President Donald Trump’s excitement about decades-old anti-malarial drugs to treat the coronavirus has touched off widespread interest in the medications, hoarding by some doctors, new clinical trials on the fly and desperation among patients who take them for other conditions.
Many experts say there isn’t enough evidence that the drugs work for the coronavirus, but at least a few say there’s little to lose in giving hydroxychloroquine to patients who are severely ill with coronavirus.
“It’s unlikely to worsen COVID-19, and given that it might help ... we have literally nothing else to offer these patients other than supportive care,” said Dr. David Juurlink, an internist and head of the division of clinical pharmacology and toxicology at the University of Toronto in Canada.
Here’s what we know and don’t know about the drugs, chloroquine and hydroxychloroquine, also known by the brand name Plaquenil.
What We Know
The drugs are approved by the U.S. Food and Drug Administration, but not for the treatment of the coronavirus.
The drugs have been around for decades and are approved by the FDA. Hydroxychloroquine has been approved for the prevention and treatment of acute attacks of malaria, as well as lupus and rheumatoid arthritis. Chloroquine is approved to prevent and treat malaria.
At a briefing on March 19, Trump suggested that the FDA had approved hydroxychloroquine for treatment of the coronavirus, which was not accurate. At the same briefing, Dr. Stephen Hahn, the FDA’s commissioner said: “That’s a drug that the president has directed us to take a closer look at, as to whether an expanded-use approach to that could be done to actually see if that benefits patients. And again, we want to do that in the setting of a clinical trial — a large, pragmatic clinical trial — to actually gather that information and answer the question that needs to be answered and — asked and answered.”
On Sunday, the U.S. Department of Health and Human Services said that drugmakers had donated tens of millions of doses of hydroxychloroquine to the Strategic National Stockpile and that the FDA had issued an emergency authorization that allows hydroxychloroquine and chloroquine to be distributed from the stockpile and prescribed for patients with COVID-19 “when a clinical trial is not available or feasible.”
A release by HHS said that “although there are no currently approved treatments for COVID-19, both drugs have shown activity in laboratory studies against coronaviruses. ... Anecdotal reports suggest that these drugs may offer some benefit in the treatment of hospitalized COVID-19 patients. Clinical trials are needed to provide scientific evidence that these treatments are effective.”
Beyond that, doctors are generally allowed to prescribe drugs for unapproved uses.
A number of hospitals are using the drug to treat patients with the coronavirus.
The University of Washington, the University of Michigan and other academic medical centers have added hydroxychloroquine to their treatment protocols. “Hydroxychloroquine is an inexpensive and generally safe drug for short term use, with few drug-drug interactions,” the University of Washington protocol says. “While it is unknown if it is effective to treat COVID-19, there is a favorable risk:benefit and cost ratio. Multiple trials are ongoing, and this recommendation will be updated when further data is available.”
While Trump has talked about the combination of hydroxychloroquine and the antibiotic azithromycin, also known as Zithromax, the University of Michigan recommends against the use of azithromycin for use in treatment of COVID-19, calling the evidence “weak.”
Patients who rely on hydroxychloroquine for other conditions can’t get it.
As we reported last week, patients with lupus have not been able to refill their prescriptions. Anna Valdez, a nurse in California, told us that without the drug, she will likely have a disease flare or have to switch to stronger immune suppressing medicines that could, paradoxically, put her at more risk of serious consequences should she contract the coronavirus.
“When I think about the other people out there with lupus and other autoimmune disorders, we’re all really scared right now,” Valdez said a week ago. “If I get coronavirus, unlike someone else my age, almost 50 years old, who is likely to recover and will be fine, I will likely end up in the ICU.”
According to a report by BuzzFeed News, health insurer Kaiser Permanente seems to be prioritizing getting the drug to COVID-19 patients above patients with lupus. The insurer told a California patient that it would not refill her prescription for hydroxychloroquine. “Thank you for the sacrifice you will be making for the sake of those that are critically ill; your sacrifice may actually save lives,” her doctor’s office said in a message.
A Kaiser regional medical director told BuzzFeed that Kaiser, like other health care organizations, “has had to take steps to control the outflow of the medication to ensure access to severely sick patients, including both COVID-19 and those with acute lupus.”
She said the decision wouldn’t adversely affect lupus patients. “Extensive experience and research show that hydroxychloroquine builds up in the body and continues to work for an average of 40 days even after the last dose is taken. By then, we expect the drug manufacturers to have ramped up production to meet the increased demand.”
Some doctors and their families are hoarding the drug.
We reported that pharmacies and state pharmacy boards are concerned about hoarding by doctors and their families.
“It’s disgraceful, is what it is,” said Garth Reynolds, executive director of the Illinois Pharmacists Association. “And completely selfish.”
“We even had a couple of examples of prescribers trying to say that the individual they were calling in for had rheumatoid arthritis,” he said, explaining that pharmacists suspected that wasn’t true. “I mean, that’s fraud.”
Some state pharmacy boards have put in place restrictions on prescribing of the drug. And the American Medical Association called on doctors to stop hoarding the drug.
“The AMA is calling for a stop to any inappropriate prescribing and ordering of medications, including chloroquine or hydroxychloroquine, and appealing to physicians and all health care professionals to follow the highest standards of professionalism and ethics,” said Patrice A. Harris, president of the American Medical Association.
In a memo to his staff on Thursday, Dr. Craig R. Smith, the chair of surgery at NewYork-Presbyterian/Columbia University Irving Medical Center, responded to the reports of hoarding. “Doesn’t that make you proud?” he wrote sarcastically. Instead, he encouraged randomized double-blind clinical trials to assess whether the drugs work.
There are efforts to increase the supply of the drug, but other moves could tighten it.
Several drugmakers have said they plan to step in. Novartis said it would donate up to 130 million doses of generic hydroxychloroquine globally to support the response to COVID-19. Other companies have also pledged millions of doses.
At the same time, the Indian government last week imposed a moratorium on the export of hydroxychloroquine, except under certain conditions including “humanitarian grounds on case to case basis.” India is a major supplier of generic drugs used in the United States.
Conservative groups and television hosts are talking up the benefits of the drug.
As we reported last week, a conservative business group is pushing the Trump administration to use hydroxychloroquine, saying in an online petition that “red tape, regulation, and a dysfunctional healthcare supply chain” are impeding the ability of plants in the United States to produce the drug.
The Job Creators Network, founded by Republican political donor and Home Depot co-founder Bernard Marcus, has taken out Facebook ads and texted supporters to sign a petition urging the president to “CUT RED TAPE” and make the drug available.
Fox News likewise has been touting the drug. Tucker Carlson said: “Several days ago, the president expressed confidence in hydroxychloroquine as a treatment for the epidemic. That was it for the media. If Trump is for it, they’re against it, even if it might save American lives.” He added: “What reactive children they are. And they immediately began a sustained push to discredit the drug long before the clinical results were in.”
Trump’s personal lawyer Rudy Giuliani on Friday tweeted a quote from a conservative activist who falsely called hydroxychloroquine 100% effective at treating COVID-19 and said Michigan’s governor was threatening doctors who prescribe it, Mediaite reported. (The drug has not been shown to be 100% effective and Michigan, like many states, has warned doctors against hoarding the drugs for themselves.) Twitter removed Giuliani’s tweet because it violated the site’s rules.
And cardiac surgeon Dr. Mehmet Oz enthusiastically spoke of the drug on Sean Hannity’s Fox News program: “So we don’t want people using this stuff willy nilly. You must talk to your physician. But a lot of doctors here in New York and around the country are getting comfortable with the idea of using this earlier in the course of the treatment of their patients.”
Clinical trials are underway.
New York state, which has been the epicenter of the U.S. outbreak, has acquired 70,000 doses of hydroxychloroquine, 10,000 doses of azithromycin and 750,000 doses of chloroquine to be used in clinical trials.
“The president is optimistic about these drugs, and we are all optimistic that it could work,” New York Gov. Andrew Cuomo said on March 22. “I’ve spoken with a number of health officials, and there is a good basis to believe that they could work. Some health officials point to Africa, which has a very low infection rate, and there’s a theory that because they’re taking these anti-malaria drugs in Africa, it may actually be one of the reasons why the infection rate is low in Africa. We don’t know, but let’s find out and let’s find out quickly. And I agree with the president on that.”
The University of Minnesota is also enrolling patients in a clinical trial. But it isn’t getting enough volunteers, according to ABC News. In a story Wednesday, ABC reported that the lead investigator is seeking 1,500 volunteers for one clinical trial, “but in the week since he obtained FDA approval, he has managed to recruit only 411.” Only 25 of 1,500 volunteers needed for a second trial had signed up.
Some people are self-medicating with harmful results.
Banner Health in Arizona reported last week that a man died and his wife was hospitalized after the couple, both in their 60s, took chloroquine phosphate, an additive commonly used at aquariums to clean fish tanks. “Within 30 minutes of ingestion, the couple experienced immediate effects requiring admittance to a nearby Banner Health hospital,” the system said.
The man’s wife told NBC News that she saw the president’s briefings in which he promoted the value of chloroquine and hydroxychloroquine. “I saw it [chloroquine phosphate] sitting on the back shelf and thought, ‘Hey, isn’t that the stuff they’re talking about on TV?’” she told the network. “We were afraid of getting sick.”
On Saturday, the Centers for Disease Control and Prevention warned that “chloroquine phosphate, when used without a prescription and supervision of a healthcare provider, can cause serious health consequences, including death. Clinicians and public health officials should discourage the public from misusing non-pharmaceutical chloroquine phosphate (a chemical used in home aquariums).”
What We Don’t Know
Whether the drugs are effective at treating the coronavirus.
One small study in France seemed to suggest that hydroxychloroquine, combined with azithromycin, could work as a treatment for COVID-19. A different small study out of China suggests that hydroxychloroquine was not effective in patients compared with those who did not get the medication.
“I think this is an example where the speed of the virus is moving faster than the speed of the evidence,” Joel F. Farley, a professor at the University of Minnesota College of Pharmacy, wrote in an email to ProPublica.
Juurlink of the University of Toronto said he supports the use of the drugs in patients with serious illness but not those with mild symptoms or to try to keep people from getting infected.
“I might have a completely different answer a month or two from now once we have better data,” he said. “I have no idea whether the advice I’m giving you is good or not, but it’s the best I can come up with as of March 27.”
Update, April 1, 2020: This story has been updated to note a donation by drugmakers and an emergency authorization by the FDA.