- Mark Abramowicz, M.D., President: no disclosure or potential conflict of interest to report
- Jean-Marie Pflomm, Pharm.D., Editor in Chief: no disclosure or potential conflict of interest to report
- Brinda M. Shah, Pharm.D., Consulting Editor: no disclosure or potential conflict of interest to report
- Michael Viscusi, Pharm.D., Associate Editor: no disclosure or potential conflict of interest to report
- Discuss the recent updates in COVID-19 vaccination and treatment recommendations.
On April 29, the NIH recommended against use of the antiparasitic drug ivermectin for treatment of COVID-19 outside of a clinical trial. The recommendation was made because recent randomized, placebo-controlled trials of ivermectin have produced negative results and because alternative drugs that have been shown to be effective for treatment of COVID-19 are available.1
IVERMECTIN – Ivermectin has been used for years for treatment of infections caused by parasitic organisms such as Strongyloides stercoralis and Onchocerca volvulus. In vitro, high concentrations of ivermectin inhibit SARS-CoV-2 replication,2 but achieving comparable concentrations of the drug in lung tissue or plasma would require doses much higher than those typically used in humans.3
CLINICAL STUDIES – In a randomized, double-blind trial, 1358 outpatient adults with COVID-19 and at least one risk factor for disease progression whose symptoms had begun ≤7 days previously received ivermectin 400 mcg/kg or placebo once daily for 3 days. The proportion of patients who required emergency department observation lasting >6 hours or hospitalization due to COVID-19 within 28 days, the primary endpoint, did not differ significantly between the ivermectin and placebo groups (14.7% vs 16.3%; HR 0.90 [95% CI 0.70-1.16]).4
In another double-blind trial (IVERCOR-COVID19), 501 nonhospitalized adults in Argentina who had tested positive for SARS-CoV-2 infection ≤48 hours previously were randomized to receive ivermectin (12-24 mg based on weight) or placebo once daily for 2 days. The rate of hospitalization for any cause lasting ≥24 hours, the primary endpoint, did not differ significantly between the ivermectin and placebo groups (5.6% vs 8.4%; HR 0.65 [95% CI 0.32-1.31]). Time to hospitalization was also not significantly different between the two groups.5
In a third double-blind trial, 400 adults in Columbia with mild COVID-19 whose symptoms had begun ≤7 days previously were randomized to receive ivermectin 300 mcg/kg or placebo once daily for 5 days. The median time to symptom resolution, the primary endpoint, did not differ significantly between the ivermectin and placebo groups (10 vs 12 days; HR for resolution 1.07 [95% CI 0.87-1.32]).6
In an open-label trial in Malaysia (I-TECH), 490 adults ≥50 years old with mild to moderate COVID-19 whose symptoms had begun ≤7 days previously were randomized to receive ivermectin 400 mcg/kg or placebo once daily for 5 days. The rate of progression to severe disease (defined as a need for supplemental oxygen to maintain SpO2 ≥95%), the primary endpoint, did not differ significantly between the ivermectin and placebo groups (21.6% vs 17.3%; RR 1.25 [95% CI 0.87-1.80]).7
RECOMMENDATIONS – The NIH recommends that nonhospitalized adults with COVID-19 be treated with either oral ritonavir-boosted nirmatrelvir (Paxlovid) or IV remdesivir (Veklury); ritonavir-boosted nirmatrelvir is preferred.8 Both of these therapies decreased the risk of hospitalization or death significantly more than placebo in large, randomized, double-blind trials.9,10 If these drugs are inappropriate or unavailable, use of molnupiravir (Lagevrio) or bebtelovimab (both available under FDA Emergency Use Authorization) is recommended.8
- NIH. COVID-19 treatment guidelines. Ivermectin. April 29, 2022. Available at: https://bit.ly/3L7Jbhg. Accessed May 23, 2022.
- L Caly et al. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178:104787.
- B Jermain et al. Development of a minimal physiologically-based pharmacokinetic model to simulate lung exposure in humans following oral administration of ivermectin for COVID-19 drug repurposing. J Pharm Sci 2020; 109:3574.
- G Reis et al. Effect of early treatment with ivermectin among patients with COVID-19. N Engl J Med 2022; 386:1721.
- J Vallejos et al. Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial. BMC Infect Dis 2021; 21:635.
- E Lopez-Medina et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: a randomized clinical trial. JAMA 2021; 325:1426.
- SCL Lim 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; 182:426.
- NIH. COVID-19 treatment guidelines. Therapeutic management of nonhospitalized adults with COVID-19. April 8, 2022. Available at: https://bit.ly/3w5TdLB. Accessed May 23, 2022.
- J Hammond et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022; 386:1397.
- RL Gottlieb et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med 2022; 386:305.