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Pharmacology 101: The Hype With Hydroxychloroquine
If you’ve been following the news lately, you've seen a massive surge in the level of interest in hydroxychloroquine (HCQ) and chloroquine (CQ). The mainstream media has been reporting on President Donald Trump’s continued interest in these drugs and use of HCQ. However, the debate continues as to whether it can 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 shown to have less toxicity in animals, and additionally has been used to treat autoimmune diseases.1
Why is there interest in using it for COVID-19?
There are in vitro data suggesting that HCQ and CQ can inhibit SARS-CoV-2, the virus that causes COVID-19, by preventing entry into cells. Additionally, HCQ may have anti-inflammatory effects which may reduce the inflammation response to the virus.1,2
On March 20, a French study was published in the International Journal of Antimicrobial Agents which showed that 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 having been “seriously flawed."4
President Trump has promoted HCQ as a treatment for COVID-19, even to the point of announcing that he has taken it recently, and many hospitals are investigating its use.5 The current surge in interest for its use to treat patients with COVID-19 has led the FDA to update its drug shortages webpage. They note that both HCQ and CQ are “currently in shortage” as of the time of this writing. The FDA also noted that that U.S. Department of Health and Human Services had accepted 30 million doses to its stockpile with the hopes of alleviating anticipated supply pressures.6
What do the WHO, CDC and FDA say about hydroxychloroquine?
The World Health Organization (WHO) states “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.”7
The CDC’s official stance at this time is that “There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19.”8
The FDA echoes this, saying that “There is no U.S. Food and Drug Administration (FDA) approved product available to treat COVID-19.”9 However, at this time the FDA has approved the release of hydroxychloroquine from the Strategic National Stockpile. According to them, 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.”10
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 note that “We need to point out, although HCQ is less toxic than CQ, prolonged and overdose usage can still cause poisoning.”11 In fact, HCQ can cause a long list of adverse drug reactions, including heart failure and arrhythmias, severe skin reactions, blood disorders, seizures, vision problems, and psychiatric effects.12 These adverse drug 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, stating “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,” but more concerning, went on to note that “an association of increased overall mortality was identified in patients treated with hydroxychloroquine alone.”13
Indeed, on April 24, 2020, 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”.14
Even more recently, on May 25, 2020, the WHO halted a trial on HCQ in patients with COVID-19, concerned that the risks outweighed the benefits.15 Following this, France then disallowed the use of HCQ in French hospitals.16
The Bottom Line
At this point in time there are very limited clinical data suggesting that HCQ and CQ may have a role to play in treating COVID-19, and at this time, the data show that the risks may even outweigh the benefits. As Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, once stated, “We still need to do the definitive studies to determine whether any intervention, not just this one, is truly safe and effective.”17 As our clinical experience with the drugs used for COVID-19 is increasing, we may soon see which treatments are effective and which are ineffective. Currently, Fauci’s opinion about the drug seems unenthusiastic, stating, “The scientific data is really quite evident now about the lack of efficacy.”18 It appears that HCQ may not be the wonder drug it once seemed to be.
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). doi:doi.org/10.1038/s41421-020-0156-0
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):269-271. doi:10.1038/s41422-020-0282-0
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. doi:10.1016/j.ijantimicag.2020.105949
4. Cohen E, Nigam M. Publisher of hydroxychloroquine study touted by Trump says the research didn’t meet its standards. CNN. https://www.cnn.com/2020/04/08/health/drug-hydroxychloroquine-french-study/index.html. Published 2020. Accessed April 9, 2020.
5. Chalfant M. White House says Trump would take hydroxychloroquine again. The Hill. https://thehill.com/homenews/administration/499990-white-house-says-trump-would-take-hydroxychloroquine-again. Published 2020.
6. US Food and Drug Administration. Coronavirus (COVID-19) Update: Daily Roundup March 31, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-march-31-2020. Accessed April 9, 2020.
7. World Health Organization. Malaria and the COVID-19 pandemic. https://www.who.int/news-room/q-a-detail/malaria-and-the-covid-19-pandemic. Accessed April 9, 2020.
8. Centers for Disease Control and Prevention. Information for Clinicians on Therapeutic Options for Patients with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html. Accessed April 9, 2020.
9. US 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. https://www.fda.gov/media/136538/download. Published 2020. Accessed April 9, 2020.
10. US Food and Drug Administration. FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF HYDROXYCHLOROQUINE SULFATE SUPPLIED FROM THE STRATEGIC NATIONAL STOCKPILE FOR TREATMENT OF COVID-19 IN CERTAIN HOSPITALIZED PATIENTS. https://www.fda.gov/media/136537/download. Published 2020. Accessed April 9, 2020.
11. 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). doi:10.1038/s41421-020-0156-0
12. Micromedex Solutions. Hydroxychloroquine. https://micromedex.com/. Accessed April 9, 2020.
13. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. doi:https://doi.org/10.1101/2020.04.16.20065920
14. 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. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-reiterates-importance-close-patient-supervision-label-use. Published 2020. Accessed April 26, 2020.
15. Li D. WHO temporarily halts trial of hydroxychloroquine over safety concerns. NBC News. https://www.nbcnews.com/news/world/who-temporarily-halts-trial-hydroxychloroquine-over-safety-concerns-n1214341. Published 2020.
16. Chappell B. France Bars Use Of Hydroxychloroquine In COVID-19 Cases. NPR. https://www.npr.org/sections/coronavirus-live-updates/2020/05/27/863197161/france-bars-use-of-hydroxychloroquine-in-covid-19-cases. Published 2020.
17. Lovelace B. Coronavirus: Dr. Anthony Fauci warns Americans shouldn’t assume hydroxychloroquine is a ‘knockout drug.’ https://www.cnbc.com/2020/04/03/coronavirus-fauci-warns-americans-shouldnt-assume-hydroxychloroquine-is-a-knockout-drug.html. Accessed April 9, 2020.
18. Brennan Z. Fauci: Hydroxychloroquine not effective against coronavirus. Politico. Published 2020.
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.
