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Toxicology Rounds: Ivermectin is not the crisis it claims… : Emergency Medicine News

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ivermectin, COVID-19

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Yesou are not a horse. You are not a cow. Seriously, y’all. Stop that.

—Tweet from @US_FDA, August 21, 2021

I can’t remember a time when the US Food and Drug Administration had to resort to the faux-folksy mode of expression to try to get their point across. We live in strange times.

The FDA was, of course, reacting to the precipitous increase in ivermectin use last summer by people trying to treat or prevent COVID-19. Doctors are prescribing off-label ivermectin to patients, and the Centers for Disease Control and Prevention has reported that the number of prescriptions filled for the drug has risen from an average of 3,600 a week before the pandemic to 88,000 a week. August 7 only. That’s an increase of over 2300 percent!

Many people dose themselves with veterinary preparations intended for large farm animals. These products are usually available over the counter without a prescription. Many grocery stores have resorted to locking down or rationing their supplies, with some requiring customers to produce a photo of themselves with a large farm animal to prove a legitimate need for the product.

Illinois has many farming communities, but I don’t recall our poison control center or toxicology department being contacted for ivermectin toxicity in the last few decades. My own unfamiliarity with the drug felt like a good time to answer 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), in particular glutamate-gated Cl channels channels found only in invertebrates. This allows increased entry of negative ions into the cell, hyperpolarizing the cell membrane and impairing nematode nerve and muscle cell function. 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 in 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 generally safe at the commonly prescribed single oral dose of 100 to 300 mcg/kg. Therapeutic doses can, however, be toxic under conditions that impair blood-brain barrier function. An interesting recent case report described a 13-year-old boy who developed coma, ataxia, pyramidal signs, and diplopia after receiving a single oral dose of ivermectin (230 mcg/kg) as prophylaxis for scabies.

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

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

The US poison control centers have found toxicity from ivermectin exposure, but not as much as you might think from reading reports online. Oklahoma hospitals don’t have to turn away gunshot victims because they’re overrun with ivermectin-poisoned patients, and 70% of recent calls from the Mississippi Poison Control Center were about veterinary ivermectin exposure. (Reporters misunderstood a clear statement from the center that said 70% of their calls about ivermectin were for veterinary, not human, exposures.)

In the absence of a specific antidote, treatment remains supportive and symptomatic, including fluids and vasopressors as needed for hypotension, benzodiazepines for seizures, and, of course, cessation of exposure to ivermectin. Most manifestations seem to disappear after 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 NOT-acetylcysteine. And remember that the local poison control center is available 24/7 to provide advice on managing this unknown exposure.

Ivermectin has been shown to be remarkably safe when used to treat parasitic infections, but we have little experience or data on the drug being taken in high doses, day after day, as some patients have for the COVID-19 pandemic. I expect the published literature on ivermectin toxicity to grow much richer over the coming months and years.

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

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