Ivermectin, a medication known for its antiparasitic properties, has been used globally for decades to treat various parasitic infections in both humans and animals. This drug, first approved for human use in 1987, addresses conditions such as river blindness, strongyloidiasis, scabies, and head lice. During the COVID-19 pandemic, ivermectin gained considerable public attention as a potential therapeutic or preventative measure against the SARS-CoV-2 virus, leading to widespread interest and scientific investigation.
Initial Scientific Interest and Early Data
Early scientific exploration into ivermectin’s potential against COVID-19 stemmed from its observed antiviral activity in laboratory settings. In vitro studies indicated that ivermectin could inhibit the replication of SARS-CoV-2. One frequently cited study reported a substantial reduction in viral RNA within 48 hours when ivermectin was applied to infected cells.
This antiviral activity was not unique to SARS-CoV-2, as ivermectin had previously demonstrated effects against a range of other RNA and DNA viruses in similar laboratory experiments. However, a significant challenge emerged: the concentrations of ivermectin needed to achieve these antiviral effects in vitro were considerably higher than the doses approved for human use. These required concentrations were estimated to be thousands of times greater than what could be safely administered orally. Preliminary observational studies and pre-print data also suggested potential benefits, yet these early findings were often limited by small sample sizes or methodological issues, with some subsequently retracted due to concerns about data integrity.
Major Clinical Trials and Their Findings
Several large, well-designed randomized controlled trials (RCTs) were conducted to rigorously assess ivermectin’s efficacy against COVID-19. These trials aimed to determine if the drug could prevent infection, reduce hospitalizations, shorten recovery times, or lower mortality rates in both outpatient and inpatient settings. Their findings have been instrumental in shaping the understanding of ivermectin’s role in COVID-19 management.
The TOGETHER trial, a randomized study conducted in Brazil, investigated ivermectin at a dose of 400 micrograms per kilogram of body weight, administered once daily for three days to outpatients with early COVID-19. This trial concluded that ivermectin did not result in a lower incidence of medical admission to a hospital or prolonged emergency department observation for participants. While some analyses noted a reduction in risks for death, mechanical ventilation, and hospitalization, these findings were not deemed statistically significant, and the trial was halted early due to a lack of demonstrated effect.
Similarly, the ACTIV-6 trial, a large, National Institutes of Health-funded platform study, evaluated ivermectin in two different dosing regimens: 400 micrograms per kilogram daily for three days and a higher dose of 600 micrograms per kilogram daily for six days. This trial involved outpatients experiencing mild-to-moderate COVID-19 symptoms. The results indicated no benefit of ivermectin in accelerating the resolution of symptoms, nor did it reduce hospitalizations or emergency room visits. The higher dose of ivermectin showed even less benefit than the lower dose, and the median time to sustained recovery remained similar between the ivermectin and placebo groups.
The PRINCIPLE trial, a United Kingdom-led, multi-center, open-label, adaptive platform trial, also investigated ivermectin’s effects on COVID-19 outcomes in community settings, primarily among a vaccinated population. Participants received ivermectin at a target dose of 300-400 micrograms per kilogram daily for three days. The study found no clinically meaningful improvements in recovery times, hospital admissions, or mortality rates. Although a modest two-day reduction in self-reported symptom duration was observed, from 16 days to 14 days, this difference was not considered clinically significant. Based on these comprehensive findings, further trials of ivermectin appear unnecessary.
Regulatory and Medical Body Guidance
Based on the comprehensive review of evidence from clinical trials, major national and international health organizations have issued clear guidance regarding ivermectin’s use for COVID-19. The U.S. Food and Drug Administration (FDA) has consistently stated it has not authorized or approved ivermectin for COVID-19 prevention or treatment. The agency highlights that clinical trial data do not demonstrate ivermectin’s effectiveness and warns against using animal ivermectin products due to different formulations and unknown safety profiles.
The European Medicines Agency (EMA) advises against using ivermectin for COVID-19 outside of well-designed clinical trials. The EMA concluded that existing data do not support its use, despite acknowledging in vitro activity at concentrations much higher than what is safely achievable. Within the European Union, ivermectin medicines are not authorized for COVID-19. The World Health Organization (WHO) also recommends ivermectin only be used within clinical trials, citing “very low certainty” evidence regarding its impact on mortality, mechanical ventilation, hospitalization, and clinical improvement. The WHO further updated its guidelines in November 2023 to strongly recommend against its use due to a persistent lack of supporting evidence or biological plausibility.
The National Institutes of Health (NIH) also recommends against using ivermectin for COVID-19, except within clinical trials. This position is informed by negative results from recent randomized, placebo-controlled trials. Even Merck, the developer of ivermectin, affirmed in February 2021 that its analysis found no scientific basis for a therapeutic effect against COVID-19, citing a lack of evidence from pre-clinical studies, clinical activity, and safety data.
Ivermectin Safety Profile
Ivermectin has a well-tolerated safety profile when administered at approved doses for its indicated parasitic conditions. Common side effects associated with standard uses are mild to moderate and include tiredness, loss of energy, stomach pain, nausea, vomiting, diarrhea, dizziness, sleepiness, itchiness, headache, and muscle aches. Serious neurological complications, such as seizures, confusion, or encephalopathy, are rare but possible. These more severe effects have been reported, particularly at higher doses or in individuals co-infected with certain parasites, like Loa loa.
Concerns arise when ivermectin is used off-label for COVID-19, especially at unapproved doses or with formulations intended for animals. Taking large doses of ivermectin, or using formulations meant for livestock, can lead to serious adverse effects including low blood pressure, allergic reactions, balance problems, seizures, coma, and even death. The FDA has documented multiple reports of individuals requiring medical attention, including hospitalization, after self-medicating with ivermectin products intended for animals, highlighting the risks of misuse.