Which ivermectin blood levels correlate with severe adverse effects in humans?
Executive summary
There is no clear, agreed numeric ivermectin blood concentration in humans that definitively correlates with “severe” adverse effects in the published reports and guidance available here; case series and toxicology reviews tie severe neurotoxicity and ICU admissions to supratherapeutic or massively excessive dosing rather than a specific blood level [1] [2] [3]. Pharmacokinetic and assay work shows methods exist to measure ivermectin in plasma and whole blood, but clinical reports commonly lack measured serum concentrations when describing severe events [4] [2].
1. No single toxic threshold in human plasma is reported — clinical descriptions focus on dose and presentation
Published case series and reviews document severe ivermectin toxicity — confusion, ataxia, seizures, hypotension and ICU care — in people who took doses far above recommended regimens or who used veterinary formulations, but these reports do not establish a numeric plasma concentration that predicts severe harm [1] [2]. The New England Journal of Medicine series described 6 hospitalizations (4 ICU) for toxic effects after preventive use during the COVID-19 era but did not report a concentration cutoff tied to severity [1]. Cureus and other case reports emphasize clinical syndromes and confounders rather than blood‑level thresholds [5] [2].
2. Pharmacokinetic capability exists — assays can measure ivermectin in plasma and whole blood, but clinical correlation is sparse
Validated LC‑MS/MS methods have been published and were used to analyze >1,200 plasma samples in a clinical trial setting, demonstrating that laboratories can quantify ivermectin across a calibration range suitable for clinical research [4]. Those analytical capabilities confirm that measuring blood levels is feasible, but the literature here shows few clinical reports that pair measured concentrations with specific severe outcomes, so assay availability has not yet produced an evidence‑based human “toxic level” [4] [2].
3. Toxicity is linked to supratherapeutic dosing, route and host factors rather than a universal mg/L cutoff
Toxicology references and poison‑control guidance note that ivermectin is well tolerated at standard single oral doses (typically 100–300 µg/kg) and that human poisonings reported severe signs after ingestion of dosages many times higher than therapeutic, including veterinary product exposures [3] [6]. Historical toxicology summaries describe animal toxic doses and human poisonings after very large ingestions but do not translate these to a single human plasma concentration applicable across populations [7] [6] [8].
4. Blood–brain barrier function and genetic factors change risk — complicating any concentration-based rule
Authors and reviewers point out that therapeutic ivermectin normally does not penetrate the CNS because P‑glycoprotein (P‑gp) pumps it out; conditions that impair the blood–brain barrier or rare ABCB1 (P‑gp) mutations can permit neurotoxicity at doses that might otherwise be safe [3] [2]. These host vulnerabilities mean the same plasma concentration could be harmless in one person and dangerous in another, making a single numeric cutoff misleading [3] [2].
5. Regulatory and safety literature emphasizes adverse-event patterns and high‑dose risk, not a standard blood level
Regulatory assessments and product safety summaries underline the known severe events — encephalopathy in Loa loa‑infected patients, dermatologic catastrophes, liver enzyme elevations — and recommend adhering to official dosing guidance [9]. These sources focus on known clinical syndromes and risk contexts rather than specifying a concentration above which severe adverse effects will occur [9].
6. What the available reporting does and does not provide — practical implications for clinicians and researchers
Available reporting documents severe ivermectin toxicity after excessive or inappropriate use, confirms laboratories can measure ivermectin levels, and identifies host and dosing factors that raise risk [1] [4] [3]. Available sources do not mention a validated plasma/whole‑blood concentration that reliably correlates with severe outcomes across patients; therefore clinicians cannot rely on a single laboratory cutoff to predict severe toxicity [4] [2]. When confronted with suspected toxicity, clinicians should base urgent care on signs/symptoms, dosing history, possible co‑morbidities (e.g., blood‑brain barrier compromise, Loa loa), and, where available, quantitative assays as supportive information [1] [2] [9].
Limitations and competing viewpoints: case reports and poison‑center guidance imply thresholds by dose (e.g., recommendations to evaluate patients after >2 mg/kg exposures) but these are dose‑based heuristics rather than blood‑level standards, and some animal‑to‑human extrapolations cited in review pieces vary widely [8] [7]. Reported assay work demonstrates measurement feasibility [4] but the clinical literature has not yet converted those measurements into evidence‑based toxic concentration thresholds [4] [2].