What are the known adverse effects of ivermectin at different doses in humans?
Executive summary
Approved human doses of ivermectin for parasitic diseases are typically 150–400 μg/kg as single or annual doses; these standard regimens have a low incidence of serious adverse events in large mass-treatment programs [1] [2]. Reports of toxicity cluster around higher or non‑recommended doses—especially use of veterinary formulations or repeated high dosing—producing neurologic symptoms (dizziness, confusion, ataxia, stupor, coma), gastrointestinal upset, and rarely hospitalization [3] [4] [5].
1. Standard human dosing and the safety baseline
Ivermectin for onchocerciasis and other human parasitic infections is given by weight at about 150–400 μg/kg (commonly 200 μg/kg as a single dose); mass global programs using these regimens have documented a very low incidence of serious adverse events over decades [1] [2] [6].
2. Common, expected side effects at recommended doses
Clinical and patient‑information sources list relatively common, usually mild effects: fever, itching, rash, dizziness, headache, somnolence, and gastrointestinal symptoms such as nausea, diarrhea, or abdominal pain after oral dosing [7] [5] [8]. Authoritative drug information pages and reviews warn that “other side effects” may occur and recommend reporting suspected reactions to regulators [9] [10] [11].
3. Neurologic risks and the Loa loa interaction
Serious neurologic events — encephalopathy, confusion, stupor, seizures, coma and in rare historical series even death — have been reported mainly in settings of heavy Loa loa microfilarial burden after ivermectin distribution campaigns. The literature links these events to either parasite‑related pathology when microfilariae die or to situations that allow ivermectin to penetrate the CNS (e.g., P‑glycoprotein/ABCB1 defects) [12] [13] [6].
4. Toxicity from excessive dosing and veterinary products
Toxicity reports during the COVID‑19 era show most serious cases involved ingestion of veterinary formulations or doses above human recommendations. Reported ingested veterinary doses ranged widely (e.g., 6.8–125 mg of 1.87% paste; 20–50 mg of 1% solution) and human‑use misdosing examples included regimens like 21 mg twice weekly; six of 21 callers in one series were hospitalized with neurologic toxicity (confusion, ataxia, seizures) [3] [4] [14]. Poison‑center and case‑series data show gastrointestinal distress, vision changes, rash and dizziness among non‑hospitalized patients [3] [14].
5. Dose ranges cited in pharmacology and high‑dose studies
Pharmacology and early clinical work note that standard human dosing (~100–300 μg/kg) is well characterised; experimental or repurposing efforts have explored higher doses (e.g., 300 μg/kg and above, or multiple‑day regimens) with mixed safety data. Systematic reviews conclude ivermectin is generally safe at usual doses but emphasize that higher or prolonged dosing has potential for toxicity and drug–drug interactions via cytochrome P450 pathways [13] [6] [15].
6. Mechanisms behind severe toxicity — blood‑brain barrier and genetics
Ivermectin normally has poor CNS penetration because of P‑glycoprotein (encoded by ABCB1/mdr‑1); loss‑of‑function variants (documented in animals and discussed in human case analyses) permit brain accumulation and neurotoxicity. This pharmacogenetic mechanism explains why some patients develop severe neurologic signs even when doses might not seem extreme [12] [15].
7. Gaps in available reporting and limitations
Available sources document adverse effects across a range of doses and formulations, but they do not provide a single, consistently defined dose‑response table for every adverse event. Large mass‑treatment datasets report low serious‑event rates after standard doses [1], while poison‑center and case reports focus on atypical high‑dose or veterinary‑product exposures [3] [4]. Direct long‑term sequelae and pregnancy‑specific safety remain incompletely characterised in the provided reporting [16] [8].
8. Practical takeaway and competing viewpoints
Public‑health and pharmacology sources converge: standard, supervised human dosing (≈150–400 μg/kg, weight‑based) is widely used and generally safe [2] [6] [1]. Independent reports and poison‑center data emphasize that off‑label high dosing and veterinary formulations cause most clinically significant toxicity [3] [4] [5]. Some reviews suggest higher doses can be studied under controlled settings but warn of drug interactions and genetic susceptibility that raise the risk of severe neurologic events [13] [12].
If you want, I can extract the specific adverse‑event lists by dose ranges from each cited paper and present them side‑by‑side, or compile the case reports that document hospitalizations and their reported ingested amounts [3] [4].