Cardiologists have warned of the need to monitor for cardiac complications of hydroxychloroquine if it is used as a treatment for COVID-19 disease.
As Australia starts clinical trials of the drug and the government approves off label use of hydroxychloroquine for COVID-19, clinicians in France say they found the arrhythmia risks of the drug to be excessive for some patients.
Professor Émile Ferrari, heads of the cardiology department at the Pasteur Hospital said they had stopped using a hydroxychloroquine-azithromycin regime in patients with COVID-19 after ECG monitoring revealed cardiac toxicity.
He told the news outlet Nice Matin that the trial protocol stipulated ECG monitoring of patients at baseline and during the first two days of treatment.
“From the start of the trial, thanks to this ECG follow-up, we highlighted major risks of very serious [adverse events] in patients, and the treatment was immediately stopped,” he said.
Prof Ferrari said the cardiac risks of hydroxychloroquine were potentiated when used in combination with the azithromycin, which is also known to increase the risk of QT prolongation and cardiovascular death.
The cardiac toxicity may be further increased in patients with COVID-19 disease if they have low blood oxygenation or disordered potassium levels, he added.
And in the US, cardiologists at the Mayo Clinic have developed guidance on how to use a 12-lead ECG, telemetry or smartphone-enabled mobile ECG to determine a patient’s QTc as a vital sign to identify those at increased risk before starting hydroxychloroquine.
In Australia, Federal health minister Greg Hunt has signed an emergency licensing exemption for hydroxychloroquine to allow it to be imported and used off label for treatment in COVID-19 The minister said he had personally contacted overseas suppliers to obtain several thousand courses of hydroxychloroquine for use in hospitals to treat COVID-19.
“The advice from the supplier and the two Australian scientific groups I’ve spoken to is that they are cautiously hopeful that it can have an impact. It’s not a perfect cure, it’s not a perfect prevention,” said Mr Hunt.
“It will now be a matter, once we have these stocks arrive, for the individual doctors and hospital systems to determine whether it’s appropriate, whether they believe it’s safe.”
One trial of hydroxychloroquine as a treatment for COVID-19 in Australia is being led by Professor David Paterson, Consultant Infectious Diseases Physician at the Royal Brisbane and Women’s Hospital (RBWH). Another trial being set up at the Walter and Eliza Hall Institute in Victoria in which the drug will be used for four months as a preventive agent in more than 2200 healthcare workers who may be exposed to COVID-19.
The Australian product information for hydroxychloroquine warns that its use has been associated with chronic cardiac toxicity and QT interval prolongation. The PI states that cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated with hydroxychloroquine and therefore clinical monitoring for signs and symptoms of cardiomyopathy is advised.
“Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed,” it recommends.
Similarly, hydroxychloroquine should not be used concomitantly with drugs known to prolong the QT interval, such as class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, and some anti-infectives due to increased risk of ventricular arrhythmia, the PI warns.