Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol

Eur Heart J Acute Cardiovasc Care. 2020 Apr;9(3):215-221. doi: 10.1177/2048872620922784. Epub 2020 May 6.


More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.

Keywords: COVID-19; adverse effects; arrhythmias; cardiac; drugs; treatment.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Antibodies, Monoclonal / adverse effects
  • Antimalarials / adverse effects*
  • Antimalarials / pharmacokinetics
  • Antimalarials / toxicity
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / complications
  • Betacoronavirus / drug effects*
  • COVID-19
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / complications
  • Cardiotoxicity / epidemiology
  • Chloroquine / adverse effects*
  • Chloroquine / pharmacokinetics
  • Chloroquine / toxicity
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / virology
  • Cytochrome P-450 CYP3A Inhibitors / adverse effects
  • Drug Monitoring / methods*
  • Humans
  • Hydroxychloroquine / adverse effects*
  • Hydroxychloroquine / pharmacokinetics
  • Hydroxychloroquine / toxicity
  • Off-Label Use / statistics & numerical data
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Torsades de Pointes / chemically induced
  • Torsades de Pointes / epidemiology


  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Antimalarials
  • Cytochrome P-450 CYP3A Inhibitors
  • Hydroxychloroquine
  • Chloroquine