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.