The Most-Reported Veterinary Drug Ingredients in the FDA Adverse-Event Database
Ranking the top 40 active ingredients by report volume in the FDA CVM adverse-event database: Spinosad, Milbemycin Oxime, Ivermectin, and the drug classes that dominate veterinary pharmacovigilance.
The FDA Center for Veterinary Medicine (CVM) collects adverse-event reports for animal drugs through a combination of mandatory manufacturer submissions and voluntary reports from veterinarians, owners, and other professionals. The resulting openFDA database contains over 1.34 million reports spanning 1987 through early 2026, covering 21,690 distinct active ingredients.
This article ranks the most-reported ingredients, examines what drives their report volume, and discusses what high report counts do and do not mean about drug safety. Every number comes from a direct computation of the FDA CVM animal drug adverse-event database (analysis run date: 2026-06-09).
Why report volume is not a risk score
Before looking at the rankings, three caveats are essential:
Widely used drugs accumulate more reports. A parasiticide prescribed to millions of dogs each month will generate more reports than a niche oncology drug used in hundreds — even if both have identical per-dose risk profiles. Report volume primarily reflects market penetration and prescription frequency.
Reports are suspicions, not causal proof. The FDA explicitly states that reports in this database have not been verified for causality. A report linking an ingredient to vomiting does not mean the ingredient caused the vomiting.
Under-reporting is substantial. The FDA acknowledges that only a fraction of adverse events are reported. The gap between actual events and reported events varies by product, reporter type, and public awareness.
With those caveats, the data reveals which drug classes dominate veterinary pharmacovigilance — and where monitoring attention concentrates.
The top 40 active ingredients by report count
The database contains 2,122,812 total ingredient mentions (reports can list multiple ingredients). The top 40 ingredients account for 66.1% of all mentions. The top 10 alone account for 44.4%.
| Rank | Active ingredient | Reports | % of total | Cumulative % |
|---|---|---|---|---|
| 1 | Spinosad | 206,522 | 9.7% | 9.7% |
| 2 | Milbemycin Oxime | 182,072 | 8.6% | 18.3% |
| 3 | Ivermectin | 118,426 | 5.6% | 23.9% |
| 4 | Pyrantel As Pamoate Salt | 89,876 | 4.2% | 28.1% |
| 5 | Moxidectin | 74,377 | 3.5% | 31.6% |
| 6 | Selamectin | 61,977 | 2.9% | 34.5% |
| 7 | Praziquantel | 54,541 | 2.6% | 37.1% |
| 8 | Afoxolaner | 53,081 | 2.5% | 39.6% |
| 9 | Carprofen | 50,978 | 2.4% | 42.0% |
| 10 | Pyrantel Pamoate;Sarolaner | 49,878 | 2.3% | 44.4% |
| 11 | Ivermectin, Pyrantel | 39,413 | 1.9% | 46.2% |
| 12 | Fluralaner Chew Tablets | 35,502 | 1.7% | 47.9% |
| 13 | Oclacitinib Maleate | 28,535 | 1.3% | 49.2% |
| 14 | Fluralaner 13.64% 12-Week Chew | 27,173 | 1.3% | 50.5% |
| 15 | Milbemycin | 23,168 | 1.1% | 51.6% |
| 16 | Imidacloprid | 21,273 | 1.0% | 52.6% |
| 17 | Nitenpyram | 21,208 | 1.0% | 53.6% |
| 18 | Bedinvetmab | 17,894 | 0.8% | 54.5% |
| 19 | Sarolaner | 17,264 | 0.8% | 55.3% |
| 20 | Meloxicam | 16,916 | 0.8% | 56.1% |
| 21 | Melarsomine Dihydrochloride | 16,865 | 0.8% | 56.9% |
| 22 | Cyclosporine | 16,311 | 0.8% | 57.6% |
| 23 | Fluralaner Spot-On Solution | 14,110 | 0.7% | 58.3% |
| 24 | Maropitant Citrate | 12,594 | 0.6% | 58.9% |
| 25 | Pyrantel Pamoate | 12,577 | 0.6% | 59.5% |
| 26 | Lufenuron | 12,175 | 0.6% | 60.0% |
| 27 | Deracoxib | 11,930 | 0.6% | 60.6% |
| 28 | Trilostane | 11,789 | 0.6% | 61.2% |
| 29 | Lotilaner | 11,064 | 0.5% | 61.7% |
| 30 | Pyrantel | 9,765 | 0.5% | 62.1% |
| 31 | Gabapentin | 9,677 | 0.5% | 62.6% |
| 32 | Cefovecin | 9,194 | 0.4% | 63.0% |
| 33 | Selamectin;Sarolaner | 9,069 | 0.4% | 63.5% |
| 34 | Prednisone | 8,981 | 0.4% | 63.9% |
| 35 | Milbemycin, Lufenuron | 8,393 | 0.4% | 64.3% |
| 36 | Enrofloxacin | 8,338 | 0.4% | 64.7% |
| 37 | Grapiprant | 7,991 | 0.4% | 65.1% |
| 38 | Firocoxib | 7,670 | 0.4% | 65.4% |
| 39 | Frunevetmab | 7,389 | 0.3% | 65.8% |
| 40 | Florfenicol | 6,834 | 0.3% | 66.1% |
Product-class patterns
The top 40 ingredients cluster into five therapeutic classes:
1. Parasiticides (ranks 1–6, 8, 10–17, 19, 23, 26, 29–30, 33, 35)
Parasiticides dominate the list. Spinosad, milbemycin oxime, ivermectin, pyrantel, moxidectin, selamectin, afoxolaner, fluralaner, sarolaner, lotilaner, imidacloprid, nitenpyram, and lufenuron collectively account for the majority of report volume. This is not surprising: parasite prevention is the most frequently prescribed drug category in companion-animal veterinary medicine. Monthly dosing year-round means billions of doses over the dataset's 39-year span.
Several parasiticides appear multiple times under different combination-product names. Ivermectin appears at rank 3 (standalone), rank 11 (combined with pyrantel), and in the background of combination products. Pyrantel appears at ranks 4, 10, 25, and 30 in different salt forms and combinations. Fluralaner appears at ranks 12 (chew tablets), 14 (12-week chew formulation), and 23 (spot-on solution). This fragmentation reflects the market reality of multi-indication parasiticide products.
2. NSAIDs (ranks 9, 20, 27, 37, 38)
Carprofen (50,978), meloxicam (16,916), deracoxib (11,930), grapiprant (7,991), and firocoxib (7,670) together represent the veterinary NSAID class. Carprofen is the clear report-volume leader — it has been the most widely prescribed canine NSAID for over two decades. The NSAID class carries inherent pharmacovigilance weight because of gastrointestinal, renal, and hepatic monitoring requirements.
Carprofen's report profile is notable: 13.8% of its reports list "Died" as an outcome and 3.1% list "Euthanized," giving it the highest combined fatality rate among the top 10 ingredients. This does not mean carprofen is more dangerous — it reflects its use in older dogs with comorbidities, the long duration of NSAID therapy, and the tendency to report serious outcomes. Its top reactions are vomiting (24.8%), anorexia (19.2%), elevated ALT (16.8%), and elevated SAP (14.9%) — the classic NSAID monitoring panel.
3. Monoclonal antibodies (ranks 18, 39)
Bedinvetmab (17,894 reports) for canine osteoarthritis pain and frunevetmab (7,389 reports) for feline osteoarthritis pain represent the newest therapeutic class on the list. Both are anti-nerve-growth-factor (anti-NGF) monoclonal antibodies with relatively recent FDA approvals (frunevetmab in January 2022, bedinvetmab in May 2023). Their presence in the top 40 reflects rapid clinical uptake and the heightened reporting that accompanies new biologic therapies. For bedinvetmab specifically, 17,894 reports for a drug approved in 2023 represents one of the most concentrated reporting bursts in the database — likely driven by manufacturer reporting obligations for a new molecular entity.
4. Neurological and endocrine drugs (ranks 13, 22, 28, 31, 34)
Oclacitinib maleate (28,535) for allergic dermatitis, cyclosporine (16,311) for immune-mediated conditions, trilostane (11,789) for hyperadrenocorticism, gabapentin (9,677) for chronic pain, and prednisone (8,981) represent the chronic-therapy segment. These drugs require ongoing monitoring and generate report volume through repeated dosing and documented monitoring events.
Oclacitinib's 28,535 reports are remarkable for a drug approved in 2013 — it has accumulated report volume at a pace exceeded only by the highest-volume parasiticides, reflecting the enormous demand for allergic-dermatitis treatment in dogs.
5. Antibiotics and anti-infectives (ranks 32, 36, 40)
Cefovecin (9,194), enrofloxacin (8,338), and florfenicol (6,834) are the anti-infective representatives. Cefovecin's report volume reflects the convenience-driven adoption of this long-acting injectable cephalosporin, particularly in cats. Enrofloxacin carries a well-documented adverse-event profile including retinal toxicity in cats. Florfenicol is primarily a cattle antibiotic.
Deep dive: the top 3 ingredients
Spinosad — 206,522 reports
Spinosad is the single most-reported active ingredient in the entire database. It is a nicotinic acetylcholine receptor agonist used primarily as a flea treatment, most widely known as a component of combination heartworm/flea preventive products.
- Species: 87.2% dog, 5.7% cat, 6.9% unspecified
- Top outcomes: Recovered/Normal 50.4%, Outcome Unknown 22.3%, Recovered with Sequela 4.7%
- Top reactions: Emesis 29.0%, Vomiting 23.7%, Lethargy 11.2%, Flea LOE 10.0%, Unpalatable 8.2%
- Died: 3,551 reports (1.7%)
The signature issue is emesis and vomiting — together accounting for over 52% of spinosad reports. This is a well-documented palatability and GI-tolerance issue recognized in the product label. The high report volume also reflects the product's ivermectin interaction warning (spinosad can potentiate ivermectin toxicity when used concurrently, which generated a specific FDA safety communication).
Milbemycin Oxime — 182,072 reports
Milbemycin oxime is a macrocyclic lactone antiparasitic used for heartworm prevention, intestinal parasites, and as part of combination products.
- Species: 92.2% dog, 0.3% cat, 7.4% unspecified
- Top outcomes: Recovered/Normal 47.6%, Outcome Unknown 31.2%, Ongoing 7.5%
- Top reactions: Emesis 23.4%, Vomiting 20.5%, Lethargy 11.6%, Unpalatable 7.5%, Heartworm LOE 7.2%
- Died: 2,942 reports (1.6%)
Like spinosad, milbemycin oxime's report profile is dominated by GI effects and palatability complaints. The heartworm LOE signal (7.2%) reflects the intense scrutiny applied to heartworm prevention efficacy — every positive heartworm test in a dog on preventive generates a report.
Ivermectin — 118,426 reports
Ivermectin is the broadest-spectrum ingredient on the list, used across dogs, cattle, horses, and other species. It has been in veterinary use since the 1980s.
- Species: 86.7% dog, 9.1% unspecified, 1.5% cattle, 1.0% horse, 0.8% cat
- Top outcomes: Outcome Unknown 43.3%, Recovered/Normal 15.6%, Ongoing 12.2%, Recovered with Sequela 11.9%
- Top reactions: Heartworm LOE 18.7%, Hookworm LOE 12.2%, Ineffective heartworm larvae 11.7%, Vomiting 11.3%
- Died: 3,115 reports (2.6%)
Ivermectin's reaction profile is dominated by lack-of-efficacy reports (42.6% combined heartworm and hookworm LOE) — reflecting its long history as a heartworm preventive and the accumulated efficacy-questioning volume over decades. The high "Outcome Unknown" rate (43.3%) reflects the historical reporting patterns of earlier decades, when outcome tracking was less systematic.
What report volume tells us about veterinary pharmacovigilance
Several patterns emerge from the ingredient-level data:
Report volume follows prescription volume. The most-prescribed drug classes — parasiticides and NSAIDs — dominate the report counts. No rare or niche drug appears in the top 40 purely on the basis of risk.
New drugs generate concentrated reporting. Bedinvetmab's 17,894 reports from a 2023 approval, and oclacitinib's 28,535 reports from a 2013 approval, both outpace many older drugs with decades of use. Manufacturer reporting obligations for new molecular entities, post-marketing surveillance requirements, and heightened clinician awareness all contribute.
Combination products fragment the data. The same active ingredient appears under multiple product names. Total ivermectin exposure, for example, is distributed across at least three entries in the top 40. Total fluralaner exposure spans three formulations. Total pyrantel spans four. This fragmentation makes per-ingredient risk assessment more complex than the raw ranking suggests.
The LOE signal is enormous. Lack-of-efficacy reports for parasiticides — heartworm, flea, hookworm — collectively represent one of the largest single categories in the database. This is a data artifact of the reporting system (product failure is a reportable event) and a reflection of the compliance-dependent nature of parasite prevention.
Sources
- FDA Center for Veterinary Medicine, Adverse Event Reporting System. openFDA Animal Drug Adverse Event API. Available at: https://open.fda.gov/apis/animalandveterinary/event/
- FDA CVM, "Adverse Event Reports for Animal Drugs and Devices." Available at: https://www.fda.gov/animal-veterinary/product-safety-information/adverse-event-reports-animal-drugs-and-devices
- Elanco, Trifexis (spinosad + milbecinm oxime) prescribing information. Available at: https://my.elanco.com/us/campaign/trifexis
- FDA CVM, "Animal Drug Safety-Related Labeling Changes." Available at: https://www.fda.gov/animal-veterinary/drug-labels/animal-drug-safety-related-labeling-changes
- EMA CVMP, Trifexis EPAR Public Assessment Report. Available at: https://www.ema.europa.eu/en/documents/assessment-report/trifexis-epar-public-assessment-report_en.pdf
