Last Updated: April 29, 2022
Ivermectin is a Food and Drug Administration (FDA)-approved antiparasitic drug used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies.1 For these indications, ivermectin has been widely used and is generally well-tolerated.1,2 Ivermectin is not approved by the FDA for the treatment of any viral infection.
Proposed Mechanism of Action and Rationale for Use in Patients With COVID-19
Reports from in vitro studies suggest that ivermectin acts by inhibiting host importin alpha/beta-1 nuclear transport proteins, which are part of a key intracellular transport process.3,4 Viruses hijack the process and enhance infection by suppressing the host’s antiviral response. In addition, ivermectin docking may interfere with SARS-CoV-2 spike protein attachment to the human cell membrane.5 Some studies of ivermectin have also reported potential anti-inflammatory properties, which have been postulated to be beneficial in people with COVID-19.6-8
Ivermectin has been shown to inhibit replication of SARS-CoV-2 in cell cultures.9 However, pharmacokinetic and pharmacodynamic studies suggest that achieving the plasma concentrations necessary for the antiviral efficacy detected in vitro would require administration of doses up to 100-fold higher than those approved for use in humans.10,11 Although ivermectin appears to accumulate in lung tissue, predicted systemic plasma and lung tissue concentrations are much lower than 2 µM, the half-maximal inhibitory concentration (IC50) observed in vitro for ivermectin against SARS-CoV-2.12-15 Subcutaneous administration of ivermectin 400 µg/kg had no effect on SARS-CoV-2 viral loads in hamsters.16 However, there was a reduction in olfactory deficit (measured using a food-finding test) and a reduction in the interleukin (IL)-6:IL-10 ratio in lung tissues.
The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 have been evaluated in clinical trials and observational cohorts. Summaries of the studies that informed The COVID-19 Treatment Guidelines Panel’s (the Panel) recommendation can be found in Table 4c. The Panel reviewed additional studies, but these studies are not summarized in Table 4c because they have study design limitations or results that make them less definitive and informative.
- The Panel recommends against the use of ivermectin for the treatment of COVID-19, except in clinical trials (AIIa)
Recommendation Rating Scheme
|Strength of Recommendation||Quality of Evidence for Recommendation|
|A: Strong recommendation for the statement|
B: Moderate recommendation for the statement
C: Weak recommendation for the statement
|I: One or more randomized trials without major limitations |
IIa: Other randomized trials or subgroup analyses of randomized trials
IIb: Nonrandomized trials or observational cohort studies
III: Expert opinion