Fenbendazole, Ivermectin, Praziquantel: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Fenbendazole, Ivermectin, Praziquantel, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Panacur® Plus (NADA/ANADA 141-286)
Panacur® Plus NADA 141-286, Original approval, May 09, 2008; sponsor Intervet, Inc.; species: Dogs; foi_id 850; FDA PDF
Indication
Treatment and control of adult Toxocara canis, Ancylostoma caninum, Trichuris vulpis and Dipylidium caninum, and prevention of heartworm disease caused by Dirofilaria immitis, in adult dogs.
Dose regimen
Minimum 100 mg fenbendazole, 6 mcg ivermectin and 5 mg praziquantel per kg body weight, Oral, Monthly, Administered at monthly intervals
PANACUR Plus Soft Chews should be administered orally at monthly intervals at the recommended minimum dose level of 100 mg fenbendazole, 6 mcg ivermectin, and 5 mg praziquantel per kg of body weight.
Target-animal safety
dose multiples 0X, 1X, 3X, 5X; duration Once every two weeks for a total of six treatments (Days 0, 14, 28, 42, 56, 70); 77-day study; animals 12 males and 12 females (Twenty four).
Twenty four 16 ± 1 week-old Beagles (12 males and 12 females), weighing 4.7 to 6.75 kg (10.34 to 14.85 pounds) on Day -1, were blocked by weight and randomized to one of four treatment groups.
| Finding | Quote |
|---|---|
| No clinically relevant treatment-related changes in food consumption, clinical pathology, necropsy or histopathology; all dogs healthy and gained weight | There were no clinically relevant treatment related changes in food consumption, hematology, clinical chemistries, coagulation parameters, urinalyses, necropsies, or histopathology. |
| Gastrointestinal signs (soft feces, diarrhea, vomiting) within 24 hours of dosing in all groups | The primary clinical signs were gastrointestinal reactions, including soft feces, diarrhea and vomiting, observed within 24 hours of dosing in all groups. |
| Increased vomiting 4 hours post-dose in the 5X group on 3 of 6 dosing days | A significant increase in vomiting (p = 0.06) was observed 4 hours post-dosing in the 5X group on 3 out of 6 dosing days. |
| Ivermectin-sensitive Collie study (Study 2045-013-01, 16 Collies at 0X/1X/3X/5X of the maximum Shetland Sheepdog exposure): mild mydriasis in one 5X dog only | A mild ivermectin toxicity reported as mydriasis was observed in one dog treated with the 5X dose as a single observation 8 hours post-treatment lasting 1 hour. |
Effectiveness
Eight controlled laboratory dose-confirmation studies (single oral dose, placebo control, necropsy worm/scolex counts on Day 7 or 12, or Day 125 for heartworm), several including non-interference arms with single actives: T. canis natural (20 dogs) and induced (12); A. caninum natural (24) and induced (40); T. vulpis induced (20) and natural (40); D. caninum natural (20 and 40); D. immitis induced (20 and 40). No effectiveness field study; a 106-dog field safety/palatability study was conducted; primary endpoint: Percent effectiveness from geometric mean worm counts at necropsy versus control (threshold 90%); result: T. canis 94.8% (natural) and 92.9% (induced); A. caninum 94.6% and 96.2%; T. vulpis 99.2% and 99.6%; D. caninum 100% in both studies; D. immitis 100% in both studies. Single actives were not effective against the non-target parasites (e.g. praziquantel 0% vs A. caninum; ivermectin 76.4% and praziquantel 27.8% vs T. vulpis; fenbendazole and ivermectin 0% vs D. caninum)
The results of the worm counts at necropsy demonstrate that the control dogs were adequately infected with T. canis, the geometric mean worm count for the PANACUR Plus Soft Chew group was significantly less than the geometric mean worm count of the control group (p <0.001), and the PANACUR Plus Soft Chew was 94.8% (≥ 90%) effective against natural T. canis infections.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea / soft stool (field study, N = 105) | 9 (8.6%) | Diarrhea / soft stool 9 (8.6) | |
| Light colored stool (field study, N = 105) | 9 (8.6%) | Light colored stool 9 (8.6) | |
| Vomiting (field study, N = 105) | 7 (6.7%) | Vomiting 7 (6.7) | |
| Decreased appetite (field study, N = 105) | 2 (1.9%) | Decreased appetite 2 (1.9) | |
| Lethargy (field study, N = 105) | 2 (1.9%) | Lethargy 2 (1.9) | |
| Death/euthanasia after dark diarrhea and dehydration (one dog, D. caninum non-interference laboratory study; pre-existing subclinical disease) | One dog treated with the PANACUR Plus Soft Chews developed dark diarrhea, dehydration and was euthanized six days after treatment. |
Extraction notes: Original approval (2008). No PK section. Target animal safety: margin-of-safety study 2045-003-01 in 24 Beagles at 1X/3X/5X of the maximum toy-breed exposure dose every 2 weeks for 6 doses (Table 11 mg/kg levels: 1X = 324 mg/kg fenbendazole, 19.3 mcg/kg ivermectin, 16.4 mg/kg praziquantel); n_animals expressed as '12 males and 12 females' because 'Twenty four' is spelled out in the design quote. A separate Collie ivermectin-sensitivity study (16 dogs) is summarised in findings. Effectiveness has no field study; n_dogs left null and per-study counts are in design; the quoted result is the first pivotal T. canis study. Adverse reaction rows are from the uncontrolled 106-dog field safety study (Table 9, N = 105, single column: number of dogs and percent); hypersalivation 1 (1.0) omitted. Palatability was not demonstrated in that study (59-68% voluntary acceptance).
Reproduce: foi_structured_search(query="Fenbendazole, Ivermectin, Praziquantel") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).