Use of chloroquine, azithromycin and ivermectin during the COVID-19 pandemic: An integrative review

Authors

DOI:

https://doi.org/10.33448/rsd-v12i13.44225

Keywords:

Azithromycin; Chloroquine; Ivermectin; COVID-19; Adverse effects.

Abstract

During the COVID-19 pandemic, the scientific community vehemently searched for medicines that could help treat the disease in question. Medications such as chloroquine, azithromycin and ivermectin were used as self-medication, before confirming their effectiveness against the virus and the disease. After just over two years since the start of the global COVID pandemic, the way we take care of our health still raises hypotheses among the population about the different correct ways of dealing with the disease, stating that different approaches would be effective or not? The objective gathered evidence on the pharmacokinetics, proposed mechanism of action in COVID-19, adverse effects, efficacy and safety of chloroquine/hydroxychloroquine, azithromycin and ivermectin for prophylaxis and treatment of COVID-19. The methodology used was an integrative review, which followed the recommendations of the adapted PRISMA guideline. The literature search was conducted in the PubMed, LILACS and MEDLINE databases. A critical analysis was carried out to determine the methodological rigor of the studies, based on the assessment of the level of scientific evidence. The results showed that the use of hydroxychloroquine, chloroquine, azithromycin or ivermectin, in mild or severe forms of COVID-19, both in treatment and prophylaxis, did not demonstrate any benefit in reducing mortality, hospitalizations or other unfavorable outcomes, without limiting transmission. virus nor preventing the installation of infection. Concluding that the use of these aforementioned medications as prophylactic and therapeutic measures for COVID-19 is contraindicated, due to the lack of consistent favorable evidence and the numerous reports of adverse outcomes in such treatments.

References

Axfors, C., Schmitt, A. M., Janiaud, P., van’t Hooft, J., Abd-Elsalam, S., Abdo, E. F., Abella, B. S., Akram, J., Amaravadi, R. K., Angus, D. C., Arabi, Y. M., Azhar, S., Baden, L. R., Baker, A. W., Belkhir, L., Benfield, T., Berrevoets, M. A. H., Chen, C. P., Chen, T. C., & Hemkens, L. G. (2021). Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-22446-z

Barbosa, A. N., Chebabo, A., Starling, C., Pérez, C., Cunha, C. A., de Luna, D., Nunes, E. P., Zambrano, G., Ferreira, J. C., Croda, J., Falavigna, M., Gomes-da-Silva, M. M., Thormann, M., Cimerman, S., Parahiba, S. M., Tanni, S., Bernardo, W. M., & Rodriguez-Morales, A. J. (2023). Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API). Em Annals of Clinical Microbiology and Antimicrobials 22(1). https://doi.org/10.1186/s12941-023-00623-w

Das, R., Behera, B., Mishra, B., & Naik, S. (2020). Effect of chloroquine and hydroxychloroquine on COVID-19 virological outcomes: An updated meta-Analysis. Em Indian Journal of Medical Microbiology. 38(3–4), 265–272. https://doi.org/10.4103/ijmm.IJMM_20_330

Dauner, D. G., & Dauner, K. N. (2021). Summary of adverse drug events for hydroxychloroquine, azithromycin, and chloroquine during the COVID-19 pandemic. Journal of the American Pharmacists Association, 61(3), 293–298. https://doi.org/10.1016/j.japh.2021.01.007

Della Porta, A., Bornstein, K., Coye, A., Montrief, T., Long, B., & Parris, M. A. (2020). Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians. Em American Journal of Emergency Medicine. 38(10), 2209–2217. https://doi.org/10.1016/j.ajem.2020.07.030

Ferreira, P. M. P., de Sousa, R. W. R., Dittz, D., E Sousa, J. M. de C., Torres-Leal, F. L., & Bezerra, D. P. (2023). Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic. Brazilian Journal of Pharmaceutical Sciences, 59. https://doi.org/10.1590/s2175-97902023e21067

Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V. E., Tissot Dupont, H., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J. M., Brouqui, P., & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, 56(1). https://doi.org/10.1016/j.ijantimicag.2020.105949

Gumilang, R. A., Siswanto, Anggraeni, V. Y., Trisnawati, I., Budiono, E., & Hartopo, A. B. (2021). QT interval and repolarization dispersion changes during the administration of hydroxychloroquine/chloroquine with/without azithromycin in early COVID 19 pandemic: A prospective observational study from two academic hospitals in Indonesia. Journal of Arrhythmia, 37(5), 1184–1195. https://doi.org/10.1002/joa3.12623

Heidary, F., & Gharebaghi, R. (2020). Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. Em Journal of Antibiotics (Vol. 73, Número 9, p. 593–602). Springer Nature. https://doi.org/10.1038/s41429-020-0336-z

Izcovich, A., Peiris, S., Ragusa, M., Tortosa, F., Rada, G., Aldighieri, S., & Reveiz, L. (2022). Bias as a source of inconsistency in ivermectin trials for COVID-19: A systematic review. Ivermectin’s suggested benefits are mainly based on potentially biased results. Journal of Clinical Epidemiology, 144, 43–55. https://doi.org/10.1016/j.jclinepi.2021.12.018

Kamel, A. M., Monem, M. S. A., Sharaf, N. A., Magdy, N., & Farid, S. F. (2022). Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials. Em Reviews in Medical Virology. 32(1). https://doi.org/10.1002/rmv.2258

Kashour, Z., Riaz, M., Garbati, M. A., AlDosary, O., Tlayjeh, H., Gerberi, D., Hassan Murad, M., Rizwan Sohail, M., Kashour, T., & Tleyjeh, I. M. (2021). Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: A systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, 76(4), 30–42. https://doi.org/10.1093/JAC/DKAA403

Marcolino, M. S., Meira, K. C., Guimarães, N. S., Motta, P. P., Chagas, V. S., Kelles, S. M. B., de Sá, L. C., Valacio, R. A., & Ziegelmann, P. K. (2022). Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype. BMC Infectious Diseases, 22(1). https://doi.org/10.1186/s12879-022-07589-8

Meo, S. A., Zaidi, S. Z. A., Shang, T., Zhang, J. Y., Al-Khlaiwi, T., Bukhari, I. A., Akram, J., & Klonoff, D. C. (2020). Biological, molecular and pharmacological characteristics of chloroquine, hydroxychloroquine, convalescent plasma, and remdesivir for COVID-19 pandemic: A comparative analysis. Journal of King Saud University - Science, 32(7), 3159–3166. https://doi.org/10.1016/j.jksus.2020.09.002

Naggie, S., Boulware, D. R., Lindsell, C. J., Stewart, T. G., Gentile, N., Collins, S., McCarthy, M. W., Jayaweera, D., Castro, M., Sulkowski, M., McTigue, K., Thicklin, F., Felker, G. M., Ginde, A. A., Bramante, C. T., Slandzicki, A. J., Gabriel, A., Shah, N. S., Lenert, L. A., & Hernandez, A. F. (2022). Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA, 328(16), 1595–1603. https://doi.org/10.1001/jama.2022.18590

Nicol, M. R., Joshi, A., Rizk, M. L., Sabato, P. E., Savic, R. M., Wesche, D., Zheng, J. H., & Cook, J. (2020). Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection. Em Clinical Pharmacology and Therapeutics. 108(6), 1135–1149.

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., & Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Journal of Clinical Epidemiology, 134, 178–189. https://doi.org/10.1016/j.jclinepi.2021.03.001

Rezai, M. S., Ahangarkani, F., Hill, A., Ellis, L., Mirchandani, M., Davoudi, A., Eslami, G., Roozbeh, F., Babamahmoodi, F., Rouhani, N., Alikhani, A., Najafi, N., Ghasemian, R., Mehravaran, H., Hajialibeig, A., Navaeifar, M. R., Shahbaznejad, L., Rahimzadeh, G., Saeedi, M., & Valadan, R. (2022). Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.919708

Sekhavati, E., Jafari, F., SeyedAlinaghi, S. A., Jamalimoghadamsiahkali, S., Sadr, S., Tabarestani, M., Pirhayati, M., Zendehdel, A., Manafi, N., Hajiabdolbaghi, M., Ahmadinejad, Z., Kouchak, H. E., Jafari, S., Khalili, H., Salehi, M., Seifi, A., Golestan, F. S., & Ghiasvand, F. (2020). Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial. International Journal of Antimicrobial Agents, 56(4). https://doi.org/10.1016/j.ijantimicag.2020.106143

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. Em European Journal of Medical Research. 27(1). https://doi.org/10.1186/s40001-022-00645-8

Tavares De Souza, M., Dias Da Silva, M., & De Carvalho, R. (2010). Revisão integrativa: o que é e como fazer Integrative review: what is it? How to do it? (Vol. 8, Número 1).

Tleyjeh, I. M., Kashour, Z., AlDosary, O., Riaz, M., Tlayjeh, H., Garbati, M. A., Tleyjeh, R., Al-Mallah, M. H., Sohail, M. R., Gerberi, D., Bin Abdulhak, A. A., Giudicessi, J. R., Ackerman, M. J., & Kashour, T. (2021). Cardiac Toxicity of Chloroquine or Hydroxychloroquine in Patients With COVID-19: A Systematic Review and Meta-regression Analysis. Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 5(1), 137–150. https://doi.org/10.1016/j.mayocpiqo.2020.10.005

Touret, F., & de Lamballerie, X. (2020). Of chloroquine and COVID-19. Em Antiviral Research (Vol. 177). https://doi.org/10.1016/j.antiviral.2020.104762

Ursi, E. S., & Gavão, C. M. (2006). Prevenção de lesões de pele no perioperatório: revisão integrativa da literatura. Revista Latino-Americana de Enfermagem, 14(1), 124–131. https://doi.org/10.1590/S0104-11692006000100017

Yao, X., Yan, X., Wang, X., Cai, T., Zhang, S., Cui, C., Wang, X., Hou, Z., Liu, Q., Li, H., Lin, J., Xiong, Z., & Liu, D. (2021). Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients. European Journal of Clinical Pharmacology, 77(4), 583–593. https://doi.org/10.1007/s00228-020-03032-6

Yuan, Y., Jiao, B., Qu, L., Yang, D., & Liu, R. (2023). The development of COVID-19 treatment. Em Frontiers in Immunology (Vol. 14). Frontiers Media S.A. https://doi.org/10.3389/fimmu.2023.1125246

Zaidi, A. K., & Dehgani-Mobaraki, P. (2022). The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review. Em Journal of Antibiotics 75(2), 60–71. https://doi.org/10.1038/s41429-021-00491-6

Published

28/11/2023

How to Cite

REIS, F.; ROCHA JUNIOR, J. de J. .; DOMINATO, A. A. G. . Use of chloroquine, azithromycin and ivermectin during the COVID-19 pandemic: An integrative review. Research, Society and Development, [S. l.], v. 12, n. 13, p. e44121344225, 2023. DOI: 10.33448/rsd-v12i13.44225. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/44225. Acesso em: 14 may. 2024.

Issue

Section

Health Sciences