It is known that medicinal products containing chloroquine and hydroxychloroquine can potentially cause cardiovascular disorders, namely heart rhythm disorders, which may be aggravated if the treatment of COVID-19 is combined with other medicinal products, such as the antibiotic azithromycin, which has a similar effect on the heart.
Recent studies2,3 have reported serious, in some cases fatal, heart rhythm problems associated with the use of chloroquine and hydroxychloroquine products, especially when used in high doses or in combination with the antibiotic azithromycin.
Currently, chloroquine and hydroxychloroquine preparations are authorized for use in malaria and certain autoimmune diseases. In addition to cardiovascular side effects, they are known to potentially cause problems in the hepatobiliary and urinary systems and to damage nerve cells, which can lead to seizures and to a decrease in blood sugar levels (hypoglycemia).
These medicinal products are used in the context of the ongoing pandemic to treat patients with COVID-19 and have been studied in clinical trials. However, clinical data are still very limited and inconclusive, and beneficial effects of these medicinal products in COVID-19 have not been demonstrated. To draw any conclusions, results of large, well-designed studies are needed.
Some clinical trials are investigating the efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19 using higher doses than those recommended for the approved indications. Although serious adverse reactions may occur at the recommended doses, higher doses may increase the risk of these adverse effects, including abnormal electrical activity affecting heart rhythm (QT interval prolongation).
Healthcare professionals are advised to closely monitor patients with COVID-19 who are receiving chloroquine and hydroxychloroquine products, and to take into account existing heart problems that may make patients more prone to heart rhythm problems. Healthcare professionals should carefully consider the possibility of adverse reactions, especially when higher doses are used, and exercise particular caution when combining treatment with other medicinal products, such as azithromycin, that may cause similar adverse cardiovascular effects.
Patients and healthcare professionals are encouraged to report all suspected adverse reactions to the national regulatory authority (in Ukraine, medicinal product safety monitoring is carried out by the State Enterprise “State Expert Center of the Ministry of Health of Ukraine”. An adverse reaction can be reported at the link https://aisf.dec.gov.ua).
A number of large randomized clinical trials are studying the benefits and risks of medicinal products containing chloroquine and hydroxychloroquine in patients with COVID-19. In the treatment of COVID-19, these products should be used only as part of clinical trials or in accordance with a nationally approved protocol. The use of chloroquine and hydroxychloroquine products without a prescription and physician supervision is unacceptable.
EMA and national regulatory authorities are closely monitoring the situation and have intensified safety monitoring of medicinal products used in the treatment of COVID-19, in order to take timely action if necessary.
This EMA public health statement was published by the EMA COVID-19 pandemic task force (COVIDETF), in agreement with the PRAC committee, in light of the ongoing discussion on the use of chloroquine and hydroxychloroquine in the treatment of COVID-19.
EMA aims to provide accessible information to help healthcare professionals and patients make informed decisions while awaiting the results of clinical trials on whether chloroquine and hydroxychloroquine have a positive benefit/risk balance in the treatment of COVID-19.
Linkhttps://www.ema.europa.eu/en/news/covid-19-reminder-risk-serious-side-effects-chloroquine-hydroxychloroquine
2 Mayla Gabriela Silva Borba, Fernando Fonseca Almeida Val, Vanderson Sousa Sampaio et al. Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, doubleblinded, phase IIb clinical trial (CloroCovid-19 Study). medRxiv doi: 10.1101/2020.04.07.20056424
3 Lane J.C.E., Weaver J., Kosta K. et al. Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study. medRxiv doi: 10.1101/2020.04.08.20054551
