What adverse effects have been reported with high-dose or long-term ivermectin use?
Executive summary
High‑dose or prolonged ivermectin use has most often produced mild, transient symptoms—headache, dizziness, nausea, rash and gastrointestinal upset—across clinical studies, but rare serious events including encephalopathy, seizures and deaths have been reported in specific circumstances such as heavy Loa loa infection or when blood‑brain barrier protection is compromised [1] [2] [3] [4]. Randomized trials and pooled reviews show many high‑dose regimens were tolerated without increased common adverse events, yet case reports, pharmacovigilance signals and known drug–drug or genetic vulnerabilities mean safety is not absolute and warrants caution [5] [1] [6].
1. How “high‑dose” and “long‑term” are described in the literature
Studies and reviews define “high” ivermectin doses variably: standard antiparasitic dosing centers on ~150–200 µg/kg, trials have tested single doses up to 800 µg/kg and repeated regimens such as 1.2–1.6 mg/kg for days to weeks, and some mass‑administration research looked at 600 µg/kg for several days—all of which appear in the safety literature and regulatory discussions [1] [7] [8].
2. The common, usually mild adverse effects documented
Across randomized trials, systematic reviews and pharmacokinetic studies the most frequently reported complaints were headache, dizziness, fatigue, nausea, diarrhea and skin reactions such as rash or itching, with incidences often similar between ivermectin and placebo arms in trials and not clearly dose‑dependent in pooled analyses [1] [2] [9] [3].
3. The rare but serious neurologic and systemic harms that have been reported
A contrasting body of evidence contains case reports and series of severe neurologic events—encephalopathy, coma, seizures, ataxia and altered consciousness—including “post‑ivermectin encephalopathy” described after dosing errors or in patients with heavy Loa loa infection, and fatal outcomes in select, complex cases; these accounts are rare but serious and have prompted calls for pharmacovigilance [6] [10] [4] [3].
4. Why some studies show high‑dose safety while case reports show harm — mechanisms and modifiers
Clinical trials and systematic reviews have often found no increase in common adverse events even with multi‑fold higher dosing (for example, up to 0.6–0.8 mg/kg in several trials) and cohorts tolerating single high doses, but mechanistic caveats matter: loss or inhibition of the ABCB1 (P‑glycoprotein) transporter, drug interactions (e.g., ketoconazole) and very high microfilarial loads in onchocerciasis/Loa infections can permit CNS exposure and toxicity, explaining why population trials can read differently than individual adverse‑event reports [5] [1] [6] [4].
5. Patterns tied to misuse, formulations and surveillance signals
Public health agencies and poison‑control reports during recent periods of off‑label use show spikes in emergency visits linked to overdoses or veterinary formulations; observational signals therefore reflect both misuse and real, albeit uncommon, risk, while advocacy or promotional sources emphasize tolerability—an implicit agenda that can underplay rare harms seen in case reports and specific clinical settings [10] [11] [5].
6. Practical takeaways and limits of the reporting
The assembled evidence supports that ivermectin’s most common adverse effects remain mild and similar across many studied doses, yet rare severe neurologic events and isolated fatalities have occurred in contexts documented in case reports (heavy Loa loa burden, dosing mistakes, drug–drug or genetic vulnerabilities), so high‑dose or long‑term use should be considered only with clinical oversight and heightened monitoring; these conclusions are drawn from randomized trials, systematic reviews and case series cited above, and sources differ in emphasis—trial data on tolerability [5] [1] [9] versus case reports of encephalopathy and dosing errors [6] [10] [4]. The available reporting does not comprehensively define risk for every patient subgroup, and randomized long‑term safety data remain limited in certain populations [1] [8].