The Drug Invermectin - Dr. Winsome Christie, President of the Pharmaceutical Society of Jamaica

Dr. Winsome Christie,
President of the Pharmaceutical
Society of Jamaica

Ivermectin is an anthelmintic agent but because of its ability to inhibit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures. Due to the extremely deadly nature of this disease many clinicians are desperately trying to save lives by using agents which attack the virus at different stages of the life cycle of the virus. The use of many agents such as ivermectin was based on pre-clinical research in-vitro (not in humans).^1,2  For human use and effectiveness it had to be used in too large a dose (100 times higher than the safe dose that is approved for use in humans). There was a warning issued in April 2020 by the FDA that the use of ivermectin in humans for Covid-19 treatment was not allowed. 

The latest update information from the Centres for Disease Control (CDC) February 11, 2021, still does not support the use of ivermectin to treat Covid-19.

Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in cell cultures.² 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. 

The revised guidelines and the results of several randomized trials and retrospective cohort studies of ivermectin used in patients with COVID-19 have been published in peer-reviewed journals or have been made available as manuscripts ahead of peer review. Some clinical studies showed no benefits or worsening of disease after ivermectin use, whereas others reported shorter time to resolution of disease manifestations that were attributed to COVID-19, greater reduction in inflammatory marker levels,6,7 shorter time to viral clearance,8,9 or lower mortality rates in patients who received ivermectin than in patients who received comparator drugs or placebo.^8,9,10

Most of these studies contain incomplete information and also had important methodological limitations, which made it difficult to excluded common causes of bias, and which would render a trial flawed. 

The limitations identified include: 

• The sample size of most of the trials was small. 
• Various doses and schedules of ivermectin were used. 
• Some of the randomized controlled trials were open-label studies in which neither the participants nor the investigators were blinded to the treatment arms. 
• Patients received various concomitant medications (e.g., doxycycline, hydroxychloroquine, azithromycin, zinc, corticosteroids) in addition to ivermectin or the comparator drug. This confounded the assessment of the efficacy or safety of ivermectin. 
• The severity of COVID-19 in the study participants was not always well described. 
• The study outcome measures were not always clearly defined. 

Due to the important limitations of these studies, the expertise panel was prevented from arriving at definitive conclusions on the clinical efficacy of ivermectin for the treatment of Covid-19. 

So Pharmacists utilise treatments or try to promote only drugs that have been approved for use by bodies like the FDA, CDC and European bodies. In Jamaica we abide by the guidelines of the Ministry of Health and Wellness which advises us of safe evidenced based approaches to use.

Dr. Winsome Christie

Clinical Pharmacist

President of the Pharmaceutical Society of Jamaica

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1.      Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer. Antiviral Res. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32135219. 

2.      Arévalo AP, Pagotto R, Pórfido J, et al. Ivermectin reduces coronavirus infection in vivo: a mouse experimental model. bioRxiv. 2020;Preprint. Available at: https://www.biorxiv.org/content/10.1101/2020.11.02.363242v1 

3.      Tay MY, Fraser JE, Chan WK, et al. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor ivermectin. Antiviral Res. 2013;99(3):301-306. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23769930. 

4.      Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-856. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22417684. 

5.      Barrows NJ, Campos RK, Powell ST, et al. A screen of FDA-approved drugs for inhibitors of Zika virus infection. Cell Host Microbe. 2016;20(2):259-270. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27476412. 

6.      Elgazzar A, Hany B, Youssef SA, Hafez M, Moussa H, Eltaweel A. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Research Square. 2020;Preprint. Available at: https://www.researchsquare.com/article/rs-100956/v2. 

7.      Niaee MS, Gheibi N, Namdar P, et al. Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: a randomized multi-center clinical trial. Research Square. 2020;Preprint. Available at: https://www.researchsquare.com/article/rs-109670/v1. 

8.      Ahmed S, Karim MM, Ross AG, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 2020;103:214-216. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33278625. 

9.      Elgazzar A, Hany B, Youssef SA, Hafez M, Moussa H, Eltaweel A. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Research Square. 2020;Preprint. Available at: https://www.researchsquare.com/article/rs-100956/v2. 

10.  Khan MSI, Khan MSI, Debnath CR, et al. Ivermectin treatment may improve the prognosis of patients with COVID-19. Arch Bronconeumol. 2020;56(12):828-830. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33293006.