Miconazole Nitrate, Polymyxin B Sulfate, Prednisolone Acetate: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Miconazole Nitrate, Polymyxin B Sulfate, Prednisolone Acetate, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Surolan® (NADA/ANADA NADA 141-298)
Surolan® NADA NADA 141-298, Original approval, November 23, 2009; sponsor Elanco US Inc.; species: Dogs; foi_id 862; FDA PDF
Indication
Treatment of canine otitis externa associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Staphylococcus pseudintermedius).
Dose regimen
5 drops, Otic (instilled in the ear canal), Twice daily, 7 consecutive days; ear cleaned and dried before treatment; eardrum verified intact
Instill 5 drops of SUROLAN in the ear canal twice daily and massage the ear. Therapy should continue for 7 consecutive days.
Target-animal safety
dose multiples 1X, 3X, 5X; duration 42 consecutive days of daily application (6X the recommended treatment duration); study period day -7 to day 56; animals 32 adult Beagles (twenty-four treated, 8 control; 4/sex/group).
A total of 32 adult Beagle dogs were used in this study. Twenty- four dogs were treated with SUROLAN and 8 dogs were used as a control. Body weights ranged from 8.84 to 16.38 kg. Four males and four females were randomly assigned to four groups (4/sex/group).
| Finding | Quote |
|---|---|
| Up to 5X dose volume for 42 days caused hypersensitivity reactions (mild erythema, pale ears) | Administration of SUROLAN at doses up to 5 times the recommended dose volume for 42 days in healthy Beagle dogs caused hypersensitivity reactions that included mild erythema and pale ears. |
| Painful/sensitive ear canals in 2 dogs (3X) and hyperemia and sensitive ear canals in 2 dogs (5X) | In the 3X group, SUROLAN also caused painful and sensitive ear canals on examination in 2 dogs, and in the 5X group, SUROLAN caused hyperemia and sensitive ear canals on examination in 2 dogs. |
| Clinical pathology changes in all treated groups consistent with systemic absorption of topical corticosteroid; significant GGT elevations; elevations in ALP and chloride | Changes in clinical pathology occurred in all SUROLAN treated groups consistent with the systemic absorption of topical corticosteroids. There were statistically significant elevations of GGT. There were also elevations in ALP, and chloride in the dogs treated with SUROLAN. |
| No clinically significant treatment-related effects on body weight, feed consumption, behavior or temperature | There were no clinically significant treatment- related effects on body weight, feed consumption, behavior, or temperature. |
| Serum chemistry: 3 dogs in 3X group had mild to moderate ALP elevations from day 14; 1 dog in 5X group mild ALP increase on day 42 | Beginning and beyond study day 14, 3 dogs in the 3X group had mild to moderate elevations in alkaline phosphatase (ALP). In the 5X group, only 1 dog had a mild increase in ALP on study day 42. |
| Urinalysis: low urine specific gravity in 2 dogs (3X, throughout) and 1 dog (5X) | In the 3X group, 2 dogs had a low urine specific gravity throughout the study, and in the 5X group, 1 dog had a low urine specific gravity during the study. |
| Hearing: all treated dogs scored normal; one control dog had a transient moderate deficit on day 14 | One dog in the control group was given a score of 2 (moderate deficit) on study day 14. This dog had normal hearing scores on all other study days. All other dogs in all groups were given normal hearing scores. |
Effectiveness
GCP multi-site (31 clinics in the United States and Canada) randomized, active-controlled non-inferiority field study of SUROLAN (5 drops BID) vs OTOMAX (4 or 8 drops BID) for 7 consecutive days in dogs with otitis externa (Study #IO CC-0800, Oct 2001 to Nov 2002).; n = Three hundred thirty-seven enrolled (169 SUROLAN, 168 OTOMAX); 176 evaluated for effectiveness (91 SUROLAN, 85 OTOMAX); 322 for safety (161 per group); primary endpoint: Binary improvement vs no improvement in clinical score (pain/discomfort, swelling, redness, exudate and overall) 2-4 days after treatment; non-inferiority if one-sided lower 95% confidence limit of SUROLAN minus OTOMAX difference is no less than -10%; result: 96.7% of SUROLAN cases and 95.2% of OTOMAX cases had clinical improvement; overall lower 95% CL -3.0% (difference 1.4%); SUROLAN non-inferior to OTOMAX. Mean clinical score improvement 5.6 (SUROLAN) vs 5.5 (OTOMAX).
Three hundred and thirty-seven dogs (169 treated with SUROLAN and 168 treated with OTOMAX) were enrolled ranging in weight from 1.8 to 68.0 kg and age from less than 1 year to 20 years old. Of these, 176 (91 dogs treated with SUROLAN and 85 dogs treated with OTOMAX) were used to evaluate effectiveness and 322 dogs (161 treated with SUROLAN and 161 treated with OTOMAX) were used to evaluate safety.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Total reported adverse reactions (field study) | 5 | 8 | There were 13 reported adverse reactions, 5 treated with SUROLAN and 8 treated with OTOMAX. |
| Reduced hearing | 3 | 1 | Reduced hearing 3* 1 |
| Residue build-up | 1 | 1 | Residue build-up 1 1 |
| Pain upon drug application | 1 | 0 | Pain upon drug application 1 0 |
| Vomiting | 0 | 4 | Vomiting 0 4 |
| Red pustules on pinna | 0 | 1 | Red Pustules on pinna 0 1 |
Extraction notes: No pharmacokinetic data. Table 6 rows quoted as extracted; column order is SUROLAN # of dogs, then OTOMAX # of dogs (safety population 161 per group). Table 6 also lists 'Head shaking 0 1'. The reduced-hearing asterisk notes one dog had normal investigator-assessed hearing but owner-noted decreased hearing from medication build-up. Effectiveness result sentence reads verbatim: '96.7% of the cases treated with SUROLAN and 95.2% of the cases treated with OTOMAX had clinical improvement of the inflammatory symptoms.' TAS design_quote contains 'Twenty- four' as rendered by the PDF extraction (hyphenated line break); dosages were 10, 30 and 50 drops daily (1X, 3X, 5X) vs 50 drops saline placebo.
Reproduce: foi_structured_search(query="Miconazole Nitrate, Polymyxin B Sulfate, Prednisolone Acetate") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).