What are the recognized toxic effects and clinical management steps for ivermectin overdose?
Executive summary
Ivermectin overdose most commonly produces gastrointestinal upset and a spectrum of neurologic effects ranging from dizziness and somnolence to confusion, ataxia, seizures, coma and, rarely, death; serious encephalopathy has been documented particularly in mass-treatment settings and in patients with high Loa loa parasite loads [1] [2] [3] [4]. Clinical management is largely supportive—stabilize airway/breathing/circulation, monitor and treat seizures or hypotension, consider activated charcoal if ingestion is recent, and involve poison-control and hospital care early because no specific antidote exists [5] [1] [6].
1. Recognized toxic effects: what clinicians see at the bedside
Reported manifestations of ivermectin toxicity include gastrointestinal symptoms such as nausea, vomiting and diarrhea and a constellation of nervous‑system effects—dizziness, headache, vertigo, somnolence, confusion, loss of coordination/ataxia, tremor, visual disturbance, hallucinations, seizures and decreased consciousness up to coma; severe or fatal encephalopathy has been reported albeit rarely [2] [1] [7] [8] [6]. Respiratory problems including dyspnea and laryngeal edema have been described, as have transient renal abnormalities such as proteinuria and systemic reactions like rash and pruritus in contexts of parasitic die-off [1] [6].
2. How ivermectin can cause neurological harm: plausible mechanisms and known exceptions
Ivermectin’s antiparasitic action targets glutamate‑gated chloride channels in invertebrates, but mammalian toxicity is thought to arise when central nervous system exposure increases—either via very high systemic doses, formulations intended for animals, or compromised P‑glycoprotein efflux at the blood‑brain barrier—leading to excessive GABAergic or chloride conductance and neurologic depression; mass‑treatment campaigns documented cases of serious neurologic adverse events and at least one report found drug in brain tissue, underscoring that CNS penetration and toxicity can occur [4] [6] [1]. Notably, in onchocerciasis programs, concomitant heavy Loa loa infection is a recognized contributor to post‑treatment encephalopathy, complicating attribution [4] [1].
3. Who is at higher risk and why misuse matters
Risk factors include ingestion of veterinary formulations that contain far higher concentrations than human tablets, dosing errors because human dosing is weight‑based (typically ~150–200 mcg/kg), advanced age or organ impairment that alters metabolism, interacting medications that raise ivermectin levels, and heavy parasitic co‑infections; poison control centers saw spikes in toxicity during the COVID‑19 pandemic from people self‑treating with animal products [9] [3] [6] [1].
4. Initial clinical assessment and diagnostics
Assessment centers on airway, breathing and circulation, neurologic exam for level of consciousness and focal signs, seizure monitoring, vital signs and fluid status, and basic labs including electrolytes, renal and liver function and, when indicated, imaging or EEG to evaluate altered mental status; history should ascertain exact product, dose and timing because veterinary products change management and may correlate with worse outcomes [1] [8] [6]. Clinical data in many case series lack clear overdose amounts, so clinicians rely on exam trends and response to stopping the drug [4].
5. Management: supportive care, when to use activated charcoal, and limits of therapy
There is no specific antidote for ivermectin; treatment is supportive and symptomatic—secure airway and breathing, treat seizures with standard anticonvulsants, correct hypotension with fluids and vasopressors as needed, and provide intensive monitoring for progressive neurologic decline [5] [1] [6]. Activated charcoal can be considered if presentation is early and ingestion recent to reduce absorption; because ivermectin is lipophilic with a long half‑life, symptoms can persist for days and may require hospitalization [5] [10]. Consultation with regional poison control is recommended and reporting adverse events is important for surveillance [1] [3].
6. Outcomes, reporting and public‑health context
Most reported non‑fatal adverse events resolve after discontinuation and supportive care—case series document dechallenge (symptom resolution) and even rechallenge recurrence in a minority—yet deaths linked to high‑dose misuse (including veterinary products) have been reported and public‑health agencies have repeatedly warned against off‑label self‑administration [4] [3] [6]. Clinicians and the public should balance that approved human dosing is generally safe when supervised (weight‑based regimens) against the documented harms of misuse and the absence of proven benefit for unapproved uses [9] [6].