If you’ve followed the news lately, you’ve seen a massive surge of interest in hydroxychloroquine (HCQ) and chloroquine (CQ). The mainstream media has reported on President Donald Trump’s continued interest in these drugs and use of HCQ. However, the debate continues as to whether it can effectively be used to treat COVID-19. Amid all the potential confusion, what do we tell patients who want more information?
What is hydroxychloroquine?
Hydroxychloroquine (also known by its brand name, Plaquenil) is a derivative of chloroquine, a drug used for decades to treat malaria. Many patients also take HCQ for lupus and rheumatoid arthritis. HCQ was developed in 1964 and has been shown to have less toxicity in animals. It’s additionally been used to treat autoimmune diseases.1
Why is there interest in using it for COVID-19?
There are in vitro data suggesting HCQ and CQ can inhibit SARS-CoV-2, the virus that causes COVID-19, by preventing its entry into cells. Additionally, HCQ may have anti-inflammatory effects that reduce the inflammation response to the virus.1,2
In March a French study was published that found combining HCQ with the antibiotic azithromycin reduced viral load in patients with COVID-19.3 However, the study was very small and has come under criticism as “seriously flawed.”4
Trump has promoted HCQ as a treatment for COVID-19, and many hospitals are investigating its use. The current interest has led the FDA to update its drug shortages webpage. It notes both HCQ and CQ are in shortage at the time of this writing. The FDA also noted the Department of Health and Human Services had added 30 million doses to its stockpile with the hopes of alleviating anticipated supply pressures.5
What do the WHO, CDC, and FDA say about hydroxychloroquine?
The World Health Organization says, “Currently there is insufficient data to assess the efficacy of either of these medicines in treating patients with COVID-19 or in preventing them from contracting the coronavirus.”6 The CDC’s official stance is that “There are no drugs or other therapeutics approved by the U.S. Food and Drug Administration to prevent or treat COVID-19.”7 The FDA echoes this, saying, “There is no U.S. Food and Drug Administration-approved product available to treat COVID-19.”8
However, at this time the FDA has approved the release of hydroxychloroquine from the Strategic National Stockpile. It will be used “for the unapproved treatment of adults and adolescents who weigh 50 kg or more and are hospitalized with COVID-19 for whom a clinical trial is not available or participation is not feasible.”9
What’s the harm in trying?
HCQ and CQ are not totally benign agents! In fact, even some of the authors who reported in vitro results themselves noted, “We need to point out, although HCQ is less toxic than CQ, prolonged and overdose usage can still cause poisoning.”10 In fact, HCQ can cause a long list of adverse reactions, including heart failure and arrhythmias, severe skin reactions, blood disorders, seizures, vision problems, and psychiatric effects.11 These reactions are described in numerous case reports. Whether these adverse effects would be seen to the same extent in the context of COVID-19 treatment remains unknown at this time.
A small retrospective analysis of COVID-19 patients receiving HCQ either alone or with azithromycin recently came out of the Department of Veterans Affairs, concluding, “We found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19.” More concerning, it went on to note that “an association of increased overall mortality was identified in patients treated with hydroxychloroquine alone.”12
Indeed, on April 24 the FDA published a Drug Safety Communication in response to “serious heart-related adverse events and death in patients with COVID-19 receiving hydroxychloroquine and chloroquine, either alone or combined with the antibiotic azithromycin or other medicines.”13
The Bottom Line
At this point there are very limited clinical data suggesting HCQ and CQ may have a role to play in treating COVID-19. While we think there may be benefit, it has not yet been definitively proven. As Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, has stated, “We still need to do the definitive studies to determine whether any intervention, not just this one, is truly safe and effective.”14 As our body of knowledge expands, we can hope the answers are revealed sooner rather than later.
References
1. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov, 2020; 6(16).
2. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res, 2020; 30(3): 269–71.
3. Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, 2020: 105949.
4. Cohen E, Nigam M. Publisher of hydroxychloroquine study touted by Trump says the research didn’t meet its standards. CNN, 2020 Apr 8, www.cnn.com/2020/04/08/health/drug-hydroxychloroquine-french-study/index.html.
5. U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: Daily Roundup, March 31, 2020, www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-31-2020.
6. World Health Organization. Malaria and the COVID-19 pandemic, www.who.int/news-room/q-a-detail/malaria-and-the-covid-19-pandemic.
7. Centers for Disease Control and Prevention. Information for Clinicians on Therapeutic Options for Patients with COVID-19, www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html.
8. U.S. Food and Drug Administration. Fact Sheet for Patients and Parent/Caregivers Emergency Use Authorization (EUA) of Hydroxychloroquine Sulfate for Treatment of COVID-19 in Certain Hospitalized Patients, www.fda.gov/media/136538/download.
9. U.S. Food and Drug Administration. Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Hydroxychlorine Sulfate Supplied from the Strategic National Stockpile for Treatment of COVID-19 in Certain Hospitalized Patients, www.fda.gov/media/136537/download.
10. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov, 2020; 6(1).
11. Micromedex Solutions. Hydroxychloroquine, http://micromedex.com.
12. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv, www.medrxiv.org/content/10.1101/2020.04.16.20065920v2.
13. U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Reiterates Importance of Close Patient Supervision for ‘Off-Label’ Use of Antimalarial Drugs to Mitigate Known Risks, Including Heart Rhythm Problems, www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-reiterates-importance-close-patient-supervision-label-use.
14. Lovelace B. Coronavirus: Dr. Anthony Fauci warns Americans shouldn’t assume hydroxychloroquine is a ‘knockout drug.’ CNBC, www.cnbc.com/2020/04/03/coronavirus-fauci-warns-americans-shouldnt-assume-hydroxychloroquine-is-a-knockout-drug.html.
Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals. He owns and operates Dan Hu Consulting, LLC, a business aimed at providing medical education to paramedics, nurses, physicians, and pharmacists.