FDA says chloroquine, hydroxychloroquine could be fatal

WASHINGTON - The Food and Drug Administration warned Friday that doctors should not use the malaria drugs chloroquine and hydroxychloroquine to treat COVID-19 patients outside a hospital or a clinical trial, citing reports of “serious heart rhythm problems.”

The drugs have been aggressively promoted by President Donald Trump, who has called them a potential "game-changer," even though results from clinical trials have not yet shown the drugs to be effective for COVID-19, the disease caused by the coronavirus.

An increasing number of studies and reports have raised safety issues, making the drugs an example of how the president's embrace of unproven medical ideas has potentially endangered Americans' lives and put health agencies in a tough spot.

On Thursday, after a White House presentation that touched on disinfectants that can kill the novel coronavirus on surfaces and in the air, Trump pondered whether those chemicals could be used to fight the virus inside the human body, prompting health experts and the makers of Lysol to quickly warn against ingesting disinfectants.

The FDA, in its drug safety communication Friday, said hydroxychloroquine and chloroquine have been linked to abnormal heart rhythms such as QT interval prolongation, dangerously rapid heart rates called ventricular tachycardia and ventricular fibrillation, and in some cases, death. The agency said the medications should be used only in settings where patients can be closely watched for cardiac problems. QT prolongation refers to an extension of the split-second time required for the heart to recharge between beats.

Many of the reported side effects occurred in COVID-19 patients treated with a combination of the malaria drugs and azithromycin, also known as Z-Pak, the FDA said. It added that the side-effects information came from the agency's adverse-events database, published literature and data from poison control centers.

"While clinical trials are ongoing to determine the safety and effectiveness of these drugs for COVID-19, there are known side effects of these medications that should be considered," FDA Commissioner Stephen Hahn said in a statement. "We encourage health care professionals making individual patient decisions to closely screen and monitor those patients to help mitigate these risks."

The debate about the use of chloroquine and hydroxychloroquine intensified earlier this week when Rick Bright, director of the Biomedical Advanced Research and Development Authority, was removed from his post and reassigned to a narrower role at the National Institutes of Health.

On Wednesday, Bright released a statement through his attorneys saying he was removed because of his resistance to pushing hydroxychloroquine and chloroquine as a panacea and his insistence the government invest billions of dollars appropriated by Congress into scientifically vetted solutions. He said that led to clashes with political leadership at the Department of Health and Human Services, which BARDA is under.

But a more complicated picture has emerged. Bright repeatedly clashed with his boss, Robert Kadlec, assistant secretary for preparedness and response at HHS, according to three current and former senior administration officials who spoke on the condition of anonymity to address a sensitive situation. Kadlec, who is also on the White House coronavirus task force, and top HHS officials had discussed Bright's departure for months because of dissatisfaction with his job performance, the current and former officials said. Yet a 2019 performance review obtained by The Washington Post showed Bright received glowing marks.

"I rightly resisted efforts to provide an unproven drug on demand to the American public," Bright said Wednesday. "I also resisted efforts to fund potentially dangerous drugs promoted by those with political connections."

Rep. Anna Eshoo, a California Democrat who is chairwoman of the House subcommittee on health, said she plans to have a hearing to find out why Bright was transferred to NIH from BARDA. "This man is a thoroughbred professional," she said. "Why would you do this in the middle of a pandemic? This deserves scrutiny."

Trump is livid about Bright's statement but HHS has urged the White House to stay quiet - and has not shared enough information in the view of some White House aides, according to two White House officials who spoke on the condition of anonymity to describe internal thinking.

The FDA's safety message Friday came after weeks of warnings from experts about possible complications from hydroxychloroquine and chloroquine. The agency said doctors should conduct electrocardiograms and kidney and liver tests on patients receiving the medications. The drugs, in addition to posing heart risks, can affect insulin levels, increasing the risks of severe hypoglycemia, a condition in which blood sugar levels are low, the agency said.

The FDA warning came just days after a study showed hydroxychloroquine had no benefit and was linked to higher rates of death for Veterans Affairs patients hospitalized with the novel coronavirus, raising further questions about the safety and efficacy of a treatment widely used in the pandemic.

The drugs are not approved for COVID-19, but once a drug is approved for any disease, doctors may prescribe it for any use. The FDA said it was "aware of an increased use of these medicines through outpatient prescriptions," and urged physicians and patients to be aware of the potential risks. Heart problems are a well-documented side effect among people given the drugs for malaria.

The FDA is allowing certain versions of hydroxychloroquine and chloroquine products donated to the Strategic National Stockpile to be distributed and used in limited circumstances for COVID-19, including for patients in the hospital, under an Emergency Use Authorization.

That authorization did not cite evidence of benefit in COVID-19 patients, and critics have argued the authorization - known as an EUA - was issued because of political pressure, which Hahn has denied.

"The agency's in a jam. It got badgered into the EUA in the first place, and now it's trying appropriately to warn people of the risks," said Peter Lurie, president of the consumer watchdog group Center for Science in the Public Interest and a former top FDA official. "It's unquestionable that the president, and the echo chamber of Fox News, created an atmosphere that fundamentally altered the way this product was considered.

"The overall problem is that this product, in all likelihood, will do more damage than good," he said.

But a New York internist who was an early adopter of the treatments and has publicly boosted their use, said Friday he will continue to prescribe them to patients who are not hospitalized, despite the FDA warning.

"I totally disagree with the FDA saying it should not be used outside of a clinical trial," said the doctor, Alexander Morden. "When the boat is sinking or the building is on fire, you can't wait for a study, six months later, to confirm what's going on. You have to do the best medicine you can."

Use of hydroxychloroquine has been widespread since the pandemic began, causing shortages for patients who use the medicine routinely to treat lupus and rheumatoid arthritis. Some doctors and experts, including Trump's defenders, have argued that the drug's safety profile in those patients meant it would be safe in COVID-19 patients.

"They sort of committed a first-year medical student violation by equating a safety profile in that set of patients with the safety profile in a sick, COVID-19 hospitalized patient," said Michael Ackerman, a genetic cardiologist and director of Mayo Clinic's Windland Smith Rice Sudden Death Genomics Laboratory. Ackerman and his colleagues published a warning about the risk of QT prolongation and sudden death three days before the FDA issued its emergency use authorization.

"Tragically, we've seen this already," Ackerman said. "I would not have predicted that we would see the signal of proof of the importance of this warning so quickly."

Survey data gathered by Sermo, a health-care data company, said about 60 percent of 1,400 physicians who were polled and who treat patients inside hospitals reported prescribing hydroxychloroquine for COVID-19 patients. But the same survey said only 30 percent of doctors rated the drug highly effective, and just 35 percent rated it very safe.

The dispute between the former head of BARDA and other HHS officials exposed rifts within the department over the use of the malaria drugs for COVID-19. Bright, the former BARDA head, is being represented by attorneys who represented Christine Blasey Ford, who alleged that Supreme Court Justice Brett Kavanaugh sexually assaulted her when they were teenagers. The attorneys declined to make Bright available for an interview.

Several senior administration officials expressed dismay that Bright had been removed from his post, especially in the middle of the government's coronavirus response, arguing it was disruptive and caused further turmoil at the health agency. Others, however, said BARDA was moving too slowly on COVID-19 treatments and vaccines and that issues with the agency date back to long before the crisis began.

"There were substantial problems with the organization, and some will be relieved by his departure. They have a lot of opportunity to succeed," said an industry expert familiar with BARDA who spoke on the condition of anonymity to describe the situation forthrightly.

HHS spokeswoman Caitlin Oakley said this week that Bright requested the emergency authorization from the FDA that made it possible for chloroquine to be donated to the Strategic National Stockpile and used for COVID-19 patients.

Bright’s statement, nevertheless, has made him a hero among some in the scientific community, who have expressed concern for weeks about the president’s unfounded claims about hydroxychloroquine and chloroquine without evidence.