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Ivermectin— you may have heard of it, either because you have given it to your pet to treat a parasitic worm, or if you are familiar with an international health problem called onchocerciasis, known commonly as river blindness, the second most common infectious cause of blindness. You also may have heard that ivermectin is being studied as a medication against COVID-19, but the issue of ivermectin has been rather polarizing in public discussions and over the past year of the pandemic, there has been excitement, followed by disappointment, surrounding other treatments, notably hydroxychloroquine, remdesivir, and convalescent plasma. In the case of hydroxychloroquine, the issue was politicized to an unprecedented extreme, as the former US President was literally advising people to take the drug, claiming that he was taking it himself for prevention, that the drug was effective against COVID-19, which was not true, and that it posed no risks, which also was not true. You may remember that the phenomenon of trashy medical advice coming from the former POTUS himself reached such heights about a year ago that an Arizona man died, and his wife nearly so, from ingesting chloroquine phosphate, a fishtank cleaner formulation, consumed in an attempt to protect themselves against infection with SARS-CoV2 (the virus that causes COVID-19).
So here we are a year later, with the drug ivermectin on the stage as a potential treatment, with a couple of features sounding somewhat reminiscent of the hydroxychloroquine episode: First, unlike remdesivir, which is fairly new (it was developed with the goal of treating Ebolavirus), but very much like hydroxychloroquine, ivermectin has been around the block. It is used routinely for other conditions. It can produce dangerous side effects in different situations, but its safety profile is well understood. Second, like hydroxychloroquine, despite its use in many parts of the world in settings of COVID-19, health authorities in the United States and elsewhere are warning that evidence is not adequate, at least not yet, to warrant the administration of ivermectin to patients with any stage of COVID-19. As for the differences in the big picture of the two drugs, whereas the biggest advocate for hydroxychloroquine was a politician, non-physician who knew nothing about medications or disease, the most enthusiastic proponent in the US for adding ivermectin to anti-COVID-19 regimens for all severities of SARS-CoV2 infection (including for asymptomatic and mildly symptomatic people) is a pulmonary critical care physician, Dr. Pierre Kory, who sees severe COVID-19 cases in the intensive care unit (ICU) every day and who testified as a COVID-19 expert before the US Senate Homeland Security Committee this past December. That part sounds good, but what should raise a red flag for you is the fact that Kory is being portrayed, by anti-government medicine types and by rightwing media, as a kind of Semmelweiss figure who is being shoved aside by health authorities and by leading medical journals.
My assessment of the situation is that the medical journals and health authorities know what they are doing and that the latter, furthermore, are faced with a very difficult dilemma of having to balance the standards of scientific rigor with the pandemic-imposed need to cut corners that might bring new treatments to the anti-COVID-19 arsenal more quickly. In this setting, Dr. Kory appears to be well-intentioned, but acting as a zealot, on account of seeing anecdotal evidence —patients improving, sometimes dramatically in his experience, after receiving ivermectin, and on account of reviewing many, many studies from around the world, involving the use of ivermectin in patients with COVID-19.
But they aren’t all good studies, and therein lies the problem of concluding that there is a cure for COVID-19 that should be added to the guidelines that doctors use to manage care for patients with COVID-19. Many of the data that have been cited as published evidence come from case studies (papers in which physicians publish and discuss recent patient cases) and from other retrospective analyses (papers in which the authors look back at what happened with a group of patients, trying to group the patients into a treatment group that received the therapy of interest versus a group that acts as a control, such as patients who received other treatments). Across the numerous studies with results suggesting possible benefits of ivermectin against COVID-19, the patients in different groups being compared have received all kinds of other treatments, while different studies have reported correlations between use of ivermectin and different outcomes, such as preventing death, preventing severe symptoms, or preventing any symptoms at all. Thus, of the many publications, many of them tend to be small studies involving few patients that when taken together amount to comparing apples to oranges. Also, many of the studies that have been cited as evidence of a benefit of ivermectin are preprint studies, meaning that they have not gone yet through peer review, the process in which studies seeking publication are reviewed by other experts with no stake in the particular study. In many cases, preprint studies are later retracted either during, or after the peer review process. On top of this, whereas the original idea to utilize ivermectin against COVID-19 came from a finding that when supplied in very high concentrations in laboratory (in vitro) samples of SARS-CoV2, the drug kills the virus, there has not been any evidence published saying that similar concentrations of the drug can be reached safely in plasma (the liquid portion of blood). At the normal dosage of ivermectin that is given to kill parasites (200 µg per kg of body weight), plasma concentrations do not reach anywhere close to the test tube levels, nor are such plasma levels achieved when the dosage is increased many times above the normal dosage.
Keeping the dosage within the range in which the medical community has experience is important, because, despite being a fairly safe medication, ivermectin can cause problems in certain people and in certain situations, and the risk of such complications increases with dosage. One such example is that ivermectin can interfere with warfarin, a drug that is given commonly to reduce the blood’s ability to clot. This is a drug that doctors try to avoid given throughout pregnancy and must avoid during the first trimester and during the final pregnancy weeks. But it is extremely relevant to COVID-19, because one of the things that SARS-CoV2 does in moderate and severe cases is to disrupt the blood clotting system, leading to small clots (microthrombi), which have been linked to organ failure and complications in the brain. Consequently, drugs such as warfarin have been found to decrease mortality of COVID-19 and thus are given to many patients. When it comes to pregnancy, health authorities, such as the US Food and Drug Administration (FDA) warn against the use of ivermectin, as its effects on the fetus/embryo have not been worked out adequately for the drug to be given the green light in pregnant women.
All of these factors notwithstanding, there is some good news about ivermectin in that some recent meta-analyses — studies that have pooled data from various small studies and run statistical analysis on those data— do reveal signs that ivermectin seems to blunt the severity of COVID-19 and may reduce mortality. On top of this, the drug is known to have both antiviral effects (which could be useful in anyone infected with COVID-19 from asymptomatic to severe at at any point after infection) and anti-inflammatory effects (which could be useful in moderate to severe cases), so there really is a case to be made that —potentially— it could become a drug to be given to nearly anyone with a SARS-CoV2 infection, including people who simply test positive for the virus, analogous to treating people who test positive for human immunodeficiency virus (HIV) to keep them from getting sick. The point though, is that we do need to get the science right. There needs to be proper clinical studies. These studies need to be controlled and double blinded (the patients and researchers do not know who is receiving the ivermectin), to avoid factors that can confuse the results, and they must be designed from the ground up, what researchers call prospective. This means don’t rush to take ivermectin, until more is known, and by the way, even if it is determined that ivermectin can thwart COVID-19, you must obtain the medication, only from your physician —your human physician, not your veterinarian. Do not ever, ever, ever take your pet’s parasite medication. It is not formulated for humans, nor dosed accordingly.
