Abstract
Ivermectin is a classic antiparasitic drug that is widely used around the world. After the outbreak of coronavirus disease 2019, many studies have reported the potential effectiveness of ivermectin against coronavirus disease 2019; however, it is not recommended by the World Health Organization because of insufficient evidence and significant adverse effects. Owing to the abovementioned findings, the number of reports of poisoning and other serious reactions caused by ivermectin abuse have increased in recent years. Notably, no previous cases of transdermal ivermectin poisoning with documented blood concentrations has been reported to date. We report a rare fatal case of ivermectin misuse with a review of recent literature. The patient suffered from ivermectin poisoning due to transdermal overdose. The patient’s plasma concentration was 27 ng/mL. The main clinical manifestations were gastrointestinal symptoms in the early stage and diffuse cerebral edema and intracranial hypertension in the later stage. Despite active treatment, including hemoperfusion and cardiorespiratory support, the patient died. Many recent in vitro studies have shown that ivermectin has the potential to become a new anticancer drug. If clinical research proves its effectiveness against cancer, it may also lead to ivermectin overuse. This study aimed to raise awareness regarding ivermectin poisoning among clinicians and the public, thereby preventing drug abuse.
Keywords
Introduction
Ivermectin is a semisynthetic derivative of avermectin, a macrolide compound isolated from Streptomyces fermentans. Ivermectin was initially marketed for animal use in 1981. In 1987, it was registered for human use as a treatment option for onchocerciasis (river blindness). Currently, ivermectin is used in humans as a prescription medication for Strongyloides stercoralis infection, Onchocerca volvulus infection, ascariasis, lice, scabies, and rosacea. 1 It has significantly reduced human suffering from river blindness and continues to benefit global health. Although ivermectin is effective against specific diseases, it exerts adverse effects that cannot be ignored. Although ivermectin poisoning cases surged during the coronavirus disease 2019 (COVID-19) pandemic, only a few cases were documented in detail or confirmed through toxicological analysis. Moreover, most reported cases involved poisoning caused by oral administration of ivermectin. There have been no reports of transdermal toxicity. To date, no studies have reported the specific blood drug concentration that causes ivermectin poisoning. Most recent in vitro studies suggest that ivermectin is promising as a new anticancer drug,2–4 and this may lead to increased misuse. Therefore, we report a rare fatal case of ivermectin misuse to raise awareness among clinicians and the public regarding ivermectin poisoning.
Case report
The reporting of this study conforms to Case Report (CARE) guidelines. 5
Chief complaints
A woman in her early 40s was found unconscious approximately 1 h prior to her admission to Tsinghua Changgung Hospital in the first half of 2024.
History of present illness
Approximately 1 h prior to admission, the family reported that the patient was unconscious and had fallen to the ground. A large amount of brown vomit was observed nearby, and there was no evidence of incontinence. According to the information provided by the patient’s mother, during the preceding month, the patient had developed multiple rashes and ulcerations on her back following contact with her pet cat and was diagnosed with sarcoptic scabies at another hospital. The use of sulfur ointment proved ineffective. The patient was a physician. She applied approximately 200 mL (1%, 2 g) ivermectin solution to the rash on her back and waist once a night; she wrapped a wet compress with a plastic film and left it overnight. She continued this application for 1 month. One week before admission, she occasionally experienced nausea, vomiting, loss of appetite, abdominal pain, and colic, for which she had visited another hospital and received symptomatic treatment. However, she continued to apply ivermectin.
Medical history
The patient's medical history included diabetes, high blood pressure, hypothyroidism, and psoriatic arthritis. She had previously received metformin for glycemic control and amlodipine besylate for hypertension management, both of which were discontinued ≥3 months prior to admission. She had no history of alcohol consumption and had never been exposed to any other toxic substances, except for ivermectin.
Physical examination
On admission, her vital signs were as follows: body temperature, 36°C; pulse, 71 beats/min; blood pressure, 100/63 mmHg; and peripheral oxygen saturation (SpO2), 70%. The patient was unconscious; she had a Glasgow Coma Scale (GCS) score of E1V1M1; cyanosis in the limbs; and scattered ulcers on the face, lower extremities, back, and waist (Figure 1(a)).
Dermatotoxic manifestations and toxicological confirmation. (a) The patient’s dermatotoxic manifestations: multiple ulcerative lesions on the back (arrows indicate typical application sites of ivermectin) and (b) liquid chromatography–mass spectrometry (LC–MS/MS) showed ivermectin peak at 27 ng/mL.
Diagnostic workup
The patient presented with acute respiratory failure requiring emergent intubation and mechanical ventilation. To determine the disease etiology, a comprehensive diagnostic workup was performed, including routine laboratory tests, radiographic imaging studies, and toxicological screening for drug detection. Based on the confirmed history of transdermal ivermectin exposure (reported by her family member) and consultation with hospital toxicologists, we initiated toxicological screening using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to detect ivermectin, amitraz, and sedative-hypnotic drugs. Subsequently, we initiated hemoperfusion therapy to enhance toxin elimination. Laboratory tests revealed severe metabolic acidosis, respiratory failure, abnormal renal function, and blood hypercoagulability (Table 1). The patient’s thyroid function tests were all within normal ranges. Chest computed tomography (CT) upon admission revealed a localized inflammatory lesion in the lower lobe of the right lung (Figure 2(a)). Head CT upon admission indicated diffuse cerebral edema, with disappearance of the sulci and gyri (Figure 2(c)). Two days later, LC–MS/MS analysis revealed a significantly elevated ivermectin concentration of 27 ng/mL. Healthy skin has limited absorption, and the blood drug concentration is usually less than 2 ng/mL (or even undetectable) at the therapeutic dose. Damaged skin may exhibit a slightly higher concentration. No amitraz or sedative-hypnotics (benzodiazepines) were detected.
Laboratory data.
WBC: white blood cell; Hb: hemoglobin; Plt: platelet; CRP: C-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase, TBil: total bilirubin; DBil: direct bilirubin; K: serum potassium; BUN: blood urea nitrogen; Cre: creatinine; LDH: lactate dehydrogenase; Glu: glucose; Na: sodium; CK: creatine kinase; CK-MB: creatine kinase-myocardial band; MYO: myoglobin; hs-cTnT: high-sensitivity cardiac troponin-T, PH: potential of hydrogen; PaCO2: partial pressure of carbon dioxide; PO2: partial pressure of oxygen;
Imaging findings in ivermectin toxicity. (a) Admission chest computed tomography (CT) demonstrated right lower lobe consolidation (arrows indicate air bronchograms). (b) Follow-up CT after 7-day antibiotic therapy showed interval resolution of pulmonary opacities. (c) Initial noncontrast head CT revealed diffuse cerebral edema with sulcal/gyral effacement. (d) Delayed head CT indicated pseudosubarachnoid hemorrhage (arrows) secondary to refractory intracranial hypertension and (e–f) CT angiography (CTA) confirmed nonvisualization of the anterior and middle cerebral arteries, consistent with cerebral circulatory arrest.
Treatment and outcome
The patient had a lung infection and received 1 g of latamoxef every 12 h for 7 days. Latamoxef undergoes predominant renal elimination with minimal hepatic involvement, whereas ivermectin is extensively metabolized by hepatic CYP3A4 and excreted primarily in the feces. Crucially, owing to latamoxef’s water-soluble structure, it avoids interaction with cytochrome P450 enzymes. In contrast, ivermectin’s lipophilicity necessitates its CYP3A4-mediated detoxification. The two drugs exhibit fundamentally different metabolic profiles and therefore do not interact with each other. Finally, the patient’s consciousness was not restored and breathing did not improve. The patient presented with severe cerebral edema, prompting implementation of targeted temperature management with core temperature maintenance at 36.0°C and osmotherapy using 20% mannitol (1 g/kg every 6 h) for intracranial pressure control. Therefore, we continued to perform hemoperfusion. After 1 week of treatment, reexamination via chest CT indicated that the patient’s pneumonia had improved (Figure 2(b)); however, the degree of brain edema remained very high. Even a repeat head CT revealed pseudosubarachnoid hemorrhage due to intracranial hypertension (Figure 2(d)), and CT angiography (CTA) indicated that multiple large arteries in the brain were not clearly visualized (Figure 2(e) and (f)), suggesting cerebral circulatory arrest. The patient’s spontaneous breathing and consciousness had never recovered, based on the following criteria: (a) irreversible coma (GCS score, E1V1M1); (b) absence of all brainstem reflexes (pupillary light/corneal/oculocephalic/gag reflexes); and (c) apnea (ventilator-dependent). Although the formal apnea test (partial pressure of carbon dioxide (PaCO2) ≥60 mmHg), 12-hour confirmation assessment, and electroencephalogram were waived per family request, radiographic evidence of diffuse cerebral edema with nonvisualization of multiple intracranial arteries satisfied the criteria for “clinically presumed brain death” according to the Chinese Guidelines for the Determination of Brain Death (2020 version). At the request of the family members, life support was withdrawn, and the patient was declared deceased. The family declined an autopsy.
Laboratory examinations
Laboratory tests revealed severe metabolic acidosis, respiratory failure, abnormal renal function, and hypercoagulability (Table 1).
Discussion
Ivermectin is a broad-spectrum antiparasitic drug. Its mechanism of action involves enhancing the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the parasite, which opens the Cl− channels controlled by glutamate, increases the permeability of the nerve membrane to Cl−, blocks nerve conduction, and eventually leads to paralysis of the parasite. The mammalian peripheral neurotransmitter is acetylcholine, and GABA is found only in the central nervous system. Ivermectin exhibits limited penetration into the blood–brain barrier (BBB) in humans due to active efflux mediated by P-glycoprotein (P-gp/ABCB1), a drug transporter encoded by the MDR1 gene. 6 Ivermectin is usually prescribed in humans as an oral drug. However, veterinary formulations are available in many forms. As mammals have a BBB, the recommended drug dose is very low. A single oral dose of 150–300 µg/kg is typically recommended, with a dose of 200 µg/kg in the case of scabies; these therapeutic doses are safe for mammals. A standard therapeutic dose of ivermectin has both excellent parasiticidal efficacy and high tolerability. 7
In March 2025, we conducted a search on the PubMed database using “ivermectin” and “poisoning” as keywords. Only a few reports referred to cases of human poisoning due to ivermectin. 8 An increase in the number of reports of human ivermectin poisoning was observed after the outbreak of the novel coronavirus. On 3 April 2020, an invitro study by Caly et al. demonstrated that ivermectin could effectively clear the viral RNA of severe acute respiratory syndrome coronavirus 2 within 48 h. 9 Subsequently, ivermectin was used by some frontline doctors and the public for the treatment of COVID-19. Consequently, the number of reported cases of ivermectin poisoning increased. The recommended dose of ivermectin for COVID-19 treatment is 150–200 µg/kg twice daily. 10 In May and August 2022, two highly influential articles were published consecutively, which demonstrated that the effectiveness of ivermectin was not significantly different from that of placebo in COVID-19 treatment.11,12 Moreover, several articles claiming that ivermectin is effective in treating COVID-19 have been withdrawn (e.g. Elshafie et al., 2022).13,14 Therefore, the United States Food and Drug Administration (FDA) has not yet approved ivermectin for the treatment or prevention of COVID-19 in humans or animals. Nevertheless, some clinical physicians and the public continue to use ivermectin for treating COVID-19. Therefore, since the outbreak of the pandemic, the number of reports of ivermectin poisoning has increased. A literature search revealed that the causes of human ivermectin poisoning include evidence of overdose, veterinary use, drug combination, and secondary damage to the BBB. 15 Ivermectin is also a substrate of P-gp, which limits its neurotoxicity. Genetic polymorphisms of human P-gp or the combined use of P-gp inhibitors may increase the neurotoxicity of ivermectin. 16 However, studies on ivermectin poisoning are mostly limited to case reports, and large-scale studies are currently lacking. A retrospective study conducted in South Africa included the largest number of ivermectin poisoning cases; a total of 71 patients seeking help due to ivermectin poisoning were screened. In the cases of ivermectin poisoning, the most common organ systems involved were the central nervous system (40.0%), gastrointestinal system (27.7%), ocular system (13.8%), and dermatological system (7.7%). 17 Numerous studies have indicated that the clinical manifestations of animal and human ivermectin poisoning are mainly neurological symptoms, including ataxia, seizures, muscle weakness, tremors, blindness, coma, or even death in severe cases. 18 Other symptoms include gastrointestinal symptoms such as abdominal pain, diarrhea, and loss of appetite. 19 Furthermore, research has shown that ivermectin poisoning can cause adverse skin reactions. Ivermectin may lead to pruritus, lymphadenitis, arthralgia, and fever, sometimes as part of the Mazzotti reaction. Although the most serious safety concern associated with ivermectin is neurotoxicity, several cases of severe allergic reactions following systemic ivermectin have been reported. In recent years, a study identified 25 cases of ivermectin-related severe allergic reactions, mostly Stevens–Johnson syndrome, toxic epidermal necrolysis, and polymorphic erythema–like reactions, which were associated with 20% mortality. 20 In addition, sporadic cases are reported, suggesting that ivermectin poisoning can cause visual impairment and liver injury.21,22
At present, there is no specific antidote for ivermectin poisoning. 23 The therapeutic approach primarily focuses on toxin elimination and comprehensive supportive measures. After oral poisoning with ivermectin, active gastric lavage should be performed, and activated charcoal and oral laxatives should be used. However, in this case, ivermectin was absorbed into the bloodstream through skin abrasions, precluding gastrointestinal decontamination. Ivermectin has high lipid solubility (logP = 4.5). Polyethylene glycol 400 (PEG-400), a nonpolar solvent, can potentially dissolve the unabsorbed drugs on the skin surface through the principle of similar solubility. However, further clinical evidence is needed for confirmation. Based on the documented efficacy of hemoperfusion in avermectin poisoning 24 and considering the structural homology between avermectin and ivermectin (both sharing a 16-membered macrocyclic lactone core with 82.4% molecular similarity), we initiated hemoperfusion for this patient. Even after undergoing hemoperfusion, the patient ultimately died. This finding suggests that hemoperfusion may have limited efficacy in severe ivermectin poisoning cases with high blood concentrations (27 ng/mL). Emerging evidence from preclinical studies and clinical case reports suggests the utility of intravenous lipid emulsion therapy for ivermectin toxicity, attributable to the drug’s high lipophilicity. 25 Moreover, benzodiazepines are closely related to the binding sites of GABA and ivermectin; therefore, the use of benzodiazepines such as diazepam should be avoided in the treatment of convulsions or tremors caused by cerebral edema to prevent the enhancement of toxic effects.
In this case, the patient applied the veterinary ivermectin preparation externally at high doses over an extended period. Both the initial treating physician and the patient overlooked the significance of abdominal pain and diarrhea at the initial consultation. These might have been the prodromal symptoms of ivermectin poisoning. The patient continued using ivermectin, which eventually led to severe cerebral edema, resulting in irreversible damage to the central nervous system. Despite aggressive interventions including hemoperfusion and intracranial pressure management, the clinical course culminated in death.
Conclusion
Ivermectin is a broad-spectrum antiparasitic drug. The FDA has not yet approved the use of this drug for other diseases. Unauthorized and excessive use of the drug may be unsafe even when applied topically. Moreover, the ivermectin preparations available on the market may be intended for use on animals, and their dosage recommendations are too high for humans, posing a risk of toxicity. Therefore, not only clinical physicians but also the general public should use the drug as indicated and not exceed the recommended dosages. The most commonly affected organ system is the central nervous system. Gastrointestinal symptoms may be prodromal symptoms and should be given attention. In the presence of skin lesions, enhanced dermal absorption may lead to excessive drug intake. There is no specific antidote to ivermectin poisoning, and the effect of hemoperfusion may be limited. The treatment plan is to promote the elimination of toxins and provide symptomatic treatment. Although this study provides valuable insights, certain limitations should be acknowledged. First, the findings are based on a single case, which may limit the generalizability of the results to broader populations or contexts. Further research with larger and more diverse samples is needed to confirm the robustness of our findings.
Footnotes
Acknowledgment
We would like to thank the patient and her family.
Authors’ contributions
He Yin and Sheng Wu are responsible for writing the manuscript. All authors have read and approved the manuscript.
Data availability statement
The data supporting the findings of this study are available within the article.
Declaration of conflicting interests
The authors report no conflicts of interest.
Ethics statement and informed consent
Ethical approval was not required for this study in accordance with national guidelines. Written informed consent for the publication of patient data was obtained from the patients’ families. The reporting of this study conforms to the Case Report (CARE) guidelines. This retrospective case report used anonymized data.
Funding
Not applicable.
