Imidocarb Dipropionate: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Imidocarb Dipropionate, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Imizol® (NADA/ANADA 141-071)
Imizol® NADA 141-071, Original approval, November 07, 1997; sponsor Intervet, Inc.; species: Dogs; foi_id 3635; FDA PDF
Indication
Treatment of babesiosis in dogs with clinical signs and/or demonstrated Babesia organisms in the blood.
Dose regimen
6.6 mg/kg b.w. (3 mg/lb; 0.25 mL/10 lb), intramuscular or subcutaneous injection, single injection, repeated in two weeks (total of two treatments), two treatments two weeks apart
IMIZOL® is to be administered at a rate of 6.6 mg/kg b.w. (3 mg/lb) (i.e. 0.25 mL/10 lb.). Repeat the dose in two weeks for a total of two treatments.
Target-animal safety
dose multiples 2.2 mg/kg, 5.5 mg/kg, 7.7 mg/kg, 9.9 mg/kg; duration two subcutaneous doses two weeks apart; clinical chemistry followed through Day 42; animals ten per group (four Imizol dose groups plus one saline control group).
Imizol was administered to four groups of ten, 9 month-old Beagle dogs at 2.2, 5.5, 7.7 or 9.9 mg/kg b.w. subcutaneously, given twice with two weeks between doses. A control group (ten similar animals) was administered saline in an identical manner.
| Finding | Quote |
|---|---|
| Pain on injection in nearly all dogs at every dose | Imizol® caused pain on injection in nearly all animals, regardless of dose. |
| Injection site swelling after the second injection: 4/10 at 2.2 mg/kg and all dogs at higher doses | Injection site reactions (swelling) after the second injection of Imizol were present in 4 out of the 10 dogs which received the lowest dose (2.2 mg/kg) and in all of the dogs which received the higher doses of Imizol. |
| One injection site ulceration at the highest dose (9.9 mg/kg), recurring after the second dose | One injection site reaction (ulceration of injection site) occurred at the highest dose (9.9 mg/kg). |
| Post-treatment vomiting in 1 to 4 of 10 dogs in every Imizol group, not dose related (cholinergic effect) | Post-treatment vomiting was seen in all Imizol-treated groups at a frequency of 1 to 4 out of 10 dogs. The adverse effect was not dose related nor did the dogs respond the same to both injections. These results are consistent with the cholinergic effects attributed to Imizol. |
| Statistically significant ALT and AST increases at 9.9 mg/kg on Days 21, 28 and 35, resolved by Day 42 | On Days 21, 28 and 35 of the study there was a statistically significant increase in serum alanine aminotransferase (ALT, SGPT) and arginine aminotransferase (AST, SGOT) in the 9.9 mg/kg b.w. as compared to the placebo group. At Day 42, these differences were no longer apparent. |
| No effect at any dose on body temperature, body weight, hematology, other clinical chemistry or gross pathology; margin of safety at 6.6 mg/kg SC repeated in two weeks judged adequate | Imizol® had no effects, at any dose level, on body temperature, body weight, hematology, other clinical chemistry values or gross pathology. This study demonstrates that the margin of safety for Imizol® administered to dogs at 6.6 mg/kg b.w. subcutaneously and repeated in two weeks is adequate for its intended use. |
| 90-day oral tolerance study (5, 20 or 80 mg/kg daily): all four males died and two females euthanized in extremis at 80 mg/kg | In the 80 mg/kg group, all the male dogs(4) died during the trial and two of the females were euthanized in extremis. Their clinical signs included salivation, diarrhea, anorexia, dyspnea, tachycardia, listlessness and weakness. |
| Oral tolerance study: no toxicologically significant changes at 5 mg/kg; liver and intestines were the target organs | There were no changes of toxicological significance in the 5 mg/kg group as compared to controls. The target organs of toxicity were liver and intestines in this study of imidocarb using the oral route of administration. |
Effectiveness
Field trials: two published papers (Irwin 1991, Australia; Adeyanju 1982, Nigeria) and one 1996 U.S. multi-investigator clinical trial in pet dogs naturally infected with Babesia canis alone or with other hemoparasites; Imizol 4-5 mg/kg or 10 mg/kg IM or SC; 8 untreated puppies (Irwin 1991) served as controls (all died); n = 325 treated (313 at 4 to 5 mg/kg plus twelve at 10 mg/kg); primary endpoint: Complete recovery or progressive remission of clinical signs (relapse and death also tabulated); result: Complete recovery or progressive remission in 90% (294/325) of treated dogs; two 5 mg/kg dogs relapsed; seven dogs died of babesiosis despite 4-5 mg/kg; none of the 10 mg/kg dogs died; all eight untreated control puppies died; one dog accidentally overdosed at 24 mg/kg died of Imizol toxicity
Imizol® was administered at a dose rate of 4 to 5 mg/kg b.w. by intramuscular or subcutaneous injection to a total of 313 dogs. Twelve dogs received 10 mg/kg b.w. Complete recovery or a progressive remission of clinical signs was reported in 90% (294/325) of the cases treated with either 4 to 5 mg/kg or 10 mg/kg of imidocarb.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Pain at injection and salivation (U.S. field trial) | Pain at the time of injection and salivation were frequently reported by veterinarians in the United States. | ||
| Nasal drips, vomiting, panting, agitation, injection site swelling (transient; field trial) | Other transient adverse effects reported were nasal drips, vomiting, panting, agitation, and injection site swelling. | ||
| Death from Imizol toxicity after accidental overdose (field trial) | 1 dog (24 mg/kg overdose) | One (1) dog which received 24 mg/kg b.w. (accidental overdose) died of Imizol® toxicity. | |
| Post-treatment vomiting (laboratory toxicity study) | 1 to 4 out of 10 dogs per Imizol group | Post-treatment vomiting was seen in all Imizol-treated groups at a frequency of 1 to 4 out of 10 dogs. | |
| Injection site swelling after second injection (laboratory toxicity study) | 4 out of 10 dogs at 2.2 mg/kg; all dogs at higher doses | Injection site reactions (swelling) after the second injection of Imizol were present in 4 out of the 10 dogs which received the lowest dose (2.2 mg/kg) and in all of the dogs which received the higher doses of Imizol. |
Extraction notes: Original NADA (1997). No PK parameters reported (an Abdullah 1984 IV 4 mg/kg study is cited only for adverse effects: 1 of 13 dogs died). Target animal safety dose_multiples are the actual SC doses tested; the summary does not express them as multiples of the 6.6 mg/kg label dose (9.9 mg/kg is 1.5x by arithmetic). Dose determination (93 dogs, 0-6 mg/kg; Guelfi 1980/1981, Euzeby 1981, Awaz 1984) and dose confirmation (1,031 dogs; Ogunkoya 1981 5 mg/kg SC, Bodade 1986 6 mg/kg IM) are literature summaries whose tables were flattened by PDF extraction and are not captured. Field-trial adverse reactions are reported qualitatively with no frequencies and no treated control group (the only controls were 8 untreated puppies). Summary General Information has no Species/Class field; species taken from the indication.
Reproduce: foi_structured_search(query="Imidocarb Dipropionate") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).