The isoxazoline class of flea and tick preventives — Bravecto (fluralaner), NexGard (afoxolaner), Simparica (sarolaner), and Credelio (lotilaner) — has been widely prescribed since the first product was approved in 2013. These medications are effective. They are also the subject of an FDA safety communication that every pet owner using them should understand.

This article focuses specifically on the neurologic risk signal: what the FDA said, what the labels now state, which patients are most affected, and how to have a productive conversation with your veterinarian about whether an isoxazoline is appropriate for your pet.

What the FDA said

In September 2018, the FDA Center for Veterinary Medicine issued an Animal Drug Safety Communication alerting pet owners and veterinarians to the potential for neurologic adverse events in dogs and cats treated with isoxazoline-class products. The alert was updated in 2019 and again in 2021 to include additional products as they received approval.

The agency stated that post-marketing data showed some animals receiving Bravecto, NexGard, or Simparica experienced adverse events including muscle tremors, ataxia (loss of coordination), and seizures. The FDA noted these reactions occurred in animals both with and without a prior history of neurologic disorders.

The FDA did not recall or withdraw any product. The agency stated it "considers products in the isoxazoline class to be safe and effective for dogs and cats" but asked manufacturers to update labeling so veterinarians and pet owners could make individualized treatment decisions.

A companion FDA Fact Sheet for pet owners summarized the position: these products "can and have been safely used in the majority of dogs and cats," but owners should consult their veterinarian and review medical history before choosing an isoxazoline.

Which products carry the label warning

The FDA worked with manufacturers to add a class-wide neurologic warning to labels. Products in the isoxazoline class include:

Revolution Plus was approved after the initial FDA alert and was the first product to launch with the updated label language already included. NexGard's labeling was subsequently updated by the sponsor (then Merial, now Boehringer Ingelheim). All isoxazoline-containing products now carry the class warning.

What the neurologic reactions look like

The FDA describes three categories of neurologic adverse events in its communication:

• Muscle tremors — involuntary shaking or twitching
• Ataxia — uncoordinated movement, stumbling, or appearing "drunk"
• Seizures — convulsive episodes, which may occur in animals with no prior seizure history

Onset timing varies. Some reports describe reactions within hours of the first dose; others occur after multiple doses with no prior issues. This inconsistency is one reason the FDA chose to issue a class-wide alert rather than flag a single product.

What the evidence actually shows

FDA post-marketing data

The FDA's alert was based on routine post-marketing surveillance — the adverse event reports that manufacturers are required to submit to the agency. The FDA has not published the raw count of neurologic events, citing limitations in the reporting system: adverse event reports are voluntary, may be incomplete, and cannot by themselves determine causation.

Key context: reporting rates for veterinary adverse events are widely acknowledged to be low. A medication with relatively few reports may still cause more events than the data capture.

The Project Jake survey

An independent online survey called "Project Jake" collected responses from 2,751 pet owners and veterinarians between 2017 and 2020. Of the 1,594 dogs in the survey that received a flea treatment, 1,325 received an isoxazoline product. Among those, 66.6% were reported to have experienced an adverse event, including tremors, ataxia, seizures, and death.

This survey has significant limitations: it was not a controlled clinical study, it relied on owner self-reporting, and it likely attracted respondents whose pets had already experienced problems (selection bias). The findings cannot establish incidence rates in the general population. The survey is useful for understanding the range of reported experiences, not for calculating actual risk.

Clinical trial and prescribing data

In pre-approval clinical trials, neurologic adverse events were reported at low frequencies. The labels for Bravecto and NexGard describe seizures and tremors as uncommon. Post-approval, Merck has described the neurologic effect classification for Bravecto as "rare," which in pharmacovigilance terminology corresponds to an incidence of roughly 1 in 10,000.

Individual veterinary clinics have reported widely varying experiences — some with thousands of doses prescribed and no neurologic reactions observed, others with sporadic cases.

Who is at higher risk

The FDA's guidance and the updated labels emphasize one clear risk factor: pets with a history of seizures or neurologic disorders are at higher risk. The agency specifically recommends that veterinarians review patient medical histories before prescribing.

What is less clear — and what the FDA explicitly acknowledges — is whether apparently healthy animals with no prior neurologic history can be predicted to have a reaction. The agency states that "seizures may occur in animals without a prior history," which means the absence of a seizure history does not guarantee safety, only that the baseline risk is lower.

Additional factors that are biologically plausible but not well quantified in the veterinary literature:

• Species sensitivity — cats may have different thresholds than dogs, though the data for cats is more limited
• Age — very young or very old animals may be more susceptible
• Concurrent medications — interactions have not been systematically studied
• Underlying, undiagnosed neurologic conditions — a pet that has never had a seizure may still have a low seizure threshold

What the label says you should do

The updated labels for all isoxazoline products now include language directing veterinarians to:

1. Use their training to evaluate the patient's medical history
2. Discuss the risks and benefits with the pet owner
3. Consider whether an isoxazoline is appropriate for each individual pet

For pet owners, the labels recommend:

• Monitoring for signs of neurologic adverse events after administration
• Contacting a veterinarian immediately if tremors, ataxia, or seizures are observed
• Reporting adverse events to the manufacturer or to the FDA (1-888-FDA-VETS)

Alternatives to isoxazolines

Isoxazolines are not the only option for flea and tick prevention. Alternatives include:

• Fipronil-based topicals (e.g., Frontline) — different mechanism of action, no class-wide neurologic warning, but may be less effective against ticks in some regions
• Selamectin (Revolution, without the sarolaner component) — not an isoxazoline; covers fleas, some ticks, heartworm, and ear mites
• Spinosad (Comfortis) — oral flea-only product; the label notes it should be used with caution in dogs with a seizure history
• Imidacloprid-based topicals (e.g., Advantage) — flea-only, no tick coverage
• Nitenpyram (Capstar) — short-acting oral flea treatment; can be used for rapid knockdown but is not a preventive
• Physical barriers — tick checks, lawn management, limiting exposure to tall grass and wooded areas

No preventive is risk-free. The question for each pet is whether the benefits of a product (especially tick-borne disease prevention) outweigh the risks, given that animal's individual history.

What to ask your veterinarian

If your pet is on an isoxazoline or you are considering one, the following questions are directly informed by the FDA's guidance and the updated label language:

1. "Does my pet have any history of seizures, tremors, or neurologic episodes?" — If yes, the FDA recommends extra caution. Ask about non-isoxazoline alternatives.

2. "What is the tick-borne disease risk where we live?" — In areas with high Lyme, anaplasmosis, or ehrlichiosis prevalence, the disease-prevention benefit of an effective tick product may outweigh the neurologic risk. In low-risk areas, the calculus shifts.

3. "Are there alternatives that provide comparable protection without the isoxazoline class warning?" — Your veterinarian can tell you whether alternatives like fipronil or selamectin (without sarolaner) are sufficient for your pet's exposure level.

4. "What should I watch for after giving the dose?" — Know the signs of muscle tremors, ataxia, and seizures. Most reactions occur within hours to days of dosing.

5. "If my pet has a reaction, what do I do?" — Have a plan. Know the after-hours emergency clinic. Ask whether you should induce vomiting (the answer depends on timing and product).

6. "Should I report an adverse event?" — Both the FDA and the product manufacturer track these reports. Reporting helps the agency update its safety signals.

A note on risk perspective

The FDA has not withdrawn isoxazoline products, and many veterinary professionals continue to prescribe them — often to their own pets. The known risk of tick-borne and flea-borne disease is well-established and, in endemic areas, may be more consequential than the low individual risk of a neurologic event.

At the same time, the agency's decision to add a class-wide label warning — and its explicit statement that seizures can occur without prior history — is not routine. It reflects a signal serious enough to warrant transparency and individualized decision-making.

The right answer depends on your pet's medical history, your geographic risk, and your tolerance for uncertainty. That decision is between you and your veterinarian — but it should be an informed one.

Sources

• FDA Animal Drug Safety Communication: FDA Alerts Pet Owners and Veterinarians About Potential for Neurologic Adverse Events Associated with Certain Flea and Tick Products. U.S. Food and Drug Administration. https://www.fda.gov/animal-veterinary/cvm-updates/animal-drug-safety-communication-fda-alerts-pet-owners-and-veterinarians-about-potential-neurologic
• FDA Fact Sheet for Pet Owners and Veterinarians about Potential Adverse Events Associated with Isoxazoline Flea and Tick Products. U.S. Food and Drug Administration. https://www.fda.gov/animal-veterinary/animal-health-literacy/fact-sheet-pet-owners-and-veterinarians-about-potential-adverse-events-associated-isoxazoline-flea
• Bravecto (fluralaner) prescribing information. Merck Animal Health / Intervet Inc.
• NexGard (afoxolaner) prescribing information. Boehringer Ingelheim.
• Simparica (sarolaner) prescribing information. Zoetis.
• Credelio (lotilaner) prescribing information. Elanco.
• Project Jake: Pet Owner and Veterinarian Survey on Isoxazoline Flea and Tick Products. Published June 2020.