Imidacloprid, Ivermectin: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Imidacloprid, Ivermectin, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Canine.
Products
- Advantage® DUO (NADA/ANADA 141-208)
Advantage® DUO NADA 141-208, Original approval, September 27, 2002; sponsor Elanco US Inc.; species: Canine; foi_id 728; FDA PDF
Indication
Prevention of heartworm disease caused by Dirofilaria immitis; kills adult fleas and treats flea infestations (Ctenocephalides felis).
Dose regimen
Minimum 10 mg/kg imidacloprid + 80 mcg/kg ivermectin (4.5 mg/lb + 36.4 mcg/lb), Topical (entire contents of a unit applicator tube), Once a month, Tube size by body weight: 0.4 mL (up to 9 lb), 1.0 mL (10.1-20 lb), 2.5 mL (20.1-55 lb), 4.0 mL (55.1-88 lb); dogs over 88 lb use a combination of tubes
Recommended minimum dosage is 4.5 mg/lb (10 mg/kg) of imidacloprid + 36.4 mcg/lb (80 mcg/kg) of ivermectin once a month.
Target-animal safety
dose multiples 1X, 3X, 5X; duration Once weekly for 8 treatments (Days 0-49) in 53-59-day-old Beagle puppies; 65-day study (Report #75084); animals 32.
Animals: 32 beagle puppies (16 males and 16 females), 53 – 59 days old, 2.8 to 5.2 lbs.
| Finding | Quote |
|---|---|
| Vomiting within hours of dosing in two 3X and one 5X puppy | Gastrointestinal: Two dogs treated with the 3X dose and one dog treated with the 5X dose vomited within hours of receiving the test article. |
| Leukocytosis with neutrophilia in 1X (1 dog), 3X (3/8) and 5X (1 dog); none in controls | Hematology and Chemistry: One dog in the 1X group, 3/8 dogs in the 3X group, and one dog in the 5X group had a leukocytosis with a concomitant neutrophilia. |
| Transient vomiting, diarrhea and leukocytosis at 1X, 3X and 5X; alopecia/erythema at application site at 3X | Conclusions: Transient vomiting, diarrhea, and leukocytosis were associated with administration of imidacloprid + ivermectin at one, three and five times the recommended dosage. |
| No ivermectin toxicosis in ivermectin-sensitive collies at 3X and 5X dermal doses (Report #75087) | Conclusions: Dermal application of imidacloprid/ivermectin at 3X and 5X the maximum recommended dosage did not produce clinical signs of ivermectin toxicosis in ivermectin-sensitive collies. |
| 10X for three consecutive days: application-site and pinna erythema, vomiting, transient amylase elevation and leukocytosis (Report #75086-1) | Conclusions: Administration of ten times the recommended topical dosage for three consecutive days produced erythema of the application site and of the pinna, white residue and pruritus at the application site, vomiting, and a transient elevation of amylase and leukocytosis with neutrophilia and lymphopenia in beagle dogs. |
| Single oral dose at the dermal 1X dose causes immediate transient vomiting (Report #75085-1) | Conclusions: A single oral dose of 10 mg/kg imidacloprid + 80 mcg/kg ivermectin administered at the recommended dermal dose causes immediate transient vomiting (within 3 hours). |
Effectiveness
Laboratory heartworm prevention study (Report #75123): Beagles experimentally infected with ~50 D. immitis L3 and treated once topically with 10 mg/kg imidacloprid + 80 or 160 mcg/kg ivermectin at 30 or 45 days post-infection (imidacloprid-only controls); necropsy Day 157; n = 48 (8 per group); primary endpoint: Adult heartworm counts at necropsy; result: No heartworms recovered from any combination-treated group (100% effective at 30 and 45 days post-infection); imidacloprid-only controls had 27.8 and 24 worms/dog
Animals: 48 beagles (24 males and 24 females), 20 – 22 weeks old, 8 dogs per group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Pruritus | 10 (5.9%) | 2 (2.7%) | Pruritus 10 (5.9%) 2 (2.7%) |
| Diarrhea/Inappropriate elimination | 10 (5.9%) | 0 | Diarrhea/Inappropriate Elimination 10 (5.9%) 0 |
| White/oily residue | 6 (3.6%) | 2 (2.7%) | White/Oily Residue 6 (3.6%) 2 (2.7%) |
| Vomiting | 5 (2.0%) | 0 | Vomiting 5 (2.0%) 0 |
| Hyperactivity | 3 (1.8%) | 0 | Hyperactivity 3 (1.8%) 0 |
| Anorexia | 2 (1.2%) | 0 | Anorexia 2 (1.2%) 0 |
Extraction notes: Species/Class recorded as 'Canine' exactly as stated. Indication quote is the heartworm sentence as extracted (flea indication sentence is letter-spaced in the PDF text). No PK data. Effectiveness quote gives the study population; the result sentence reads 'No heartworms were recovered from dogs in Groups 1, 2, 3, and 4 on Day 157.' Flea effectiveness (Report #75108, 24 dogs): 95.1-100% through Day 35; bathing studies support labeling. Adverse reaction rows are from the clinical field safety study (Report #75193; 169 test dogs vs 73 control dogs given Advantage + Heartgard), quoted as flattened table rows; one dog died of congestive heart failure (relationship undetermined).
Reproduce: foi_structured_search(query="Imidacloprid, Ivermectin") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).