This study evaluated treatment of canine generalized demodicosis with off-label milbemycin oxime.Therapeutic ivermectin doses can cause neurotoxicity in dog breeds that harbor a mutation in the ABCB1 gene (ABCB1-1Δ). In addition, neurologic side effects have been previously identified with milbemycin at therapeutic dosages for generalized demodicosis.This study assessed the association of the ABCB1-1Δ mutation with milbemycin-induced neurologic toxicity.Dogs with generalized demodicosis (n = 22) who demonstrated breed sensitivity to ivermectin or poor clinical responses to previous therapies were included in the study.Generalized demodicosis was confirmed by skin scrapes, and buccal swabs were used for ABCB1-1Δ genotyping. Identified genotypic groups included ABCB1-1Δ wt/wt (n = 19, normal), ABCB1-1Δ wt/mut (n = 1, normal, carrier), and ABCB1-1Δ mut/mut (n = 2,mutant).Adverse neurologic events occurred in 2 dogs, and both dogs were genotypic mutants. Milbemycin doses in both dogs were decreased to tolerable levels.The neurologic side effect identified in this study was ataxia, unlike the ataxia,mydriasis, tremors, hypersalivation, coma, respiratory compromise, and death seen in ivermectin toxicosis.These data suggest that milbemycin might be a safer therapy for generalized demodicosis in dogs with mutant alleles.

COMMENTARY: This study identifies milbemycin as a potential toxicant for dogs with the ABCB1-1Δ genotype although the toxicity is less severe than with ivermectin.This finding suggests that the clinical veterinarian should carefully monitor medication type and dosage in patients with such mutations.Additional studies with larger sample sizes might lead to more consistent and robust associations.—Indu Mani, DVM, DSc (infectious disease)

ABCB1-1Δ(MDR1-1Δ) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Barbet JL, Snook T, Gay JM,Mealey KL.VET DERMATOL 20:111-114, 2008.