How does ivermectin interact with liver or kidney function?
Executive summary
Ivermectin is extensively metabolized by the liver and is eliminated mainly via feces rather than the kidneys, which helps explain why clinically significant renal clearance is minimal [1] [2]. Human pharmacovigilance finds only rare, usually mild liver enzyme elevations and very infrequent clinically apparent liver injury, while animal experiments show dose- and duration-dependent liver and kidney changes that merit caution when extrapolating to people [3] [4] [5].
1. How the drug is handled by the body: hepatic metabolism, not renal excretion
Pharmacokinetic summaries and clinical guidance emphasize that ivermectin is extensively metabolized in the liver, undergoes cytochrome P450–mediated biotransformation, and is eliminated mainly in the feces with only a trace (reported <1%) of unchanged drug appearing in urine, so renal excretion is not a primary route of clearance [1] [2]. This hepatic-centered elimination profile is the principal reason many reviewers and clinical resources state that impaired kidney function alone is unlikely to markedly change ivermectin clearance, although direct clinical studies in severe renal impairment are limited [1] [2].
2. Human safety data: uncommon liver enzyme changes, very rare clinical liver injury
Clinical surveillance and LiverTox conclude that single-dose ivermectin has been associated with a low rate of transient serum aminotransferase elevations and that clinically apparent drug‑induced liver injury is very rare — with isolated case reports describing hepatocellular enzyme elevations after single doses [3]. Consumer-facing summaries likewise note that kidney side effects are not commonly observed in typical use, while caution about rare liver damage is advised [6] [3].
3. Animal and experimental evidence: signals of hepatic and renal toxicity at repeated or high doses
Multiple animal studies—including repeated-dosing experiments in rats and other preclinical models—report biochemical and histopathological changes in liver and kidney with repeated or high-dose ivermectin, such as elevations in serum creatinine and urea, altered liver enzymes, and tissue damage, and some studies find that antioxidants or vitamins can attenuate those effects [4] [5] [7]. Other experimental work shows that ivermectin can be protective or modulatory in certain toxic models at particular doses, underscoring that outcomes depend on dose, species, and co‑exposures and making direct translation to routine human dosing uncertain [8].
4. Clinical implications for patients with kidney or liver impairment
Because ivermectin clearance is primarily hepatic and fecal, many reviewers state dose adjustment is usually unnecessary in isolated renal impairment, but they also acknowledge limited direct clinical data in patients with severe kidney disease; classical prescribing references recommend caution and clinical monitoring for older patients or those with multi-organ impairment [1] [9]. For hepatic impairment, the drug’s metabolism in liver cells makes hepatic function more relevant to clearance and potential accumulation, and isolated human liver injury reports argue for vigilance when treating patients with preexisting liver disease [3] [9].
5. Reconciling the evidence and practical advice
The combined evidence supports a pragmatic, risk‑aware stance: routine single‑dose therapy at recommended antiparasitic doses carries a low reported risk of clinically important liver or kidney injury in humans, but repeated high doses or off‑label heavy use—scenarios modeled in animals—produce hepatic and renal toxicity signals that justify caution, monitoring, and skepticism of claims that the drug is entirely risk‑free [3] [4] [5]. Given gaps in large-scale clinical data for people with severe renal or hepatic dysfunction, clinicians generally monitor liver enzymes and renal markers when treating at-risk patients and avoid unapproved high‑dose regimens; several studies also report that antioxidants can ameliorate experimental toxicity, a finding that is hypothesis‑generating rather than practice‑changing (p1_s1; [10] not used because published date beyond search window).