Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19
Keywords:
Chloroquine, Hydroxychloroquine, COVID-19, risk, benefits
Abstract
Chloroquine (CQ) and Hydroxychloroquine (HCQ) are highly prescribed as medications for COVID-19 infection, although no robust or convincing data has yet been published about the efficacy in COVID-19 patients. Therefore, risk and benefit assessment are necessary for decision to prescribe these drugs in COVID-19 patient in hospitals settings. We systematically searched from MEDLINE Database which investigate the benefits and risks of HCQ and CQ among COVID-19 patients. All records were searched using the search terms Hydroxychloroquine, Chloroquine, COVID-19, and SARS-CoV-2. The selection criteria include all clinical trials and observational studies. We found 11 records about benefit and 7 records about risks on HCQ and CQ in COVID-19 patients after following inclusion and exclusion criteria. From clinical trial and observational studies have showed that HCQ is very limited benefit particularly on reduction of mortality or clinical improvement. Similarly, there were seven observational studies have estimated the cardiac event in use of HCQ or CQ in COVID-19. Even though no increase death, but these studies reported the increase risk of prolong QT-interval in high proportion and other cardiac events such as arrythmia, torsade de pointes and conduction block. We conclude that the benefit effect of HCQ and CQ in COVID-19 remains very limited. However, both medications have independently shown to increase the risk in other populations for QT-interval prolongation, drug-induced torsades de pointes/TDP (a form of polymorphic ventricular tachycardia) and drug-induced other cardiac events.
References
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Gautret, P., Lagier, J.-C., Parola, P., Meddeb, L., Sevestre, J., Mailhe, M., Doudier, B., Aubry, C., Amrane, S., Seng, P., & others. 2020. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Medicine and Infectious Disease. 34: 101663
Geleris, J., Sun, Y., Platt, J., Zucker, J., Baldwin, M., Hripcsak, G., Labella, A., Manson, D. K., Kubin, C., Barr, R. G., & others. 2020. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. New England Journal of Medicine. 382: 2411-2418
Gérard, A., Romani, S., Fresse, A., Viard, D., Parassol, N., Granvuillemin, A., Chouchana, L., Rocher, F., & Drici, M.-D. 2020. “Off-label” use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapies. 75(4):371-379
Gevers, S., Kwa, M. S. G., Wijnans, E., & Van Nieuwkoop, C. 2020. Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clinical Microbiology and Infection. 26(9): 1276–1277
Huang, M., Tang, T., Pang, P., Li, M., Ma, R., Lu, J., Shu, J., You, Y., Chen, B., Liang, J., Hong, Z., Chen, H., Kong, L., Qin, D., Pei, D., Xia, J., Jiang, S., & Shan, H. 2020. Treating COVID-19 with Chloroquine. Journal of Molecular Cell Biology. 12(4): 322–325
Jorge, A. M., Melles, R. B., Zhang, Y., Lu, N., Rai, S. K., Young, L. H., Costenbader, K. H., Ramsey-Goldman, R., Lim, S. S., Esdaile, J. M., & others. 2018. Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines. Arthritis Research & Therapy. 20(1): 133
Ladipo, G. O. A., Essien, E. E., & Andy, J. J. 1983. Complete heart block in chronic chloroquine poisoning. International Journal of Cardiology. 4(2): 198–200
Lim, H.-S., Im, J.-S., Cho, J.-Y., Bae, K.-S., Klein, T. A., Yeom, J.-S., Kim, T.-S., Choi, J.-S., Jang, I.-J., & Park, J.-W. 2009. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrobial Agents and Chemotherapy. 53(4): 1468–1475
Mahévas, M., Tran, V.-T., Roumier, M., Chabrol, A., Paule, R., Guillaud, C., Fois, E., Lepeule, R., Szwebel, T.-A., Lescure, F.-X., & others. 2020. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ. 369: 1844.
Pratama, B. A., Rachman, A. M., Anggraeni, V. Y., Maharani, E., Trisnawati, I., Riyanto, B. S., & Hartopo, A. B. (2020). Deteriorating Atrioventricular Block in COVID-19 Suspected Patient after Receiving Initial Dose of Azythromycin and Hydroxychloroquine. Preprints 2020, 2020050190 https://doi.org/10.20944/preprints202005.0190.v1
RECOVERY Collaborative Group. 2020. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. New England Journal of Medicine. 383(21): 2030–2040
Rosenberg, E. S., Dufort, E. M., Udo, T., Wilberschied, L. A., Kumar, J., Tesoriero, J., Weinberg, P., Kirkwood, J., Muse, A., DeHovitz, J., & others. 2020. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA. 323(24):2493-2502
Sarayani, A., Cicali, B., Henriksen, C. H., & Brown, J. D. 2020. Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine. Research in Social and Administrative Pharmacy. 17(2). 483-486
World Health Organization. 2017. The cardiotoxicity of antimalarials: Malaria Policy Advisory Committee Meeting, Geneva, WHO.
Cavalcanti, A. B., Zampieri, F. G., Rosa, R. G., Azevedo, L. C. P., Veiga, V. C., Avezum, A., Damiani, L. P., Marcadenti, A., Kawano-Dourado, L., Lisboa, T., Junqueira, D. L. M., de Barros e Silva, P. G. M., Tramujas, L., Abreu-Silva, E. O., Laranjeira, L. N., Soares, A. T., Echenique, L. S., Pereira, A. J., Freitas, F. G. R., Berwanger, O. 2020. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. New England Journal of Medicine. 383(21): 2041–2052
Chatre, C., Roubille, F., Vernhet, H., Jorgensen, C., & Pers, Y.-M. 2018. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Safety. 41(10): 919–931
Chen, C.-P., Lin, Y.-C., Chen, T.-C., Tseng, T.-Y., Wong, H.-L., Kuo, C.-Y., Lin, W.-P., Huang, S.-R., Wang, W.-Y., Liao, J.-H., Liao, C.-S., Hung, Y.-P., Lin, T.-H., Chang, T.-Y., Hsiao, C.-F., Huang, Y.-W., Chung, W.-S., Cheng, C.-Y., Cheng, S.-H., & Taiwan HCQ Study Group. 2020. A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19). PloS One. 15(12): e0242763
Chen, Z., Hu, J., Zhang, Z., Jiang, S., Han, S., Yan, D., Zhuang, R., Hu, B., & Zhang, Z. 2020. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. MedRxiv. doi: https://doi.org/10.1101/2020.03.22.20040758
Chorin, E., Wadhwani, L., Magnani, S., Dai, M., Shulman, E., Nadeau-Routhier, C., Knotts, R., Bar-Cohen, R., Kogan, E., Barbhaiya, C., & others. 2020. QT interval prolongation and torsade De pointes in patients with COVID-19 treated with Hydroxychloroquine/azithromycin. Heart Rhythm. 17(9): 1425–1433
Colson, P., Rolain, J.-M., & Raoult, D. 2020. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. International Journal of Antimicrobial Agents. 55(3): 105923.
Costedoat-Chalumeau, N., Hulot, J.-S., Amoura, Z., Leroux, G., Lechat, P., Funck-Brentano, C., & Piette, J.-C. 2007. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology. 46(5): 808–810
de Novales, F. J. M., Rammirez-Olivencia, G., Estébanez, M., de Dios, B., Herrero, M. D., Mata, T., Borobia, A. M., Gutiérrez, C., Simón, M., Ochoa, A., & others. 2020. Early hydroxychloroquine is associated with an increase of survival in COVID-19 patients: an observational study. Preprints, 2020050057 https://doi.org/10.20944/preprints202005.0057.v1
Friedman, D. M., Kim, M., Costedoat-Chalumeau, N., Clancy, R., Copel, J., Phoon, C. K., Cuneo, B. F., Cohen, R., Masson, M., Wainwright, B. J., Zahr, N., Saxena, A., Izmirly, P. M., & Buyon, J. P. 2020. Electrocardiographic QT intervals in infants exposed to hydroxychloroquine throughout gestation. Circulation: Arrhythmia and Electrophysiology. 13: 1213–1219.
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
Gautret, P., Lagier, J.-C., Parola, P., Meddeb, L., Sevestre, J., Mailhe, M., Doudier, B., Aubry, C., Amrane, S., Seng, P., & others. 2020. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Medicine and Infectious Disease. 34: 101663
Geleris, J., Sun, Y., Platt, J., Zucker, J., Baldwin, M., Hripcsak, G., Labella, A., Manson, D. K., Kubin, C., Barr, R. G., & others. 2020. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. New England Journal of Medicine. 382: 2411-2418
Gérard, A., Romani, S., Fresse, A., Viard, D., Parassol, N., Granvuillemin, A., Chouchana, L., Rocher, F., & Drici, M.-D. 2020. “Off-label” use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapies. 75(4):371-379
Gevers, S., Kwa, M. S. G., Wijnans, E., & Van Nieuwkoop, C. 2020. Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clinical Microbiology and Infection. 26(9): 1276–1277
Huang, M., Tang, T., Pang, P., Li, M., Ma, R., Lu, J., Shu, J., You, Y., Chen, B., Liang, J., Hong, Z., Chen, H., Kong, L., Qin, D., Pei, D., Xia, J., Jiang, S., & Shan, H. 2020. Treating COVID-19 with Chloroquine. Journal of Molecular Cell Biology. 12(4): 322–325
Jorge, A. M., Melles, R. B., Zhang, Y., Lu, N., Rai, S. K., Young, L. H., Costenbader, K. H., Ramsey-Goldman, R., Lim, S. S., Esdaile, J. M., & others. 2018. Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines. Arthritis Research & Therapy. 20(1): 133
Ladipo, G. O. A., Essien, E. E., & Andy, J. J. 1983. Complete heart block in chronic chloroquine poisoning. International Journal of Cardiology. 4(2): 198–200
Lim, H.-S., Im, J.-S., Cho, J.-Y., Bae, K.-S., Klein, T. A., Yeom, J.-S., Kim, T.-S., Choi, J.-S., Jang, I.-J., & Park, J.-W. 2009. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrobial Agents and Chemotherapy. 53(4): 1468–1475
Mahévas, M., Tran, V.-T., Roumier, M., Chabrol, A., Paule, R., Guillaud, C., Fois, E., Lepeule, R., Szwebel, T.-A., Lescure, F.-X., & others. 2020. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ. 369: 1844.
Pratama, B. A., Rachman, A. M., Anggraeni, V. Y., Maharani, E., Trisnawati, I., Riyanto, B. S., & Hartopo, A. B. (2020). Deteriorating Atrioventricular Block in COVID-19 Suspected Patient after Receiving Initial Dose of Azythromycin and Hydroxychloroquine. Preprints 2020, 2020050190 https://doi.org/10.20944/preprints202005.0190.v1
RECOVERY Collaborative Group. 2020. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. New England Journal of Medicine. 383(21): 2030–2040
Rosenberg, E. S., Dufort, E. M., Udo, T., Wilberschied, L. A., Kumar, J., Tesoriero, J., Weinberg, P., Kirkwood, J., Muse, A., DeHovitz, J., & others. 2020. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA. 323(24):2493-2502
Sarayani, A., Cicali, B., Henriksen, C. H., & Brown, J. D. 2020. Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine. Research in Social and Administrative Pharmacy. 17(2). 483-486
World Health Organization. 2017. The cardiotoxicity of antimalarials: Malaria Policy Advisory Committee Meeting, Geneva, WHO.
Published
2021-08-10
How to Cite
At Thobari, J. (2021). Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19. Indonesian Journal of Pharmacy, 32(3), 266-279. https://doi.org/10.22146/ijp.1187
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Review Article
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