Hospitals Update Hydroxychloroquine Protocols After FDA Warning

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APRIL 28, 2020 -- Across the country, hospitals are incorporating Friday's warning from the US Food and Drug Administration (FDA) about the risks of prescribing hydroxychloroquine and chloroquine for COVID-19 into their treatment protocols. 

For some hospitals, the message affirmed the cautious approach they were already taking with hydroxychloroquine. "From a New York state or Northwell perspective, there is no major change," said Onisis Stefas, PharmD, vice president of pharmacy at Northwell Health in New York. "We were not prescribing it out in the community very early on because of the concerns associated with the heart arrhythmias." 

Brigham and Women's Hospital in Boston, Massachusetts, is currently in the process of updating its publicly available COVID-19 protocols website "to incorporate the FDA's updated safety assessment and ongoing clinical trials," a hospital spokesperson told Medscape Medical News. Prior to the updates, the treatment protocols indicated that hydroxychloroquine should only be considered after weighing the risks and benefits for patients who are not candidates for other clinical trials and meet a specific set of health criteria. 

The warning is a timely and important synthesis of what physicians know about the drugs so far and how cautiously clinicians across the country should be using them, said Rajesh T. Gandhi, MD, infectious diseases physician at Massachusetts General Hospital (MGH), Boston, professor of medicine at Harvard Medical School, member of the Infectious Diseases Society of America (IDSA), and chair-elect of the HIV Medicine Association. 

"I think to be honest it's a really important message to the public and clinicians across the country," said Gandhi. "Because we all know there is just a ton of discussion around this drug...and it came out fairly and said what we know right now."

The two antimalarial drugs have been at the center of much political debate and scientific scrutiny in recent weeks, following President Trump's endorsement and the FDA's emergency use authorization for the two medications in March. Hospitals across the country had incorporated hydroxychloroquine and chloroquine into their constantly evolving treatment protocols for patients with COVID-19. 

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But the evidence that these drugs actually help treat COVID-19 remains scant. Some small studies suggest the therapies help patients with COVID-19, while others conclude the drugs have no effect or even harm patients. In the United States, medical societies including the American Heart Association have also warned about the serious cardiac issues that can accompany these drugs for some patients. 

In the new warning, the FDA said it "cautions against use of hydroxychloroquine or chloroquine for COVID-19 patients outside of the hospital setting or a clinical trial" and urged "close supervision" of patients treated with these therapies, citing cardiac side effects. 

The FDA also said it is aware that the outpatient prescription of these medications has increased since its March authorization, but the drugs still have not been shown to be safe or effective in treating or preventing COVID-19. 

The FDA announcement is consistent with protocols established by the National Institutes of Health and IDSA earlier this month that recommend against using hydroxychloroquine or chloroquine, except when these drugs are administered as part of a clinical trial. 

"We agree wholeheartedly with the FDA and have been hoping that the FDA would in fact issue that kind of clarification," said Samuel Brown, MD, study committee cochair of the ORCHID clinical trial, a multicenter, blinded study investigating the safety and efficacy of hydroxychloroquine. These medications need to be tested in clinical trials that are able to focus closely on safety monitoring, he said. Experts at Vanderbilt University, one of the medical centers participating in the ORCHID clinical trial, decided before Tennessee had any cases of COVID-19 that unproven therapies like hydroxychloroquine would only be available through clinical trials, said Wesley Self, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tennessee, and chair of the ORCHID study committee.

Northwell Health, like other hospitals in New York, has been following a March executive order issued by Governor Andrew Cuomo limiting the use of these drugs for COVID-19 outside of clinical trials, said Stefas. At Northwell Health, patients with COVID-19 only receive hydroxychloroquine or chloroquine when treated in hospital, where they can be closely monitored, or as part of a clinical trial. The hospital system's protocols currently do not recommend pairing hydroxychloroquine with azithromycin, said Stefas. The new FDA announcement is "very similar" to New York's existing executive order, he said. "Reading through this reinforces a lot of what we originally thought."

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At MGH in Boston, the FDA safety warning is in-line with and "solidifies" the hospital's evolving protocols, said Gandhi. Clinicians at MGH have been steadily moving away from prescribing hydroxychloroquine outside of clinical trials as the efficacy has remained murky, the serious side effects have become more evident, and clinical trials to assess the drug have gotten underway in recent weeks, he said. Given the conflicting evidence, Gandhi feels the use of these drugs needs to be focused in clinical trials, where scientists can truly evaluate how much they help or harm. 

"We know fundamentally that's the way to do this," Gandhi said. "We also don't know that it doesn't work, so it is ethical and incumbent upon us to do a study," Gandhi said. 

Other hospitals are already heeding the FDA's warning. At UW Medicine in Washington state, for example, hydroxychloroquine was considered a possible treatment for COVID-19 prior to the FDA's recent announcement. "Based on FDA guidance, hydroxychloroquine is no longer recommended as therapy for COVID-19 unless done through a clinical trial," said Tim Dellit, MD, chief medical officer for UW Medicine.

Michigan Medicine stopped using hydroxychloroquine and azithromycin (both separately and in combination) about a month ago, said Daniel Kaul, MD, a professor of infectious disease at the University of Michigan. "When we reviewed the data that was available in more detail, we realized that it was essentially uninterpretable," he said. As of Monday, the only patients receiving this drug at Michigan Medicine are those enrolled in the ORCHID clinical trial.  

But that does not seem to be the case everywhere. Most patients transferred to Michigan Medicine from other hospitals have received these drugs, indicating they are still being widely used, said Kaul. "I think this FDA guidance is appropriate and may reduce usage of this drug and make people more aware of the potential side effects both in inpatient and outpatient settings."

Hopefully, the FDA guidance will help slow the use of these drugs outside the appropriate clinical trial setting, said Kaul. "I think that the kind of politicization of this drug, which is pretty much unprecedented in my experience, created a really harmful environment where calm decision-making and assessment of the relative risks and benefits became somewhat impossible," said Kaul.  

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