SHOULD IVERMECTIN BE USED IN THE TREATMENT OF COVID-19?

            The COVID-19 pandemic has been going on for almost two years around the world. This has had an impact in various fields such as the economy, tourism, health, education and so on. Approximately 14% of patients with severe symptoms and 5% critical (Chosidow et al., 2021). Various treatments have been carried out but have not found the right treatment. So far, most of the treatment is aimed at dealing with complaints that occur, such as fever, abdominal pain, nausea, vomiting, weakness and so on (Wijaya et al., 2021). Several months ago, rumors circulated that ivermectin could be used in the treatment of COVID-19. Until now, there are still many pros and cons to this. Should Ivermectin be used in the treatment of COVID-19?

             Ivermectin is a class of macrocyclic lactones and usually functions as an anti-parasitic, especially worms (Caly et al., 2020; Indarjulianto et al., 2020; Wijaya et al., 2021). This drug has been used on animals about 40 years ago. Apart from being anti-parasitic, ivermectin also functions as an anti-virus and immunomodulator (Caly et al., 2020; Wijaya et al., 2021). Replication of cancer cells is also inhibited by this drug. In animals, this drug can regulate cholesterol and glucose (Wijaya et al., 2021).

             As an anti-COVID, ivermectin works directly or indirectly (Wijaya et al., 2021; Zaidi and Dehgani-Mobaraki, 2021). Directly, it is interfering with the entry of viruses and importins, also acting as an ionophore (Wijaya et al., 2021; Zaidi and Dehgani-Mobaraki, 2021). Indirectly, in host receptors, it play an important role in viral replication and inflammation as well as other targets such as plasmin, annexin A2, CD147 on red blood cells and mitochondrial ATP during hypoxia (Zaidi and Dehgani-Mobaraki, 2021). This drug releases and binds to the subunit of GABA which is a glutamate-gated chloride channels (GluCl) receptor, resulting in signal severance and resulting in paralysis and death.(Puspitasari et al., 2015; Lestari et al., 2018; Tinkov et al., 2021).

The concentration of this drug in plasma is influenced by route of administration, solvent, species, body weight, physiological conditions, type and volume of intake. These things must be considered so that ivermectin can be used safely. Ivermectin levels of 5 M are safe to use and can reduce the cleavage of the corona virus RNA within 48 hours by 99.98% so that there is a decrease in the number of viruses in the human body (Tinkov et al., 2021). In contrast to the Food and Drug Administration (FDA) (2022) which says that as an antiviral, a dose of 100 times the approved dose is required in humans. Giving ivermectin 400 μg/ kg can improve olfactory function and reduce the ratio between Interleukin (IL-6) and IL-10 (NIH, 2022).

Generally the route, a person's sensitivity and excessive doses of ivermectin, can cause poisoning which is characterized by the presence of mydriasis, depression, ataxia, lying down and death. Treatment of poisoning can be symptomatic or supportive, but it is more appropriate to give antidotes such as picrotoxin or physostigmine.(Indarjulianto et al., 2020).

The Food and Drug Administration (FDA) only apporved the use of ivermectin as an antiparasitic and not an antiviral or COVID-19 treatment (NIH, 2022). In its article, the NIH (2022) said that the use of ivermectin as an anti-coronavirus drug was not significantly different in decreasing progression and mortality from COVID-19 when compared to placebo. Until now there has been no research on ivermectin with complete information and good methodology, so there is a lot of bias. The effectiveness of ivermectin is also difficult to measure because the dose and duration of treatment studied varied. Ivermectin doses of 300-400 μg/ kg for 3-5 days have been shown to be ineffective in the treatment of COVID-19 (NIH, 2022). Currently, ivermectin as a COVID-19 drug is allowed only for clinical trials (BPOM, 2021; NIH, 2022). Ivermectin, chloroquine, oseltamivir, convalescent plasma azythromycin are no longer included in the guidelines for handling COVID-19 made by five professional organizations in Indonesia, because they are not useful. In accordance with the recommendations of the FDA, BPOM and five professional organizations in Indonesia, the use of ivermectin in the treatment of COVID-19 is not necessary due to no significant benefits in humans and many side effects.                 

Bibliography

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Fauzia M. 2022.IDI Reveals 5 Covid-19 Drugs No Longer Effective, There is Ivermectin and Convalescent Plasma. Accessed: May, 11th 2022. Available at:https://national.kompas.com/read/2022/02/06/14562341/idi-Revelation-5-obat-covid-19-tak-lagi-ampuh-ada-ivermectin-dan-plasma?page=all

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NIH. Ivermectin. Accessed May 10th, 2022.https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ivermectin/

Puspitasari, S. et al. (2015) “Effectiveness of Ivermectin and Albendazole Against Ostertagia on Sheep in Bogor, Indonesia,” Indonesian Journal of Agricultural Science, 20(3): 257–264. doi: 10.18343/jipi.20.3.257.

Tinkov, OV, Grigorev, VY and Grigoreva, LD (2021) “Prediction of an Organic Compound's Biotransformation Time: A Study Using Avermectins,” Moscow University Chemistry Bulletin, 76(4): 231–247. doi: 10.3103/s0027131421040088.

Wijaya, H., Saraswati, NAS and Amanda, DA (2021) “Indonesian Health Magazine Ivermectin and Covid-19: a literature review,” 2(1): 9–15. doi: 10.30604/makein.202119.

Zaidi, AK and Dehgani-Mobaraki, P. (2021) “The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article,” Journal of Antibiotics. doi:10.1038/s41429-021-00430-5.