Is hydroxychloroquine a generally safe drug?
The politically charged atmosphere surrounding the drug in the context of COVID-19 can present a distorted picture. But the best evidence suggests that it has few adverse effects, although it does present some risks for patients with heart conditions.
Dr. Alieta Eck, who prescribed hydroxychloroquine for her patients who had COVID-19 symptoms, was confident the drug was safe.
“My feeling was that it was not going to do any harm, which is true. It’s a very safe medicine,” said Eck, an internist in New Jersey.
The Food and Drug Administration approved the use of hydroxychloroquine in 1955. The approved uses include treatment for malaria, lupus, and rheumatoid arthritis. In late March of this year, the FDA issued an emergency use authorization for hydroxychloroquine, which allowed state and local supplies of the drug to be supplemented from the strategic national stockpile.
“It is a very safe drug as far as drugs go,” said Dr. Kevin Pham, a physician and a visiting policy analyst at the conservative Heritage Foundation. “But we should remember that there are no drugs that are benign. All drugs that have some effect on the human body have the potential for a side effect.”
A review of nine randomized controlled trials, often considered the gold standard for medical research, found that hydroxychloroquine caused greater skin pigmentation than a placebo. It did not cause other possible adverse events, such as dizziness, gastrointestinal distress, or vision problems. However, the research did not examine cardiovascular problems.
Pham noted that one well-known side effect of hydroxychloroquine is a “QT prolongation.” A QT prolongation occurs when the heart muscle takes longer than normal to recharge between beats. It can result in an arrhythmia in which the heart beats faster than normal, a potentially deadly condition. A recent study of patients using hydroxychloroquine found that those with a history of heart disease and kidney disease were more susceptible to QT prolongation.
Eck, though, thinks that heart problems are not likely with short-term use.
“Any medicine you give for [only] five to seven days is probably not going to cause an arrhythmia,” she said. “Once a person is already in the hospital with this disease, once they are already intubated, there is a host of reasons why they are going to start getting an arrhythmia. To blame hydroxychloroquine is almost unfair because the patient is probably on eight other drugs.”
While some research shows that long-term use of the drug can cause heart problems, there is little evidence that it causes heart problems in otherwise healthy patients taking the drug for a short period.
The FDA cited about 109 cases of serious cardiac complications when, on June 15, it revoked its emergency authorization for hydroxychloroquine. Of those, 80 reported QT prolongation. However, the FDA’s database only contained patients who took hydroxychloroquine and suffered an adverse event. It did not have data on the total number of patients, making it impossible to know how often cardiac complications occurred.
“In a vacuum, the FDA’s decision wouldn’t be incorrect,” said Pham. “But we don’t live in a vacuum. We live in a political reality where it has become this ideological totem. And it really needs to not be that. It needs to be based on whatever evidence becomes available.”
Jack Mozloom, vice president of public affairs at the National Community Pharmacists Association, concurred that politics has affected the debate over hydroxychloroquine.
“It’s undeniable. The president started it when he opined on the effectiveness of the drug, and then his adversaries latched on to that as a political football,” he said. “It’s been a mess ever since.”
President Trump touted the drug at a press conference in early March. In late May, the atmosphere became more charged when the medical journal The Lancet published a study showing that patients taking hydroxychloroquine for COVID-19 had a 34% increased risk of dying and a 137% increased risk of a heart arrhythmia. It was used by some to criticize Trump’s promotion of the drug. The study was later retracted when the data it used turned out to be fraudulent.
The debate was rekindled last week when America’s Frontline Doctors held a press conference saying they’d successfully treated COVID-19 patients with hydroxychloroquine. The presser went viral after hundreds of thousands of people, including Trump, shared a video of it. Soon, the video was pulled by YouTube, Facebook, and Twitter on the grounds that it spread misinformation about the coronavirus. Twitter even suspended the account of Donald Trump Jr. after he shared it.
While many claims from America’s Frontline Doctors are at odds with the available evidence, it is still unclear what impact hydroxychloroquine, when combined with other medications, has on patients who are in the early stages of the disease.
“There are open questions about how to administer this drug. The science isn’t settled yet,” said Pham. “We should be open to the possibility that either it works or it doesn’t work.”
