Dexmedetomidine: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Dexmedetomidine, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dog.
Products
- SILEO® (NADA/ANADA 141-456)
SILEO® NADA 141-456, Original approval, November 19, 2015; sponsor Orion Corp.; species: Dog; foi_id 942; FDA PDF
Indication
Treatment of noise aversion in dogs.
Dose regimen
125 mcg/m2, Oromucosal (onto the oral mucosa between cheek and gum; must not be swallowed), first dose 30-60 minutes before the noise stimulus or at first signs; may be repeated if the event lasts longer than 2-3 hours, with at least two hours between doses, No more than 5 doses per noise event; if swallowed do not repeat for at least two hours
SILEO is administered onto the oral mucosa between the dog’s cheek and gum at the dose of 125 mcg/m2. The gel is absorbed through the oral mucosa and therefore it should NOT be swallowed. If the gel is swallowed, the product may not be effective. If the gel is swallowed, do not repeat the dose for at least two hours. The first dose of SILEO should be administered approximately 30-60 minutes before the fear and/or anxiety-eliciting noise stimulus, immediately after the dog shows first signs of anxiety or fear related to noise, or when the owner detects a typical noise stimulus (e.g. sound of fireworks) eliciting anxiety or fear in the dog. If the noise event lasts longer than 2-3 hours and the dog’s signs of fear and/or anxiety reappear, another dose may need to be given. To avoid overdosing, there should always be at least two hours’ pause between dosages. No more than 5 doses can be given during one noise event.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | 28% (average, oromucosal) | oromucosal administration in dogs (stated in TAS section, bridging to DEXDOMITOR injectable) | On average the bioavailability of dexmedetomidine after oromucosal administration is 28%. |
| tmax | 45-60 minutes | single oromucosal dose, healthy Beagle dogs, pilot non-clinical laboratory studies | Dexmedetomidine was absorbed from the mucosa of dogs and had maximum plasma concentrations 45-60 minutes after a single dose. |
Target-animal safety
dose multiples 375, 1125, 1875 mcg/m2 IV, 500, 1500, 2500 mcg/m2 IM; duration once daily on three consecutive days.
A target animal safety study of dexmedetomidine hydrochloride sterile injectable (DEXDOMITOR) was conducted at doses of 375, 1125, and 1875 mcg/m2
| Finding | Quote |
|---|---|
| Injectable dexmedetomidine well tolerated even at high doses; physiologic effects related to pharmacology; no toxicological effects on body weight, clinical variables, gross or microscopic pathology | Dexmedetomidine was well tolerated in the study even at the high dose levels, and adverse effects on physiology were related to the pharmacology of the drug. There were no toxicological effects on body weight, clinical variables, gross or microscopic pathology. |
| Pilot lab studies: 125 and 250 mcg/m2 repeated up to 5 times at 2-hour intervals did not sedate excessively; reversible bradycardia, hypothermia and blood pressure changes in non-anxious dogs | Reversible changes in bradycardia, hypothermia, and blood pressure were seen in non-anxious/fearful dogs in the 125 mcg/m2 and 250 mcg/m2 dosing groups in the studies. |
| DEXDOMITOR TAS study dosing: IV 375/1125/1875 or IM 500/1500/2500 mcg/m2 once daily for three consecutive days (continuation of the design sentence across a page break) | administered once daily intravenously (IV), or 500, 1500, and 2500 mcg/m2 administered once daily intramuscularly (IM), on three consecutive days. |
Effectiveness
Pivotal randomized, vehicle-controlled, masked multicenter field study (Finland and Germany, 14 investigators) during New Year's Eve fireworks; 125 mcg/m2 oromucosal gel, re-dosing allowed at >= 2 h intervals; owner-assessed co-primary endpoints; 187 randomized, 182 treated (89 dexmedetomidine, 93 vehicle); n = 144 evaluated for effectiveness (71 treated, 73 control); primary endpoint: Co-primary: owner overall treatment effect vs previous years (excellent/good/some/none/worse) and sum of 12 behavior scores 1 hour after each dose; result: Good or excellent effect in 53/71 dexmedetomidine vs 24/73 control dogs (p<0.0001, odds ratio 5.5876); mean behavior sum score lower with dexmedetomidine (LSMeans 4.9661 vs 7.2456, p=0.0069); no excessive sedation
d. Results: 144 animals (71 treated and 73 control) were evaluated for effectiveness. For the first co -primary endpoint, the proportion of dogs with good or excellent treatment effect was higher in dogs treated with dexmedetomidine oromucosal gel (53/71 dogs) than in those administered control (24/73 dogs).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Emesis | 4 (4.5) | 1 (1.1) | Emesis 1 (1.1) 4 (4.5) Gastroenteritis 0 1 (1.1) |
| Gastroenteritis | 1 (1.1) | 0 | Emesis 1 (1.1) 4 (4.5) Gastroenteritis 0 1 (1.1) |
| Periorbital edema | 1 (1.1) | 0 | Periorbital edema 0 1 (1.1) Drowsiness 0 1 (1.1) Sedation 0 1 (1.1) |
| Drowsiness | 1 (1.1) | 0 | Periorbital edema 0 1 (1.1) Drowsiness 0 1 (1.1) Sedation 0 1 (1.1) |
| Sedation | 1 (1.1) | 0 | Periorbital edema 0 1 (1.1) Drowsiness 0 1 (1.1) Sedation 0 1 (1.1) |
Extraction notes: Original approval. No SILEO-specific TAS study: safety relies on the DEXDOMITOR (NADA 141-267) injectable TAS study; the target_animal_safety entry records that bridging statement (the summary does not label those doses as 1X/3X/5X). Adverse reaction table (Table 5) columns are Control N = 93 first, then Dexmedetomidine N = 89, number (%) of dogs; treated/control fields have been assigned accordingly. The summary misprints the field-study dose as '125 mg/m2' in places.
Reproduce: foi_structured_search(query="Dexmedetomidine") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).