Gentamicin Sulfate, Hydrocortisone aceponate, Miconazole Nitrate: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Gentamicin Sulfate, Hydrocortisone aceponate, Miconazole Nitrate, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Easotic® (NADA/ANADA 141-330)
Easotic® NADA 141-330, Original approval, October 31, 2011; sponsor Virbac AH, Inc.; species: Dogs; foi_id 889; FDA PDF
Indication
Treatment of otitis externa in dogs associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Staphylococcus pseudintermedius).
Dose regimen
1 mL (a single pump) per affected ear, Otic (into the affected external ear canal), Once per day, 5 days; verify that the tympanic membrane is intact
Carefully insert the canula into the affected external ear canal(s) and apply 1 mL (a single pump) once per day for 5 days.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | Miconazole plasma accumulation 4.1, 2.3 and 5.7 (1X, 3X, 5X) | Plasma drug analysis in 12-week-old Beagles dosed aurally for 15 days (margin-of-safety study); steady state approximately 2-6 X single-dose concentrations | The average accumulation of miconazole in the plasma over the 14 days of dosing in 1X, 3X, and 5X dogs were 4.1, 2.3, and 5.7, respectively, i.e. steady state plasma concentrations were approximately 2-6 X higher than observed after a single dose regardless of the amount of dose administered. |
| other | Gentamicin plasma accumulation 8.3, 8.8 and 9.2 (1X, 3X, 5X) | Same 15-day aural dosing study; only minimal accumulation of hydrocortisone aceponate (mainly 5X) | The corresponding accumulation for gentamicin was 8.3, 8.8, and 9.2 for 1X, 3X, and 5X dogs, respectively. |
Target-animal safety
dose multiples 0X, 1X, 3X, 5X; duration 15 days (three times the 5-day treatment length); 1, 3 or 5 mL/ear/day; animals 32.
Test Animals: A total of 32 twelve-week old Beagle dogs were used in this study.
| Finding | Quote |
|---|---|
| HPA-axis suppression: lower pre-ACTH cortisol in all treated groups | Each of the treated groups had significantly different and numerically lower cortisol values pre-ACTH as compared to the control group. |
| Otitis externa (neutrophilic inflammation) in three 3X and three 5X dogs | Gross Pathology: Otitis externa, characterized by focal areas of supe rficial neutrophilic inflammatory responses in the external ear canal, was seen in three 3X dogs and three 5X dogs. |
| Hyperplastic changes of the external ear canal in most treated dogs, none in controls | Histopathology: Most animals in all groups administered EASOTIC (eight 1 X dogs, eight 3X dogs, and five 5X dogs) had hyperplastic changes in the external ear canal. |
| Renal tubular crystals across all groups including controls (3 control, 6 1X, 6 3X, 7 5X) | Renal tubular crystals in the cortex and medulla were seen across all g roups, as three control dogs, six 1X dogs, six 3X dogs, and seven 5X dogs were noted to have this lesion. |
| Treatment-related ALT, ALP, cholesterol, total protein and albumin elevations; elevated liver weights; otitis media in two 5X dogs | Conclusions: Aural administration of EASOTIC to 12 week old Beagle dogs at 1, 3 , and 5 times the recommended dose (1 mL/ear/day) for 15 days (three times the treatment length) was associated with alterations of the hypothalamic- pituitary-adrenal axis as evidenced by the ACTH stimulation results. |
Effectiveness
Double-masked, placebo-controlled multi-site field study (U-184.030000-30004; 8 US clinics); 1 mL once daily for 5 days; 216 dogs enrolled (145 EASOTIC, 71 placebo), 157 evaluable; n = 104 EASOTIC, 53 control (effectiveness analysis); primary endpoint: Treatment success: total clinical score (malodor, discharge, pruritus, erythema, swelling, pain) of 2 or below at visit 4 (Days 26-30) with no single sign worse; result: Estimated success 68.5% (68/104) EASOTIC vs 21.8% (14/53) placebo; P = 0.0179
EASOTIC 104 68.5 (44.3, 85.6) Control 53 21.8 (7.6, 48.5) P-value 0.0179
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| None reported in field study | Adverse Reactions: No adverse reactions were reported in this study. |
Extraction notes: Indication quote is reproduced as extracted (PDF flattening displaced 'Malassezia'). Effectiveness quote is the flattened Table 3 row (treatment group, number of dogs, percent success, 95% CI); the results sentence in the text has the control n split as '5 3'. PK entries are plasma accumulation ratios from the target animal safety study, not conventional PK parameters. No adverse reactions were reported in the field study; foreign pharmacovigilance (~0.006% suspected reactions) most commonly reported transient hearing loss and application-site erythema. In vitro non-interference (FICI) study supports both antimicrobial actives.
Reproduce: foi_structured_search(query="Gentamicin Sulfate, Hydrocortisone aceponate, Miconazole Nitrate") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).