Trilostane: what the FDA reviewed for dog products
2 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Trilostane, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- VETORYL® CAPSULES (NADA/ANADA 141-291)
VETORYL® CAPSULES NADA 141-291, Original approval, December 05, 2008; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 855; FDA PDF
Indication
Treatment of pituitary-dependent hyperadrenocorticism in dogs; treatment of hyperadrenocorticism due to adrenocortical tumor in dogs
Dose regimen
1.0-3.0 mg/lb (2.2 – 6.7 mg/kg) starting dose, oral (capsule), with food, once a day, Starting dose by body weight and capsule size; adjust based on clinical signs, ACTH stimulation test results and adverse reactions
The starting dose for the treatment of hyperadrenocorticism in dogs is 1.0-3.0 mg/lb (2.2 – 6.7 mg/kg) once a day based on body weight and capsule size. VETORYL Capsules should be administered with food.
Target-animal safety
dose multiples 1X (6.7 mg/kg twice daily), 3X (20.1 mg/kg twice daily), 5X (33.5 mg/kg twice daily); duration 90 days (3 months), twice daily with food; animals Thirty-two.
Purpose of the Study: To evaluate the safety of trilostane in dogs after oral administration at 1X, 3X, and 5X the recommended maximum starting dosage (6.7 mg/kg) twice daily for 3 consecutive months (90 days). Description of Test Animals: Thirty-two 6-month old Beagles; the females weighed 5.0 to 8.9 kg and males weighed 6.4 to 10.3 kg at the start of the study.
| Finding | Quote |
|---|---|
| Deaths: 3 dogs at 3X and 5 dogs at 5X died between days 23 and 46 | Three dogs from the 3X and five dogs from the 5X group died between 23 and 46 days on the drug. |
| Hyponatremia, hyperkalemia and azotemia consistent with hypoadrenal crisis in dogs that died | Bloodwork showed hyponatremia, hyperkalemia, and azotemia, which are consistent with hypoadrenal crisis. |
| No ACTH stimulation response at 3X and 5X; 1X retained some stimulation | ACTH stimulation tests: The dogs in the 3X and 5X groups had no stimulation. The 1X dogs mean pre-stimulation cortisol was similar to the 0X groups. |
| Dose-dependent adrenal hypertrophy in all treated groups (adrenal cortical hypertrophy on histopathology) | Dose-dependent adrenal hypertrophy was seen in all treated groups. |
| 3X and 5X dogs had lower sodium, albumin, total protein and cholesterol; dose-dependent amylase increase | The 3X and 5X dogs had lower sodium, albumin, total protein, and cholesterol compared to the 0X dogs. There was a dose-dependent increase in the amylase in all treated groups. |
| 6.7 mg/kg twice daily for 90 days generally well tolerated; 20.1 and 33.5 mg/kg caused significant morbidity and mortality | Trilostane administered at 6.7 mg/kg twice daily for 90 days was generally well-tolerated by healthy Beagle dogs. |
Effectiveness
US multi-center open-label field study with historical control (Report EC/TRILO2005/PROTO(FDA001)): 107 client-owned dogs with spontaneous hyperadrenocorticism enrolled, 83 evaluable, starting dose 2.2-6.7 mg/kg/day once daily with food, dose titrated by ACTH stimulation test, 84 days. Supported by two UK open-label field studies (75 enrolled, 30 evaluable; 26/30 = 86.7% success at 24 weeks).; n = 80; primary endpoint: Day 84 treatment success: post-ACTH cortisol <9.1 µg/dL AND investigator-documented clinical improvement; effective if lower one-sided 95% CI >50%; result: 64/80 (80.0%) treatment successes at Day 84 (lower one-sided 95% CI 72.6%); mean post-ACTH cortisol fell from 32.3 to 4.5 µg/dL (p<0.0001); 93% of dogs clinically improved by Day 84
Of the 80 cases remaining for the evaluation of treatment success on Day 84, 64 (80.0%) were considered treatment successes.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Adrenal necrosis/rupture | 2 dogs | Adrenal necrosis/rupture (2 dogs) and hypoadrenocorticism (2 dogs) were the most severe adverse reactions in the study. | |
| Hypoadrenocorticism | 2 dogs | Adrenal necrosis/rupture (2 dogs) and hypoadrenocorticism (2 dogs) were the most severe adverse reactions in the study. | |
| Diarrhea | 31 dogs | The most common of these included diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs), musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs), otitis externa (8 dogs), respiratory signs (coughing, congestion) (7 dogs), and skin/coat abnormality (seborrhea, pruritus) (7 dogs). | |
| Lethargy | 30 dogs | The most common of these included diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs), musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs), otitis externa (8 dogs), respiratory signs (coughing, congestion) (7 dogs), and skin/coat abnormality (seborrhea, pruritus) (7 dogs). | |
| Vomiting | 28 dogs | The most common of these included diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs), musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs), otitis externa (8 dogs), respiratory signs (coughing, congestion) (7 dogs), and skin/coat abnormality (seborrhea, pruritus) (7 dogs). | |
| Inappetence/anorexia | 27 dogs | The most common of these included diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs), musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs), otitis externa (8 dogs), respiratory signs (coughing, congestion) (7 dogs), and skin/coat abnormality (seborrhea, pruritus) (7 dogs). | |
| Musculoskeletal signs (lameness, worsening of degenerative joint disease) | 25 dogs | The most common of these included diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs), musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs), otitis externa (8 dogs), respiratory signs (coughing, congestion) (7 dogs), and skin/coat abnormality (seborrhea, pruritus) (7 dogs). |
Extraction notes: Open-label field study with no control group; adverse reaction counts are from the 107-dog US safety population (denominator not in the quoted sentence). Enrollment 107, evaluable 83, 80 remaining at Day 84 (n_dogs). No pharmacokinetic data in this summary. TAS n_animals is spelled out in the text ('Thirty-two'; 8 per group, 4M/4F). A 1979 dose-tolerance study (8/32/128 mg/kg once daily, 90 days; 4 deaths at 128 mg/kg) is also summarized but not captured as the margin-of-safety study.
VETORYL® CAPSULES NADA 141-291, Supplemental approval, June 05, 2009; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 856; FDA PDF
Indication
Treatment of pituitary-dependent hyperadrenocorticism and of hyperadrenocorticism due to adrenocortical tumor in dogs.
Dose regimen
Starting dose 1.0-3.0 mg/lb (2.2-6.7 mg/kg), Oral, Once a day, with food, Starting dose by body weight band and capsule size (10 mg for 3.8 to <10 lb; 30 mg for 10 to <22 lb; 60 mg for 22 to <44 lb; 120 mg for 44 to <88 lb; 180 mg for 88 to <132 lb)
The starting dose for the treatment of hyperadrenocorticism in dogs is 1.0-3.0 mg/lb (2.2 – 6.7 mg/kg) once a day based on body weight and capsule size. VETORYL Capsules should be administered with food.
Extraction notes: Supplemental approval adding a 10 mg capsule size only. CVM did not require effectiveness or target animal safety studies; the summary refers to the original NADA 141-291 FOI summary (December 5, 2008) for dosage characterization, effectiveness and safety. No PK, safety or effectiveness content (validator warning expected).
Reproduce: foi_structured_search(query="Trilostane") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).