The possible cytotoxicity developed by the use of ivermectin in patients with COVID-19: an integrative review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i11.33611

Keywords:

Ivermectin; Cytotoxicity; SARS-CoV-2

Abstract

Objective: To analyze the scientific literature that deals with the possible cytotoxicity developed by the use of ivermectin in patients with COVID-19: an integrative review. Methods: This is an integrative literature review, designed as an observational, cross-sectional and qualitative study, data collection was carried out from recent literary and scientific sources, from the year 2020 to the year 2022. Results: Ivermectin is metabolized in the liver, has a half-life four times longer than other drugs, and has great hepatoxic potential. Scientific evidence for its use was based on in vitro research, which shows insufficient results to determine its safety and efficacy. It was found that 05 days of treatment with ivermectin was a safe time to show effective results, with a dose of 0.4 - 0.6mg/kg per day. The interactions of ante - COVID 19 drug candidates with hepatic transporters were identified, these drugs have multiple inhibitory effects on hepatic membrane transporters and can cause toxicity and affect pharmacokinetics. Conclusion: The imprecision of data on the therapeutic use of ivermectiva is evidenced, together with low quality information for clinical guidance, with regard to use, dosage and duration of treatment. As for the possible cytotoxic effect of Ivermectin in patients with covid-19, there were no clinical studies to show such a result, however, its use is contraindicated due to the scarcity of data. Therefore, further randomized clinical trials are needed to determine the level of toxicity of ivermectin in the treatment of SARS-CoV-2.

References

Ahmed, S., Karim, M. M., Ross, A. G., Hossain, M. S., Clemens, J. D., Sumiya, M. K., & Khan, W. A. (2021). A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. International Journal of Infectious Diseases, 103, 214-216.

Ambrus, C., Bakos, É., Sarkadi, B., Özvegy-Laczka, C., & Telbisz, Á. (2021). Interactions of anti-COVID-19 drug candidates with hepatic transporters may cause liver toxicity and affect pharmacokinetics. Scientific Reports, 11(1), 1-10.

Barbosa, A. M., C., Dias, A. M., Lambert, G. C., Freire, J. O., Marques, J. C., de Oliveira Santana, K., & de Araújo Paula, F. B. (2021). Reaproveitamento de medicamentos para a COVID-19: aconselhável ou não? Research, Society and Development, 10(17), e197101724278-e197101724278.

Botelho et al. (2011) O Método da Revisão Integrativa nos Estudos Organizacionais. Gestão e Sociedade 5(11), 121-136.

Buonfrate, D., Salas-Coronas, J., Muñoz, J., Maruri, B. T., Rodari, P., Castelli, F., & Bisoffi, Z. (2019). Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. The Lancet infectious diseases, 19(11), 1181-1190.

Buonfrate, D., Chesini, F., Martini, D., Roncaglioni, M. C., Fernandez, M. L. O., Alvisi, M. F., & Bisoffi, Z. (2022). High dose ivermectin for the early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof of concept clinical trial. International journal of antimicrobial agents, 106516.

Centers for Disease Control and Prevention. (2021). Rapid increase in ivermectin prescriptions and reports of severe illness associated with use of products containing ivermectin to prevent or treat COVID-19. CDC Health Alert Network no. CDCHAN-00449, 8, 26.

Ercole et al. (2014). Revisão integrativa versus revisão sistemática. Revista Mineira de Enfermagem. 18(1).

Figueiredo, B. Q., Cancela, B. R., Rodrigues, A. E. L., Falcão, A. L. S., do Prado, D. M. M., da Rocha, D., & Segundo, S. (2022). Análise das possíveis intoxicações decorrentes do uso indiscriminado da ivermectina e hidroxicloroquina durante a pandemia de COVID-19. Research, Society and Development, 11(3), e14511326441-e14511326441.

Gupta, D., Sahoo, A. K., & Singh, A. (2020). Ivermectin: potential candidate for the treatment of Covid 19. Brazilian Journal of Infectious Diseases, 24, 369-371.

Heidary, F., & Gharebaghi, R. (2020). Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. The Journal of antibiotics, 73(9), 593-602.

Khan, Z., Karataş, Y., & Rahman, H. (2020). Anti COVID-19 drugs: need for more clinical evidence and global action. Advances in therapy, 37(6), 2575-2579.

López-Medina, E., López, P., Hurtado, I. C., Dávalos, D. M., Ramirez, O., Martínez, E., & Caicedo, I. (2021). Efeito da ivermectina no tempo de resolução dos sintomas entre adultos com COVID-19 leve: um ensaio clínico randomizado. Jama, 325(14), 1426-1435.

Marques, L. L. M., Beneti, S. C., Pinzon, C., & Cardoso, F. A. R. (2022). Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols. Brazilian Journal of Biology, 84.

Medeiros, J. P., dos Santos Silva, R. R., de Brito, L. P., da Costa, M. A. S., Falcão, D. M. S., da Silva, M. E., & Neto, J. E. (2021). Aspectos toxicológicos da ivermectina: um estudo dos efeitos na morfologia do fígado de ratas prenhes. Research, Society and Development, 10(1), e25410111693-e25410111693.

Molento, M. B. (2020). COVID-19 and the rush for self-medication and self-dosing with ivermectin: a word of caution. One Health, 10.

Pandey, S., Pathak, S. K., Pandey, A., Salunke, A. A., Chawla, J., Sharma, A., & Ratna, H. V. (2020). Ivermectin in COVID-19: What do we know? Diabetes & metabolic syndrome, 14(6), 1921.

Pedroso, L. A., Binda, N. S., Teixeira, M. C., & Guimarães, A. G. (2020). Aspectos farmacológicos da ivermectina e seu potencial uso no tratamento da COVID-19. Brazilian Journal of Health and Pharmacy, 2(3), 11-20.

Person, O. C., Puga, M. E. D. S., Amaral, J. L. G., & Atallah, A. N. (2021). Intervenção com ivermectina para COVID-19 (SARS-CoV-2): sinopse baseada em evidências. Diagnóstico e Tratamento, 26, 27-34.

Ponte, A. R., de Aragão, C. R. B., Novaes, C. D. P., de Morais Trindade, G. B., Nascimento, K. I. M., Cardoso, L. R., & Guimarães, M. C. M. (2021). O uso da Ivermectina no tratamento da COVID-19: uma revisão integrativa da literatura. Brazilian Journal of Health Review, 4(2), 7546-7554.

Popp, M., Stegemann, M., Metzendorf, M. I., Gould, S., Kranke, P., Meybohm, P., & Weibel, S. (2021). Ivermectin for preventing and treating COVID‐19. Cochrane Database of Systematic Reviews, (7).

Rendic, S. P. (2021). Metabolism and interactions of Ivermectin with human cytochrome P450 enzymes and drug transporters, possible adverse and toxic effects. Archives of Toxicology, 95(5), 1535-1546.

Roman, Y. M., Burela, P. A., Pasupuleti, V., Piscoya, A., Vidal, J. E., & Hernandez, A. V. (2022). Ivermectin for the treatment of coronavirus disease 2019: a systematic review and meta-analysis of randomized controlled trials. Clinical Infectious Diseases, 74(6), 1022-1029.

Shirazi, F. M., Mirzaei, R., Nakhaee, S., Nejatian, A., Ghafari, S., & Mehrpour, O. (2022). Repurposing the drug, ivermectin, in COVID-19: toxicological points of view. European Journal of Medical Research, 27(1), 1-11.

Temple, C., Hoang, R., & Hendrickson, R. G. (2021). Toxic effects from ivermectin use associated with prevention and treatment of COVID-19. New England Journal of Medicine, 385(23), 2197-2198.

Xavier, M. A., Xavier, J. M. A., Moreira, M. O., Soares, R. D. S. C., da Silva Oliveira, N. M., & Ribeiro, A. I. A. M. (2020). A efetividade da Ivermectina® na atenuação de vírus de RNA: uma alternativa para enfrentar o SARS-CoV-2. Brazilian Journal Of Development, 6(7), 47400-47411.

Zaidi, A. K., & Dehgani-Mobaraki, P. (2021). The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review. The Journal of antibiotics, 1-12.

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Published

02/09/2022

How to Cite

SILVA, D. H. da .; OROZCO, D. L. B. .; COROA , E. .; COÊLHO, K. . A. A. .; BAIA, R. .; VALENTE, R. L. .; GUIMARÃES, M. The possible cytotoxicity developed by the use of ivermectin in patients with COVID-19: an integrative review. Research, Society and Development, [S. l.], v. 11, n. 11, p. e555111133611, 2022. DOI: 10.33448/rsd-v11i11.33611. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/33611. Acesso em: 21 dec. 2024.

Issue

Vol. 11 No. 11

Section

Health Sciences

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Copyright (c) 2022 Danieli Henriques da Silva; Darling Lorena Barros Orozco; Eduardo Coroa ; Katiane Alexandre Alves Coêlho; Rayane Baia; Ricardo Leão Valente; Marcia Guimarães

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