What serious adverse reactions have been reported with ivermectin (seizures, liver injury)?

1. Background: what the safety literature says about ivermectin

Ivermectin is widely used for parasitic diseases and is generally considered to have an “excellent safety profile,” with many adverse events attributed to inflammatory reactions when parasites are killed (Mazzotti reactions), but serious adverse drug reactions (sADRs) have been reported in both trials and post-marketing surveillance ^{[5] [4]}. Large community treatment campaigns for onchocerciasis have produced the bulk of historical safety data and revealed rare but serious neurological and systemic reactions in particular contexts ^{[1] [2]}.

2. Seizures and other neurological events: what has been observed

Reports include inability to walk, depressed consciousness, seizures or convulsions, encephalopathy, coma and tremor following ivermectin exposures at doses ranging from typical human doses up to higher amounts reported in some case series ^[1]. Pharmacovigilance studies show an increased reporting of severe encephalopathies after ivermectin compared with some alternative antiparasitic drugs—especially in sub-Saharan Africa—while formal disproportionality analyses did not find seizures to be reported more often with ivermectin than with benzimidazole drugs overall ^{[2] [6]}. Case series and post‑marketing reports have described seizures during postmarketing experience and in patients with heavy Loa loa infection, and veterinary literature and animal knockout models implicate MDR1 (P‑glycoprotein) dysfunction as a mechanism that can allow ivermectin to penetrate the brain and cause neurotoxicity ^{[7] [1]}.

3. Liver injury: rare but documented instances

Ivermectin has been linked to minor, usually self-limited aminotransferase elevations and to very rare instances of clinically apparent drug‑induced liver injury (DILI) in humans, including a published severe hepatitis case from 2006 and more recent single‑patient reports with biopsy‑confirmed injury after off‑label use ^{[3] [8]}. Systematic pharmacovigilance work lists hepatic disorders among the suspected serious adverse reactions reported to global databases, although population-level disproportionality signals for hepatic disorders were not consistently elevated in sensitivity analyses ^{[4] [2]}.

4. Who appears most at risk and plausible mechanisms

The strongest and most consistent risk factor for severe neurological events is concomitant heavy Loa loa infection—microfilarial burden appears to trigger encephalopathy after microfilaricidal therapy—while genetic or pharmacologic impairment of P‑glycoprotein (MDR1/ABCB1) offers a separate biological explanation seen in animal models and breed‑specific veterinary sensitivity ^{[1] [5]}. For liver injury, case reports and animal studies point to hepatocellular injury patterns and enzyme elevations after single or repeated doses, but causality in single cases relies on clinical assessment tools (e.g., RUCAM) and biopsy findings rather than population-level proof ^{[8] [9] [3]}.

5. What pharmacovigilance and comparative studies add — and their limits

Large WHO and VigiBase‑based analyses identify signals—especially for encephalopathy in Loa‑endemic settings and for other serious reactions such as toxidermias and renal disorders—but these databases reflect reporting biases, variable clinical detail, and cannot by themselves prove causation; some disproportionality analyses did not find increased reporting for seizures or hepatic disorders in all comparisons ^{[4] [2] [6]}. Randomized trials and community studies document that most adverse reactions during mass treatment are predictable, transient Mazzotti reactions linked to parasite killing, while the rare catastrophic events appear clustered by geography, infection status, dose misuse, or unusual host vulnerability ^{[5] [1]}.

6. Bottom line: measured risks and unanswered questions

Ivermectin can—rarely—be associated with severe neurological events (including seizures and encephalopathy) particularly in persons with high Loa loa microfilaremia or when P‑glycoprotein protection is compromised, and hepatotoxicity is uncommon but documented in case reports and surveillance systems as isolated DILI occurrences ^{[1] [2] [3] [8]}. Available evidence supports vigilance: clinicians should consider travel and parasitic infection history, avoid inappropriate high‑dose or veterinary formulations, and report suspected sADRs to pharmacovigilance systems, while researchers continue to clarify incidence, mechanisms and risk modifiers beyond the well‑recognized Loa loa context ^{[7] [4] [6]}.