What are common side effects of ivermectin at doses higher than approved?
Executive summary
High or non‑prescribed doses of ivermectin have been linked in recent reports and reviews to a spectrum of chiefly neurological and gastrointestinal toxicities — including dizziness, ataxia, tremor, seizures, decreased consciousness, coma, and in some cases death — and large‑dose exposures have led to hospitalizations (NEJM case series; MedlinePlus; Medical News Today) [1] [2] [3]. Pharmacovigilance studies and reviews also flag encephalopathy and rare fatal outcomes, especially in particular contexts such as heavy Loa loa infection or very large overdoses [4] [5].
1. Acute neurologic syndrome: loss of coordination, somnolence, tremor, seizures
High or excessive ivermectin exposures repeatedly produce central‑nervous‑system signs. Drug references and reviews list dizziness, somnolence, vertigo, tremor and headache as reported nervous‑system adverse events, while case reports and safety reviews add ataxia, loss of coordination, seizures and reduced level of consciousness up to coma [5] [6] [7]. Systematic pharmacovigilance work explicitly quantified a signal for ivermectin‑associated encephalopathy, showing higher reporting odds in sub‑Saharan Africa but significant signals globally as well [4].
2. Respiratory depression and life‑threatening CNS depression
Authoritative summaries and encyclopedic accounts note that very high doses can cause respiratory depression and profound CNS depression that may progress to coma and death; animal overdosage studies showed bradypnea and fatal outcomes at several‑fold above recommended human doses [8] [9]. Medical consumer guides and health sites warn that large doses have caused coma and death in humans [3] [10].
3. Gastrointestinal effects: nausea, vomiting, diarrhea and hypotension
Gastrointestinal symptoms are common in overdoses and have been repeatedly described in clinical guidance: nausea, vomiting and diarrhea are listed among overdose and side‑effect presentations and were reported in case series of people who ingested veterinary products or very large first doses [1] [7] [3]. Some reports also associate hypotension with severe ivermectin toxicity [7].
4. Visual and psychiatric disturbances: blurred vision, hallucinations, confusion
Several sources list visual disturbances (blurred vision, impaired vision, mydriasis) and neuropsychiatric symptoms including confusion and visual hallucinations in the context of large or off‑label dosing [7] [8] [9]. Case summaries and consumer sites cite disorientation and altered mental status among serious adverse events [11] [3].
5. Contextual risk factors: Loa loa coinfection and off‑label veterinary use
A recurring theme in the literature is that certain contexts magnify the danger. People heavily infected with the filarial parasite Loa loa can develop serious or fatal encephalopathy spontaneously or after effective microfilaricidal treatment with ivermectin; product labeling and systematic studies call this out as a known risk [4] [5]. Public health reporting also documents many toxicities from people taking veterinary formulations or self‑medicating at doses far above human prescriptions [1].
6. Magnitude of doses and real‑world harms: case series and surveillance
A U.S. NEJM case series found multiple people who took veterinary products or non‑prescribed human tablets and developed symptoms quickly; reported veterinary‑product ingestions ranged widely (e.g., 6.8 mg to 125 mg of paste or 20–50 mg of solution), and six of 21 people in that report required hospitalization after preventive/off‑label use [1]. Pharmacovigilance analyses and reviews supplement those clinical reports with broader signal detection for encephalopathy and serious neurologic events [4] [5].
7. What controlled dosing studies show — and their limitations
A small controlled dose‑escalation study cited in reviews did not find CNS toxicity up to 10× the highest FDA‑approved dose, but authors and reviewers cautioned that the study was small (68 subjects) and not powered to detect rare idiosyncratic reactions; surveillance remains important [5]. Available sources therefore indicate that while some controlled data exist suggesting tolerance at certain higher multiples in healthy volunteers, they explicitly warn about limitations and the inability to rule out rare or context‑specific severe events [5].
8. How public messaging and misuse shaped harms
Reporting links many recent toxicities to self‑medication driven by off‑label claims and use of veterinary formulations; the NEJM series found most people either purchased veterinary products or obtained nonstandard prescriptions, and public health and consumer sites have issued warnings about large‑dose use and potential fatalities [1] [10]. Sources show an implicit agenda in some advocacy for unproven uses that downplays dose‑dependent toxicity risk; conversely, regulatory and clinical sources emphasize evidence limits but consistently warn against high‑dose, nonprescribed use [3] [2].
Limitations and open questions: available sources do not provide a single, comprehensive toxic‑dose threshold that applies to every patient; susceptibility varies with cofactors (age, coinfection, co‑medications) and many large‑dose human experiences involve veterinary products and unmeasured amounts [1] [4]. For individual risk assessment, clinicians should rely on the patient‑specific context and poison‑control guidance; population‑level surveillance continues to evolve [5] [4].