FDA and European regulators have received tens of thousands of adverse event reports, including seizures and deaths, prompting updated safety warnings for isoxazoline-class drugs
The FDA continues to warn pet owners about the potential for neurologic adverse events in dogs and cats treated with popular flea and tick medications. Products containing isoxazoline compounds, sold under brand names including Bravecto, NexGard, Simparica, and Credelio, have been associated with seizures, muscle tremors, and loss of coordination in some animals, even those with no prior history of neurological problems.
These chewable tablets have become among the most prescribed flea and tick preventatives since NexGard first received FDA approval in 2013. However, according to the FDA, post-market surveillance has revealed a troubling pattern of neurological reactions that prompted the agency to require updated labeling across all isoxazoline products beginning in 2018.
The scope of reported adverse events
The numbers paint a concerning picture for pet owners weighing their options. According to research published in Veterinary Medicine and Science in June 2020, FDA adverse event reports from January 2013 to September 2017 documented over 32,000 reportable events in dogs treated with these medications. Data from the European Medicines Agency covering the same period showed approximately 7,000 reports, but with notably higher rates of severe outcomes, including seven to ten times more deaths and seizures reported compared to US figures.
The American Veterinary Medical Association has confirmed that all four major isoxazoline products may cause seizures, tremors, and lost coordination. The organization reported in November 2018 that the FDA had received approximately 5,400 reports of adverse events connected with these drugs by late 2018, with neurologic events occurring at similar rates across the entire product class.
What makes these reactions particularly concerning is their unpredictability. Seizures have occurred in animals with no prior history of neurological disorders, and researchers have been unable to identify specific breeds, ages, or risk factors that might predict which pets will be affected.
How these medications work and why they may affect mammals
Isoxazoline drugs kill parasites by blocking GABA-gated chloride channels in the nervous system of insects and arachnids, causing paralysis and death. The medications were designed to be selective for invertebrate nervous systems, with manufacturers claiming adequate safety margins for dogs and cats.
However, the Project Jake study authors concluded that these compounds can function as intrinsic neurotoxins across species, meaning the mechanism that kills fleas and ticks may occasionally affect the mammalian nervous system as well. GABA is also the primary inhibitory neurotransmitter in mammalian brains, which may explain why some pets experience neurological symptoms.
The most serious adverse events typically appear within 24 hours of the first dose, according to European regulatory data, with additional peaks following second and third doses. Symptoms can range from mild muscle twitching to severe, prolonged seizures.
The regulatory response
The FDA maintains that isoxazoline products remain safe and effective for the majority of pets but has taken several steps to improve transparency. Updated product labels now include explicit warnings about potential neurological effects, and veterinarians are advised to review patient medical histories before prescribing these medications.
For pets with pre-existing seizure disorders or other neurological conditions, veterinary experts generally recommend avoiding isoxazoline products altogether. Some practitioners suggest topical alternatives for these at-risk animals, though these may offer somewhat less effective protection against parasites.
Pet owners who observe adverse reactions are encouraged to contact both their veterinarian and the drug manufacturer. Reports can also be submitted directly to the FDA, which continues to monitor these products through its post-market surveillance program.
Balancing risks and benefits
The situation presents veterinarians and pet owners with difficult decisions. In regions where tick-borne diseases like Lyme disease are prevalent, or in areas with paralysis ticks such as coastal Australia, effective parasite prevention can be lifesaving. Australian veterinarians have noted dramatic reductions in tick paralysis cases since isoxazoline products became widely available, according to Pet Circle's veterinary guide.
For dogs living outside high-risk tick zones, however, the calculation may differ. Some veterinarians recommend discussing individual risk factors with pet owners before prescribing these medications, considering factors such as geographic location, lifestyle, and any history of neurological sensitivity.
Alternative flea and tick prevention methods exist, including topical treatments, flea collars, and environmental management strategies. While generally considered less effective than the newer oral medications, these options may be appropriate for pets who cannot tolerate isoxazoline products.
What's next
Ongoing class action litigation in US courts alleges that manufacturers failed to adequately disclose neurological risks to consumers and veterinarians during the early years these products were on the market. According to court documents, plaintiffs claim they would not have purchased these medications, or would have paid significantly less, had they been aware of the potential for serious adverse reactions.
The FDA has indicated it will continue reviewing adverse event data and working with manufacturers to ensure accurate labeling. For now, the agency's guidance remains unchanged: pet owners should consult their veterinarian about their pet's medical history before choosing any flea and tick prevention product, and should report any concerning symptoms immediately.
Pet owners can report suspected adverse events by contacting manufacturers directly: Merck Animal Health for Bravecto at 800-224-5318, Boehringer Ingelheim for NexGard at 888-637-4251, Zoetis for Simparica at 888-963-8471, or Elanco for Credelio at 888-545-5973. Reports can also be submitted directly to the FDA.
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