DISCUSSION
Due to SARS-CoV2 global pandemic, treatment with HCQ, although
controversial, has been widely prescribed. These prescriptions have been
made in an emergency context and lack of open clinical trials at the
very beginning of the outbreak. Although the side effects profile of HCQ
is well known for decades, the population receiving this medication is
different from the one usually treated for auto-immune
diseases6, so the DDIs encountered could be unusual.
We, hereby, analyze the potential DDIs found in this population with a
focus on cardiac side effects.
In this study, a large number of patients had risk factors of QT
prolongation (age over 65, sex or comorbidities as renal or heart
failure)9. These patients’ characteristics may explain
the number of long-term treatments, increasing risk of QT prolongation
due to DDIs, especially with HCQ. More than a half of patients had at
least one DDIs between their long-term treatments and HCQ. A large
number of drug classes were involved, included contraindicated drugs
which were discontinued at the beginning of HCQ treatment. However, as
some of these drugs have a long elimination half-life (30 hours for
escitalopram, up to 100 days for amiodarone11), a
residual risk could persist, even after the drug in question is stopped.
For each not recommended drug, benefit-risk ratio was assessed by
physicians and clinical pharmacists. Among the involved drugs, there
were also some widespread medications, like PPIs or
inhaled-bronchodilators. These drugs were often continued during HCQ
treatment, which could be explained by lack of information about their
potential impact on the QT interval. Nevertheless these DDIs have to be
taken into account during treatment with HCQ especially as COVID-19 can
manifest by acute myocardial injury, which could lead to cardiac
arrhythmias12.
This study shows that a huge number of drugs could interact with HCQ.
Consequently, it is of great interest to upstream study the QT
prolongation risks due to co-medication in COVID-19 patients treated
with this drug. Physicians must be aware of QT prolongation risk when
HCQ is associated with other drugs increasing the QT interval per
se in the treatment of COVID-19, such as azithromycin or protease
inhibitors.
In addition to this well described cardiac toxicity, it is also
important to consider DDIs which may lead to other side effects such as
hypoglycemia or increasing risk of convulsion13.
Moreover HCQ is substrate of CYP 450 and is an inhibitor of CYP 2D6 so
pharmacokinetics DDIs should be taken into account.
In this context of pandemic, clinical pharmacists should analyze all the
prescriptions of COVID-19 patients in order to detect DDIs and discuss
with physicians the opportunity of stopping a medication, adapting a
posology or in some cases, pursuing the involved drug.
To our knowledge this is the first study about DDIs between HCQ and
long-term treatments of COVID-19 patients.
Other studies, including clinical and pharmacokinetic parameters, need
to be carried out subsequently to measure impact of DDIs among COVID-19
patients.