Last Updated: March 6, 2023
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
Ivermectin has been shown to inhibit replication of SARS-CoV-2 in cell cultures.3 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.4,5
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 7b. The Panel reviewed additional studies, but these studies are not summarized in Table 7b 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 (AIIa).
The Panel’s recommendation is primarily informed by adequately powered, randomized trials of ivermectin that reported clinical outcomes. Studies that randomized participants to ivermectin or a matched placebo had the greatest impact on the Panel’s recommendation.6-13
Trials have failed to find a clinical benefit from the use of ivermectin for the treatment of COVID-19 in outpatients. In TOGETHER, an adaptive platform trial conducted in Brazil, there was no apparent difference between the ivermectin and placebo arms for the primary outcome of risk of emergency department visits or hospitalization (14.7% vs. 16.4%).14 In addition, there was no statistically significant difference between the ivermectin and placebo arms in mortality (3.1% vs. 3.5%). In COVID-OUT, a randomized factorial trial, the use of ivermectin when compared with a matched control (5.7% vs. 4.1%) did not reduce occurrences of a composite outcome of emergency department visits, hospitalization, or death.6
The ACTIV-6 trial was an adaptive platform trial conducted in outpatients with mild to moderate COVID-19 in the United States.15,16 Participants were randomized to an ivermectin regimen (either 400 μg/kg for 3 days or 600 μg/kg for 6 days) or a matching placebo. In the 400 μg/kg phase of the study, the median time to sustained recovery was 12 days for the ivermectin arm and 13 days for the placebo arm. In the 600 μg/kg phase of the study, the median time to sustained recovery was 11 days for both arms.
I-TECH, an open-label trial conducted in Malaysia, found no difference between the ivermectin and standard of care arms (21.6% vs. 17.3%) for the primary outcome of risk of progression to severe COVID-19.17 The ivermectin arm had a lower risk of mortality than the standard of care arm (1.2% vs. 4.0%) (relative risk 0.31; 95% CI, 0.09–1.11; P = 0.09), but this difference was not statistically significant.
The study populations in most of the reviewed trials were patients with mild to moderate COVID-19 who had a relatively low risk for disease progression, and the number of deaths was low (as expected). In these randomized trials, completely excluding an effect of ivermectin on COVID-19 disease progression is difficult because the trials were not powered to detect differences in secondary outcomes, such as death. However, data from these trials do not provide evidence that the use of ivermectin is effective for the treatment of COVID-19. For this reason, and because other medications now have demonstrated clinical benefit for the treatment of COVID-19, the Panel recommends against the use of ivermectin for the treatment of COVID-19 (AIIa).
See Table 7b for summaries of the key studies that informed the Panel’s recommendation.
Ivermectin is not approved or authorized by the FDA for the treatment of COVID-19.
- Omura S, Crump A. Ivermectin: panacea for resource-poor communities? Trends Parasitol. 2014;30(9):445-455. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25130507.
- Kircik LH, Del Rosso JQ, Layton AM, Schauber J. Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications. J Drugs Dermatol. 2016;15(3):325-332. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26954318.
- Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32251768.
- Chaccour C, Hammann F, Ramón-García S, Rabinovich NR. Ivermectin and COVID-19: keeping rigor in times of urgency. Am J Trop Med Hyg. 2020;102(6):1156-1157. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32314704.
- Guzzo CA, Furtek CI, Porras AG, et al. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002;42(10):1122-1133. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12362927.
- Bramante CT, Huling JD, Tignanelli CJ, et al. Randomized trial of metformin, ivermectin, and fluvoxamine for COVID-19. N Engl J Med. 2022;387(7):599-610. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36070710.
- Vallejos J, Zoni R, Bangher M, et al. Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial. BMC Infect Dis. 2021;21(1):635. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34215210.
- López-Medina E, López P, Hurtado IC, et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: a randomized clinical trial. JAMA. 2021;325(14):1426-1435. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33662102.
- Buonfrate D, Chesini F, Martini D, et al. High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, Phase II, dose-finding, proof-of-concept clinical trial. Int J Antimicrob Agents. 2022;59(2):106516. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34999239.
- Abd-Elsalam S, Noor RA, Badawi R, et al. Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: a randomized controlled study. J Med Virol. 2021;93(10):5833-5838. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34076901.
- Ravikirti, Roy R, Pattadar C, et al. Evaluation of ivermectin as a potential treatment for mild to moderate COVID-19: a double-blind randomized placebo controlled trial in Eastern India. J Pharm Pharm Sci. 2021;24:343-350. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34265236.
- Mohan A, Tiwari P, Suri TM, et al. Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial. J Infect Chemother. 2021;27(12):1743-1749. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34483029.
- Bermejo Galan LE, Dos Santos NM, Asato MS, et al. Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection. Pathog Glob Health. 2021;115(4):235-242. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33682640.
- TOGETHER Investigators. Effect of early treatment with ivermectin among patients with COVID-19. N Engl J Med. 2022;40(5):1721-1731. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35353979.
- Naggie S, Boulware DR, Lindsell CJ, et al. Effect of ivermectin vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized controlled trial. JAMA. 2022;328(16):1595-1603. Available at: https://pubmed.ncbi.nlm.nih.gov/36269852.
- Naggie S, Boulware DR, Lindsell CJ, et al. Effect of higher-dose ivermectin for 6 days vs placebo on time to sustained recovery in outpatients with COVID-19: a randomized clinical trial. JAMA. 2023;Published online ahead of print. Available at: https://pubmed.ncbi.nlm.nih.gov/36807465.
- Lim SCL, Hor CP, Tay KH, et al. Efficacy of ivermectin treatment on disease progression among adults with mild to moderate COVID-19 and comorbidities: the I-TECH randomized clinical trial. JAMA Intern Med. 2022;182(4):426-435. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35179551.