Dosing and Toxicity
An article in Antiviral Research, June 2020, titled “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro” reported on the effectiveness of ivermectin against SARS-CoV-2 (the Covid-19 virus) in vitro . The test was done on cells in culture in a lab; the cells were infected with the real Covid-19 virus, and subsequently treated with ivermectin. The researchers concluded: “A single treatment able to effect ~5000-fold reduction in virus at 48 h in cell culture.” This result was widely reported in the popular press.
An article in Clinical Pharmacology & Therapeutics, May 2020, determined that at doses of ivermectin from 12 mg/day to 120 mg/day, the concentration of ivermectin in the blood and in the lungs was nowhere near the concentration (5 µM) found to be effective in the prior study . (Note that the May-published study followed after the June-published study, due to early “preprint” availability of the June study.)
The above studies have led some physicians, researchers, and medical officials to conclude that concentrations needed to inhibit SARS-COV-2 would be difficult to achieve in humans as this concentration, from the in vitro study, would be toxic. That conclusion is based on the above single study , done in the lab. The assumption is that ivermectin can’t work at any lower concentration than was found to be effective against cells in vitro (i.e. in lab glassware). This assumption has turned out to be proven false by subsequent medical studies in vivo, that is, in human patients.
A high concentration of ivermectin worked in the lab against a cell culture. This does not mean that a lower and entirely safe dosage of ivermectin would not work in humans. The mechanism of action in patients may be quite different than the mechanism when ivermectin is used on a culture of cells in a lab. And, as it turns out from multiple peer-reviewed randomized controlled trials (RCTs), ivermectin has shown itself to be highly effective against Covid-19.
The website IVMmeta.com lists 67 studies of Ivermectin and Covid-19 with results comparing treatment and control groups; these studies involved a total of 649 scientists and 49,492 patients. The studies showed an overall 66% improvement in Covid-19 patients with treatment with ivermectin. There were 15 trials studying ivermectin as a preventative measure, with an overall effectiveness of 85%. Then 29 trials tested Covid-19 as an early treatment, with 66% improvement, while 23 late treatment trials showed only a 38% improvement. Late treatment of any disease is less effective. In 28 studies which also tracked mortality, there was a 58% reduction in death for patients given ivermectin. Then the 31 Randomized Controlled Trials (RCTs) found a 57% improvement in patients given ivermectin versus controls.
All of these trials used safe doses of ivermectin, and most used the usual dosing for ivermectin (0.2 mg per kg of body weight). However, two studies using high doses of ivermectin (Krolewiecki: 0.6 mg/kg x 5 days; Buonfrate: 0.6 mg/kg x 5 days or 1.2 mg/kg x 5 days) proved ineffective [3, 4], while the vast majority of the other studies found ivermectin to be highly effective at lower dosing . Thus, not only is high dosing not needed, it is not supported by trials. Even so, none of the trials reported toxicity from ivermectin.
Therefore, the claim that an effective dose of ivermectin in patients could not be achieved due to the necessity of very high dosing that would be toxic is FALSE.
Another common claim about ivermectin and Covid-19 is that there is no available data on outcomes or efficacy in humans from RCTs. The website IVMmeta.com lists 31 RCTs of ivermectin used as a treatment for Covid-19. Of those 31 RCTs, two studies with negative results were the high-dose studies mentioned above (Krolewiecki  and Buonfrate ). Excluding high doses, in the 29 RCTs remaining, 24 showed ivermectin to be highly effective against Covid-19, from 63% to 96% effective .
Another claim against the use of ivermectin is that it is a “horse paste” used to treat animals, not humans. There is such a version of ivermectin for horses. There is also a version available for dogs. This is because ivermectin was originally discovered and used as a treatment for parasites. Ivermectin was approved for human use in the late 1980s and over 3 billion doses have been distributed to humans worldwide since that time. Ivermectin is FDA-approved for treatment of parasites. It is available from almost any pharmacy in the U.S. It is also available over-the-counter in Mexico. The pharmaceutical version of ivermectin is a pill manufactured and approved for human use. So those persons taking ivermectin for Covid-19 are not taking “horse paste”.
Another common claim is that using ivermectin results in many visits to the ER by persons who have taken a toxic dose. A study of a dosing 10 times the prescription dose, 120 mg instead of 12 mg, was found to be safe in one study . Two other studies used dosing 3 or 6 times the usual dose of 12 mg per day, without toxicity. Claims of many visits to ERs for ivermectin toxicity were made by the popular press and are unsubstantiated, but often repeated.
Lack of Evidence
Wikipedia gives a good backgrounder on ivermectin:
“Ivermectin was discovered in 1975 and first marketed as a veterinary medicine in 1981. Human applications followed in the late 1980s. William Campbell and Satoshi Ōmura won the 2015 Nobel Prize in Physiology or Medicine for its discovery and applications. The medication is on the World Health Organization’s List of Essential Medicines, and is approved by the U.S. Food and Drug Administration as an antiparasitic agent. In 2018, ivermectin was the 420th most commonly prescribed medication in the United States, with more than one hundred thousand prescriptions. It is available as a generic medicine.”
Unfortunately, Wikipedia also makes false claims about ivermectin: “During the COVID-19 pandemic, misinformation has been widely spread claiming that ivermectin is beneficial for treating and preventing COVID-19. Such claims are not backed by credible scientific evidence.”
The credible scientific evidence is that cited above, as summarized at IVMmeta.com; this evidence includes many RCTs, as well as other relevant peer-reviewed scientific studies.
Why The Misinformation?
Why has misinformation and falsehoods about an effective prophylactic and early treatment for Covid-19 prevailed in many nations? Why do medial authorities and the mass media generally adhere to these falsehoods and reject ivermectin during the pandemic? I don’t know. Perhaps it is because other treatments, which are less effective, have the backing of powerful pharmaceutical corporations with billions of dollars in resources as well as great influence in the medical establishment. Or perhaps it is because we live in a highly polarized and politicized society, in which ideology has more influence then truth. Most people cannot read and understand an RCT study on ivermectin or any other medication. So they rely on medical authorities, but such institutions are obtuse bureaucracies which do not rely solely on science for their decisions.
Ronald L. Conte Jr.
an author, not a doctor