A 65-year-old drug used mainly for treating malaria has suddenly become the world’s most hotly debated pharmaceutical, thanks to the novel coronavirus and President Trump.
Since the U.S. Food and Drug Administration cleared chloroquine and its next-generation derivative, hydroxychloroquine, for treating COVID-19, social media has been ablaze with warnings about the drug’s potentially deadly side effects.
“Human beings are not guinea pigs. We took a solemn oath to ‘first, do no harm,’” tweeted Dr. Eugene Gu, a prominent Trump critic. “That means not testing drugs that have deadly side effects without any proven benefit against the coronavirus with no evidence from clinical trials. This is the most basic rule of ethics in medicine.”
Both chloroquine and hydroxychloroquine come with a risk of sudden drug-induced cardiac arrest for those with prolonged QTc, a lengthier-than-normal interval between heartbeats as shown on an electrocardiogram [ECG], said Dr. Michael J. Ackerman, a genetic cardiologist and director of Mayo Clinic’s Windland Smith Rice Sudden Death Genomics Laboratory.
“The patient’s QTc value reflects the health of the heart’s electrical recharging system,” said Dr. Ackerman. “If the QTc is prolonged, it indicates that the system is inefficient or pokey, and in that setting, if QT-prolonging medications like hydroxychloroquine are added to the mix, that can be a dangerous and even deadly combination.”
He said the good news is that the danger of such reactions is “really rare” and can be mitigated. How rare?
“About 90% of us would be absolutely fine being exposed to these medications,” said Dr. Ackerman. “Five to 10% of us would be at increased risk where I would want my physician to make some adjustments … and 1% of us are at significantly increased risk for this tragic side effect.”
Taking azithromycin with hydroxychloroquine or chloroquine, as some U.S. medical centers are now recommending to treat COVID-19, can exacerbate the situation. The solution begins with awareness.
Even before the FDA took action, Mayo Clinic Proceedings published an “urgent guidance” for health-care providers recommending that they identify at-risk patients and determine their “baseline QTc status,” either by using an ECG or a mobile device, such as AliveCor’s KardioMobile 6L, which recently received FDA emergency clearance.
Instead of being unaware or resigned to the side effects — or too “QT paranoid” to prescribe hydroxychloroquine for COVID-19 — Dr. Ackerman recommended that medical professionals be aware of the issue and navigate it.
“Even if you are in that 1%, that doesn’t mean that sudden cardiac death is around the corner,” Dr. Ackerman said. “It just means that your risk has increased enough that there had better be a tremendous amount of respect and awareness given to this QTc issue.”
A COVID-19 vaccine is at least 12 to 18 months away, but there is hope that hydroxychloroquine “may have life-saving therapeutic efficacy against COVID-19,” said the Mayo Clinic guidance.
“And if it does, we hope that this simple QTc surveillance strategy, enabled by innovation and FDA’s emergency approval, will help prevent altogether or at least significantly reduce the number of drug-induced ventricular arrhythmias and sudden cardiac deaths,” said the guidance.
After Mr. Trump touted hydroxychloroquine two weeks ago as a potential “game changer,” reaction has ranged from fans celebrating the drug as a savior to critics blasting the president for pushing “snake oil,” as a USA Today editorial put it.
At least two states with Democratic governors — Michigan and Nevada — have issued restrictions on the antimalarial drugs, citing concerns about hoarding as well as the lack of clinical evidence on their efficacy in treating the novel coronavirus.
After the FDA authorization, however, the Michigan Health and Human Services Department changed course.
“Based on the FDA’s Emergency Use Authorization to allow the use of hydroxychloroquine sulfate and chloroquine phosphate products donated to the Strategic National Stockpile (SNS) for certain patients with COVID-19, we are pursuing a request for hydroxychloroquine/chloroquine from SNS,” said Lynn Sutfin, Michigan HHS spokesperson, in an email.
Last week, the state Department of Licensing and Regulatory Affairs warned doctors against prescribing the drugs, citing lack of evidence about their efficacy against COVID-19 and reports of stockpiling, adding that reports of such conduct “may be further investigated for administrative action.”
Pharmacists were also instructed not to fill prescriptions if they believed they could be used for reasons “other than legitimate medical purposes” or “cause harm to a patient,” adding that medical providers had an obligation to report “inappropriate prescribing practices.”
The Trump administration said it had received 30 million doses of hydroxychloroquine sulfate donated by Sandoz and one million doses of chloroquine phosphate donated by Bayer Pharmaceuticals for the national stockpile of pharmaceuticals and medical supplies.
At a Monday press conference, Michigan Gov. Gretchen Whitmer said her administration needed to be “nimble in this crisis,” adding that “we are continually updating and adjusting as we need to.”
“We want to ensure that doctors have the ability to prescribe these medicines,” Ms. Whitmer said. “We also want to make sure that people who have prescriptions that predated COVID-19 have access to the medication that they need. And so all of the work that we’ve done is trying to strike that balance.”
Most of the evidence behind using hydroxychloroquine for COVID-19 is anecdotal, although small studies out of France and China have found the drug to be beneficial.
A study published Wednesday in medRXiv by Chinese researchers found that in a trial of 62 COVID-19 patients, the duration of coughing and fever were “significantly shortened” in the hydroxychloroquine treatment group, although two suffered “mild adverse reactions.”
The research was conducted Feb. 4-28 at Renmin Hospital at Wuhan University.