INTRODUCTION
Hydroxychloroquine (HCQ) is a hemi-synthetic drug used for its immunomodulatory activity in a wide range of pathologies, in particular autoimmune and inflammatory diseases since years. The mechanism of action remains unclear but it seems probably multifactorial including immunomodulatory and anti-inflammatory effects. Knowing its effect on the immune system and its safety profile, researchers wondered about its use in other areas, such as viral infections1.
Since the beginning of coronavirus disease 2019 (COVID-19) outbreak, several studies report in vitro activity of HCQ on Sars-Cov-22,3, but its clinical efficacy remains controversial at this time, because of the lack of strong in vivodata from randomized studies4. However, with the rapid spread of COVID-19 and on the basis of current knowledge, many prescribers have already introduced HCQ-based therapies which became a standard of care in many guidelines5.
Safety profile and side effects are well known for patients with autoimmune or inflammatory diseases. As part of COVID-19 pandemic, Yaoet al . report that using HCQ is safe2. Indeed, HCQ treatment is generally well tolerated and side effects are usually dose and duration related6.
However, adverse effects can occur for short-term treatments and one of the most described side effect could be the risk of cardiovascular disorders, such as QT prolongation7.
In the context of COVID-19 pandemic and off-label HCQ treatment, 80 cases of heart disorders associated with HCQ prescription (alone or in combination) were reported on April 24th by the French National Agency for Medicines and Health Products Safety8.
Treatment by drugs known to prolong the QT interval increases the risk of developing arrhythmia during HCQ-treatment. Indeed, the combination of several drugs prolonging the QT interval enhances this risk9.
In the largest cohort to date, investigators stated that they discontinued any drug potentially prolonging the QT during HCQ treatment but the number and frequency of treatment at risk of increasing the QT are not specified10.
Thus, the aim of our study is to identify drug-drug interactions (DDIs) between HCQ and long-term treatments of COVID-19 patients focusing on drugs that can cause or promote QT prolongation and way to manage them.