To the editors:
Ivermectin is approved by the Food and Drug Administration as an oral treatment for intestinal strongyloidiasis and onchocerciasis and as a topical treatment for pediculosis and rosacea. It is also used as a treatment for parasites in pets and livestock. Ivermectin may reduce the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro,1.2 but randomized controlled trials have shown no clinical benefit in the prevention or treatment of coronavirus 2019 (Covid-19) disease.3 Veterinary use of ivermectin has increased and the number of prescriptions for human use in the United States is 24 times the number before the pandemic. In addition, the number of such regulations in August 2021 was 4 times the number in July 2021.3.4
The Oregon Poison Center is a telephone consultation center staffed by specially trained nurses, pharmacists and physicians who provide treatment advice to the public and provide comprehensive treatment advice to health professionals caring for patients in Oregon, Alaska and Guam. The center has recently received an increasing number of calls about ivermectin exposure related to Covid-19. The number of calls related to ivermectin was 0.25 calls per month in 2020 and had increased to 0.86 calls per month from January to July 2021; in August 2021, the center received 21 calls. Monthly total call volumes for all poison exposures were stable in 2020 and 2021.
Of the 21 individuals who called in August, 11 were male and most were over 60 years of age (median age 64; range 20 to 81 years). About half (11 people) were said to have taken ivermectin to prevent Covid-19, and the rest had taken the drug to treat Covid-19 symptoms. Three individuals had received prescriptions from physicians or veterinarians and 17 had purchased veterinary formulations; the source of ivermectin for the remaining person was not confirmed. Symptoms had developed in most subjects within 2 hours of a large, single, first dose. In 6 subjects, symptoms had developed gradually over several days to weeks of repeated doses taken every other day or twice a week. One person had also taken vitamin D to treat or prevent Covid-19. The reported doses taken by the subjects who had used veterinary products ranged from 6.8 mg to 125 mg, 1.87% paste and 20 to 50 mg of the 1% solution. The dose of the tablets for human use was 21 mg per dose twice weekly for prevention.
Six of the 21 individuals were hospitalized for toxic effects of ivermectin use; all 6 reported preventive use, including the 3 who received the prescription. Four were treated in an intensive care unit and none died. Symptoms were gastrointestinal distress in 4 subjects, confusion in 3, ataxia and weakness in 2, hypotension in 2, and convulsions in 1. Of the non-hospitalized subjects, most had gastrointestinal distress, dizziness, confusion , vision symptoms, or rash.
These cases illustrate the potential toxic effects of ivermectin, including severe episodes of confusion, ataxia, seizures and hypotension, and the increasing frequency of inappropriate use. There is insufficient evidence to support the use of ivermectin for the treatment or prevention of Covid-19,3 and misuse, as well as the possible occurrence of drug interactions,5 can lead to serious side effects requiring hospitalization.
Courtney Temple, Maryland
Ruby Hoang, DO
Robert G. Hendrickson, MD
Oregon Health and Science University, Portland, OR
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on NEJM.org on October 20, 2021.
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2. Lehrer S, Rheinstein Ph. Ivermectin links to the SARS-CoV-2 spike receptor binding domain attached to ACE2. in vivo 2020;34:3023–3026.
3. Center for Disease Control and Prevention. Rapid increase in ivermectin prescriptions and reports of serious illness associated with the use of products containing ivermectin to prevent or treat COVID-19. CDC Health Alert Network No. CDCHAN-00449. August 26, 2021 (https://emergency.cdc.gov/han/2021/han00449.asp).
4. Lind JN, Lovegrove MC, Geller AI, Uyeki TM, Data SD, Budnitz DS. Increase in ivermectin release in the US during the COVID-19 pandemic: a cross-sectional analysis. J Gen Intern Med 2021;36:2909–2911.
5. Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria J 2003;2:supplement 1:S8–S8.