Ivermectin for COVID-19 Linked to Severe Toxicity in Small Study

Ivermectin taken to prevent or treat COVID-19 led to toxic effects, including severe episodes of confusion, ataxia, seizures, and hypotension, a small observational study showed.

Of 21 callers to the Oregon Poison Center in August — including 11 people who said they used ivermectin to prevent COVID-19 and 10 who used the drug to treat COVID symptoms — six were hospitalized for toxic effects from ivermectin use, reported Robert Hendrickson, MD, of Oregon Health and Science University in Portland, and co-authors in the New England Journal of Medicine.

Four people were admitted to an ICU; none died. All hospitalized patients said they had taken ivermectin to prevent COVID, including three people who had obtained the drug by prescription.

Four hospitalized patients had gastrointestinal distress, three had confusion, two had ataxia and weakness, two had hypotension, and one had seizures.

“There’s been a lot of discussion that either ivermectin works or it doesn’t, but not a lot about the downsides of prescribing it,” Hendrickson said in an interview with MedPage Today.

“There is not good evidence that it can prevent or treat COVID-19,” Hendrickson maintained. “But it can cause toxicity, and has caused toxicity, when used for that specific reason.”

“It’s important for clinicians to recognize this toxicity and include it in the questions you ask your patients when you have someone who is acutely confused or unable to walk or ataxic,” he continued. “This is not something most of us were thinking of before.”

Ivermectin is approved to treat certain infections caused by internal and external parasites in humans. Both retail pharmacy dispensing of the drug and sales of veterinary formulations have climbed during the pandemic. By August 13, ivermectin prescriptions had jumped to more than 88,000 a week, CDC researchers reported in a Health Alert Network warning — a 24-fold increase over the pre-pandemic baseline weekly average of 3,600 scripts.

Even when used for approved indications, “ivermectin actually has a fair number of adverse effects,” Hendrickson said. “It is pumped out of the brain with P-glycoprotein, and if you are taking a medication, either prescribed or over-the-counter, that inhibits P-glycoprotein, you are at much higher risk for toxicity.”

At the Oregon Poison Center, calls regarding ivermectin averaged 0.25 calls per month in 2020 and increased to 0.86 calls per month from January through July 2021. In August, the center received 21 calls. The median age of callers was 64, and 11 were men. Of the 21 callers, three had received prescriptions from physicians or veterinarians, and 17 had purchased veterinary formulations (the source for the remaining person was not confirmed).

Symptoms developed in most callers within 2 hours after a large, single, first-time dose. In six people, symptoms emerged gradually after several days to weeks of repeated doses taken every other day or twice weekly.

Reported doses ingested by people who used veterinary products ranged from 6.8 mg to 125 mg of a 1.87% paste and 20 to 50 mg of a 1% solution. The dose of the human-use tablets was 21 mg per dose twice weekly for prevention.

Of the 15 people not admitted to a hospital, most had gastrointestinal distress, dizziness, confusion, vision symptoms, or rash.

“It’s easy to understand where people are getting mixed messages about ivermectin,” Hendrickson noted. Early studies showed that ivermectin may decrease SARS-CoV-2 replication in vitro, but large randomized controlled trials have shown no clinical benefit in preventing or treating COVID-19, he pointed out.

“There’s a lot of pressure, particularly on primary physicians, from patients to prescribe this,” Hendrickson said. “But with no effectiveness, and certainly a risk of toxicity — and in several cases, severe toxicity — it’s not worth it.”