What serious adverse reactions have been reported with ivermectin use (e.g., neurotoxicity, liver injury)?
Executive summary
Serious adverse reactions reported with ivermectin include neurologic events (encephalopathy, confusion, coma), severe cutaneous reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis, DRESS), hepatic and renal disorders, cardiac and respiratory events, and deaths—particularly in settings of loiasis co-infection, overdoses, or misuse of veterinary formulations [1] [2] [3] [4]. Pharmacovigilance analyses and case series show these events are uncommon relative to the drug’s long history of safe use for approved parasitic indications, but signal detection studies and case reports document patterns that clinicians and public-health programs monitor closely [5] [6].
1. Neurological harms: encephalopathy, confusion, coma — the clearest signal
Ivermectin has a well-documented association with severe neurological adverse events in people heavily infected with Loa loa, including encephalopathy and fatal brain dysfunction, and pharmacovigilance data show increased reporting of encephalopathies and confusional disorders after ivermectin versus comparator antiparasitics both inside and outside loiasis-endemic areas [6] [2]. Case series identified multiple serious neurologic reports in VigiBase and other databases where some cases showed dechallenge/rechallenge patterns implicating ivermectin, and WHO database analyses found neurologic disorders among the most frequent serious events reported when ivermectin was used off-label during the COVID-19 era, including encephalitis, coma, and deaths [7] [4] [5].
2. Severe cutaneous adverse reactions: SJS, TEN, DRESS — rare but high-mortality
Postmarketing surveillance and targeted pharmacovigilance analyses have linked systemic ivermectin to severe cutaneous adverse reactions (SCARs) such as Stevens–Johnson syndrome, toxic epidermal necrolysis, and DRESS, with case compilations and FAERS signal detection reporting dozens of cases and mortality around 20% in a case series of reported SCARs [3] [8]. The PLOS pharmacovigilance study likewise flagged toxidermias among the signals more reported after ivermectin than benzimidazoles, underscoring a reproducible but infrequent pattern in disparate databases [6] [8].
3. Hepatic and renal injury: reported in pharmacovigilance analyses
Hepatic and renal disorders have been described as suspected serious adverse drug reactions after ivermectin in global safety-database studies, with disproportionality analyses pointing to increased reporting of hepatic and renal signals compared with other anthelmintics in some datasets, and case reports supporting isolated instances of clinically significant transaminase elevations and renal impairment [6] [2]. Systematic reviews of pharmacovigilance entries emphasize these are suspected associations derived from spontaneous reports, which cannot by themselves prove causality but warrant clinical caution and monitoring in at-risk populations [6].
4. Overdose, misuse, and veterinary formulations: an avoidable source of harm
Emergency-room and toxicology surveillance documented clusters of ivermectin-related presentations tied to self-medication and ingestion of veterinary formulations during the COVID-19 period; in one toxicology consortium report 40 patients were identified, many having used veterinary products, with neurologic toxicity the most frequent finding and multiple hospital admissions, illustrating that dose, formulation, and context importantly mediate serious harms [9] [4]. Pharmacovigilance studies of COVID-19–related reports also describe life-threatening events and deaths among cases where ivermectin was reported as the single suspect, and some overdoses were associated with severe neurologic outcomes [4].
5. How common are these events and what are the limitations of the data?
Despite reproducible signals for encephalopathy, toxidermias, hepatic and renal disorders, large-scale programmatic experience treating millions for onchocerciasis and other parasitoses suggests such severe events are rare overall, though concentrated risk exists in populations with high Loa loa microfilaremia and in settings of misuse or overdose [5] [10]. The evidence base relies heavily on spontaneous reporting systems (VigiBase, FAERS, WHO databases) and case reports that are subject to underreporting, reporting bias, confounding by co-administered drugs or underlying infections, and inability to establish causality in many entries—limitations the original studies explicitly acknowledge [7] [6] [8].
6. Practical implications and alternative perspectives
Regulatory and clinical responses reflect a balance: ivermectin remains widely used and generally safe when prescribed for approved parasitic indications under recommended dosing, but programs in Loa loa endemic regions incorporate test-and-treat strategies and other mitigations because of known CNS risk, and clinicians are advised to avoid off-label high-dose use or veterinary products and to monitor for neurologic, hepatic, renal, and severe dermatologic reactions [10] [6] [3]. Some advocates argue pharmacovigilance reports overstate risk because denominators (total treated) are large and cases few, while safety researchers counter that the reproducible disproportionality signals and fatal case reports demand caution and targeted screening where risk factors exist [5] [2].