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Toxicology Rounds

Toxicology Rounds

Ivermectin Not the Crisis It's Claimed to Be

Gussow, Leon MD

doi: 10.1097/01.EEM.0000800476.28069.a2
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    ivermectin, COVID-19
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    You are not a horse. You are not a cow. Seriously, y'all. Stop it.

    —Tweet from @US_FDA, Aug. 21, 2021

    I can't remember any time when the U.S. Food and Drug Administration had to resort to the faux-folksy mode of expression to try to get its point across. We live in strange times.

    The FDA was responding, of course, to the precipitous increase in using ivermectin this past summer by people attempting to treat or prevent COVID-19. Physicians are prescribing ivermectin off-label for patients, and the Centers for Disease Control and Prevention reported that the number of prescriptions filled for the drug went from an average of 3600 per week before the pandemic to 88,000 the week of Aug. 7 alone. That's an increase of more than 2300 percent!

    Many people are dosing themselves with veterinary preparations intended for large farm animals. These products are generally available over the counter without a prescription. Many feed stores have resorted to locking up or rationing their supplies, with some demanding that customers produce a picture of themselves with a large farm animal to prove a legitimate need for the product.

    Illinois has many farm communities, but I cannot recall our poison center or toxicology service being contacted for ivermectin toxicity over the past several decades. My own lack of familiarity with the drug made it seem like a good time to address some key questions about it.

    Significant Toxicity

    Ivermectin is a broad-spectrum antiparasitic agent used orally to treat and prevent human diseases such as river blindness, strongyloidiasis, and lymphatic filariasis (a form of elephantiasis). It is also used in veterinary medicine to control parasitic conditions such as heartworm in horses and other animals. A usual single human dose is 150-200 mcg/kg.

    Ivermectin activates and opens chloride (Cl-) channels, especially glutamate-gated Cl- channels found only in invertebrates. This allows increased entry of negative ions into the cell, hyperpolarizing the cell membrane and impairing function of nematode nerve and muscle cells. Ivermectin kills parasitic worms by inducing toxic paralysis.

    Ivermectin can also cause human neurotoxicity by interacting with inhibitory GABA receptors in the brain. Fortunately, ivermectin taken at therapeutic doses does not effectively cross the blood-brain barrier because it is pumped out of the CNS by the P-glycoprotein (P-gp) transporter.

    Side Effects

    Ivermectin is typically safe at the commonly prescribed one-time oral dose of 100-300 mcg/kg. Therapeutic doses can be toxic, however, in conditions that impair the function of the blood-brain barrier. An interesting recent case report described a 13-year-old boy who developed a coma, ataxia, pyramidal signs, and diplopia after receiving a single oral dose of ivermectin (230 mcg/kg) as prophylaxis for scabies.

    A genetic workup revealed that the boy had nonsense mutations in both genes that code for the P-gp transporter. (N Engl J Med. 2020;383[8]:787; https://bit.ly/3nWuFRF.) The child recovered after two days in the pediatric ICU.

    Side effects reported after exposure to therapeutic doses of ivermectin include hives and itching, dizziness, headache, and gastrointestinal distress with nausea, vomiting, diarrhea, and abdominal pain. Certain individuals with “leaky” blood-brain barriers or those who take significantly supratherapeutic doses can develop severe neurotoxicity with lethargy, decreased level of consciousness, seizures, and coma. (N Engl J Med. 2020;383[8]:787; https://bit.ly/3nWuFRF.)

    U.S. poison centers have been seeing toxicity from exposure to ivermectin, but not nearly to the extent you might think from reading reports online. Oklahoma hospitals are not having to turn away gunshot victims because they are overrun with patients poisoned by ivermectin, and 70 percent of the Mississippi Poison Control Center's recent calls concerned exposure to veterinary ivermectin. (Reporters misunderstood a clear statement from the center that stated 70 percent of their calls about ivermectin concerned exposures to the veterinary—not human—product.)

    With no specific antidote, treatment remains supportive and symptomatic, including fluids and pressors as needed for hypotension, benzodiazepines for seizures, and, of course, stopping exposure to ivermectin. Most manifestations seem to resolve with several days of observation and supportive care. No good data are available, but it seems reasonable to treat elevated liver enzymes with standard doses of N-acetylcysteine. And remember that the local poison center is available 24/7 to provide advice on managing this unfamiliar exposure.

    Ivermectin has proved remarkably safe when used to treat parasitic infections, but we have little experience or data about the drug taken in large doses, day after day, as some patients have been doing during the COVID-19 pandemic. I expect that published literature on ivermectin toxicity will become much richer over the next fewmonths and years.

    Read a more comprehensive version of this article with comments from the directors of poison control centers in Texas and Oklahoma on our website: https://bit.ly/3zDku6I.

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    Comments? Write to us at [email protected].

    Dr. Gussowis a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Follow him on Twitter@poisonreview, and read his past columns athttp://bit.ly/EMN-ToxRounds.

    Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
    • npina112:51:54 PM It's a shame the FDA has to resort to calling a medicine names. Ivermectin has an excellent safety profile, and has been used in human beings for years. Coumadin is a rat poison. The bureaucrats in charge of banning "misinformation" should look themselves in the mirror. I've seen more misinformation coming from the FDA and CDC than any other source. I have yet to find any convincing evidence of even small numbers of ivermectin poisonings.