Potential Toxicity of The Combination of Hydroxychloroquine and Azithromycin for Covid-19 Therapy: Literature Review



  • M. Sabir Mangawing Laboratory of Molecular Microbiology and Immunology of Tropical Diseases, Department of Medical Microbiology, Faculty of Medicine, Tadulako University, Palu, Central of Sulawesi, Indonesia
  • Rosa Dwi Wahyuni Laboratory of Clinical Pathology, Immunology and Tropical Diseases, Department of Clinical Pathology, Faculty of Medicine, Tadulako University, Palu, Central of Sulawesi, Indonesia


Hydroxychloroquine (HCQ), Azithromycin (AZM), Therapy, COVID-19


One of the therapies often used for COVID-19 patients is a combination of Hydroxychloroquine and Azithromycin. Although only short-term treatment, Hydroxychloroquine and Azithromycin may increase the risks of QTc and TdP intervals prolongation. This literature review aims to determine the potential toxicity of the combination of Hydroxychloroquine and Azithromycin for COVID-19 therapy. This study involved the PubMed, NCBI, Science Direct, NIH MEDLINE, Google Scholar and ProQuest databases. The 24 articles collected were then selected. Finally, 15 articles were found feasible for references in a literature review. The study results showed that combined Hydroxychloroquine and Azithromycin in COVID-19 therapy could increase the risk of QTc and TdP waves prolongation. It can be concluded that the combination of Hydroxychloroquine and Azithromycin carried the risk of prolongation of QTc and TdP waves in the heart rhythm cycle. There is a need for monitoring and/or recommendation regarding instructions for the use of combination therapy of the two types of drugs among patients with COVID-19.


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Özdemir İH, Özlek B, Özen MB, Gündüz R, Çetin N, Bilge AR. Hydroxychloroquine/azithromycin treatment, QT interval and ventricular arrhythmias in hospitalised patients with COVID‐19. International journal of clinical practice. 2021 Feb;75(2):e13896.

Yendrapalli U, Ali H, Green JL, Edwards J. Effects of cardiac toxicity of combination therapy with hydroxychloroquine and azithromycin in COVID-19 patients. Journal of Infection and Public Health. 2021 Nov 1;14(11):1668-70.

Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. Cmaj. 2020 Apr 27;192(17):E450-3.

Eftekhar SP, Kazemi S, Barary M, Javanian M, Ebrahimpour S, Ziaei N. Effect of hydroxychloroquine and azithromycin on QT interval prolongation and other cardiac arrhythmias in COVID-19 confirmed patients. Cardiovascular Therapeutics. 2021 Feb 27;2021:1-7.

Mégarbane B, Scherrmann JM. Hydroxychloroquine and azithromycin to treat patients with COVID‐19: both friends and foes?. Journal of clinical pharmacology. 2020 Jul;60(7):808.

Li C, Cheng G. Will hydroxychloroquine still be a game-changer for COVID-19 by combining azithromycin?. Frontiers in Immunology. 2020 Aug 7;11:1969.

Huang HD, Jneid H, Aziz M, Ravi V, Sharma PS, Larsen T, Chatterjee N, Saour B, Aziz Z, Nayak H, Trohman RG. Safety and effectiveness of hydroxychloroquine and azithromycin combination therapy for treatment of hospitalized patients with COVID-19: a Propensity-Matched study. Cardiology and Therapy. 2020 Dec;9:523-34.

Voisin O, le Lorc’h E, Mahé A, Azria P, Borie MF, Hubert S, Ménage E, Guillerm JC, Mourad JJ. Acute QT interval modifications during hydroxychloroquine-azithromycin treatment in the context of COVID-19 infection. InMayo Clinic Proceedings 2020 Aug 1, 95,(8), 696-1700. Elsevier.

Echarte-Morales J, Minguito-Carazo C, del Castillo-García S, Borrego-Rodríguez J, Rodríguez-Santamarta M, Sánchez-Muñoz E, Bergel-García R, González-Maniega C, Prieto-González S, Menéndez-Suarez P, Tundidor-Sanz E. Effect of hydroxychloroquine, azithromycin and lopinavir/ritonavir on the QT corrected interval in patients with COVID-19. Journal of Electrocardiology. 2021 Jan 1;64:30-5.

O'Connell TF, Bradley CJ, Abbas AE, Williamson BD, Rusia A, Tawney AM, Gaines R, Schott J, Dmitrienko A, Haines DE. Hydroxychloroquine/azithromycin therapy and QT prolongation in hospitalized patients with COVID-19. Clinical Electrophysiology. 2021 Jan 1;7(1):16-25.

Hache G, Rolain JM, Gautret P, Deharo JC, Brouqui P, Raoult D, Honoré S. Combination of hydroxychloroquine plus azithromycin as potential treatment for COVID-19 patients: safety profile, drug interactions, and management of toxicity. Microbial Drug Resistance. 2021 Mar 1;27(3):281-90.

Tuncer T, Karaci M, Boga A, Durmaz H, Guven S. QT interval evaluation associated with the use of hydroxychloroquine with combined use of azithromycin among hospitalised children positive for coronavirus disease 2019. Cardiology in the Young. 2020 Oct;30(10):1482-5.

Ramireddy A, Chugh H, Reinier K, Ebinger J, Park E, Thompson M, Cingolani E, Cheng S, Marban E, Albert CM, Chugh SS. Experience with hydroxychloroquine and azithromycin in the coronavirus disease 2019 pandemic: implications for QT interval monitoring. Journal of the American Heart Association. 2020 Jun 16;9(12):e017144.

Ouarradi AE, Abdeladim S, Oualim S, Filali RA, Bensahi I, Elharass M, Hafid S, Tazi H, Naitlhou A, Bouaiti EA, Moustaghfir A. Hydroxychloroquine and azithromycin as a treatment of Covid-19: electrocardiogram variability. Journal of the Saudi Heart Association. 2020;32(3):350.

Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LC, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Lisboa T, Junqueira DL. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. New England Journal of Medicine. 2020 Nov 19;383(21):2041-52.



How to Cite

Mangawing, M. S., & Wahyuni, R. D. . (2023). Potential Toxicity of The Combination of Hydroxychloroquine and Azithromycin for Covid-19 Therapy: Literature Review. Poltekita : Jurnal Ilmu Kesehatan, 17(2), 421–425. https://doi.org/10.33860/jik.v17i2.2890



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