FDA Withdraws Emergency Use Authorization for Hydoxychloroquine

A month ago the skeptical cardiologist detailed the potential for lethal cardiotoxicity of the antimalarial drug hydroxychloroquine  (HCQ) concluding:

  1. HCQ and chloroquine (CQ)  have associated and well-documented, albeit rare cases of potentially lethal cardiotoxicity.
  2. The benefit of these drugs in the treatment of coronavirus infection is currently unproven.
  3. Data from high-quality randomized trials of HCQ treatment in patients with coronavirus is needed before we can assess whether the drug benefits outweigh its risk in COVID-19 patients.

The drugs had been approved by the FDA for emergency use authorization (EUA),  many physicians and hospitals were using them for patients with COVID-19. Even more disturbing,, President Trump was enthusiastically promoting HCQ and revealed that he was taking it as a prophylaxis against COVID-19.

Intense demand for HCQ  led to a shortage for patients who needed it  for proven indications such as systemic lupus erythematosus.

Since I highlighted the drug’s cardiotoxicity a series of papers have either shown a lack of benefit or potential worsening of outcomes with these drugs. Recognizing this the FDA withdrew its EUA for HCQ and CQ yesterday.

On June 15, 2020, based on FDA’s continued review of the scientific evidence available for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) to treat COVID-19, FDA has determined that the statutory criteria for EUA as outlined in Section 564(c)(2) of the Food, Drug, and Cosmetic Act are no longer met.  Specifically, FDA has determined that CQ and HCQ are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of CQ and HCQ no longer outweigh the known and potential risks for the authorized use. This warrants revocation of the EUA for HCQ and CQ for the treatment of COVID-19.

Fortunately, as more data became available over the last month hospitals which were previously routinely giving HCQ (and often azithromycin) dropped these drugs from their treatment protocols.

Hopefully, now we can get back to deliberately and scientifically validating the safety and efficacy of drugs for COVID-19. We still need more data from the dozens of ongoing randomized controlled trials (RCTs) on treatment.

Two large randomized controlled trials will be particularly helpful in determining the best treatment for SARS-CoV2 infection.

One of them, theRandomised Evaluation of COVid-19 thERapY (RECOVERY) Trial   published preliminary findings on 5 June 2020 showing a lack of benefit of HCQ.

In addition to HCQ, RECOVERY is analyzing treatment effects of the antivirals lopinavir-ritonavir, low-dose steroid therapy and interferon.

SOLIDARITY is an international clinical trial to help find an effective treatment for COVID-19, launched by the World Health Organization and partners.

 

The Solidarity Trial will compare four treatment options against the standard of care, to assess their relative effectiveness against COVID-19.

Until we get results from high-quality RCTs like these, the antimalarials  HCQ and CQ should not be utilized for either prevention of or treatment of COVID-19.

Skeptically Yours,

-ACP

5 thoughts on “FDA Withdraws Emergency Use Authorization for Hydoxychloroquine”

  1. I’d like to think you were’nt refencing ‘that’ “RCT” pitting HCQ against a placebo….a rather special placebo…ascorbic acid. The trial designed to fail (HCQ) perhaps shifting attention and Faith to the yet-to-be-invented vaccine…
    HCQ’s main benefit is it’s function as a zinc transporter (into cells) yet I found no mention of Zn it that or other HCQ trial.
    A safer alternative exists, Quercetin which is also a Zn ionophore / transporter.
    Would it not be preferable to shore up people’s immune systems ? – reducing the imperitive for heroic treatments .

  2. I think your audience might be interested in Yale Epidemiologist Harvey Risch, MD’s thoughts:

    Using Hydroxychloroquine and Other Drugs to Fight Pandemic
    June 01, 2020

    Hydroxychloroquine

    Professor Harvey Risch, MD, PhD., is a researcher at the Yale School of Public Health with a specialty in cancer etiology, prevention and early diagnosis, and epidemiologic methods.

    He recently studied the efficacy of hydroxychloroquine (used in conjunction with two other drugs) to treat people infected with COVID-19 and concluded that the approach should be “widely available” in the fight against the current pandemic.

    The results of his research are published in the American Journal of Epidemiology.

    HR: COVID-19 is really two different diseases. In the first few days, it is like a very bad cold. In some people, it then morphs into pneumonia which can be life-threatening. What I found is that treatments for the cold don’t work well for the pneumonia, and vice versa. Most of the published studies have looked at treatments for the cold but used for the pneumonia. I just looked at how well the treatments for the cold worked for the cold. There are five studies done this way, four of hydroxychloroquine plus azithromycin and one with hydroxychloroquine plus doxycycline, and they all show that treating the cold part of COVID-19—the early part—works very well.
    Do you think that these drug combinations should be used for all people with COVID-19, or only certain patients?

    HR: Most people less than 60 years old who are of healthy weight and who don’t have other conditions like heart disease or diabetes can get by without medications. But if anyone starts to have shortness of breath while doing normal activities like walking around at home, they should get medical care immediately.
    But the use of hydroxychloroquine to treat COVID-19 remains highly controversial. Why is there so much disagreement if it is effective?

    This pandemic is undoubtedly the biggest public health crisis of our time.
    Harvey Risch

    HR: I think that there has been confusion about treating the cold versus treating the pneumonia. These medications don’t seem to work so well for treating the pneumonia. As early as possible is crucial, within the first five to six days of symptoms.
    Are these drugs safe?

    HR: The combination of hydroxychloroquine and azithromycin has been used for decades in hundreds of thousands of people with rheumatoid arthritis. There is a concern that these medications do change the heart pacing a little and could cause cardiac arrhythmias. However, these arrhythmias are still very rare in people using these medications. People who already have heart arrhythmias or are predisposed to them or have family histories of them should discuss this with their health care providers and see if using hydroxychloroquine plus doxycycline or some other medications would be a better choice.
    Does hydroxychloroquine have the potential to be a “game-changer” in the fight against this pandemic?

    HR: Hydroxychloroquine alone is not the whole story. It needs to be combined with azithromycin or doxycycline and probably with zinc to make it most effective. The game changer is to aggressively treat people as soon as possible, before they are hospitalized, to keep them from becoming hospitalized in the first place. Hydroxychloroquine plus the other medications is what we know about now. In a few months we may have data on other medications that also work. We just have to start with something now.
    How widely is the drug currently being used to treat people infected with COVID-19? What do you recommend?

    HR: Various places around the world have started using these drugs. An international survey of doctors who treat COVID-19 patients recently showed 72 percent of doctors in Spain say that they have been using them. I think that doctors need to be able to use their own clinical judgement about their patients and have objective information about drugs that can work for the early part of the infection, the cold part.
    Why did you study this?

    HR: This pandemic is undoubtedly the biggest public health crisis of our time. I started seeing reports of treatment benefit in France and New York and couldn’t understand where the controversy was coming from. So, I did an exhaustive search of studies and data on medication use in COVID-19 outpatients and the paper I wrote just describes everything that I found. Every study has details and the details are important.
    Submitted by Sayuri Gavaskar on June 01, 2020

  3. In the first harrowing months, we simply did not have time to do the randomized trials needed to determine the efficacy of HCQ. There were many physicians treating large numbers of patients each who independently claimed significant benefits. The side effects of this drug are already well known. The heart dangers are indeed rare, as the Skeptical Cardiologist slips in, and are something to monitor, especially in long-term situations that are not really relevant for early, short-term Covid treatment.

  4. Properly carried out RCTs take the sort of time period to complete and report on that will, over the coming year, account for many COVID-19 illnesses leading some to terrible deaths. (RCTs on ACEis & ARBs in C-19 are due next April.)
    That’s Science in harsh reality.

    Medicine’s reality is to treat how you can with what you have at hand in your current Physician’s Armamentarium. (That HAD included early intubation!)

    Granted, hydroxychloroquine was a mistake in hopeful bias, but is there no room for compromise in this time-sensitive knowledge-scarce situation?

    1. No, really. I’m interested in what this experienced cardiologist has to say about waiting for all the full RCTs before stepping out from the edge a bit. How would you go about it? was Cameron Kyle-Sidell wrong to unilaterally change ventilation ptotocol? Is this fellow wrong:
      https://twitter.com/califf001/status/1272905044468391937
      The successful guy out on a limb is lauded. The failed guy on a very similar limb is a pariah or worse. That have something to do with it?

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