Reported Adverse Effects of Isoxazolines in Dogs & Cats

Jason W. Stull, VMD, MPVM, PhD, DACVPM, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada

ArticleLast Updated November 20243 min read
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In the Literature

Bates N, Dijkman MA, Edwards JN. Neurological adverse effects of isoxazoline exposure in cats and dogs. Vet Rec. 2024;194(12):e4149. doi:10.1002/vetr.4149


The Research …

Isoxazolines (eg, afoxolaner, esafoxolaner, fluralaner, lotilaner, sarolaner, tigolaner) are frequently administered orally or topically for treatment and prevention of flea, tick, and mite infestations in dogs and cats. Concerns that drugs in this class may be linked to neurologic adverse effects in dogs and cats have been raised, but the FDA reaffirmed that isoxazoline products are considered safe and effective following a review of internal data.1,2 Data on incidence, risk factors, clinical signs (including duration), and outcomes of neurologic adverse effects are limited but important for identification of potential associations between product use and clinical signs and selection of the optimal product for a patient.

In this study, databases of the Veterinary Poisons Information Service in the United Kingdom and the Dutch Poisons Information Center in the Netherlands were searched for reports of ataxia, muscle tremors, convulsions, or hyperesthesia in dogs and cats exposed to isoxazolines. Cases involving combination products were excluded. A total of 79 cases over a 9-year period were identified; 22 included outcome information. Muscle tremors and convulsions were the most reported neurologic signs. Signs were observed following accidental or intentional administration of doses at or above the label dose, and time to onset in cases with follow-up ranged from 15 minutes to 30 hours in dogs (median, 5 hours) and 1 to 4 hours in cats. All patients with outcome information recovered (dogs, 1 hour to 15 days; cats, 5 hours to 9 days).

Neurologic adverse effects appeared to be infrequently reported, but incidence could not be determined because the frequency of isoxazoline exposure was unknown. Reporting bias was likely, as cases discussed with poison centers tend to involve more severe signs, and pet owners may report adverse effects not associated with drug administration.


… The Takeaways

Key pearls to put into practice:

  • Isoxazoline products are rarely reported to be associated with neurologic adverse effects in dogs and cats. Reported effects are most commonly muscle tremors and convulsions that occur within 24 hours following administration and appear to resolve completely.

  • Owners should be informed of the benefits and potential risks of isoxazoline products.

  • Owners should be advised that a delay of several hours or longer between administration and an adverse effect is possible. Any apparent adverse effects should be reported to the prescribing clinic, including timing of onset and duration to help inform diagnosis and rule out association between clinical signs and the suspected drug.

  • Veterinary team members should immediately report adverse effects that occur following administration of a licenced medication to the drug manufacturer and/or appropriate regulatory authority (eg, FDA in the United States).3