Avermectin-induced neurotoxicity and mortality reported more commonly in cats homozygous for ABCB11930_1931del TC after application of eprinomectin- versus selamectin-containing products.

Objective: To determine the frequency of the feline multidrug resistance 1 (MDR1) mutation (ABCB11930_1931del TC) among cats experiencing macrocyclic lactone neurotoxicosis after treatment with the labeled dosage of eprinomectin- or selamectin-containing parasiticides.

Methods: Feline patients that suffered neurological adverse effects after application of the labeled dosage of eprinomectin- or selamectin-containing parasiticide products were recruited to provide medical records and submit a DNA sample. Those with reactions highly consistent with macrocyclic lactone toxicosis were deemed cases and were compared on the basis of the macrocyclic lactone involved, outcome (survived or died), and MDR1 genotype.

Results: Between March 1 and December 31, 2024, 47 potential cases were identified. Twenty-seven of these met the inclusion criteria. For 26 of the 27 cases, eprinomectin was the causative macrocyclic lactone, while selamectin was the causative macrocyclic lactone for 1 case. The MDR1 genotype distribution for the 26 cases of eprinomectin-induced toxicosis was 21 of 26 (81%) homozygous for ABCB11930_1931del TC, 4 of 26 (15%) homozygous wild type, and 1 (4%) unknown. The genotype for the selamectin-induced toxicosis case was unknown. Eprinomectin-induced neurological toxicosis resulted in death or euthanasia in 12 of 27 cases (44%; 10 homozygous for ABCB11930_1931del TC, 1 homozygous wild type, and 1 unknown).

Conclusions: Neurotoxicosis was observed in cats treated with parasiticide products containing eprinomectin and selamectin at their labeled dosage. Cats with P-glycoprotein deficiency appear to be at increased risk for eprinomectin toxicity.

Clinical relevance: Eprinomectin-containing parasiticides should not be used in cats with P-glycoprotein deficiency. A label warning is indicated to prevent additional serious and fatal adverse reactions in this identifiable subpopulation of cats.