Skylocalm 16 mg Film-coated Tablets for Dogs

Composition

Active substance:

Each film-coated tablet contains 16 mg oclacitinib (as oclacitinib maleate)

For the full list of excipients, see section 6.1.

6.1 List of excipients

Tablet core:

Cellulose, microcrystalline

Lactose monohydrate

Magnesium stearate

Sodium starch glycolate

Tablet coating:

Lactose monohydrate

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 400 (E1521)

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Pharmaceutical form

Film-coated tablets.

White to off-white, oblong shaped film-coated tablets with a score-line on both sides and marked with the letters "AQ" and "L" on both sides.

The tablets can be divided into halves.

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Pharmacological properties

Pharmacotherapeutic group: Agents for dermatitis, excluding corticosteroids.

ATC Vet Code: QD11AH90

5.1 Pharmacodynamic properties

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.

5.2 Pharmacokinetic particulars

Following oral administration in dogs, oclacitinib maleate is rapidly and well absorbed, with a time to peak plasma concentration (tmax) 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 t½s 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 Cmax (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.

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Target species

Dogs.

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Indications

Treatment of pruritus associated with allergic dermatitis in dogs.

Treatment of clinical manifestations of atopic dermatitis in dogs.

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Dosage

For oral use.

Dosage and treatment schedule:

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.

Strength and number of tablets to be administered:

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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.

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Adverse reactions

Dogs:

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 4.5.

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.

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Warnings

i) Special precautions for use in animals

Oclacitinib modulates the immune system and may increase susceptibility to infection and exacerbate neoplastic conditions. Dogs receiving Skylocalm tablets 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 4.6), periodic monitoring with complete blood counts and serum biochemistry is recommended when dogs are on long-term treatment.

ii) 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.

iii) Other precautions

None.

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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.

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Interactions

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

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 naïve 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.

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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.

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Special warnings

None.

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Withdrawal period

Not applicable.

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Incompatibilities

Not applicable.

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Immediate packaging

Aluminium/PVC/Aclar or aluminium/PVC/PVDC blisters (each strip containing 10 film-coated tablets) packed into an outer cardboard box. Pack sizes of 100 tablets.

Not all pack sizes may be marketed.

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Storage

Store below 25°C.

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

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years. Any remaining half tablets should be discarded after 3 days.

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Disposal of unused product

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

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Additional information

Vm 42058/5098

9 DATE OF FIRST AUTHORISATION

10 January 2023

10 DATE OF REVISION OF THE TEXT

October 2023

Approved: 13 April 2024

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Registration holder

Zoetis UK Limited

1st Floor, Birchwood Building

Springfield Drive

Leatherhead

Surrey

KT22 7LP

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