What are the typical therapeutic doses of ivermectin for approved human uses and how do they compare to doses that cause toxicity?
Executive summary
Typical, approved human ivermectin doses are in the range of 0.15–0.20 mg/kg as single oral doses for parasitic infections (for example, 150 µg/kg for onchocerciasis and 200 µg/kg for many indications), with tablet strengths often given as 3 mg and dosing based on weight [1] [2] [3]. Toxicity in humans is uncommon at those doses; animal LD50s and human case reports show neurologic and systemic toxicity at much higher exposures (multiple mg/kg to tens of mg/kg, or with repeated misuse or veterinary formulations), though measured toxic thresholds vary by species and by blood‑brain barrier/P‑glycoprotein function [4] [5] [6] [7] [8].
1. What regulators approve and what doses they endorse
Major prescribing references and health centers list ivermectin as an approved antiparasitic with human oral regimens dosed by weight: standard single‑dose regimens include about 0.15 mg/kg for onchocerciasis and about 0.20 mg/kg for strongyloidiasis and other uses; tablets are typically 3 mg and clinicians calculate a one‑time dose by body weight [1] [2] [3]. Topical formulations for lice and rosacea are approved separately [9] [10].
2. How typical therapeutic doses compare to experimentally measured lethality
Preclinical LD50 data differ by species: oral LD50 values reported in mice and dogs translate to very large mg/kg ranges compared with human therapeutic mg/kg: Wikipedia cites mouse LD50 ~25 mg/kg and dog LD50 ~80 mg/kg, giving an approximate human‑equivalent LD50 range of roughly 2–43 mg/kg—far above the 0.15–0.20 mg/kg therapeutic window [4]. Human poisoning reports typically involve doses far above therapeutic levels (for example, repeated 21 mg tablets twice weekly or veterinary product ingestion) and have led to hospitalizations [6].
3. What “high dose” human safety data show
Clinical and trial literature indicates researchers have administered and studied higher-than-standard doses for purposes like malaria transmission reduction; some trials and reviews report tolerability up to several hundred to 2,000 µg/kg (i.e., 0.8–2.0 mg/kg) under monitoring, and meta-analyses say usual doses (0.2–0.4 mg/kg) are considered extremely safe [11] [12]. Yet “higher” in trial settings still remains well below animal LD50 estimates and is supervised, not a blanket endorsement for unsupervised self‑medication [11] [12].
4. Where and how toxicity occurs — mechanisms and risk factors
Toxic effects reported in humans center on neurologic signs (confusion, ataxia, seizures, coma), gastrointestinal symptoms, and liver or metabolic issues in some settings; severe cases have been linked to high cumulative or repeated dosing and to use of veterinary products with unintended concentrations or excipients [13] [6] [9]. Genetic or physiologic impairments of P‑glycoprotein (MDR1/ABCB1) increase brain penetration of ivermectin and dramatically raise sensitivity in animal models — a mechanism that plausibly explains human susceptibility variation [8].
5. Practical thresholds cited by clinicians and poison centers
Emergency and prehospital guidance notes limited human overdose data but points to animal models where toxicity appeared between about 5–15 mg/kg; some poison‑control guidance recommends hospital evaluation for ingestions exceeding ~2 mg/kg because of potential central‑nervous‑system effects [7]. Case series from the COVID‑era document hospitalizations after non‑standard regimens — e.g., 21 mg tablets taken twice weekly — and veterinary product ingestion with higher milligram exposures [6] [9].
6. Why public discourse sometimes confuses dose and safety
Public debate around repurposing (for COVID‑19 or cancer) mixed in vitro antiviral concentrations with achievable human plasma levels; critics note the concentrations that inhibited SARS‑CoV‑2 in petri dishes would require doses many times higher than approved human doses and approach toxic ranges in animals, a key reason regulators did not approve ivermectin for COVID‑19 [4] [10]. Meanwhile, legislative changes in some U.S. states expanding access to ivermectin have increased availability without changing clinical dosing guidance, raising concerns among clinicians about unsupervised high‑dose use [14] [15].
7. Bottom line for clinicians and the public
Approved human dosing is weight‑based and low (0.15–0.20 mg/kg single doses) and is safe when used for labeled parasitic indications [1] [2] [3]. Toxicity emerges at much higher exposures, with case reports and animal data showing neurologic and systemic harm when people take multiple milligrams per kilogram or veterinary formulations; individual susceptibility varies and can be amplified by P‑glycoprotein dysfunction or drug interactions [6] [5] [8]. Available sources do not mention an authoritative single human LD50; human risk assessment relies on animal toxicology, clinical trials of higher doses, and poisoning case series [4] [11] [7].