Betamethasone Acetate, Florfenicol, Terbinafine: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Betamethasone Acetate, Florfenicol, Terbinafine, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Osurnia™ (NADA/ANADA 141-437)
Osurnia™ NADA 141-437, Original approval, November 04, 2014; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 928; FDA PDF
Indication
Treatment of otitis externa in dogs associated with susceptible strains of bacteria (Staphylococcus pseudintermedius) and yeast (Malassezia pachydermatis)
Dose regimen
1 tube (1 mL) per affected ear, Otic (external ear canal), twice, 7 days apart, administered in the clinic; clean and dry the ear canal before the initial dose; do not clean the ear canal for 45 days after initial administration
Administer one dose (1 tube) per affected ear(s) and repeat administration in 7 days. Do not clean the ear canal for 45 days after the initial administration to allow contact of the gel with the ear canal.
Target-animal safety
dose multiples 0X, 1X, 5X; duration 6 administrations over 5 weeks (Study Days 1, 8, 15, 22, 29, 36); total study 37 days; animals Twenty four (8 per group).
Dogs were administered control article (saline) or OSURNIA at 1X or 5X the recommended dose via instillation into both ear canals on Study Day (SD) 1, 8, 15, 22, 29, and 36. The 1X recommended dose was 1 mL/ear or 2 mL/dog with repeated administration in 7 days and the 5X dose was 5 mL/ear or 10 mL/dog with repeated administration in 7 days.
| Finding | Quote |
|---|---|
| Lower body weight gain (about 17%) in 1X and 5X groups | Body weight gain was lower (approximately 17%) in both the 1X and 5X groups compared to the control (0X) group. |
| Elevated ALT in three 5X dogs with hepatocellular vacuolation in two | There was also elevated alanine aminotransferase (ALT) activity in three dogs in the 5X group, accompanied by minimal or mild microscopic hepatocellular vacuolation observed at necropsy in two of these dogs. |
| HPA-axis suppression at 5X: reduced post-ACTH cortisol, decreased adrenal and thymic weights | There was a decrease in serum cortisol levels after ACTH stimulation (below normal reference range) in the 5X group accompanied by decreased adrenal gland and thymic weights with minimal adrenal cortical atrophy and lymphoid depletion of the thymus. |
| Tympanic membrane epithelial vesicles in 2 dogs (1X) and 4 dogs (5X) | Unilateral vesicle formation within the epithelium of the tympanic membrane was observed in two dogs in the 1X group, and in four dogs in the 5X group. |
| Unilateral middle ear mucosal necrosis/ulceration in three 5X dogs | In three dogs in the 5X group, there was unilateral mucosal necrosis and ulceration of the lining of the middle ear cavity. |
| Normal hearing and good health throughout | All dogs were in good health with normal hearing throughout the study. |
Effectiveness
Randomized, double-masked, placebo (vehicle)-controlled, multi-center field study (15 US clinics; Study 12-001); 2:1 OSURNIA:placebo, 1 mL per ear on Days 0 and 7; 284 dogs treated (190 OSURNIA, 94 placebo); n = 235 (159 OSURNIA, 76 placebo) evaluated for effectiveness; primary endpoint: Clinical success = total otitis externa score of the evaluable ear ≤2 on Day 45 (12-point scale: pain, erythema, exudate, swelling, odor, ulceration); result: Clinical success 64.78% (103/159) OSURNIA vs 43.42% (33/76) placebo; p=0.0094
Two hundred and thirty-five (235) cases (159 OSURNIA and 76 placebo) were included in the effectiveness evaluation. The OSURNIA group was statistically significantly different (p=0.0094) from the placebo group with clinical success rates of 64.78% and 43.42%, respectively.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Elevated Alkaline Phosphatase | 15 (7.9%) | 3 (3.2%) | Elevated Alkaline Phosphatase 15 (7.9%) 3 (3.2%) |
| Vomiting | 7 (3.7%) | 1 (1.1%) | Vomiting 7 (3.7%) 1 (1.1%) |
| Elevated AST, ALT, ALP | 2 (1.1%) | 0 (0.0%) | Elevated AST, ALT, ALP* 2 (1.1%) 0 (0.0%) |
| Weight loss (>10% body weight) | 1 (0.53%) | 0 (0.0%) | Weight loss (>10% body weight) 1 (0.53%) 0 (0.0%) |
| Hearing Decrease/Loss | 1 (0.53%) | 1 (1.1%) | Hearing Decrease/Loss 1 (0.53%) 1 (1.1%) |
Extraction notes: Adverse reaction rows quoted from flattened Table 4: term, OSURNIA n (%) of n=190, placebo n (%) of n=94. No numeric plasma PK reported; TAS notes low, less-than-dose-proportional plasma concentrations of all three actives, and an ear-swab depletion study (33 dogs) suggested therapeutic concentrations may persist to Day 45. Pilot dose-selection field study (121 dogs) and in vitro non-interference/MIC study also in summary. P. aeruginosa-only cases (3) were all failures.
Reproduce: foi_structured_search(query="Betamethasone Acetate, Florfenicol, Terbinafine") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).