Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies

Am J Vet Res. 1991 Jul;52(7):1170-2.


Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / toxicity*
  • Ataxia / chemically induced
  • Ataxia / veterinary*
  • Depression / chemically induced*
  • Dog Diseases / chemically induced*
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Macrolides
  • Male
  • Mydriasis / chemically induced
  • Mydriasis / veterinary
  • Random Allocation
  • Salivation / drug effects


  • Anti-Bacterial Agents
  • Macrolides
  • moxidectin