ATCvet code: QS02CA90
Pharmacodynamics
The veterinary medicinal product is a fixed combination of two active substances (a corticosteroid and an antifungal):
Terbinafine is an allylamine with a pronounced fungicidal activity. It selectively inhibits the early synthesis of ergosterol, which is an essential component of the membrane of yeasts and fungi including Malassezia pachydermatis. Resistance to terbinafine and other allylamines is rare and is usually associated with point mutations in the squalene epoxidase gene that cause amino acid changes in the enzyme necessary for the ergosterol synthesis pathway, impairing the binding of the allylamines. An MIC50 of 0.12 µg/mL and an MIC90 of 0.5 µg/mL have been calculated based on isolates (n=113) collected from dogs with yeast predominant otitis externa in several European countries between 2021 and 2023. Terbinafine has a different mode of action than azole antifungals, therefore there is no cross resistance with azole antifungals. Cross-resistance with other antifungals has not been reported.
Betamethasone acetate belongs to the diesters class of glucocorticosteroids with a potent intrinsic glucocorticoid activity which relieves both inflammation and pruritus leading to an improvement of clinical signs observed in otitis externa.
Pharmacokinetics
The formulation dissolves in ear wax and is slowly eliminated from the ear mechanically.
Systemic absorption of the active substances was determined in multiple-dose studies using a related, similar product. After placing this veterinary medicinal product into both ear canals of healthy mixed breed dogs, absorption occurred primarily during the first two to four days after administration, with low peak plasma concentrations of betamethasone and terbinafine (1.5 and 3.7 ng/ml respectively). The extent of percutaneous absorption of topical medications is determined by many factors including the integrity of the epidermal barrier. Inflammation can increase the percutaneous absorption of veterinary medicinal products.