 1,000 ng/ml.

Oclacitinib is metabolised in the dog to multiple metabolites. One major oxidative metabolite was identified in plasma and urine.

Overall, the major clearance route is metabolism, with minor contributions from renal and biliary elimination. Inhibition of canine cytochrome P450s is minimal, with IC₅₀s 60-fold greater than the observed mean C_max (281 ng/ml or 0.833 μM) following 0.6 mg/kg bw oral administration in the target animal safety study. Therefore, the risk of metabolic drug-drug interactions due to oclacitinib inhibition is very low.

5. PHARMACEUTICAL PARTICULARS

5.1 Major incompatibilities

Not applicable.

5.2 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale in blisters: 3 years.

5.3 Special precautions for storage

Store in the original package in order to protect from moisture.

Remaining tablet parts should be stored in the blister and be given at the next administration.

5.4 Nature and composition of immediate packaging

Aluminium/PVC/Aclar blisters (each strip containing 10 chewable tablets) packed into an outer cardboard box. Pack sizes of 20, 50 or 100 tablets.

Not all pack sizes may be marketed.

5.5 Special precautions for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products

Medicines should not be disposed of via wastewater or household waste.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

6. NAME OF THE MARKETING AUTHORISATION HOLDER

Zoetis Belgium

7. MARKETING AUTHORISATION NUMBER(S)

EU/2/13/154/028–036

8. DATE OF FIRST AUTHORISATION

Date of first authorisation: 12/09/2013.

9. DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

10. CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription.

Detailed information on this veterinary medicinal product is available in the Union Product Database.

ANNEX II

OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION

None.

ANNEX III

LABELLING AND PACKAGE LEAFLET

A. LABELLING

PARTICULARS TO APPEAR ON THE OUTER PACKAGE

CARDBOARD CARTON FOR BLISTER

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel 3.6 mg film-coated tablets.

Apoquel 5.4 mg film-coated tablets.

Apoquel 16 mg film-coated tablets.

2.	STATEMENT OF ACTIVE SUBSTANCES

3.6 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.	PACKAGE SIZE

20 tablets

50 tablets

100 tablets

4.	TARGET SPECIES

Dogs.

5.	INDICATIONS

6.	ROUTES OF ADMINISTRATION

Oral use.

7.	WITHDRAWAL PERIODS

8.	EXPIRY DATE

Exp. {mm/yyyy}

9.	SPECIAL STORAGE PRECAUTIONS

Store below 25 °C.

Any remaining half tablet should be stored in the blister and discarded if not used within 3 days.

10.	THE WORDS “READ THE PACKAGE LEAFLET BEFORE USE”

Read the package leaflet before use.

11.	THE WORDS “FOR ANIMAL TREATMENT ONLY”

For animal treatment only.

12.	THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”

Keep out of the sight and reach of children.

13.	NAME OF THE MARKETING AUTHORISATION HOLDER

Zoetis Belgium

14.	MARKETING AUTHORISATION NUMBERS

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)

15.	BATCH NUMBER

Lot {number}

PARTICULARS TO APPEAR ON THE OUTER PACKAGE

CARDBOARD CARTON FOR BLISTER

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel 3.6 mg chewable tablets.

Apoquel 5.4 mg chewable tablets.

Apoquel 16 mg chewable tablets.

2.	STATEMENT OF ACTIVE SUBSTANCES

3.6 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.	PACKAGE SIZE

20 tablets

50 tablets

100 tablets

4.	TARGET SPECIES

Dogs.

5.	INDICATIONS

6.	ROUTES OF ADMINISTRATION

Oral use.

7.	WITHDRAWAL PERIODS

8.	EXPIRY DATE

Exp. {mm/yyyy}

9.	SPECIAL STORAGE PRECAUTIONS

Store in the original package in order to protect from moisture.

Remaining tablet parts should be stored in the blister and be given at the next administration.

10.	THE WORDS “READ THE PACKAGE LEAFLET BEFORE USE”

Read the package leaflet before use.

11.	THE WORDS “FOR ANIMAL TREATMENT ONLY”

For animal treatment only.

12.	THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”

Keep out of the sight and reach of children.

13.	NAME OF THE MARKETING AUTHORISATION HOLDER

Zoetis Belgium

14.	MARKETING AUTHORISATION NUMBERS

EU/2/13/154/028 (2 x 10 chewable tablets, 3.6 mg)

EU/2/13/154/034 (5 x 10 chewable tablets, 3.6 mg)

EU/2/13/154/029 (10 x 10 chewable tablets, 3.6 mg)

EU/2/13/154/030 (2 x 10 chewable tablets, 5.4 mg)

EU/2/13/154/035 (5 x 10 chewable tablets 5.4 mg)

EU/2/13/154/031 (10 x 10 chewable tablets, 5.4 mg)

EU/2/13/154/032 (2 x 10 chewable tablets, 16 mg)

EU/2/13/154/036 (5 x 10 chewable tablets 16 mg)

EU/2/13/154/033 (10 x 10 chewable tablets, 16 mg)

15.	BATCH NUMBER

Lot {number}

PARTICULARS TO APPEAR ON THE OUTER PACKAGE

(IMMEDIATE) LABEL FOR BOTTLE

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel 3.6 mg film-coated tablets

Apoquel 5.4 mg film-coated tablets

Apoquel 16 mg film-coated tablets

2.	STATEMENT OF ACTIVE SUBSTANCES

3.6 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.	PACKAGE SIZE

20 tablets

50 tablets

100 tablets

4.	TARGET SPECIES

5.	INDICATIONS

6.	ROUTES OF ADMINISTRATION

Oral use.

7.	WITHDRAWAL PERIODS

8.	EXPIRY DATE

Exp. {mm/yyyy}

9.	SPECIAL STORAGE PRECAUTIONS

Store below 25 °C.

Any remaining half tablet should be stored in the bottle and discarded if not used within 3 days.

10.	THE WORDS “READ THE PACKAGE LEAFLET BEFORE USE”

Read the package leaflet before use.

11.	THE WORDS “FOR ANIMAL TREATMENT ONLY”

For animal treatment only.

12.	THE WORDS “KEEP OUT OF THE SIGHT AND REACH OF CHILDREN”

Keep out of the sight and reach of children.

13.	NAME OF THE MARKETING AUTHORISATION HOLDER

Zoetis Belgium

14.	MARKETING AUTHORISATION NUMBERS

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)

15.	BATCH NUMBER

Lot {number}

1.	NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel film-coated tablets.

2.	QUANTITATIVE PARTICULARS OF THE ACTIVE SUBSTANCES

3.6 mg

5.4 mg

16 mg

oclacitinib

3.	BATCH NUMBER

Lot {number}

4.	EXPIRY DATE

Exp. {mm/yyyy}

1.	NAME OF THE VETERINARY MEDICINAL PRODUCT

Apoquel chewable tablets.

2.	QUANTITATIVE PARTICULARS OF THE ACTIVE SUBSTANCES

3.6 mg

5.4 mg

16 mg

oclacitinib

3.	BATCH NUMBER

Lot {number}

4.	EXPIRY DATE

Exp. {mm/yyyy}

B. PACKAGE LEAFLET

PACKAGE LEAFLET

1. Name of the veterinary medicinal product

Apoquel 3.6 mg film-coated tablets for dogs

Apoquel 5.4 mg film-coated tablets for dogs

Apoquel 16 mg film-coated tablets for dogs

2. Composition

Each film-coated tablet contains:

Active substance:

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 with the letters "AQ" and "S", "M" or "L" on both sides. The letters "S", "M" and "L" refer to the different strengths of tablets: "S" is on the 3.6 mg tablets, "M" on the 5.4 mg tablets, and "L" on the 16 mg tablets.

The tablets can be divided into equal halves.

3. Target species

Dogs.

4. Indications for use

Treatment of pruritus associated with allergic dermatitis in dogs.

Treatment of clinical manifestations of atopic dermatitis in dogs.

5. Contraindications

Do 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 with evidence of progressive malignant neoplasia as the active substance has not been evaluated in these cases.

6. Special warnings

Special warnings:

None.

Special precautions for safe use in the target species:

Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbate neoplastic conditions. Dogs receiving the veterinary medicinal product should therefore be monitored for the development of infections and neoplasia.

When treating pruritus associated with allergic dermatitis with oclacitinib, investigate and treat any underlying 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 treat complicating 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 7 "Adverse events"), periodic monitoring with complete blood counts and serum biochemistry is recommended when dogs are on long-term treatment.

Special precautions to be taken by the person administering the veterinary medicinal product to animals:

Wash hands after administration.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Special precautions for the protection of the environment: Not applicable.

Pregnancy and lactation:

The safety of the veterinary medicinal product has not been established during pregnancy and lactation, or in breeding male dogs, therefore its use is not recommended during pregnancy, lactation or in dogs intended for breeding.

Interaction with other medicinal products and other forms of interaction:

No drug interactions were observed in field studies where oclacitinib was administered concomitantly with veterinary medicinal products such as endo- and ectoparasiticides, antimicrobials and antiinflammatories.

The impact of oclacitinib administration on vaccination with modified live vaccines, canine parvovirus

(CPV), canine distemper virus (CDV) and canine parainfluenza (CPI) and inactivated rabies vaccine

(RV), on 16 week old vaccine naive puppies has been studied. An adequate immune response

(serology) to CDV and CPV vaccination was achieved when puppies were administered oclacitinib at 1.8 mg/kg bodyweight (bw) twice daily for 84 days. However, the findings of this study indicated a reduction in serological response to vaccination with CPI and RV in puppies being treated with oclacitinib compared to untreated controls. The clinical relevance of these observed effects for animals vaccinated while being administered oclacitinib (in accordance with the recommended dosing regimen) is unclear.

Overdose:

Oclacitinib 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 total of 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 or more feet during the study with the number and frequency of observations increasing with increasing dose. Lymphadenopathy of peripheral nodes was noted in all groups, increasing in frequency with increasing 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 treated symptomatically.

Special restrictions for use and special conditions for use: Not applicable.

Major incompatibilities:

Not applicable.

7. Adverse events

Dogs:

Very common (>1 animal / 10 animals treated):

pyoderma, skin lump, papilloma

Common (1 to 10 animals / 100 animals treated):

lethargy, lipoma, polydipsia, increased appetite nausea, vomiting, diarrhoea, anorexia histiocytoma, fungal skin infection, pododermatitis otitis lymphadenopathy cystitis aggression

Very rare (<1 animal / 10,000 animals treated, including isolated reports):

anaemia, lymphoma, convulsion

Treatment-related clinical pathology changes were restricted to an increase in mean serum cholesterol and a decrease in mean leukocyte count, however, all mean values remained within the laboratory reference range. The decrease in mean leukocyte count observed in oclacitinib-treated dogs was not progressive, and affected all white blood cell counts (neutrophil, eosinophil and monocyte counts) except lymphocyte counts. Neither of these clinical pathology changes appeared clinically significant.

Regarding susceptibility to infection and neoplastic conditions, see section 6 "Special warnings".

Reporting adverse events is important. It allows continuous safety monitoring of a product. If you notice any side effects, even those not already listed in this package leaflet, or you think that the medicine has not worked, please contact, in the first instance, your veterinarian. You can also report any adverse events to the local representative of the marketing authorisation holder using the contact details at the end of this leaflet, or via your national reporting system.

8. Dosage for each species, routes and method of administration

For oral use.

The recommended initial dose of Apoquel tablets to be given to the dog is to achieve 0.4 to 0.6 mg oclacitinib/kg bodyweight, administered orally, twice daily for up to 14 days.

For maintenance therapy (after the initial 14 days of treatment), the same dose (0.4 to 0.6 mg oclacitinib/kg bodyweight) should then be administered only once a day. The requirement for longterm maintenance therapy should be based on an individual benefit-risk assessment by the responsible veterinarian.

These tablets can be administered with or without food.

Please see dosing table below for the number of tablets required to achieve the recommended dose. The tablets are breakable along the score line.

Bodyweight (kg) of dog	Strength and number of tablets to be administered:
	Apoquel 3.6 mg tablets	Apoquel 5.4 mg tablets	Apoquel 16 mg tablets
3.0–4.4	½
4.5–5.9		½
6.0–8.9	1
9.0–13.4		1
13.5–19.9			½
20.0–26.9		2
27.0–39.9			1
40.0–54.9			1½
55.0–80.0			2

9. Advice on correct administration

Dogs should be carefully observed following administration to ensure that each tablet is swallowed.

10. Withdrawal periods

Not applicable.

11. Special storage precautions

Keep out of the sight and reach of children.

Store below 25 °C.

Any remaining half tablet should be placed back in the opened blister and stored in the original cardboard carton, or in the HDPE bottle (for a maximum of 3 days).

Do not use this veterinary medicinal product after the expiry date which is stated on the blister or bottle after Exp.

12. Special precautions for disposal

Medicines should not be disposed of via wastewater or household waste.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any applicable national collection systems. These measures should help to protect the environment.

Ask your veterinary surgeon how to dispose of medicines no longer required.

13. Classification of veterinary medicinal products

Veterinary medicinal product subject to prescription.

14. Marketing authorisation numbers and pack sizes

EU/2/13/154/001-27

All 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 HDPE plastic bottle with child resistant closure. Pack sizes of 20, 50 or 100 tablets.

Not all pack sizes may be marketed.

15. Date on which the package leaflet was last revised

Detailed information on this veterinary medicinal product is available in the Union Product Database.

16. Contact details

Marketing authorisation holder:

Zoetis Belgium

Rue Laid Burniat 1

1348 Louvain-La-Neuve

Belgium

Manufacturer responsible for batch release:

Pfizer Italia S.r.l.

Viale Del Commercio 25/27

Ascoli Piceno

63100

Italy

or

Zoetis Belgium

Rue Laid Burniat 1

1348 Louvain-La-Neuve

Belgium

Local representatives and contact details to report suspected adverse reactions:

België/Belgique/Belgien Zoetis Belgium Mercuriusstraat 20 BE-1930 Zaventem Tél/Tel: +32 (0) 800 99 189	Lietuva Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Belgija Tel: +370 610 05088
Република България Zoetis Belgium Rue Laid Burniat 1 1348 Louvain-La-Neuve Белгия Teл: +359 888 51 30 30	Luxembourg/Luxemburg Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Belsch Tél/Tel: +32 (2) 746 80 11
Česká republika Zoetis Česká republika, s.r.o. náměstí 14. října 642/17 CZ 150 00 Praha Tel: +420 257 101 111	Magyarország Zoetis Hungary Kft. Csörsz u. 41. HU-1124 Budapest Tel.: +36 1 224 5200

Danmark

Zoetis Animal Health ApS

Øster Alle 48

DK-2100 København

Tlf: +45 70 20 73 05 adr.scandinavia@zoetis.com Malta

Agrimed Limited

Mdina Road, Zebbug ZBG 9016,

Deutschland Zoetis Deutschland GmbH Schellingstr. 1 DE-10785 Berlin Tel: +49 30 2020 0049 tierarzneimittelsicherheit@zoetis.com Nederland Zoetis B.V. Rivium Westlaan 74 NL-2909 LD Capelle aan den IJssel Tel: +31 (0)10 714 0900 Eesti Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Belgia Tel: +370 610 05088 Norge Zoetis Animal Health ApS Øster Alle 48 DK-2100 København Danmark Tlf: +47 23 29 86 80 adr.scandinavia@zoetis.com Ελλάδα Zoetis Hellas S.A. Φραγκοκκλησιάς 7, Μαρούσι EL-15125 Αττική Τηλ: +30 210 6791900 Österreich Zoetis Österreich GmbH Floridsdorfer Hauptstr. 1 AT-1210 Wien Tel: +43 (0)1 2701100 100 tierarzneimittelsicherheit@zoetis.com España Zoetis Spain, S.L. Parque Empresarial Vía Norte Edificio nº1, c/ Quintanavides nº13 ES-28050 Madrid Tel: +34 91 4191900 Polska Zoetis Polska Sp. z o.o. ul. Postępu 17B PL - 02-676 Warszawa Tel.: +48 22 2234800 France Zoetis France 10 rue Raymond David FR-92240 Malakoff Tél: +33 (0)800 73 00 65 Portugal Zoetis Portugal Lda. Lagoas Park, Edifício 10 PT-2740-271 Porto Salvo Tel: +351 21 042 72 00

MT Tel: +356 21 465 797

Hrvatska

Zoetis B.V.

Podružnica Zagreb za promidžbu

Petra Hektorovića 2

HR-10000 Zagreb

Tel: +385 1 6441 462

România

Zoetis România S.R.L.

Expo Business Park, 54A Aviator Popișteanu,

Clădirea 2, Etaj 1-3, Sector 1,

București, 012095 - RO

Tel: +40785019479

Ireland

Zoetis Belgium S.A. (Irish Branch)

2nd Floor, Building 10,

Cherrywood Business Park,

Loughlinstown,

Co. Dublin,

IE – Dublin D18 T3Y1

Tel: +353 (0) 1 256 9800

Slovenija Zoetis B.V.

Podružnica Zagreb za promidžbu

Petra Hektorovića 2,

10000 Zagreb,

Hrvaška

Tel: +385 1 6441 462

Ísland Zoetis Animal Health ApS Øster Alle 48 DK-2100 København Danmörku Sími: +45 70 20 73 05 adr.scandinavia@zoetis.com	Slovenská republika Zoetis Česká republika, s.r.o. náměstí 14. října 642/17 150 00 Praha Česká republika Tel: +420 257 101 111
Italia Zoetis Italia S.r.l. Via Andrea Doria 41M, IT-00192 Roma Tel: +39 06 3366 8111	Suomi/Finland Zoetis Finland Oy Bulevardi 21 / SPACES FI-00180 Helsinki/Helsingfors Suomi/Finland Puh/Tel: +358 10 336 7000 laaketurva@zoetis.com
Kύπρος Zoetis Hellas S.A. Φραγκοκκλησιάς 7, Μαρούσι 15125, Αττική Ελλάδα Τηλ: +30 210 6791900	Sverige Zoetis Animal Health ApS Øster Alle 48 DK-2100 Köpenhamn Danmark Tel: +46 (0) 76 760 0677 adr.scandinavia@zoetis.com
Latvija Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Beļģija Tel: +370 610 05088	United Kingdom (Northern Ireland) Zoetis UK Limited 1st Floor, Birchwood Building Springfield Drive Leatherhead Surrey, KT22 7LP UK Tel: +44 (0) 345 300 8034

17. Other information

Oclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokines dependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that are proinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exert effects on other cytokines (for example, those involved in host defence or haematopoiesis) with the potential for unwanted effects.

PACKAGE LEAFLET

1. Name of the veterinary medicinal product

Apoquel 3.6 mg chewable tablets for dogs

Apoquel 5.4 mg chewable tablets for dogs

Apoquel 16 mg chewable tablets for dogs

2. Composition

Each chewable tablet contains:

Active substance:

3.6 mg, 5.4 mg or 16 mg oclacitinib (as oclacitinib maleate).

Light to dark brown pentagon shaped mottled chewable tablets with score lines on both sides. The tablets are debossed with the corresponding strength (“S S” for 3.6 mg, “M M” for 5.4 mg and “L L” for 16 mg).

The tablets can be divided into equal halves.

3. Target species

Dogs.

4. Indications for use

Treatment of pruritus associated with allergic dermatitis in dogs.

Treatment of clinical manifestations of atopic dermatitis in dogs.

5. Contraindications

Do 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 with evidence of progressive malignant neoplasia as the active substance has not been evaluated in these cases.

6. Special warnings

Special warnings:

None.

Special precautions for safe use in the target species:

Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbate neoplastic conditions. Dogs receiving the veterinary medicinal product should therefore be monitored for the development of infections and neoplasia.

When treating pruritus associated with allergic dermatitis with oclacitinib, investigate and treat any underlying 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 treat complicating 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 7 “Adverse events”), periodic monitoring with complete blood counts and serum biochemistry is recommended when dogs are on long-term treatment.

The tablets are flavoured. In order to avoid accidental ingestion, store tablets in a safe place out of reach of animals.

Special precautions to be taken by the person administering the veterinary medicinal product to animals:

Wash hands after administration.

In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Ingestion of this product may be harmful for children. To avoid accidental ingestion, administer the tablet(s) to the dog immediately after removal from the blister packaging.

Special precautions for the protection of the environment: Not applicable.

Pregnancy and lactation:

The safety of the veterinary medicinal product has not been established during pregnancy and lactation, or in breeding male dogs, therefore its use is not recommended during pregnancy, lactation or in dogs intended for breeding.

Interaction with other medicinal products and other forms of interaction:

No drug interactions were observed in field studies where oclacitinib was administered concomitantly with veterinary medicinal products such as endo- and ectoparasiticides, antimicrobials and antiinflammatories.

The impact of oclacitinib administration on vaccination with modified live vaccines, canine parvovirus

(CPV), canine distemper virus (CDV) and canine parainfluenza (CPI) and inactivated rabies vaccine

(RV), on 16 week old vaccine naive puppies has been studied. An adequate immune response

(serology) to CDV and CPV vaccination was achieved when puppies were administered oclacitinib at 1.8 mg/kg bodyweight (bw) twice daily for 84 days. However, the findings of this study indicated a reduction in serological response to vaccination with CPI and RV in puppies being treated with oclacitinib compared to untreated controls. The clinical relevance of these observed effects for animals vaccinated while being administered oclacitinib (in accordance with the recommended dosing regimen) is unclear.

Overdose:

Oclacitinib 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 total of 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 or more feet during the study with the number and frequency of observations increasing with increasing dose. Lymphadenopathy of peripheral nodes was noted in all groups, increasing in frequency with increasing 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 treated symptomatically.

Special restrictions for use and special conditions for use: Not applicable.

Major incompatibilities:

Not applicable.

7. Adverse events

Dogs:

Very common (>1 animal / 10 animals treated):

pyoderma, skin lump, papilloma

Common (1 to 10 animals / 100 animals treated):

lethargy, lipoma, polydipsia, increased appetite nausea, vomiting, diarrhoea, anorexia histiocytoma, fungal skin infection, pododermatitis otitis lymphadenopathy cystitis aggression

Very rare (<1 animal / 10,000 animals treated, including isolated reports):

anaemia, lymphoma, convulsion

Treatment-related clinical pathology changes were restricted to an increase in mean serum cholesterol and a decrease in mean leukocyte count, however, all mean values remained within the laboratory reference range. The decrease in mean leukocyte count observed in oclacitinib-treated dogs was not progressive, and affected all white blood cell counts (neutrophil, eosinophil and monocyte counts) except lymphocyte counts. Neither of these clinical pathology changes appeared clinically significant.

Regarding susceptibility to infection and neoplastic conditions, see section 6 “Special warnings”.

Reporting adverse events is important. It allows continuous safety monitoring of a product. If you notice any side effects, even those not already listed in this package leaflet, or you think that the medicine has not worked, please contact, in the first instance, your veterinarian. You can also report any adverse events to the local representative of the marketing authorisation holder using the contact details at the end of this leaflet, or via your national reporting system.

8. Dosage for each species, routes and method of administration

For oral use.

The recommended initial dose of Apoquel tablets to be given to the dog is to achieve 0.4 to 0.6 mg oclacitinib/kg bodyweight, administered orally, twice daily for up to 14 days.

For maintenance therapy (after the initial 14 days of treatment), the same dose (0.4 to 0.6 mg oclacitinib/kg bodyweight) should then be administered only once a day. The requirement for longterm maintenance therapy should be based on an individual benefit-risk assessment by the responsible veterinarian.

Apoquel tablets are chewable, palatable and readily consumed by the majority of dogs.

These tablets can be administered with or without food.

Please see dosing table below for the number of tablets required to achieve the recommended dose. The tablets are breakable along the score line.

Bodyweight (kg) of dog	Strength and number of tablets to be administered:
	Apoquel 3.6 mg tablets	Apoquel 5.4 mg tablets	Apoquel 16 mg tablets
3.0–4.4	½
4.5–5.9		½
6.0–8.9	1
9.0–13.4		1
13.5–19.9			½
20.0–26.9		2
27.0–39.9			1
40.0–54.9			1½
55.0–80.0			2

9. Advice on correct administration

Dogs should be carefully observed following administration to ensure that each tablet is swallowed.

10. Withdrawal periods

Not applicable.

11. Special storage precautions

Keep out of the sight and reach of children.

Store in the original package in order to protect from moisture.

Remaining tablet parts should be stored in the blister and be given at the next administration. Do not use this veterinary medicinal product after the expiry date which is stated on the blister after Exp.

12. Special precautions for disposal

Medicines should not be disposed of via wastewater or household waste.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any applicable national collection systems. These measures should help to protect the environment.

Ask your veterinary surgeon how to dispose of medicines no longer required.

13. Classification of veterinary medicinal products

Veterinary medicinal product subject to prescription.

14. Marketing authorisation numbers and pack sizes

EU/2/13/154/028–036

Aluminium/PVC/Aclar blisters (each strip containing 10 chewable tablets) packed into an outer cardboard box. Pack sizes of 20, 50 or 100 tablets.

Not all pack sizes may be marketed.

15. Date on which the package leaflet was last revised

Detailed information on this veterinary medicinal product is available in the Union Product Database.

16. Contact details

Marketing authorisation holder and manufacturer responsible for batch release:

Zoetis Belgium

Rue Laid Burniat 1

1348 Louvain-La-Neuve

Belgium

Local representatives and contact details to report suspected adverse reactions:

België/Belgique/Belgien Zoetis Belgium Mercuriusstraat 20 BE-1930 Zaventem Tél/Tel: +32 (0) 800 99 189	Lietuva Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Belgija Tel: +370 610 05088
Република България Zoetis Belgium Rue Laid Burniat 1 1348 Louvain-La-Neuve Белгия Teл: +359 888 51 30 30	Luxembourg/Luxemburg Zoetis Belgium Mercuriusstraat 20 1930 Zaventem Belsch Tél/Tel: +32 (2) 746 80 11
Česká republika Zoetis Česká republika, s.r.o. náměstí 14. října 642/17 CZ 150 00 Praha Tel: +420 257 101 111	Magyarország Zoetis Hungary Kft. Csörsz u. 41. HU-1124 Budapest Tel.: +36 1 224 5200
Danmark Zoetis Animal Health ApS Øster Alle 48 DK-2100 København Tlf: +45 70 20 73 05 adr.scandinavia@zoetis.com	Malta Agrimed Limited Mdina Road, Zebbug ZBG 9016, MT Tel: +356 21 465 797
Deutschland Zoetis Deutschland GmbH Schellingstr. 1 DE-10785 Berlin Tel: +49 30 2020 0049	Nederland Zoetis B.V. Rivium Westlaan 74 NL-2909 LD Capelle aan den IJssel Tel: +31 (0)10 714 0900

tierarzneimittelsicherheit@zoetis.com

Eesti Norge

Zoetis Belgium Zoetis Animal Health ApS

Mercuriusstraat 20 Øster Alle 48

1930 Zaventem DK-2100 København

Belgia Danmark

Tel: +370 610 05088 Tlf: +47 23 29 86 80

adr.scandinavia@zoetis.com

Ελλάδα Österreich

Zoetis Hellas S.A. Zoetis Österreich GmbH

Φραγκοκκλησιάς 7, Μαρούσι Floridsdorfer Hauptstr. 1

EL-15125 Αττική AT-1210 Wien

Τηλ: +30 210 6791900 Tel: +43 (0)1 2701100 100

tierarzneimittelsicherheit@zoetis.com

España Polska

Zoetis Spain, S.L. Zoetis Polska Sp. z o.o.

Parque Empresarial Vía Norte Edificio nº1, ul. Postępu 17B

c/ Quintanavides nº13 PL - 02-676 Warszawa

ES-28050 Madrid Tel.: +48 22 2234800

Tel: +34 91 4191900

France Portugal

Zoetis France Zoetis Portugal Lda.

10 rue Raymond David Lagoas Park, Edifício 10

FR-92240 Malakoff PT-2740-271 Porto Salvo Tél: +33 (0)800 73 00 65 Tel: +351 21 042 72 00

Hrvatska România

Zoetis B.V. Zoetis România S.R.L.

Podružnica Zagreb za promidžbu Expo Business Park, 54A Aviator Popișteanu, Petra Hektorovića 2 Clădirea 2, Etaj 1-3, Sector 1,

HR-10000 Zagreb București, 012095 - RO

Tel: +385 1 6441 462 Tel: +40785019479

Ireland Slovenija

Zoetis Belgium S.A. (Irish Branch) Zoetis B.V.

2nd Floor, Building 10, Podružnica Zagreb za promidžbu

Cherrywood Business Park, Petra Hektorovića 2,

Loughlinstown, 10000 Zagreb,

Co. Dublin, Hrvaška

IE – Dublin D18 T3Y1 Tel: +385 1 6441 462

Tel: +353 (0) 1 256 9800

Ísland Slovenská republika

Zoetis Animal Health ApS Zoetis Česká republika, s.r.o.

Øster Alle 48 náměstí 14. října 642/17 DK-2100 København 150 00 Praha

Danmörku Česká republika

Sími: +45 70 20 73 05 Tel: +420 257 101 111 adr.scandinavia@zoetis.com

Italia Zoetis Italia S.r.l.

Via Andrea Doria 41M, IT-00192 Roma

Tel: +39 06 3366 8111Suomi/Finland

Zoetis Finland Oy

Bulevardi 21 / SPACES

FI-00180 Helsinki/Helsingfors

Suomi/Finland

Puh/Tel: +358 10 336 7000

laaketurva@zoetis.com

Kύπρος Zoetis Hellas S.A. Φραγκοκκλησιάς 7, Μαρούσι 15125, Αττική Ελλάδα Τηλ: +30 210 6791900	Sverige Zoetis Animal Health ApS Øster Alle 48 DK-2100 Köpenhamn Danmark Tel: +46 (0) 76 760 0677 adr.scandinavia@zoetis.com
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17. Other information

Oclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokines dependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that are proinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exert effects on other cytokines (for example, those involved in host defence or haematopoiesis) with the potential for unwanted effects.