Coronavirus: reminder of risk of serious adverse effects associated with chloroquine and hydroxychloroquine

The European Medicines Agency (EMA) recommends that healthcare professionals monitor cardiac adverse effects and consider pre-existing heart conditions in COVID-19 patients treated with hydroxychloroquine or chloroquine. It should also be borne in mind that there may be an increased risk of cardiac adverse effects when these treatments are administered in high doses or in combination with certain medicinal products, such as azithromycin.

Risk of side effects and interactions with other medicinal products

As mentioned in the FAMHP’s news and Flash VIG-news articles dated 01 April 2020, there is a known risk of cardiac arrhythmias linked to the use of chloroquine and hydroxychloroquine. This risk can be potentiated by its combination with other medicinal products which have a similar effect on the heart. This is the case with the antibiotic azithromycin. Certain conditions, such as hypokalemia and/or hypomagnesemia, can also increase this risk. In addition to the cardiac adverse effects, these treatments may cause liver or kidney problems, a lowering of the seizure threshold or hypoglycaemia.

Hydroxychloroquine and chloroquine are currently used, in certain circumstances, to treat patients with COVID-19 and are the subject of clinical studies. Recent studies have reported severe heart rhythm abnormalities, in some cases fatal, in COVID-19 patients treated with chloroquine or hydroxychloroquine, particularly when these treatments were administered in high doses or in combination with azithromycin.

Recommendations to healthcare professionals

The EMA recommends close monitoring of COVID-19 patients treated with hydroxychloroquine or chloroquine, especially at high doses. Any pre-existing heart condition should be taken into account, and it is recommended that healthcare professionals exercise increased caution when combining the treatment with other medicinal products that may cause similar cardiac adverse effects. You will find more information on medicinal product interactions with hydroxychloroquine and chloroquine in the Flash VIG-news dated 01 April 2020.

We would like to remind healthcare professionals that these medicinal products should only be used in the context of clinical trials or in accordance with nationally authorised protocols. They should not be used without prescription and without the supervision of a doctor.

Clinical studies in progress, risk/benefit balance and surveillance at national and European level

Large-scale, randomised clinical studies are currently looking into the risks and benefits of these therapies in COVID-19 patients. So far, clinical data remains very limited and inconclusive.

As with all medicinal products, the adverse effects of hydroxychloroquine and chloroquine are studied and monitored by FAMHP experts, in collaboration with the other competent European authorities for medicinal products.

The EMA and the competent national authorities (including the FAMHP) have stepped up the monitoring of the safety of all medicinal products used to treat COVID-19 to ensure that timely action can be taken, if necessary.

Report all adverse reactions to the FAMHP
Patients and healthcare professionals are encouraged to report suspected adverse reactions at www.notifieruneffetindesirable.be.

Reference studies

  • 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, double-blinded, phase IIb clinical trial (CloroCovid-19 Study). medRxiv doi: 10.1101/2020.04.07.20056424
  • 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
  • Joseph Magagnoli, Siddharth Narendran, Felipe Pereira, Tammy Cummings, James W Hardin, S Scott Sutton, Jayakrishna Ambati. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 - Joseph Magagnoli, Siddharth Narendran, Felipe Pereira, Tammy Cummings, James W Hardin, S Scott Sutton, Jayakrishna Ambati - medRvix doi: 10.1101/2020.04.16.20065920
Last updated on
07/05/2020