Rational Pharmacotherapy in Cardiology

Advanced search

Drug Interactions and Side Effects of Co-Administration of Chloroquine/Hydroxychloroquine and Azithromycin: on the Issue of Rational Pharmacotherapy of Patients with COVID-19 with Antimalarial Drugs

Full Text:


This review analyzes existing approaches to the treatment of COVID-19 patients with antimalarial drugs from the standpoint of rational pharmacotherapy. Particular attention is paid to drug interactions and side effects of co-administration of chloroquine/hydroxychloroquine and azithromycin, considering the problem of cardiotoxicity and the high likelihood of cardiovascular disease in middle-aged and elderly people with COVID-19. The article discusses the prospects of using another representative from the group of antimalarial drugs - mefloquine in the treatment of COVID-19. Special attention is paid to the “proarrhythmogenic” side effects of azithromycin therapy, as well as to the problem of resistance of microorganisms to macrolides during antibiotic therapy of pneumonia, in particular to azithromycin. In conclusion, the article discusses the possibilities of alternative methods in the treatment of this disease.

About the Author

O. V. Gaisenok
United Hospital with Outpatient Department, Administrative Department of the President of the Russian Federation
Russian Federation

Oleg V. Gaisenok - MD, PhD, Head of Therapeutic Department, United Hospital with Outpatient Department, Administrative Department of the President of the Russian Federation.

Michurinskypr. 6, Moscow, 119285.


1. Grasselli G., Zangrillo A., Zanella A., et al. COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-81. DOI:10.1001/jama.2020.5394.

2. Temporary methodical recommendations. Prevention, diagnostics and treatment of new coronaviral infection (COVID-19). Version 5. 08.04.2020 [cited by Apr 15, 2020]. Available from: (In Russ.)

3. Gautret F., Lagier J.C., Parola P., et al. Hydroxychloroquine and azithromycin as a treatment of COVID19: results of an open label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20;105949. DOI:10.1016/j.ijantimicag.2020.105949.

4. Plantone D., Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig. 2018;38(8):653-71. DOI:10.1007/s40261-018-0656-y.

5. Chloroquine (Chloroquinum). Instructions for use of the drug [cited by Apr 15, 2020]. Available from: (In Russ.)

6. Haeusler I.L., Chan X.H.S., Guerin PJ., White N.J. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review. BMC Med. 2018;16(1):200. DOI:10.1186/s12916-018-1188-2.

7. Blignaut M., Espach Y., van Vuuren M., et al. Revisiting the Cardiotoxic Effect of Chloroquine. Cardiovasc Drugs Ther. 2019;33(1):1-11. DOI:10.1007/s10557-018-06847-9.

8. Yogasundaram H., Hung W., Paterson I.D., et al. Chloroquine-induced cardiomyopathy: a reversible cause of heart failure. ESC Heart Fail. 2018;5(3):372-75. DOI:10.1002/ehf2.12276.

9. Hydroxychloroquine (Hydroxychlorochinum). Instructions for use of the drug [cited by Apr 15, 2020]. Available from: (In Russ.)

10. Chatre C., Roubille F., Vernhet H., et al. Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature. Drug Saf. 2018;41(10):919-31. DOI:10.1007/s40264-018-0689-4.

11. Dogar M.U., Shah N.N., Ishtiaq S., et al. Hydroxychloroquine-induced restrictive cardiomyopathy: a case report. Postgrad Med J. 2018;94(1109):185-6. DOI:10.1136/postgradmedj-2017-135236.

12. Mollerach F.B., Scolnik M., Catoggio L.J., et al. Causes of fetal third-degree atrioventricular block and use of hydroxychloroquine in pregnant women with Ro/La antibodies. Clin Rheumatol. 2019;38(8):2211-7. DOI:10.1007/s10067-019-04556-8.

13. Lewis J., Gregorian T., Portillo I., Goad J. Drug interactions with antimalarial medications in older travelers: a clinical guide. J Travel Med. 2020;27(1).pii:taz089. DOI:10.1093/jtm/taz089.

14. Polgreen L.A., Riedle B.N., Cavanaugh J.E., et al. Estimated Cardiac Risk Associated with Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities. J Am Heart Assoc. 2018;7(9).pii:e008074. DOI:10.1161/JAHA.117.008074.

15. Postma D.F., Spitoni C., van Werkhoven C.H., et al. Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial. BMC Infect Dis. 2019;19(1):17. DOI:10.1186/s12879-018-3630-7.

16. Trifiro G., de Ridder M., Sultana J., et al. Use of azithromycin and risk of ventricular arrhythmia. CMAJ. 2017;189(15):E560-E568. DOI:10.1503/cmaj.160355.

17. Yang Z., Prinsen J.K., Bersell K.R., et al. Azithromycin Causes a Novel Proarrhythmic Syndrome. Circ Arrhythm Electrophysiol. 2017;10(4).pii:e003560. DOI:10.1161/CIRCEP.115.003560.

18. Lee H., Yun K.W., Lee H.J., Choi E.H. Antimicrobial therapy of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. Expert Rev Anti Infect Ther. 2018;16(1):23-34. DOI:10.1080/14787210.2018.1414599.

19. Midouni Ayadi B., Mehiri E., Draoui H., et al. Phenotypic and molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae isolated in Tunisia. J Med Microbiol. 2020;69(4):505-20. DOI:10.1099/jmm.0.001151.

20. Rodriguez N., Mondeja B., Sardinas R., et al. First detection and characterization of macrolide-resistant Mycoplasma pneumoniae strains in Cuba. Int J Infect Dis. 2019;80:115-7. DOI:10.1016/j.ijid.2018.12.018.

21. Kastrin T, Paragi M., Erculj V., et al. Lack of correlation between reduced outpatient consumption of macrolides and macrolide resistance of invasive Streptococcus pneumoniae isolates in Slovenia during 1997-2017. J Glob Antimicrob Resist. 2019;16:242-8. DOI:10.1016/j.jgar.2018.10.022.

22. Tanaka T., Oishi T., Miyata I., et al. Macrolide-Resistant Mycoplasma pneumoniae Infection, Japan, 2008-2015. Emerg Infect Dis. 2017;23(10):1703-6. DOI:10.3201/eid2310.170106.

23. Loconsole D., De Robertis A.L., Mallamaci R., et al. First Description of Macrolide-Resistant Mycoplasma pneumoniae in Adults with Community-Acquired Pneumonia in Italy. Biomed Res Int. 2019;2019:7168949. DOI:10.1155/2019/7168949.

24. Noori Goodarzi N., Pourmand M.R., Arfaatabar M., et al. First Detection and Characterization of Macrolide-Resistant Mycoplasma pneumoniae from People with Community-Acquired Pneumonia in Iran. Microb Drug Resist. 2020;26(3):245-50. DOI:10.1089/mdr.2019.0223.

25. Mefloquin (Mefloquinum) Instructions for use of the drug [cited by Apr 15, 2020]. Available from: (In Russ.)

26. Honegr K., DuKcek K., Mirovsky P., Hozak A. Mefloquine in the treatment of malaria--initial experience in Czechoslovakia. Cesk Epidemiol Mikrobiol Imunol. 1987;36(5):292-6.

27. Jensen J.J. Mefloquine: neuropsychiatric adverse effects are often severe and persistent long after withdrawal of the drug. Ugeskr Laeger. 1998;160(16):2413.

28. FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects [cited by Apr 15, 2020]. Available from:

29. Tickell-Painter M., Saunders R., Maayan N., et al. Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review. Travel Med Infect Dis. 2017;20:5-14. DOI:10.1016/j.tmaid.2017.10.011.

30. Tickell-Painter M., Maayan N., Saunders R., et al. Mefloquine for preventing malaria during travel to endemic areas. Cochrane Database Syst Rev. 2017;10:CD006491. DOI:10.1002/14651858.CD006491.pub4.

31. Fan H.H., Wang L.Q., Liu W.L., et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020;133(9):1051-6. DOI:10.1097/CM9.0000000000000797.

32. FMBA of Russia: the antiviral activity of Mefloquine against the pathogen COVID-19 has been proven [cited by Apr 15, 2020]. Available from: (In Russ.)

33. Kim I.C., Kim J.Y., Kim H.A., Han S. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J. 2020;41(19):1859. DOI:10.1093/eurheartj/ehaa288.

34. Guo T., Fan Y., Chen M., et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;e201017. DOI:10.1001/jamacardio.2020.1017.

35. Temporary methodical recommendations. drug therapy of acute respiratory viral infections in outpatient practice during COVID-19 epidemic. Version 1 (04/12/2020) [cited by Apr 15, 2020]. Available from: (In Russ.) Доступно на:

36. Sanders J.M., Monogue M.L., Jodlowski T.Z., Cutrell J.B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;323(18):1824-36. DOI:10.1001/jama.2020.6019.

37. Agostini M.L., Andres E.L., Sims A.C., et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2).pii:e00221-18. DOI:10.1128/mBio.00221-18.

38. 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. DOI:10.1038/s41422-020-0282-0.

39. Furuta Y., Komeno T., Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-63. DOI:10.2183/pjab.93.027.

40. Delang L., Abdelnabi R., Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018;153:85-94. DOI:10.1016/j.antiviral.2018.03.003.

41. Yu L., et al. Handbook of COVID-19 Prevention and Treatment. [cited by Apr 15, 2020]. Available from:

42. Clinical guidelines. Community-acquired pneumonia (2018) [cited by Apr 15, 2020]. Available from: (In russ.)

43. Krasnovskii A.L., Grigor'ev S.P., Alekhin A.I., Potapov V.N. Application of heated oxygen-helium mixture for combined treatment of community-acquired pneumonia. Klin Med (Mosk). 2013;91(5):38-41 (In Russ.)

44. Protocol for the treatment of thermal heliox (t-He/O2) in patients with acute and exacerbation of chronic respiratory failure syndrome. Moscow, 2018 [cited by Apr 15, 2020]. Available from:,%2017.15).pdf (In Russ.)


For citations:

Gaisenok O.V. Drug Interactions and Side Effects of Co-Administration of Chloroquine/Hydroxychloroquine and Azithromycin: on the Issue of Rational Pharmacotherapy of Patients with COVID-19 with Antimalarial Drugs. Rational Pharmacotherapy in Cardiology. 2020;16(3):481-486. (In Russ.)

Views: 1295

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)