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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) with a high rate of mortality. Chloroquine and hydroxychloroquine have been used for antimalarial and autoimmune diseases for many years. Due to low toxicity and well tolerability as well as immunomodulatory properties, these drugs are proposed to treat viral infection. Some studies, both in vitro and in a clinical setting, have been evaluated for their ability to treat SARS- CoV-2 as promising therapies. Although The National Agency of Drugs and Food Control of The Republic of Indonesia issued emergency authorization for chloroquine and hydroxychloroquine to be used against COVID-19 infection, the efficacy of these drugs is still based on small clinical non- randomized trials with a limited number of patients. However, the use of these drugs without any risks. The safety of these drugs to be used in COVID-19 patients is lacking. Some experts noticed that the drugs cause harmful adverse effects, especially a harmful QT prolongation. In Indonesia, until now, no study evaluates the effectiveness as well as the safety of these drugs to be used in COVID-19 infection. This article will discuss the role of chloroquine or hydroxychloroquine and its safety to be used against COVID-19 infection.

References

Adelusi, S.A., & Salako, L.A. (1982). Kinetics of the distribution and elimination of chloroquine in the rat. General Pharmacology,13, 433–437.

Van den Broek, M.P.H., Möhlmann, J.E., Abeln, B.G.S., Liebregts, M. van Dijk, V.F., & van de Garde, E. M. W. (2020). Chloroquine-induced QTc prolongation in COVID-19 patients. The Netherlands Heart Journal, 28, 406–409.

Badan Pengawas Obat dan Makanan. (2020). Retrieved from https://www.pom.go.id/new/view/more/ klarifikasi/115/penjelasan Badan POM RI tentang informasi keamanan penggunaan klorokuin dan hidroksiklorokuin pada penyakit new corona virus 2019. html. access on June 10, 2020.

Borba, M.G.S., Val, F.F.A., Sampaio, V.S. (2020). Effect of high vs low dose of chloroquine diphosphate as adjunctive therapy for patients hospitatalized with severe acute respiratory syndrome coronavirus 2 () SARS-CoV-2) infection: A randomized clinical trial. Jama Network Open. 3(4):e208857. doi:10.1001/ jamanetworkopen.2020.8857.

Chico, R., & Chandramohan, D. (2011). Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy. Drug Metabolism and Toxicology, 7, 1153- 1167.

Cook, J. A., Randinitis, E. J., Bramson, C. R., & Wesche, D. L. (2006). Lack of a pharmacokinetic interaction between azithromycin and chloroquine. The American journal of tropical medicine and hygiene, 74(3), 407– 412.

Cortegiani, A., Ingoglia, G., Ippolito, M., Giarratano, A., & Einav, S. (2020). A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. Journal of Critical Care, 57, 279–283.

Etheridge, S.P., Compton, S.J., Tristani-Firouzi, M., & Mason, J.W. (2003). A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. Journal of the American College of Cardiology, 42(10), 1777– 1782.

Fang, L., Karakiulakis, G., & Roth, M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. The Lancet. Respiratory medicine, 8(4), e21.

Furst, D.E, Lindsley, H., & Baethge, B. (1999). Dose- loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen- week extension. Arthritis & Rheumatology, 42 (2), 357– 365.

Jorge, A., Ung, C., Young, L.H., Melles, R.B., & Choi, H.K. (2018). Hydroxychloroquine retinopathy- implications of research advances for rheumatology care. Nature Reviews Rheumatology, 14(12), 693-703.

Gao, J., Tian, Z., & Yang, X. (2020). Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioScience Trends, 14(1):72–73.

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), 105949.

Gruppo collaborativo COVID-19 Lombardia. (2020). Vademecum per la cura delle persone con malattia da COVID-19 Edizione 2.0, 13 marzo 2020. Retrieved from http://www.simit.org/m

Guo, Y.R., Cao, Q.D., & Hong, Z.S. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Military Medical Research, 7(1), 11.

Han, Y., & Yang, H. (2020). The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective. Journal of Medical Virology, 92(6), 639–644.

Hancox, J. C., Hasnain, M., Vieweg, W. V., Crouse, E. L., & Baranchuk, A. (2013). Azithromycin, cardiovascular risks, QTc interval prolongation, torsade de pointes, and regulatory issues: A narrative review based on the study of case reports. Therapeutic Advances in Infectious Disease, 1(5), 155–165.

Indonesian Society of Respirology. (2020). Tatalaksanana pasien COVID-19. Jakarta: PDPI.

Kalia, S., & Dutz, J. P. (2007). New concepts in antimalarial use and mode of action in dermatology. Dermatologic Therapy, 20(4), 160–174.

Kementerian Kesehatan Republik Indonesia. (2020). Info Infeksi Emerging Kementerian Kesehatan RI. [updated 2020 May 21]. Retrieved from: https:// infeksiemerging. kemkes.go.id/

Lee, S.J., Silverman, E., & Bargman, J.M. (2011). The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nature Reviews Nephrology, 7(12), 718- 729.

Li, X., Geng, M., Peng, Y., Meng, L., & Lu, S. (2020). Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis, 10(2), 102–108.

Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., Li, Y., Hu, Z., Zhong, W., & Wang, M. (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery, 6, 16.

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., Chen, J., ... & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 395(10224), 565–574.

Marmor, M.F., Kellner, U., Lai, T.Y., Melles, R.B., & Mieler, W.F. (2016). Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). Ophthalmology, 123, 1386–1394.

Mercuro, N. J., Yen, C. F., Shim, D. J., Maher, T. R., McCoy, C. M., Zimetbaum, P. J., & Gold, H. S. (2020). Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiology, e201834.

Mzayek, F., Deng, H., & Mather, F.J. (2007). Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial,and chloroquine in healthy volunteers. PLoS Clinical Trials, 2, 1-15.

National Health Commission & State Administration of Traditional Chinese Medicine. (2020). Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) (Released by on March 3rd, 2020). Retrieved from https://www. chinalawtranslate.com/wp- content/uploads/2020/03/Who-translation.pdf

Numaguchi, H., JohnsonJr, J.P., Petersen, C.I., & Balser, J.R. (2000). A sensitive mechanism for cation modulation of potassium current. Nature Neuroscience, 3(5), 429–430.

Pae, C.U. (2015). Why systematic review rather than narrative review. Psychiatry Investigation, 12(3), 417– 419.

Saleh, M., Gabriels, J., Chang, D., Soo Kim, B., Mansoor, A., Mahmood, E., Makker, P., Ismail, H., Goldner, B., Willner, J., Beldner, S., Mitra, R., John, R., Chinitz, J., Skipitaris, N., Mountantonakis, S., & Epstein, L. M. (2020). Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection. Circulation: Arrhythmia and Electrophysiology, 13(6), e008662.

Savarino, A., Boelaert, J.R,. Cassone, A., Majori, G., & Cauda, R. (2003). Effects of chloroquine on viral infections: an old drug against today’s diseases?. The Lancet Infectious Diseases, 3, 722–727.

Srinivasa, A., Tosounidou, S., & Gordon, C. (2017). Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine: a brand-related issue?. The Journal of Rheumatology, 44, 398.

Stas, P., Faes, D., & Noyens, P. (2008). Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. International Journal of Cardiology, 127(2), e80–e82.

Tisdale, J.E. (2016). Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention, and management. Canadian Pharmacists Journal (Ott), 149(3), 139–152.

Touret, F., & de Lamballerie, X. (2020). Of chloroquine and COVID-19. Antiviral Research, 177, 104762.

Wang, M., Cao. R., Zhang, L., Yang, X., Liu, J., & Xu, M. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019- nCoV) in vitro. Cell Research, 30, 269–271.

World Health Organization. (2020). Coronavirus disease 2019 (COVID-19) Situation Report 74. Geneva: WHO

Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., Song, C., Zhan, S., Lu, R., Li, H., Tan, W., & Liu, D. (2020). In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciaa237

Zumla, A., Hui, D.S., Azhar, E.I., Memish, Z.A., & Maeurer, M. (2020). Reducing mortality from 2019- nCoV: host-directed therapies should be an option. Lancet, 395(10224), 35-36.

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