Diazepam: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Diazepam, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Veteeze® Injection (NADA/ANADA 140-848)
Veteeze® Injection NADA 140-848, Original approval, December 17, 1992; sponsor Roche Vitamins, Inc.; species: Dogs; foi_id 2213; FDA PDF
Indication
Preanesthetic agent to reduce the amount of barbiturate required for short-duration anesthesia in dogs.
Dose regimen
0.2 mg diazepam/kg, intravenous, single dose, 3-5 minutes before inducing anesthesia with a short-acting barbiturate
A single intravenous dose of 0.2 mg diazepam/kg body weight, 3-5 minutes before inducing anesthesia with a short acting barbiturate.
Target-animal safety
dose multiples 25X (5 mg/kg IV daily for 30 days), 50X (10 mg/kg IV, acute escalating), 100X (20 mg/kg IV single dose), 5X (1.1 mg/kg IV, 20 doses over 4 weeks), 10X (2 mg/kg IV/IM, 10 doses over 2 weeks); duration 30 days daily IV (25X study); other studies 1 dose to 4 weeks; animals Four dogs (2 male, 2 female) per group.
Four dogs (2 male, 2 female) were assigned to each treatment group and were injected intravenously with 1 mL Veteeze (5 mg diazepam)/kg daily for a period of 30 days.
| Finding | Quote |
|---|---|
| Moderate to marked increase in alkaline phosphatase at 5 mg/kg/day x30 days | A moderate to marked increase of alkaline phosphatase. Dogs in control group levels were 111 and group 2 had increased levels up to 416 U/L. |
| Increased liver weight (~15% relative) in treated groups | Increased liver weights were observed in the treated groups. On an absolute basis the mean liver weight of the control dogs was 325 gms vs 434 for the medicated dogs. |
| Intracanalicular cholestasis more frequent in treated groups | Intracanalicular cholestatsis was observed more often in the treated groups. |
| Ataxia and sedation for ~3 h after each 5 mg/kg injection, mainly in week 1 | Ataxic gait and sedation were observed for approximately three hours after injection, mainly during the first experimental week. |
| 30-day dosing at 25X confirmed safety of the 0.2 mg/kg dose | This 30-day dosing at 25 times the approved level confirms the safety of the preanesthetic dose of 0.2 mg a.i./kg b.w. of injectable diazepam in the dog (a.i. means active ingredient). |
| Acute: 5 and 10 mg/kg produced ataxia/sedation; 20 mg/kg produced hypnosis 30-60 min; all survived | Diazepam at 5 and 10 mg/kg I.V. produced ataxia and sedation, while 20 mg/kg I.V. produced hypnosis for 30-60 minutes. All dogs survived and were considered normal by 48 hours postdosing. |
Effectiveness
Blinded, placebo-controlled pivotal clinical study C-88-23 in 90 client dogs (30 per group) randomized to 0.1 or 0.2 mg/kg IV diazepam or sterile water placebo 3-5 min before thiamylal induction; three further field studies (C-89-10, C-89-13, C-89-14) and a 4x4 Latin-square laboratory dose titration in 24 dogs; n = 90; primary endpoint: Amount of thiamylal (mg/kg) required for satisfactory endotracheal intubation; result: C-88-23: 7.77 mg/kg thiamylal at 0.2 mg/kg diazepam (28% reduction vs control 10.81 mg/kg); 8.8 mg/kg at 0.1 mg/kg (18.6%); pooled four studies: average 20% reduction in thiamylal (P < .017); 0.2 mg/kg consistently superior to 0.1 mg/kg
Ninety (90) dogs of various breeds, age and sex, which were surgical candidates from routine hospital admissions, were randomly assigned by a computer-generated schedule to treatments of 0.1, 0.2 mg/kg body weight of diazepam (as Veteeze Injection) or sterile water placebo.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Post-operative reactions (hyperexcitability, nausea, vomiting/retching, excessive salivation) in study C-89-10 | three in each diazepam treatment group | one (placebo) | Adverse reactions were recorded for 7 dogs; three in each of the treatment groups and one in the placebo group. |
Extraction notes: 1992 original approval. No pharmacokinetic data in the summary. Adverse reactions were reported only in study C-89-10 (90 dogs); the other three field studies and the titration study reported none. The 25X 30-day study also compared heat-stressed and degradation-product-spiked diazepam; findings were the same in all three treated groups.
Reproduce: foi_structured_search(query="Diazepam") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).