How common are renal adverse events with ivermectin compared with other antiparasitic or repurposed drugs?
Executive summary
Ivermectin–used widely as an antiparasitic and explored as a repurposed drug–is associated with renal findings only rarely and usually mildly (transient proteinuria or minor tubular markers), and large pharmacovigilance analyses did not find a signal for serious renal adverse drug reactions compared with other antinematodal agents (benzimidazoles) [1] [2] [3]. Animal and isolated case reports show potential for nephrotoxicity at high or nonstandard exposures and rare immune-mediated renal syndromes have been described, but these are exceptional and context-dependent [4] [5].
1. Renal events with ivermectin: uncommon and typically minor in clinical series
Clinical and safety summaries report renal side effects such as rare transient proteinuria and small increases in urinary albumin or tubular markers shortly after dosing, especially in patients with high parasite loads, but characterize these changes as minor and generally not clinically relevant in most treated populations [1] [6]. Pharmacokinetic data support a low biological plausibility for direct renal toxicity because ivermectin is extensively metabolized in the liver and less than 1% of the dose is excreted unchanged in urine, so standard dosing is not expected to require renal adjustment [7] [8].
2. Big‑data pharmacovigilance: no disproportional renal safety signal versus other anthelmintics
A global VigiBase analysis that compared suspected serious adverse drug reactions after ivermectin versus benzimidazole drugs found no disproportionate reporting for serious renal disorders (adjusted reporting odds ratio did not indicate association) and, overall, fewer or similar rates of serious hepatic or renal reports relative to comparators in both sub‑Saharan Africa and the rest of the world [2] [3]. That pharmacovigilance finding strengthens the clinical-trial and community-treatment literature that renal harm from ivermectin, when it occurs, is rare and not outsized compared with other commonly used antinematodal agents [2] [3].
3. Exceptions: animal toxicity and rare human case reports signal caution at nonstandard exposures
Preclinical studies in rodents have documented ivermectin-related renal histopathology at doses and regimens that exceed usual human exposures, and some experimental work shows mitigation with antioxidants, underscoring dose- and species‑dependent effects rather than routine clinical risk [4]. In human case literature and nephrology conference abstracts clinicians have reported isolated severe kidney syndromes temporally linked to ivermectin use (for example, ANCA-associated vasculitis in a case series/abstract), but these remain rare, often confounded by concomitant exposures, off‑label high‑dose use, or delayed recognition, and cannot establish frequency without systematic surveillance [5].
4. How ivermectin compares with other antiparasitics and repurposed drugs
Historical comparisons emphasize that ivermectin is generally better tolerated than older microfilaricidal agents such as thiabendazole or diethylcarbamazine for systemic adverse reactions (fever, rash, myalgia), and population data do not show higher rates of serious renal events with ivermectin than with benzimidazoles [1] [2] [3]. For “repurposed” drugs used in contexts such as COVID‑19, direct comparisons are limited in the provided reporting; many repurposed candidates have distinct renal toxicity profiles (for example, remdesivir or certain antibiotics), but the available sources do not supply head‑to‑head renal incidence rates versus ivermectin, so definitive cross‑drug rankings for kidneys cannot be made from these materials [9].
5. Limits of the record and practical takeaways
The evidence base combines clinical trials, community mass‑treatment studies, pharmacokinetic reasoning, VigiBase signal detection, animal toxicology, and a small number of case reports; each has bias and blind spots: mass‑drug programs may underreport mild lab abnormalities, pharmacovigilance is subject to reporting heterogeneity, and animal findings may not translate to standard human dosing [1] [2] [4]. Taken together, the most defensible conclusion is that renal adverse events with ivermectin are uncommon and usually mild compared with other antiparasitic agents examined in pharmacovigilance analyses, but outlier severe renal reactions have been reported in rare circumstances—especially with high parasite burdens, off‑label dosing, or when other nephrotoxic exposures are present—warranting clinical vigilance rather than alarm [2] [6] [5].