tepoxalin: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing tepoxalin, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Zubrin™ Rapidly-Disintegrating Tablets (NADA/ANADA 141-193)
Zubrin™ Rapidly-Disintegrating Tablets NADA 141-193, Original approval, March 31, 2003; sponsor Intervet, Inc.; species: Dogs; foi_id 706; FDA PDF
Indication
Control of pain and inflammation associated with osteoarthritis in dogs.
Dose regimen
10 mg/kg (4.5 mg/lb) or 20 mg/kg (9.1 mg/lb) on the initial day, then 10 mg/kg, oral (rapidly-disintegrating tablet placed in the mouth), once daily, Give with food or within 1 to 2 hours after feeding; duration based on clinical response and tolerance; dogs under 3 kg cannot be accurately dosed.
Dosage: Administer 10 mg/kg (4.5 mg/lb) or 20 mg/kg (9.1 mg/lb) on the initial day of treatment, followed by a daily maintenance dose of 10 mg/kg.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| tmax | 2.3 ± 1.4 hr (tepoxalin, Day 0) | 20 mg/kg oral on Day 0 then 10 mg/kg once daily, 12 dogs (Study N00-576) | Tepoxalin Day 0 2.3 ± 1.4** 780 ± 506 2.0 ± 1.2 3363 ± 1841 |
| cmax | 780 ± 506 ng/mL (tepoxalin, Day 0) | 20 mg/kg oral on Day 0, 12 dogs; Day 1 529 ± 182, Day 6 637 ± 317 at 10 mg/kg | Tepoxalin Day 0 2.3 ± 1.4** 780 ± 506 2.0 ± 1.2 3363 ± 1841 |
| half-life | 2.0 ± 1.2 hr (tepoxalin, Day 0) | 20 mg/kg oral on Day 0, 12 dogs; short because of conversion to active metabolite | Tepoxalin Day 0 2.3 ± 1.4** 780 ± 506 2.0 ± 1.2 3363 ± 1841 |
| auc | 3363 ± 1841 hr*ng/mL (tepoxalin, Day 0) | AUC0-24 column (for tepoxalin, AUC to the last quantifiable concentration); 20 mg/kg oral on Day 0, 12 dogs | Tepoxalin Day 0 2.3 ± 1.4** 780 ± 506 2.0 ± 1.2 3363 ± 1841 |
| tmax | 4.7 ± 6.2 hr (active metabolite, Day 0) | 20 mg/kg oral on Day 0, 12 dogs | Active Metabolite Day 0 4.7 ± 6.2 831 ± 357 13.7 ± 10.7 8460 ± 3527 |
| cmax | 831 ± 357 ng/mL (active metabolite, Day 0) | 20 mg/kg oral on Day 0, 12 dogs; Day 1 986 ± 323, Day 6 968 ± 486 | Active Metabolite Day 0 4.7 ± 6.2 831 ± 357 13.7 ± 10.7 8460 ± 3527 |
| half-life | 13.7 ± 10.7 hr (active metabolite, Day 0) | 20 mg/kg oral on Day 0, 12 dogs; long metabolite half-life justifies once-daily dosing | Active Metabolite Day 0 4.7 ± 6.2 831 ± 357 13.7 ± 10.7 8460 ± 3527 |
| auc | 8460 ± 3527 hr*ng/mL (active metabolite, Day 0) | AUC0-24 column (one complete dosing interval); 20 mg/kg oral on Day 0, 12 dogs; Day 6 (10 mg/kg) 12094 ± 8195 | Active Metabolite Day 0 4.7 ± 6.2 831 ± 357 13.7 ± 10.7 8460 ± 3527 |
Target-animal safety
dose multiples 1-2X, 10-20X, 15-30X; duration Twenty-six weeks (interim necropsy at 13 weeks); total daily dose split twice daily by oral gavage; animals 7/sex/group (four groups).
Fifty-six Beagle dogs were assigned to four groups (7/sex/group). An interim sacrifice of 3 dogs/sex/group was conducted after 13 weeks of dosing. Animals were seven months of age at the time of initiation of dosing.
| Finding | Quote |
|---|---|
| No drug-related changes in body weight gain, food consumption, clinical signs or ophthalmology. | There were no drug-related changes in body weight gain, food consumption, clinical signs, or results of ophthalmologic examinations. |
| One 300 mg/kg/day female: neutrophilic leukocytosis, decreased RBC/Hb/PCV, protein, albumin, calcium from chronic gastric ulceration. | At weeks 6 and 14, one female dog in the 300 mg/kg/day group showed neutrophilic leukocytosis, decreased RBC, Hb and PCV, decreased serum total protein, decreased albumin, and decreased calcium (later confirmed to be a result of chronic gastric ulceration at the week 27 necropsy). |
| Gross gastric lesions at 26 weeks: 0, 1, 2 and 4 dogs at 0, 20, 100 and 300 mg/kg/day. | Necropsy results demonstrated gross gastric lesions in no dogs in the 0 mg/kg/day group, one dog in the 20 mg/kg/day group, two dogs in the 100 mg/kg/day group, and four dogs in the 300 mg/kg/day group. |
| Gastric ulceration histologically confirmed in 2 of 4 high-dose dogs with gross lesions. | Gastric ulceration was confirmed by histopathology in the highest dose group (300 mg/kg/day) in 2 of the 4 dogs with gross gastrointestinal abnormalities. |
| Conclusion: dose-related adverse reactions with gastric ulceration in the high-dose group; GI abnormalities in all dose groups. | Adverse reactions were dose related and resulted in gastric ulceration (with associated clinical pathol ogy changes) in the high dose group (300 mg/kg/day). Abnormalities of the ga strointestinal tract (enteritis, mild mucosal hemorrhage and congestion) were noted in all dosage groups. |
Effectiveness
Multi-centered (10 US clinics) controlled field study (1930C-61-V98-372) with active control carprofen 2.2 mg/kg twice daily; tepoxalin 20 mg/kg on day 1 then 10 mg/kg daily for six days (7 days total); non-inferiority on Day 0 to Day 6 success rates.; n = 122 (62 tepoxalin, 60 carprofen); primary endpoint: Success (decrease of at least one score Day 0 to Day 6) for ease of ambulation, weight bearing, pain on palpation, pain on forced movement, investigator and owner overall evaluation and general attitude; lower 90% confidence bound of the difference vs carprofen.; result: Tepoxalin non-inferior to carprofen: success 92% vs 81% ease of ambulation (lower bound -2.5%), 84% vs 80% weight bearing, 86% vs 87% pain on palpation, 95% vs 90% investigator evaluation, 94% vs 92% owner evaluation.
Two-hundred and five dogs were evaluated for safety and 122 (62 tepoxalin and 60 carprofen) were evaluated for effectiveness.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomition | 2/101 | 5/104 | Tablets (n= 101) Number of dogs treated with carprofen (n= 104) Vomition 2 5 Diarrhea 4 0 Anorexia 0 1 Ineffectiveness 0 1 Incoordination 1 0 Death** 1 - |
| Diarrhea | 4/101 | 0/104 | Tablets (n= 101) Number of dogs treated with carprofen (n= 104) Vomition 2 5 Diarrhea 4 0 Anorexia 0 1 Ineffectiveness 0 1 Incoordination 1 0 Death** 1 - |
| Incoordination | 1/101 | 0/104 | Tablets (n= 101) Number of dogs treated with carprofen (n= 104) Vomition 2 5 Diarrhea 4 0 Anorexia 0 1 Ineffectiveness 0 1 Incoordination 1 0 Death** 1 - |
| Death | 1/101 | Tablets (n= 101) Number of dogs treated with carprofen (n= 104) Vomition 2 5 Diarrhea 4 0 Anorexia 0 1 Ineffectiveness 0 1 Incoordination 1 0 Death** 1 - | |
| Anorexia | 0/101 | 1/104 | Tablets (n= 101) Number of dogs treated with carprofen (n= 104) Vomition 2 5 Diarrhea 4 0 Anorexia 0 1 Ineffectiveness 0 1 Incoordination 1 0 Death** 1 - |
Extraction notes: PK values are means ± SD from Study N00-576 (12 dogs, 20 mg/kg then 10 mg/kg daily); parent tepoxalin has a short half-life because it is converted to a long-lived active metabolite; the summary notes substantial inter/intra-subject variability. Target animal safety uses the 26-week gavage study (0/20/100/300 mg/kg/day, described as 1-2X/10-20X/15-30X); a one-year study (10/30/100 mg/kg/day, 0.5-1X to 5-10X) found gastric erosion/ulceration only at 100 mg/kg/day, and an uncontrolled 28-day European field safety study (n=107) reported diarrhea 23, vomiting 21 and two deaths. Adverse reactions are from the US field study (n=101 Zubrin vs n=104 carprofen); the table quote starts after the 'ZUBRIN' word because the source renders its trademark symbol as a private-use character; the one Zubrin death occurred two days after study completion with gastric ulcerations and could not be definitively attributed. Quotes preserve source spacing artifacts ('asso ciated', 'pathol ogy', 'ga strointestinal').
Reproduce: foi_structured_search(query="tepoxalin") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).