What clinical features and outcomes distinguish toxicity from veterinary-formulated ivermectin versus human-dose ivermectin in published case series?
Executive summary
Published case series and poison‑center reviews show a clear pattern: toxicity linked to veterinary ivermectin is driven by higher ingested doses and unusual routes/formulations and presents with more abrupt and severe neurologic effects—including altered mental status and encephalopathy—than toxicity from human‑dose, prescription tablets, which more often reflects milder, chronic exposures with gastrointestinal complaints and less frequent severe CNS disturbance [1] [2] [3]. Case reports and surveillance data also document hospitalizations and ICU care in veterinary‑product exposures, particularly when doses far exceeded human therapeutic ranges or when non‑oral (intravenous) veterinary administration occurred [4] [5].
1. Who, how much, and why: exposure patterns that separate the groups
Case series from poison centers found that patients who used veterinary formulations typically ingested large single doses or repeated large daily doses—often products sized and formulated for large animals—while those taking prescription human tablets more often took typical therapeutic doses or lower repeated doses for weeks [1] [6] [3]. Reports emphasize that many veterinary exposures were intentional self‑medication for COVID‑19 prevention or treatment and involved products sold for horses or livestock, producing reported doses ranging widely (e.g., 6.8 mg up to 125 mg of paste or 20–50 mg of 1% solution in one NEJM summary) compared with human regimens like 21 mg twice weekly described in surveillance reports [4] [1].
2. Clinical features: neurotoxicity dominates with veterinary products; GI and milder complaints with human doses
Across the series, neurologic manifestations—confusion, altered mental status, ataxia, stupor, seizures, and encephalopathy—were the most prominent findings in those who had taken veterinary ivermectin in high doses or by inappropriate routes, whereas patients with chronic, lower‑dose human tablet exposures more commonly reported gastrointestinal symptoms and milder neurologic complaints [1] [2] [3]. Surveillance counted neurotoxicity in the majority of reviewed toxic events and specifically noted higher rates of altered mental status among veterinary‑product users than prescription‑tablet users [1] [2].
3. Timing, severity, and outcomes: rapid onset and higher acuity with veterinary formulations
Toxicity following large veterinary doses often began rapidly—sometimes within hours of a large initial ingestion—and led more frequently to emergency visits, hospital admissions, and ICU care, including at least some cases requiring intensive support after intravenous veterinary administration produced very high serum concentrations and severe neurotoxicity [4] [5] [6]. By contrast, chronic exposures to standard human doses tended to produce milder symptom clusters and fewer reports of severe altered mental status in the published case series [3] [6].
4. Why veterinary products are riskier: dose, formulation, excipients, and route
Veterinary ivermectin products are manufactured in strengths and formulations (pastes, injectables, pour‑ons) intended for animals, which enables human ingestion of far larger milligram amounts than recommended human weight‑based dosing; excipients and solvents used in animal preparations can differ and may present additional toxicity risks, and non‑oral routes (not approved for humans) have been implicated in especially severe outcomes—the intravenous administration case being a stark example [7] [5] [8]. Pharmacokinetic data reviewed in regulatory monographs further show that higher doses produce higher peak plasma concentrations and AUCs that correlate with toxicity risk [8].
5. Caveats, alternate interpretations, and reporting limits
The published series are retrospective and derived from poison‑center and hospital case collections, which can overrepresent severe or unusual events and undercount mild unreported cases; dose estimates sometimes rely on patient report and unquantified product content, and not all possible excipient‑related harms are proven in humans [1] [3]. Some analyses emphasize that typical human therapeutic dosing has an established safety profile for approved indications, and that the harm signal in 2020–2022 largely tracked intentional misuse during COVID‑19 rather than failure of approved human formulations [9] [4]. Reporting sources include Clinical Toxicology/poison‑center reviews and case reports; their institutional perspectives and public‑health incentives to highlight misuse should be acknowledged as a potential implicit agenda to discourage off‑label self‑medication [2] [6].
Conclusion
Published case series consistently distinguish the two scenarios: veterinary‑product exposures are associated with larger doses, atypical formulations/routes, rapid onset and more severe neurologic toxicity, and higher rates of healthcare utilization, while human‑dose tablet exposures more commonly reflect lower‑dose or chronic patterns with milder symptoms; these conclusions rest on poison‑center surveillance and case reports that document dose ranges, symptom profiles, and outcomes but are limited by retrospective design and variable dose verification [1] [4] [5] [3].