Isoxazolines in epileptic dogs: the FDA neurological alert
4-year-old Border Collie with idiopathic epilepsy, well controlled on phenobarbital (one seizure in the last 6 months). It lives in an area with many ticks and the owner asks whether it can have a tablet containing an isoxazoline (fluralaner, afoxolaner, sarolaner or lotilaner).
Which answer is most accurate?
chevron_right Show answer and explanation
A. They are not absolutely contraindicated, but tremors, ataxia and seizures have been reported; use them with caution, weighing risks and benefits with the owner
Correct. In 2018 the FDA warned of possible neurological adverse events with isoxazolines, even in dogs with no history, and the product labels advise caution in dogs with a history of seizures. They are uncommon; in a well-controlled epileptic dog they can be used with the owner informed, or another effective alternative chosen.
B. They are completely contraindicated in any dog that has ever had a seizure
The warning is one of caution, not an absolute contraindication. Many epileptic dogs receive them without problems; the decision is individual, taking into account the risk of tick-borne diseases.
C. The risk only exists in dogs with the MDR1 (ABCB1) mutation, so genotyping is sufficient
MDR1-related sensitivity is mainly associated with macrocyclic lactones (ivermectin and similar) at high doses. The FDA alert on isoxazolines is not limited to dogs with this mutation.
D. They are safe because phenobarbital speeds up their metabolism and cancels any neurological effect
There is no basis for claiming that phenobarbital protects against these effects. Enzyme induction does not make safe a warning based on reported clinical cases.
lightbulb Key takeaway
Isoxazolines act on GABA- and glutamate-gated chloride channels, with much greater affinity for those of arthropods. They are highly effective against fleas, ticks and several mites. In patients with seizures, record the decision and informed consent, and ask the owner to report any change.
Test yourself with 10 random questions
Dermatology · 100 questions, a different test every time
Related questions
Updated: October 31, 2026 · Educational content for veterinary professionals. It does not replace current clinical guidelines or the judgement of the attending veterinarian.