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.