Most Commonly Reported Pet Medications in FDA Adverse Events, PlainBreed

How We Counted Reports

The numbers in this guide come from the FDA openFDA Animal & Veterinary Adverse Events database, which covers reports from 2004 through the most recent quarterly update. Report counts represent unique adverse event submissions associated with each drug name, whether as a primary suspect drug or as a concomitant medication.

PlainBreed's drug directory covers 2,558 medications. The 15 listed here have the highest report volumes among the primary registry entry for each active ingredient across all species. Because the FDA registers drugs by individual formulation, the same active ingredient can appear under multiple names (e.g., various fluralaner dosage forms); report figures here reflect the count for the main named entry and may understate total reports for multi-formulation drugs. Figures are approximate and subject to quarterly database updates.

One important caveat: report counts are not standardized by prescription volume. A drug used by 10 million animals will naturally accumulate more reports than a drug used by 50,000 animals, even if both carry identical per-use risk. Interpreting these numbers requires holding the usage context in mind.

Top 15 Most Reported Medications

The table below ranks drugs by total adverse event report count across all species in the FDA openFDA database. Report counts are approximate figures based on the most recent available data.

#	Drug Name	Primary Species	Reports	Common Reactions
1	Spinosad (Comfortis) Oral flea preventative; spinosyn class (not isoxazoline)	Dog, Cat	66,000+	Vomiting, lethargy, tremors, hypersalivation
2	Afoxolaner (NexGard) Isoxazoline class; widely prescribed	Dog	52,000+	Vomiting, diarrhea, lethargy, seizures
3	Fluralaner (Bravecto) Isoxazoline class; FDA warning 2018; primary chew formulation	Dog, Cat	35,000+	Vomiting, lethargy, diarrhea, neurological signs
4	Carprofen (Rimadyl) NSAID; long market history	Dog	22,000+	GI upset, renal effects, hepatic events
5	Sarolaner (Simparica) Isoxazoline class	Dog	17,000+	Neurological signs, vomiting, tremors
6	Prednisone / Prednisolone Corticosteroid; many indications	Dog, Cat	16,000+	Polyuria, polydipsia, weight gain, GI effects
7	Ivermectin MDR1 gene sensitivity in herding breeds	Dog, Horse	11,500+	Neurological signs, ataxia, dilated pupils
8	Meloxicam NSAID; used for pain and inflammation	Dog, Cat	11,000+	GI irritation, renal effects, edema
9	Milbemycin Oxime Heartworm prevention; antiparasitic	Dog, Cat	9,500+	Vomiting, lethargy, ataxia
10	Cyclosporine (Atopica) Immunosuppressant; allergy management	Dog, Cat	9,500+	GI upset, infections, papillomas
11	Amoxicillin / Clavulanate Broad-spectrum antibiotic; aggregate across formulations	Dog, Cat	9,000+	GI upset, vomiting, diarrhea
12	Tramadol Opioid analgesic; pain management	Dog	3,500+	Sedation, incoordination, vomiting
13	Metronidazole Antibiotic/antiparasitic; broad use	Dog, Cat	3,000+	Vomiting, neurological signs, anorexia
14	Cephalexin First-gen cephalosporin antibiotic	Dog, Cat	2,500+	GI effects, allergic reactions
15	Phenobarbital Anticonvulsant; chronic use risk	Dog, Cat	1,500+	Hepatotoxicity, sedation, polyphagia

Source: FDA openFDA Animal & Veterinary Adverse Events API FDA openFDA Animal & Veterinary Adverse Events API Report counts are approximate and updated quarterly

Compiled by the " research team.

The Isoxazoline Story

Among the drugs in this table, three isoxazoline-class products have the highest report volumes within their class: afoxolaner (NexGard, #2), fluralaner (Bravecto, #3), and sarolaner (Simparica, #5). Spinosad (Comfortis), which tops the overall list, is a spinosyn-based oral flea preventative (a different drug class), but shares the same high-prescribing flea-prevention market that drives large report volumes. Isoxazolines and spinosyns became dominant in the market after 2014, and their report volumes surged correspondingly. They are now among the most widely prescribed veterinary medications globally.

In 2018, the FDA issued a Drug Safety Communication specifically for isoxazolines, noting reports of neurological adverse reactions including muscle tremors, ataxia, and seizures in dogs and cats. The FDA required manufacturers to add updated labeling. This does not mean the drugs are prohibited, they remain approved, but it indicates that veterinarians and pet owners should be aware of this signal, particularly in animals with prior seizure history.

You can explore individual isoxazoline drug profiles on PlainBreed's drugs directory to see the full reaction breakdown and species distribution for each product.

NSAIDs and Pain Medications

Non-steroidal anti-inflammatory drugs (NSAIDs) like carprofen, meloxicam, and deracoxib are among the most commonly prescribed veterinary medications for pain and inflammation, and they appear consistently in adverse event lists. GI irritation is the most frequently reported reaction, followed by renal effects with chronic use.

Carprofen (sold as Rimadyl and generics) has one of the longest adverse event records in the database due to its decades-long market presence. Context matters enormously here, carprofen is also one of the most prescribed canine medications, which explains its high report count without indicating it is disproportionately dangerous.

NSAID adverse events in dogs are also linked to MDR1 genetic variants in herding breeds. If your dog is a Collie, Australian Shepherd, Shetland Sheepdog, or similar breed, discuss MDR1 testing with your veterinarian before starting NSAIDs or ivermectin-class drugs. Browse breed profiles on PlainBreed to see documented reactions for your dog's breed.

Antibiotics and Antiparasitic Drugs

Metronidazole, amoxicillin-clavulanate, and cephalexin rank in the top 15 primarily because they are among the most broadly used antibiotics in veterinary practice. Their adverse event profiles are dominated by GI effects, vomiting and diarrhea, which are common across many antibiotic classes. Serious outcomes are relatively rare compared to report volume.

Ivermectin is a notable exception in the antiparasitic category. While it has a strong safety record in most animals, certain dog breeds, particularly herding breeds with the MDR1 (ABCB1) genetic mutation, can experience severe neurotoxicity at doses that are safe for other dogs. Reports for ivermectin disproportionately include neurological reactions: ataxia, dilated pupils, coma, and in some cases death.

Milbemycin oxime, another heartworm preventative, carries a similar caveat for MDR1-positive breeds. The breed directory on PlainBreed includes breed-level data on these reports, allowing you to compare the ivermectin reaction profile specifically for herding breeds versus the general dog population.

Corticosteroids and Immunosuppressants

Prednisone and prednisolone rank in the top 15 across dogs and cats due to their wide range of indications, allergies, inflammatory conditions, immune-mediated diseases, and cancer protocols. Their reported adverse events largely reflect expected pharmacological effects at therapeutic doses: increased thirst and urination, increased appetite, weight gain, and susceptibility to infections.

Long-term corticosteroid use is associated with more serious effects including adrenal suppression, diabetes mellitus, and opportunistic infections. These appear in the database at lower frequencies than the acute GI effects but represent the more clinically significant risks. Cyclosporine (Atopica), used for allergic dermatitis, has a similar profile with additional concerns around papilloma formation and secondary infections in immunocompromised animals.

Cross-Referencing with Breed Data

PlainBreed allows you to approach adverse event data from two directions: by drug (which breeds appear in reports for a given medication?) and by breed (which drugs appear in reports for a given breed?). This cross-referencing is particularly valuable for high-report drugs where risk is not evenly distributed across the animal population.

For example, if you look at ivermectin reports filtered to Collie breeds, you will see a reaction profile dominated by neurological events, very different from the broader ivermectin population. This breed-specific lens is exactly the kind of insight the database can provide that a general drug insert cannot.

Start with the drugs directory to find a drug profile, then use the breeds directory to look up your pet's specific breed and see which drugs appear most in its reports.

What to Do Before Starting a New Medication

If your veterinarian recommends a medication that appears on this list, that alone is not a reason for concern, most pets tolerate these drugs without incident. But reviewing the drug's adverse event profile on PlainBreed before starting treatment can help you:

Identify the most commonly reported early warning signs to watch for
Understand whether your pet's breed is disproportionately represented in that drug's reports
Know which reactions are classified as serious versus minor
Have an informed conversation with your veterinarian about monitoring frequency
Know when to call the veterinarian or emergency clinic if a reaction occurs

You can also check the rankings section of PlainBreed for additional comparative data on breeds and species by report volume and outcome rates.

Frequently Asked Questions

Which pet medication has the most adverse event reports in the FDA database?

Antiparasitic drugs, particularly flea, tick, and heartworm preventatives, consistently top the adverse event list by total report count. Isoxazoline-class antiparasitics (including fluralaner and sarolaner) have accumulated tens of thousands of reports, primarily neurological in nature. High report counts partly reflect widespread prescribing, not just elevated risk. The FDA issued a warning about this drug class in 2018 and required updated labeling.

Does a high report count mean a medication is dangerous?

Not necessarily. Report counts are influenced by how widely a drug is prescribed, how long it has been on the market, and how actively the manufacturer solicits feedback. A drug taken by millions of animals will accumulate more reports than a niche drug, even if both have similar adverse event rates. The more meaningful metric is the proportion of reports that resulted in serious outcomes, hospitalization, disability, or death, compared to total reports.

Are topical flea treatments safer than oral medications for adverse events?

Both have adverse event records in the FDA database. Topical treatments can cause localized skin reactions and, in cats, serious systemic toxicity if a dog-formulated product is accidentally applied. Oral medications are associated more frequently with gastrointestinal reactions and, for some drug classes, neurological effects. The "safer" choice depends on your pet's species, weight, age, and health history, always a veterinary decision.

What species appear most in medication adverse event reports?

Dogs account for the largest share of reports by far, partly because dogs are more commonly medicated than other species and because many antiparasitic drugs are labeled specifically for dogs. Cats represent the second-largest group, with horses and livestock making up most of the remainder. Species-specific reports are especially valuable because drug metabolism differs significantly between dogs and cats, a dose safe for one can be toxic for the other.

How do I find adverse event data for a specific medication on PlainBreed?

Visit the Drugs directory at plainbreed.com/drugs/ and search or browse for your medication by name. Each drug profile lists total reports, outcome distribution, most common reactions, and the species most represented. You can cross-reference with the breed directory if you want to see whether specific breeds appear disproportionately in that drug's reports.

Should I avoid all medications that appear in the adverse event database?

No. Nearly every approved medication has some adverse event record, that is expected and does not indicate the drug is unsafe. The adverse event database exists to surface patterns that might otherwise go undetected. The question for any medication is whether the documented benefit outweighs the documented risk for your individual pet, in consultation with your veterinarian who knows your animal's complete health picture.

Sources

U.S. FDA openFDA, Animal & Veterinary Adverse Events API (api.fda.gov/animalandveterinary)
FDA Center for Veterinary Medicine, Drug Safety Communication: FDA Alerts Pet Owners and Veterinarians about Potential for Neurological Adverse Events with Isoxazoline Class of Drugs (September 2018)
FDA, Animal Drug Safety Communications (fda.gov/animal-veterinary/animal-drug-safety-information)
PlainBreed database, 2,558 drugs, 1M+ reports, 2004–2025 (openFDA source)

This content is for informational purposes only and does not constitute veterinary advice. Report counts are approximate and reflect the most recent quarterly openFDA update. Consult your veterinarian before starting, stopping, or changing any pet medication.