Review highlights management of eprinomectin neurotoxicosis in cats

A new review on the management of eprinomectin neurotoxicosis in cats lands at a time when the risk is becoming harder for small-animal clinicians to ignore. The paper, published in the Journal of Veterinary Emergency and Critical Care, is designed as a clinical resource focused on diagnosis and management of a macrocyclic lactone toxicity that appears uniquely important in cats with P-glycoprotein deficiency. That matters because recent case series and follow-up reporting have tied labeled use of eprinomectin-containing parasiticides to severe, and sometimes fatal, neurologic events in this identifiable feline subpopulation. (pubmed.ncbi.nlm.nih.gov)

The backstory has developed quickly over the past few years. In 2024, Mealey and colleagues reported that application of eprinomectin-containing parasiticides at label doses caused neurologic toxicosis in cats homozygous for the feline MDR1 variant, ABCB1 1930_1931del TC. Then, a 2025 JAVMA report evaluating cases collected between March 1 and December 31, 2024, found 27 included macrocyclic lactone toxicosis cases, 26 of them linked to eprinomectin. Among those 26 eprinomectin cases, 21 cats, or 81%, were homozygous for the MDR1 variant, and overall 12 of 27 affected cats died or were euthanized. The authors concluded that eprinomectin-containing parasiticides should not be used in cats with P-glycoprotein deficiency and said a label warning is indicated. (onlinelibrary.wiley.com)

That signal is especially relevant because eprinomectin is now part of mainstream feline parasite control. FDA labeling for NexGard COMBO lists eprinomectin as one of its active ingredients, and the product is approved for multiple feline parasite indications. In addition, the FDA issued an Emergency Use Authorization on February 18, 2026, allowing NexGard COMBO to be used for treatment of New World screwworm infestations in cats and kittens, even though that is not the product’s original approved use. In practice, that means more veterinarians may encounter eprinomectin in urgent-care as well as preventive-care settings. (dailymed.nlm.nih.gov)

The new review’s core value is likely operational: helping teams recognize the syndrome early and manage it systematically. Based on the abstracted source material, diagnosis hinges on recent drug history plus neurologic examination, with signs including mydriasis and ataxia. Broader literature around feline P-glycoprotein deficiency also suggests clinicians should think beyond the parasiticide alone. Research and conference proceedings from this group have raised concern that concurrent administration of other P-glycoprotein substrate drugs, including agents such as cyclosporine or methylprednisolone in reported cases, may contribute to toxicity risk or complicate interpretation. (onlinelibrary.wiley.com)

Expert and institutional commentary has been notably direct. Washington State University, where Mealey leads related work, has said it receives frequent reports of serious reactions in cats after eprinomectin exposure and now lists eprinomectin under “do not use” for cats with the MDR1 mutation. WSU also emphasizes that, unlike in dogs, there isn’t a strong breed-based shortcut for deciding which cats to test, which shifts the conversation toward either broader genetic screening or more conservative product selection when genotype is unknown. (news.wsu.edu)

Why it matters: For veterinary professionals, this is a pharmacovigilance story with immediate exam-room implications. The key shift is that a labeled feline dose of a commercially available parasiticide may be unsafe in a genetically defined subset of cats, not merely after overdose, misuse, or exposure to livestock formulations. That raises the stakes for medication history, informed consent, adverse-event reporting, and protocol design around feline parasite prevention. It also creates a practical tension: eprinomectin-containing products offer broad-spectrum convenience, but convenience is less compelling when genotype is unknown and safer alternatives may exist for some patients. (pubmed.ncbi.nlm.nih.gov)

There’s also a broader systems issue. The feline MDR1 story is expanding from toxicology into everyday therapeutics, with newer work examining which clinically relevant drugs function as feline P-glycoprotein substrates. That means the implications may extend beyond eprinomectin alone to sedation, oncology, internal medicine, and polypharmacy decisions, especially in emergency and specialty settings. The new management review may help standardize acute care, but prevention, including pre-prescription awareness and selective genetic testing, is where the biggest clinical gains may come. (pubmed.ncbi.nlm.nih.gov)

What to watch: The next developments to watch are whether manufacturers or regulators add stronger safety language, whether MDR1 testing becomes more routine before prescribing certain feline parasiticides, and whether the literature produces clearer treatment algorithms, interaction warnings, or outcome data for supportive care in affected cats. (pubmed.ncbi.nlm.nih.gov)