Ivermectin and Hydroxychloroquine – COVID Treatments or NOT?

Ivermectin and hydroxychloroquine have been purported as potential COVID treatments. We break down where these drugs stand in regards to those claims.

The NIH COVID-19 Treatment Guidelines Panel have recommended against any use of chloroquine or hydroxychloroquine (HCQ) for the treatment of COVID-19, including concomitantly with azithromycin. At this point in the pandemic, there has been a lot of data produced on the safety and efficacy of HCQ through randomized trials and other studies. These studies have not found a clear benefit to treatment with HCQ to outweigh the risks of toxicity and other adverse effects. Patients treated with HCQ with or without azithromycin have had longer hospital stays, increased risk of intubations, and other adverse events, including the risk of QTc prolongation and cardiac events from both HCQ and azithromycin. This risk is more pronounced due to the long half-lives of HCQ (40 days) and azithromycin (72 hours). The patients in these trials and studies did not have a lower mortality rate – in some cases patients who were treated with hydroxychloroquine had increased mortality rates compared to the standard of care. There was one large study that found a survival benefit for patients receiving HCQ with or without azithromycin, but there were many problems with the study, such as the much higher percentage of patients in the HCQ group who received concomitant corticosteroids compared to the standard of care group. There are still ongoing clinical trials looking to find a benefit to HCQ, but it will take solid results to change the NIH’s recommendation against HCQ.

Ivermectin is another drug being looked at for the use of COVID-19 treatment due to its in vitro activity against some viruses, including SARS-CoV-2. There are a lot of ongoing clinical trials looking at ivermectin alone and in various combinations with other drugs, such as doxycycline and zinc. Studies that have reported their results so far have been very heterogeneous, with differences such as varying doses of ivermectin given, different concomitant medication regimens, and a duration of therapy range between one to seven days. Due to the limited information available thus far and the high risk for bias in published information, the IDSA panel has suggested against treating with ivermectin, and the NIH panel has not made a recommendation for or against ivermectin. A randomized controlled trial performed by Mahmud et al in Bangladesh treated patients with ivermectin and doxycycline plus standard of care or placebo plus standard of care and reported promising results. The rationale for using doxycycline alongside ivermectin is due to its known antiviral activity and the anti-inflammatory effect it exerts through chelating zinc compounds on matrix metalloproteinases (MMPs) in mammalian cells, and it is thought that MMPs may play a role in coronavirus disease pathogenesis. The study reported that patients in the ivermectin and doxycycline arm tended to recover 2 days quicker than patients in the placebo arm, as well as having a lower percentage of patients worsen in disease severity after receiving treatment. Other studies have reported varying outcomes in time to recovery, viral load reduction, and mortality rates. The results of many ongoing studies will be interesting to review when they are published, as it seems there may be some favorable data for ivermectin which could provide a more affordable, effective treatment option for COVID-19. 

Note; the article has not been updated since the date of release. Written by Lincoln Haiby in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed July 6, 2021.

Bhimraj A, Morgan RL, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America 2021; Version 4.4.1. Available at https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/. Accessed July 6, 2021.Mahmud, R., Rahman, et al. (2021). Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial. Journal of International Medical Research, 49(5). Available at https://journals.sagepub.com/doi/pdf/10.1177/03000605211013550.  Accessed July 6, 2021.

Written By Eric Christianson

July 11, 2021

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