Excipients
Cellulose, microcrystalline
Lactose monohydrate
Sodium starch glycolate (type A)
Tocofersolan
Hydroxypropylcellulose
Silica, colloidal anhydrous
Magnesium stearate
Pharmacodynamics properties
Atinvicitinib is a selective Janus kinase (JAK) inhibitor, highly selective for JAK1. It inhibits the function of a variety of cytokines involved in pruritus and inflammation, as well as cytokines involved in allergy, that are dependent on JAK1 enzyme activity. Inhibition of JAK1 enzyme activity leads to a reduction of inflammation-associated white blood cell counts (mean absolute counts were within the reference range in field trials). Atinvicitinib did not lead to immunosuppressive effects at the target dose.
Atinvicitinib is at least 10 times more selective for JAK1 compared to the other JAK-family members (JAK2, JAK3, tyrosine kinase (TYK) 2). Thus, it has very little to no effect on cytokines involved in haematopoiesis or host defence that are dependent on JAK2 or the other JAK family members.
Pharmacokinetics properties
Following oral administration, atinvicitinib was rapidly and well absorbed with an observed mean Cmax of 190 ng/ml, which occurred at approximately 1 hour (tmax) post dosing. The absolute bioavailability of atinvicitinib after administration once daily for four days was approximately 65%. Bioavailability was higher in fed dogs.
Total atinvicitinib clearance from plasma was 1074 ml/h/kg bodyweight (17.9 ml/min/kg bodyweight), and the apparent volume of distribution at steady state was 1.65 L/kg bodyweight. Following oral administration, the terminal half-life (t1/2) was 2 hours.
In a six-month study conducted in dogs (see section “overdose”), mild accumulation that was not considered clinically relevant was observed in some individuals; steady state was reached after 7 weeks.
Atinvicitinib has moderate protein binding with 82.3% bound in fortified canine plasma at concentrations of 1802 ng/ml (5 µM).
Atinvicitinib is metabolised in the dog to multiple metabolites and, although the extent of any hepatic metabolism has not been definitively determined, its main clearance route is metabolism with excretion in the faeces. Renal elimination, with excretion in the urine, is considered a minor route.
Dogs with hepatic impairment were not excluded from the clinical field trials conducted with this veterinary medicinal product. However, it was not specifically tested in patients with confirmed hepatic impairment and any impact of hepatic impairment on the pharmacokinetics of atinvicitinib remains uncertain.
Major incompatibilities
Not applicable.
Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 3 years.
Special precautions for storage
This veterinary medicinal product does not require any special storage conditions.
Any remaining half tablet should be placed back into the opened blister or into the bottle.
Immediate packaging
Aluminium/PVC/polychlorotrifluoroethylene blisters containing 30 tablets per strip.
Cardboard box with 1 or 3 blister strips equivalent to 30 or 90 tablets.
Cardboard box with HDPE bottle containing 30 or 90 tablets.
Not all pack sizes may be marketed.
Disposal
Medicines should not be disposed of via wastewater.
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.