The FDA issued a today warning of the known risk of potentially fatal cardiac rhythm problems with use of hydroxychloroquine (HCQ, Plaquenil) and chloroquine, now being used against COVID-19.
Hospitals and outpatient clinics have reported to the FDA's adverse event reporting database that patients taking these drugs for treating or preventing COVID-19 have "included QT interval prolongation, ventricular tachycardia and ventricular fibrillation, and in some cases death," the agency said.
the agency urged, cautioning against use for COVID-19 outside of the hospital setting or in a clinical trial -- especially from online pharmacies without a prescription. Serious poisoning and death have been reported when people have attempted using chloroquine products without medical supervision.
Use at the doses approved for malaria and various autoimmune conditions should continue as normal, as the benefits outweigh the risks in those settings, the agency noted.
Adverse events have accrued for HCQ and chloroquine, both alone and when combined with the antibiotic azithromycin or other medicines. Patients with preexisting heart or kidney disease are at particular risk for rhythm disturbances when taking these drugs, the agency noted.
The major U.S. cardiovascular societies have also called attention to the cardiac death risk from HCQ in COVID-19.
"We understand that health care professionals are looking for every possible treatment option for their patients," said FDA Commissioner Stephen M. Hahn, MD, in a . "We encourage health care professionals making individual patient decisions closely screen and monitor those patients to help mitigate these risks. The FDA will continue to monitor and investigate these potential risks and will communicate publicly when more information is available."
A highlighted just how common the cardiac electrical problems are.
Most of the 84 consecutive patients with COVID-19 treated with a 5-day course of HCQ and azithromycin at NYU Langone Health in New York City developed prolonged QTc.
This ECG measure of the time it takes for a heart to recharge between beats increased from an average 435 ms at baseline to a peak average of 463 ms on day 3.6 (P<0.001 overall).
For 11% (nine patients), QTc went above the 500 ms mark that spells high risk of malignant arrhythmia and sudden cardiac death. Five of them had been admitted with a normal QT interval. No cases of torsades de pointes events occurred.
The cohort averaged age 63, and 74% were male. While the data was reported at a point when 64 of the patients were still hospitalized, the only four deaths were from multiple organ failure, without evidence of arrhythmia and without severe QTc prolongation.
Given that a prior study in young healthy volunteers showed only mild QTc prolongation, "QT prolongation may be influenced by patient attributes such as the presence of co-morbidities and the severity of the disease," Lior Jankelson, MD, PhD, of NYU Langone, and colleagues wrote.
A prior small trial of higher-dose chloroquine plus azithromycin in Brazil had to be halted after a and a trend for higher mortality was seen, based on the preprint in medRxiv.
A nationwide study of HCQ for severe COVID-19 in the VA system also recently reported a higher mortality risk.