What regulatory dosing guidelines exist for human ivermectin and reported cases of misuse during COVID-19?
Executive summary
Regulatory bodies approve ivermectin for human parasitic infections at standard oral doses around 150–200 µg/kg (0.15–0.2 mg/kg) for one or two doses, and do not authorize it for prevention or treatment of COVID‑19 because clinical trials have not shown clear benefit and required antiviral concentrations exceed safe human plasma levels [1] [2] [3]. During the pandemic there was widespread off‑label use, including veterinary products and high or repeated dosing, which provoked increased poison‑center calls and documented hospitalizations for toxicity [4] [5].
1. What the regulators say: approved human dosing and limits
Regulatory guidance and clinical reviews note that approved human ivermectin regimens for parasitic diseases typically range from about 150–200 µg/kg orally as a single dose or one to two doses, with established safety data for those indications and formulations approved as tablets or topical products for humans [1] [6]. The U.S. Food and Drug Administration emphasises that ivermectin is not authorized or approved to prevent or treat COVID‑19 and warns against using animal formulations for people because those products are formulated differently and have not been tested for human safety [3] [7].
2. Why COVID‑era proponents looked past dosing constraints
Laboratory studies showing ivermectin inhibits SARS‑CoV‑2 in cell cultures prompted interest, but pharmacokinetic modeling consistently found that the concentrations that produced antiviral effects in vitro are 50– to 100‑fold higher than peak plasma levels obtained with standard approved doses, implying that antiviral efficacy would require doses far above approved regimens [2] [8] [9]. Some clinical trials tested higher‑than‑standard regimens (for example 400–600 µg/kg or multiple‑day courses) but did not demonstrate clear clinical benefit for COVID‑19 while raising safety questions [2] [10].
3. Documented misuse: veterinary formulations and overdoses
Public‑health surveillance and case series documented a rapid increase in prescriptions and reports of severe illness tied to attempts to prevent or treat COVID‑19 with ivermectin, including use of veterinary paste and solutions intended for animals; poison‑control center calls and hospitalizations rose, and case reports include gastrointestinal and neurological toxicity after large or first‑time high doses [4] [5] [10]. A New England Journal of Medicine case series described 21 persons with toxicity, 17 of whom had used veterinary formulations and six of whom required hospitalization, with reported doses from veterinary products varying widely and exceeding human tablet doses [5].
4. What trials and guidelines concluded about off‑label regimens
Major guideline groups including NIH, WHO and professional societies like IDSA recommend against routine ivermectin use for COVID‑19 outside clinical trials because randomized, controlled trials and larger platform studies found no consistent benefit for prevention or treatment; IDSA explicitly recommends against use outside trials and NIH states evidence is insufficient to recommend ivermectin for COVID‑19 [4] [11] [2]. Systematic reviews and dose‑finding trials found safety signals at higher doses and no reliable clinical efficacy to justify off‑label large‑dose regimens [6] [10].
5. Safety window, rare genomics and pharmacology caveats
Although ivermectin has a long history and is generally safe at recommended antiparasitic doses—with many millions of doses distributed globally—adverse events increase with dose and can include neurologic effects, especially in circumstances such as unusually high doses, interactions with other medications, or potential genetic susceptibilities affecting drug transport/metabolism [6] [8]. Some pharmacokinetic studies report tolerability of single very large experimental doses in volunteers, but even those do not achieve the plasma levels suggested by in vitro antiviral assays and are not endorsements for COVID‑19 use [8].
6. The politics of demand and misinformation shaping misuse
Demand for ivermectin during COVID‑19 was driven by early, often low‑quality studies, preprints, and social‑media amplification that overlooked dosing, formulation and pharmacology constraints; this created the market for veterinary product misuse and pressured clinicians and pharmacists, prompting public‑health alerts from the FDA and CDC and policy statements from professional societies warning against off‑label prescribing outside trials [3] [4] [12]. Reporting and advocacy for ivermectin sometimes carried implicit agendas—therapeutic optimism, distrust of regulators, or commercial/ideological motives—and regulators urged reliance on robust randomized trials rather than in vitro or anecdotal claims [8] [11].