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Current Drug Safety

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ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

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Research Article

Hydroxychloroquine and Azithromycin Combination in the Management of COVID-19 Infection: Safety and Effectiveness Challenges

Author(s): Ahmed E. Abou Warda, Mahmoud Tammam, Rabab A. El-Gazar, Rania M. Sarhan* and Sayed Gaber

Volume 17, Issue 2, 2022

Published on: 27 July, 2021

Page: [143 - 151] Pages: 9

DOI: 10.2174/1574886316666210727152609

Price: $65

Abstract

Background: The treatment of COVID-19 disease remains a dilemma so far because there is no approved therapy for it. This study aimed to evaluate the use of hydroxychloroquine and azithromycin combination in treatment.

Objectives: This study was carried out to determine the safety and effectiveness of hydroxychloroquine and azithromycin combination in COVID 19 patients.

Methods: This study included 90 adult COVID 19 patients. Treatment of all patients followed Egyptian Ministry of Health COVID-19 protocols, receiving a combination of hydroxychloroquine 400mg twice on day 1, then 200 mg twice daily in addition to azithromycin 500mg/day for 5 days. ECG findings, especially the QTc interval, were assessed before and after 5 days from the administration.

Results: All patients showed a statistically significant higher post-treatment QTc readings (433.6 ± 37.2) compared to baseline QTc (402.4 ± 31.3) at p<0.005 with a median QTc prolongation by 26 mSec and IQR (17.8-41.3), but without serious clinical complications. Only 5.6% of patients showed QTc more than 500 mSec and no torsade de points or cardiac arrest. Geriatric patients were at higher risk for QTc prolongation compared to patients aged less than 65 years but without a significant difference as regards the median max QTc difference p˂0.65. The expected therapeutic effectiveness was 82.5% for moderate patients compared to 26% for severe patients (P<0.005).

Conclusion: In a modest safety profile, we support the evidence that HQ/AZ therapy can be used to treat Covid-19 infection with more effectiveness in moderate rather than severe cases, which might be a reflection of the time of administration in the disease course.

Keywords: COVID-19, hydroxychloroquine, azithromycin, QT, oxygen saturation, CT image.

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[1]
Lei ZN, Wu ZX, Dong S, et al. Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19. Pharmacol Ther 2020; 216: 107672.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107672] [PMID: 32910933]
[2]
Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020; 382(25): 2411-8.
[http://dx.doi.org/10.1056/NEJMoa2012410] [PMID: 32379955]
[3]
Multicenter collaboration group of department of science and technology of guangdong province and health commission of guangdong province for chloroquine in the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(3): 185-8. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia].
[http://dx.doi.org/10.3760/CMA.j.issn.1001-0939.2020.03.009] [PMID: 32164085]
[4]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[5]
Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56(1): 105949.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[6]
World Health Organization. Malaria policy advisory committee meeting the cardiotoxicity of Antimalarials 2017.
[7]
Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012; 366(20): 1881-90.
[http://dx.doi.org/10.1056/NEJMoa1003833] [PMID: 22591294]
[8]
Saleh M, Gabriels J, Chang D, et al. Effect of chloroquine, hydroxychloroquine, and azithromycin on the corrected qt interval in patients with sars-cov-2 infection. Circ Arrhythm Electrophysiol 2020; 13(6): e008662.
[http://dx.doi.org/10.1161/CIRCEP.120.008662] [PMID: 32347743]
[9]
Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Canad Pharmacists J Rev 2016; 149(3): 139-52.
[http://dx.doi.org/10.1177/1715163516641136]
[10]
Vahedi E, Ghanei M, Ghazvini A, et al. The clinical value of two combination regimens in the management of patients suffering from covid-19 pneumonia: A single centered, retrospective, observational study. Daru 2020; 28(2): 507-16.
[http://dx.doi.org/10.1007/s40199-020-00353-w] [PMID: 32562159]
[11]
Prokop M, van Everdingen W, van Rees Vellinga T, et al. CO-RADS: A categorical CT assessment scheme for patients suspected of having COVID-19-definition and evaluation. Radiology 2020; 296(2): E97-E104.
[http://dx.doi.org/10.1148/radiol.2020201473] [PMID: 32339082]
[12]
Egypt uses chloroquine in treating COVID-19 patients: Minister - Egypt Today Available from: https://www.egypttoday.com/Article/1/83104/Egypt-uses-chloroquine-in-treating-COVID-19-patients-Minister [Accessed October 21, 2020
[13]
Grayson ML, Barber BE. Chloroquine and hydroxychloroquine.Kucera’ the use of antibiotics: A clinical review of antibacterial, antifungal, and antiviral drugs 7th CRC Press 2017; pp. 3030-47.
[14]
Chorin E, Dai M, Shulman E, et al. The QT interval in patients with SARS-COV-2 infection treated with hydroxychloroquine/azithromycin. medRxiv 2020; 17(9): 1425-33.
[15]
Clerkin KJ, Fried JA, Raikhelkar J, et al. COVID-19 and cardiovascular disease. Circulation 2020; 141(20): 1648-55.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046941] [PMID: 32200663]
[16]
Sarganas G, Garbe E, Klimpel A, Hering RC, Bronder E, Haverkamp W. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Europace 2014; 16(1): 101-8.
[http://dx.doi.org/10.1093/europace/eut214] [PMID: 23833046]
[17]
Roden DM. Predicting drug-induced QT prolongation and torsades de pointes. J Physiol 2016; 594(9): 2459-68.
[http://dx.doi.org/10.1113/JP270526] [PMID: 26660066]
[18]
Van Laecke S. Hypomagnesemia and hypermagnesemia. Acta Clin Belg 2019; 74(1): 41-7.
[http://dx.doi.org/10.1080/17843286.2018.1516173] [PMID: 30220246]
[19]
Khan Q, Ismail M, Haider I. High prevalence of the risk factors for QT interval prolongation and associated drug-drug interactions in coronary care units. Postgrad Med 2018; 130(8): 660-5.
[http://dx.doi.org/10.1080/00325481.2018.1516106] [PMID: 30145917]
[20]
Roden DM. Taking the “idio” out of “idiosyncratic”: Predicting torsades de pointes. Pacing Clin Electrophysiol 1998; 21(5): 1029-34.
[http://dx.doi.org/10.1111/j.1540-8159.1998.tb00148.x] [PMID: 9604234]
[21]
Selzer A, Wray HW. Quinidine syncope. Paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrhythmias. Circulation 1964; 30: 17-26.
[http://dx.doi.org/10.1161/01.CIR.30.1.17] [PMID: 14197832]
[22]
Bouchaud O, Imbert P, Touze JE, Dodoo AN, Danis M, Legros F. Fatal cardiotoxicity related to halofantrine: A review based on a worldwide safety data base. Malar J 2009; 8(1): 289.
[http://dx.doi.org/10.1186/1475-2875-8-289] [PMID: 20003315]
[23]
Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006; 44(2): 173-5.
[http://dx.doi.org/10.1080/15563650500514558] [PMID: 16615675]
[24]
Negoescu A, Thornback A, Wong E, Rheumatism AO-A. Rheumatism AO-A&, 2013 U. Long qt and hydroxychloroquine; a poorly recognised problem. Arthritis Rheumatol 2013; 65: 2045.
[25]
Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection: A randomized clinical trial. JAMA Netw Open 2020; 3(4): e208857.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.8857] [PMID: 32330277]
[26]
Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes 2013; 6(4): 479-87.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.113.000152] [PMID: 23716032]
[27]
Wilders R, Verkerk AO, Long QT. Long QT syndrome and sinus bradycardia-a mini review. Front Cardiovasc Med 2018; 5: 106.
[http://dx.doi.org/10.3389/fcvm.2018.00106] [PMID: 30123799]
[28]
Vandenberk B, Vandael E, Robyns T, et al. Which QT correction formulae to use for QT monitoring? J Am Heart Assoc 2016; 5(6): e004252.
[http://dx.doi.org/10.1161/JAHA.116.003264] [PMID: 27317349]
[29]
Matsunaga N, Oki Y, Prigollini A. A case of QT-interval prolongation precipitated by azithromycin. N Z Med J 2003; 116(1185): U666. Available from: https://mdanderson.elsevierpure.com/en/publications/a-case-of-qt-interval-prolongation-precipitated-by-azithromycin
[PMID: 14615808]
[30]
Samarendra P, Kumari S, Evans SJ, Sacchi TJ, Navarro V. QT prolongation associated with azithromycin/amiodarone combination. Pacing Clin Electrophysiol 2001; 24(10): 1572-4.
[http://dx.doi.org/10.1046/j.1460-9592.2001.01572.x] [PMID: 11707055]
[31]
Chico RM, Chandramohan D. Azithromycin plus chloroquine: Combination therapy for protection against malaria and sexually transmitted infections in pregnancy. Expert Opin Drug Metab Toxicol 2011; 7(9): 1153-67.
[http://dx.doi.org/10.1517/17425255.2011.598506] [PMID: 21736423]
[32]
Russo V, Puzio GF, Siniscalchi N. Azithromycin-induced QT prolongation in an elderly patient. Jazz Medica Ital Arch per le Sci Mediche 2005; 164(4): 309-11. Available from: https://europepmc.org/article/med/16856707 [Accessed October 30, 2020

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