https://pubmed.ncbi.nlm.nih.gov/42299164/
This is I think relevant because antihelmintics also have a mild mTOR inhibitory effect. I think that is how they can achieve surprising results from time to time.
chatGPT(6AstraMaxPaid):
This is a useful safety case report with modest novelty. It supports a diagnosis of drug-induced liver injury, but does not establish which drug caused it, whether combining them increased toxicity, or how frequently this complication occurs. Several claims in the discussion go beyond the evidence.
The paper is Drug-Induced Liver Injury Following Co-ingestion of Veterinary Fenbendazole and Ivermectin for Prostate Cancer: A Case Report, by Powderly and colleagues, published in Cureus on 15 May 2026. DOI: 10.7759/cureus.108896.
The case concerns a 65-year-old man with prostate cancer managed by active surveillance. Following advice from online support groups, he took veterinary fenbendazole and ivermectin on alternating days for approximately three months. He subsequently developed fatigue, abdominal discomfort, nausea, jaundice, dark urine and pale stools.
The authors estimated the doses from his description of taking approximately one millilitre per administration, assuming standard veterinary concentrations:
- Ivermectin: approximately 0.18 mg/kg per administration.
- Fenbendazole: approximately 0.98 mg/kg per administration.
These were reconstructed estimates, rather than verified measurements of the products or quantities consumed.
His blood results showed substantial liver injury:
| Measurement | Initial presentation | Subsequent course |
|---|---|---|
| ALT | 1,764 U/L | 741 on day 9; 25 on day 42 |
| AST | 1,132 U/L | 387 on day 9; 28 on day 42 |
| Total bilirubin | 12.9 mg/dL | Peaked at 23.1 on day 6; 2.3 on day 42 |
| INR, a measure of blood clotting | 1.7 | Follow-up values not reported |
| R-ratio, classifying the injury pattern | 37.5 | Strongly hepatocellular, meaning predominantly liver-cell injury |
Investigations did not identify an alternative explanation in the reported workup. Imaging showed no biliary obstruction. Both drugs were stopped, and he recovered without a specific pharmacological treatment.
The recovery timeline requires some precision: ALT and AST normalised within six weeks, but bilirubin remained elevated at that point. Complete biochemical normalisation was documented at day 143; the actual date of complete recovery between those measurements is unknown.
The authors calculated a RUCAM score of 9, classifying the proposed drug causation as “highly probable”. RUCAM is a structured method for assessing suspected drug-induced liver injury.
The novelty lies mainly in the exposure circumstances. This report documents serious liver injury during an alternating fenbendazole and ivermectin regimen in a patient with prostate cancer who was not receiving conventional anticancer drugs. The absence of concurrent chemotherapy or immunotherapy removes an important potential confounder.
However, liver injury associated with either drug was already reported. A 2024 fenbendazole case included a liver biopsy supporting severe drug-induced injury, and an ivermectin-associated severe hepatitis report appeared in 2006. The present paper therefore extends an existing safety signal rather than identifying a previously unknown adverse effect. It provides no new evidence about anticancer efficacy or the molecular mechanism of liver injury. pdfs.semanticscholar.org
The main strengths are the documented normal baseline, plausible timing, serial blood measurements and recovery after withdrawal. Stopping the drugs was followed by substantial improvement, which supports causality. Publishing the laboratory timeline also allows readers to check the authors’ interpretation. Avoiding deliberate re-exposure after such substantial injury was appropriate.
The principal limitations are:
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The responsible drug cannot be identified, and a harmful interaction is not demonstrated.
Both drugs were introduced during the same period and stopped together. Improvement therefore supports an association with the regimen, but cannot distinguish fenbendazole toxicity, ivermectin toxicity, an interaction, or an uncharacterised component of either formulation.
The authors suggest that combined exposure produced a greater cumulative insult. This remains a hypothesis. There are no drug concentrations, interaction experiments or comparison groups demonstrating it.
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The RUCAM assessment does not adequately separate the two drugs.
The original updated RUCAM instructions require each co-administered product to be assessed individually. Here, the authors assign one combined score and give zero points under concomitant drugs because no other medications were reported. However, when assessing either drug, the other is a potentially hepatotoxic co-exposure. Separate assessments could therefore reduce the apparent certainty for each agent. d-nb.info
There is also a subtle problem in the explanation of recovery scoring. The authors award three points using a 58% ALT decline within nine days, despite citing an eight-day threshold. Nevertheless, the three points are defensible from their underlying data: RUCAM measures the decline in ALT above the upper normal limit. Using 41 U/L as that limit, the fall from 1,764 to 899 U/L represents approximately 50.2% of the initial excess by day six. The explanation is faulty, but that particular score need not be wrong.
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The claim of greater severity than previous cases is contradicted by a cited report.
The discussion describes this patient’s injury as markedly more severe than earlier single-agent cases and uses that comparison to support a combined toxic effect.
Yet the cited Thakurdesai fenbendazole case reported ALT of 2,600 U/L, compared with 1,764 U/L here, and peak bilirubin of 24 mg/dL, compared with 23.1 mg/dL here. That earlier case also had biopsy-confirmed necrosis. It does not support the proposed severity distinction. pdfs.semanticscholar.org
Moreover, ALT magnitude alone cannot establish that one drug exposure caused clinically more severe disease than another.
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The exposure estimates are too uncertain to establish a dose-dependent mechanism.
The paper does not report verified product brands, measured concentrations, paste density, chemical analysis or blood drug levels. Converting an approximate volume of veterinary paste into milligrams introduces substantial uncertainty.
Its estimated ivermectin dose per administration falls within the usual human antiparasitic dose range. That does not establish the safety of repeated administration over three months, but it means the case cannot simply be described as a demonstrated ivermectin overdose. Approved product information distinguishes the usual single-dose treatments from other exposure schedules. dailymed.nlm.nih.gov
Similarly, a concentrated formulation is not itself proof of excessive administered dose. The proposed combination of direct toxicity and genetically determined susceptibility is speculative: neither exposure measurements nor genetic testing were performed.
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Alternative causes are less completely documented than the authors imply.
The report mentions a negative viral hepatitis panel and anti-smooth muscle antibodies, but does not clearly identify hepatitis E testing, antinuclear antibodies or serum immunoglobulin levels. These details matter when claiming comprehensive exclusion of competing diagnoses. AASLD guidance specifically discusses hepatitis E testing in selected cases and autoimmune screening with autoantibodies and immunoglobulins. PMC
This is a limitation of the published documentation; it does not prove the tests were omitted in clinical practice. It does mean that the maximum RUCAM points awarded for excluding other causes cannot be independently verified.
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Some pharmacological statements are imprecise.
The wording about a lack of human approval blurs the distinction between the drugs and their formulations. Human ivermectin products are approved for specified parasitic infections; that approval does not extend to these veterinary products or to cancer treatment. dailymed.nlm.nih.gov
The paper also describes CYP2J2- and CYP2C19-mediated fenbendazole metabolism as “hydrolysis”. Its cited experimental study describes hydroxylation, a different chemical process. That study also discusses separate pathways producing sulfoxide metabolites. This error weakens confidence in the mechanistic discussion. PMC
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The broader conclusions exceed what one case can establish.
The case supports asking patients about self-administered drugs and supplements. It cannot quantify incidence, establish an increasing population trend, compare the safety of veterinary and human formulations, or determine whether restricting veterinary sales would improve outcomes.
It also provides no prostate cancer outcomes: no PSA trajectory, tumour measurements or evidence of treatment response. Consequently, it contributes a safety observation but cannot calculate the treatment’s overall benefit-risk balance.
A stronger report would provide verified product details, a complete diagnostic workup, separate drug-specific causality assessments and a corrected comparison with previous cases. Establishing additional toxicity from the combination would require comparative clinical or experimental evidence.