Dexamethasone, Marbofloxacin, Terbinafine: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Dexamethasone, Marbofloxacin, Terbinafine, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dog.
Products
- Otiserene® (NADA/ANADA 141-598)
Otiserene® NADA 141-598, Original approval, April 10, 2025; sponsor Dechra Veterinary Products LLC; species: Dog; foi_id 16805; FDA PDF
Indication
Treatment of otitis externa associated with susceptible strains of Malassezia pachydermatis and Staphylococcus pseudintermedius in dogs.
Dose regimen
one dose (1 tube) per affected ear, Otic, once, Each tube contains 15.1 mg marbofloxacin, 22.7 mg terbinafine, 2.01 mg dexamethasone (General Information G). Administered by veterinary personnel; verify intact tympanic membrane; clean and dry ear canal before dosing; do not clean ear canal for 30 days after
Otiserene® should be administered by veterinary personnel. Verify the tympanic membrane is intact prior to administration. Clean and dry the external ear canal before administering the product. Administer one dose (1 tube) per affected ear once. Do not clean the ear canal for 30 days after administration.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | marbofloxacin ear-canal concentration predicted to fall below 0.5 μg/mL (500 ng/mL) at 27 days (median) / approximately 39 days (upper 95% prediction bound) | ear wash depletion study, 12 dogs with normal ears, 1.1 mL Otiserene in both ears; ear flush on Days 10, 15, 21; HPLC-MS/MS; linear regression extrapolation | The upper bound of the 95% prediction interval for marbofloxacin to fall below 0.5 μg/mL (500 ng/mL) was extrapolated at approximately 39 days. The median log of the marbofloxacin to fall below 0.5 μg/mL (500 ng/mL) was extrapolated at 27 days. |
Target-animal safety
dose multiples 0X, 1X, 3X, 5X; duration three dosing days 14 days apart (Days 0, 14, 28), both ears; 1X = 2 mL total per dog (1 mL per ear); animals Thirty-six (18 male, 18 female) enrolled; thirty-two randomized, eight per group.
Objective: This laboratory study evaluated the safety of the test article (MTD Otic Suspension) when administered aurally to dogs on three separate dosing days, 14 days apart, at 0X, 1X, 3X, and 5X the maximum proposed label dose. Study Animals: Thirty-six (18 male, 18 female) Beagle dogs, four-months of age and weighing 3.8-6.3 kg at enrollment, were used for the study.
| Finding | Quote |
|---|---|
| All dogs healthy with normal hearing; all survived | All dogs were in good health with normal hearing throughout the study and survived to study conclusion. |
| Lower WBC, lymphocyte and monocyte counts at 3X and 5X on Day 27 | White blood cell (WBC) values on Day 27 were significantly lower in the 3X and 5X groups as compared to the control group. Lymphocyte and monocyte counts on Day 27 were significantly lower in the 3X and 5X groups as compared to the control group. |
| Bilateral adrenal cortical atrophy (males 3X and 5X; females 5X); adrenal weights lower in treated females | Bilateral adrenal gland atrophy (i.e., narrowing) of the cortical zona fasciculata layer was observed in males in the 3X and 5X groups and females in 5X group. |
| Epidermal atrophy of external ear canals in 1X, 3X and 5X | Epidermal atrophy of the left and right external (auricular) ear canals (minimal to mild) was identified microscopically exclusively in males and females in the 1X, 3X, and 5X groups. |
| Thymic atrophy at 3X and 5X | Thymic atrophy (minimal to mild), characterized microscopically by decreased lymphocytes and thinning of the cortical layer, occurred in males and females in the 3X and 5X groups. |
| Findings (also decreased globulins, fibrinogen, APTT; decreased bone marrow cellularity; increased hepatic glycogen vacuolation) attributed to systemic dexamethasone exposure | The observations were attributed to systemic exposure to dexamethasone in Otiserene®. |
Effectiveness
Multicentered, vehicle-controlled, randomized (2:1), masked field study at 19 US clinics; single 1 mL dose to affected ear on Day 0 after saline cleaning; evaluations Days 10, 20, 30 (+2); GCP; n = 115 Otiserene / 57 control in effectiveness population (232 enrolled: 155 Otiserene / 77 control in safety); primary endpoint: Treatment success = clinical otitis score (erythema, exudate, swelling, ulceration; 0-12) of ≤3 at Day 30 (+2) with no individual sign worsening; result: 82/115 Otiserene successes (estimated 74.9%, 95% CI 61.3-84.9) vs 15/57 control (27.7%, 95% CI 14.9-45.5); p=0.0001; effective against M. pachydermatis and S. pseudintermedius cases
Study Animals: Two hundred and thirty-two client-owned dogs diagnosed with otitis externa were enrolled in the study (155 treated with Otiserene®, 77 control) and were included in the safety analysis. Of the 232 enrolled dogs, 172 dogs were considered suitable for inclusion in the effectiveness population (115 treated with Otiserene®, 57 control).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anorexia/decreased appetite | 6 (3.8%) | 2 (2.5%) | Anorexia/decreased appetite 6 (3.8%) 2 (2.5%) |
| Pruritus | 4 (2.6%) | 1 (1.3%) | Pruritus 4 (2.6%) 1 (1.3%) |
| Vomiting | 3 (1.9%) | 0 (0.0%) | Vomiting 3 (1.9%) 0 (0.0%) |
| Conjunctivitis/eye inflammation | 2 (1.2%) | 0 (0.0%) | Conjunctivitis/eye inflammation 2 (1.2%) 0 (0.0%) |
Extraction notes: Original approval. Adverse reaction table columns: Otiserene (n=155) | Control (n=77), number (%) of dogs; percentages are as printed in the summary. The 'pharmacokinetics' entry is an ear-canal drug depletion estimate (dosage characterization), not systemic PK. TAS groups: T0 vehicle 10 mL, T1 2 mL, T3 6 mL, T5 10 mL total per dog, 4M/4F each.
Reproduce: foi_structured_search(query="Dexamethasone, Marbofloxacin, Terbinafine") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).