Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygous MDR1-deficient collie dogs

J Vet Pharmacol Ther. 2022 Jul;45(4):373-379. doi: 10.1111/jvp.13064. Epub 2022 May 10.


Afoxolaner, an insecticide and acaricide compound of the isoxazoline class, is available for dogs as an oral ectoparasiticide medicine (NexGard®) and as an oral endectoparasiticide medicine in combination with milbemycin oxime (MO), a macrocyclic lactone (NexGard® Spectra). The safety of these two compounds, alone or in combination, was investigated in homozygous MDR1-deficient collie dogs, in two studies. Overall, 30 adult collie dogs were treated once orally, 9 with a placebo, 9 with afoxolaner, 6 with MO, and 6 with a combination of afoxolaner and MO. For afoxolaner, the mean investigated dosage corresponded to 3.8 and 4.7 multiples of the maximum recommended therapeutic doses (RTD) in NexGard® and NexGard® Spectra, respectively. For MO, the mean investigated dosage corresponded to 4.7 multiples of the maximum RTD in NexGard® Spectra. Dogs were closely monitored for adverse reactions on the day of treatment and for the following two days. No significant adverse reaction was observed in any dog from the afoxolaner or the afoxolaner + MO groups; in the MO-only treated group, mild and transient neurological signs were observed during the 4-8 h post-treatment window. These studies demonstrated a high level of safety of oral afoxolaner, alone or in combination with milbemycin oxime, in homozygous MDR1-deficient dogs.

Keywords: MDR1 deficient dog; afoxolaner; macrocyclic lactone; milbemycin oxime; safety.

MeSH terms

  • Administration, Oral
  • Animals
  • Dog Diseases* / chemically induced
  • Dog Diseases* / drug therapy
  • Dog Diseases* / genetics
  • Dogs
  • Isoxazoles
  • Macrolides
  • Naphthalenes


  • Isoxazoles
  • Macrolides
  • Naphthalenes
  • afoxolaner
  • milbemycin oxime