Ropinirole: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Ropinirole, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- CLEVOR® (NADA/ANADA 141-534)
CLEVOR® NADA 141-534, Original approval, June 15, 2020; sponsor Orion Corp.; species: Dogs; foi_id 9248; FDA PDF
Indication
Induction of vomiting in dogs.
Dose regimen
target 3.75 mg/m2 (dose band 2.7 - 5.4 mg/m2) as eye drops by body weight, ophthalmic (topical eye drops), single dose; a second dose may be given if the dog does not vomit within 20 minutes, 1-8 eye drops by body weight (Table 1); 30 mg/mL solution, 0.3 mL single-dose dropper (9 mg); doses of 2 or more drops divided between eyes; 6 or 8 drops given as two administrations 2 minutes apart
The number of eye drops administered corresponding to body weight results in a target dose of 3.75 mg/m2 (dose band 2.7 - 5.4 mg/m2). If the dog does not vomit within 20 minutes of the first dose, then a second dose may be administered.
Target-animal safety
dose multiples 0X (saline), 1X, 3X, 5X; duration 3 consecutive days, dosed in 2 sessions per day 20 minutes apart; necropsy Day 4; animals 24 treated (1X, 3X, 5X).
The safety of CLEVOR® was demonstrated in one laboratory study described below (III.A. Margin of Safety Study) in which 24 Beagle dogs were dosed with CLEVOR® twice daily for 3 days at either 1, 3, or 5X doses.
| Finding | Quote |
|---|---|
| Vomiting up to 2 h, retching, hunched posture, labored respiration, salivation, tremors, lethargy, recumbency, ocular signs after dosing | After dosing with ropinirole, clinical observations included vomiting (lasting up to 2 hours), retching, hunched posture, labored respiration, salivation, tremors, lethargy, ventral or lateral recumbency, ocular discharge and hyperemia, blepharospasm, ptosis, and conjunctival erythema. |
| Signs resolved within 6 hours | Dogs returned to normal within 6 hours post-dosing. |
| Positive fluorescein staining in one 3X and one 5X dog without histopathologic lesions | One dog in the 3X ropinirole group and one dog in the 5X ropinirole group had positive fluorescein staining, although corresponding lesions were not identified on histopathology. |
| Increased heart rate at 1 h post-dose in all ropinirole groups (p<0.0001) | In the 1X, 3X, and 5X ropinirole groups there was an initial increase in mean heart rate and corresponding decrease in R-R interval at 1-hour post-dose. |
| Decreased food consumption at 3X and 5X | There was a statistically significant decrease in food consumption for the 3X and 5X ropinirole groups when compared to the control group (p=0.0192 and p=0.0048, respectively). |
| No gross or microscopic pathology effects | Necropsy Examination and Histopathology: There were no drug effects on gross or microscopic pathology. |
Effectiveness
Multicenter (6 sites), prospective, randomized (3:1), masked, vehicle-controlled field study V3111003 in client-owned dogs; 132 enrolled (100 ropinirole, 32 vehicle); dose per body-weight table, repeated at 20 minutes if no vomiting; n = 128 evaluated (99 ropinirole, 29 vehicle); primary endpoint: treatment success = vomiting within 30 minutes of first administration (lower 95% CI bound above 70%); result: 94/99 (95%) ropinirole dogs vomited within 30 minutes vs 0/29 vehicle; estimated success rate 96.9% (95% CI 83.1%, 99.5%); 85 dogs vomited within 20 minutes without a second dose; mean time to vomiting 12 minutes
Effectiveness was evaluated in 128 dogs (99 dogs in the ropinirole group and 29 dogs in the vehicle group).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Conjunctival hyperemia | 51 (51%) | 6 (19%) | Conjunctival hyperemiaa 51 (51%) 6 (19%) |
| Protrusion of the third eyelid | 38 (38%) | 1 (3%) | Protrusion of the third eyelida 38 (38%) 1 (3%) |
| Conjunctival discharge | 30 (30%) | 1 (3%) | Conjunctival dischargea 30 (30%) 1 (3%) |
| Blepharospasm | 19 (19%) | 0 | Blepharospasma 19 (19%) 0 |
| Lethargy | 41 (41%) | 0 | Lethargy 41 (41%) 0 |
| Tachycardia (>160 bpm) | 14 (14%) | 0 | Tachycardia (>160 bpm)a,b 14 (14%) 0 |
Extraction notes: Adverse-reaction rows quoted as extracted from Table II.4 (CLEVOR N=100 vs vehicle N=32; footnote letters attached to terms). Margin-of-safety study enrolled 32 Beagles total (8 saline controls plus 8 per ropinirole group, 4/sex); the design quote gives the 24 treated dogs. 1X was defined as the maximum daily clinical dose of two administrations (8.5-10.6 mg/m2/day), 3X and 5X as 16 and 24 drops/day. Vomiting lasting over 1 hour occurred in 8 field-study dogs (5 received metoclopramide). No PK data in the summary.
Reproduce: foi_structured_search(query="Ropinirole") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).