The Use of Ivermectin in the Treatment of COVID-19

Dear Editor,

We read the research article “Incidence of and Ivermectin Prescription Trends for COVID-19 in Japan” by Watari et al. [1] with great interest. In this article, we would like to highlight on the rationality of using ivermectin for COVID-19 with evidence from clinical studies conducted in different parts of the world.

Ivermectin use in COVID-19 is supported by conflicting findings in the existing evidence from in silico, in vivo, and in vitro observational studies; clinical trials; and meta-analyses. Ivermectin binds to many target proteins that restrict SARS-CoV-2 entrance into host cells and prevent nuclear translocation, according to in silico research. However, in vivo and in vitro investigations have demonstrated that ivermectin can inhibit viral replication, albeit at a concentration 100 times greater than the recommended dose. Clinical investigations have yielded a range of results; some have shown no effect, while others have shown potential benefits. Numerous dosing regimens, concurrent drug usage, study designs, and demographics under consideration are only a few of the additional restrictions that have been present in the majority of small-scale investigations [2].

Ivermectin was tested in a randomised study in Columbia at a dose of 300 μg per kilogram per day for 5 days, but there was no discernible benefit.³ In a second, related trial carried out at five separate US locations, even doses of 390 to 470 g per kilogram per day for 3 days did not have any discernible effects.⁴ Ivermectin has been the subject of extensive study worldwide, and the findings of significant clinical trials suggest that it has little to no effect on the development of early COVID-19. Even at dose levels ten times the advised dose, plasma total and unbound ivermectin levels do not approach the concentration resulting in 50% viral suppression, according to pharmacokinetic simulation models [2, 3]. According to reports, American healthcare professionals continue to prescribe ivermectin for the treatment of COVID-19 despite FDA warnings and alerts. Ivermectin has not been authorised or approved by the US FDA for use in the management of COVID-19. Ivermectin intended for animal use should not be used to treat COVID-19 in people, the US FDA warned in April 2020. The National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel has also determined that there is currently insufficient data to recommend ivermectin for COVID-19 treatment. Ivermectin exposures and side effects in humans increased in 2021 compared to the pre-pandemic year, according to reports from the Centers for Disease Control and Prevention (CDC) and the American Association of Poison Control Centers (AAPCC) [4, 5].