- Hydroxychloroquine and chloroquine are two medications that have been used for many decades to treat malaria and autoimmune conditions like rheumatoid arthritis and lupus.
- There is not enough medical data at this time to prove that hydroxychloroquine and chloroquine work for COVID-19 — while some small studies suggest the medications may be helpful, other studies saw no benefit.
- There have been no studies showing that these medications work for prevention, and the FDA has issued a warning for serious heart-related side effects if hydroxychloroquine or chloroquine are taken outside of a hospital setting for COVID-19.
- There’s now a shortage of hydroxychloroquine and chloroquine, which means that people who normally take these medications to manage their health are having a harder time getting the treatment they need.
Hydroxychloroquine (Plaquenil) and chloroquine are two medications that have recently been making headlines as possible treatments for the coronavirus disease (COVID-19). Do these medications actually work against COVID-19? Here’s what we know.
What is hydroxychloroquine, and what is chloroquine?
Hydroxychloroquine is a medication first approved to treat malaria, an infection caused by a parasite. It is similar in structure to chloroquine, which was first approved by the FDA in 1949.
Hydroxychloroquine, approved in 1955, is typically preferred over chloroquine because it has fewer side effects. Side effects for both medications, which are more common at higher doses and with long-term use, include:
- Irreversible visual changes
- Long QT or QT prolongation (abnormal heart rhythm)
- Muscle weakness or nerve pain
- Hypoglycemia (low blood glucose)
- Worsening of psoriasis
What do hydroxychloroquine or chloroquine usually treat?
Hydroxychloroquine and chloroquine were first used to prevent or treat malaria. Both are available as pills that are taken by mouth. Hydroxychloroquine is also approved for long-term use in rheumatoid arthritis and lupus.
The dosage varies depending on what the medications are being used for. On the low end, hydroxychloroquine is taken as 400 mg orally once a week for malaria prevention and should be continued for 4 weeks after leaving an endemic area. On the high end, hydroxychloroquine is taken as 200 mg to 400 mg daily for rheumatoid arthritis.
Why are hydroxychloroquine and chloroquine being mentioned with COVID-19?
Recent in vitro studies (studies done in a petri dish or test tube rather than in animals or humans) have shown that both hydroxychloroquine and chloroquine have antiviral properties against SARS-CoV-2, the virus that causes COVID-19. In these studies, these medications worked by interfering with the chemical environment of human cell membranes. This blocked the virus from entering and multiplying inside the cells. A medication working in vitro does not always mean that it will work once inside a human body.
Nonetheless, based on these early findings, hospitals worldwide have begun using hydroxychloroquine and chloroquine for patients with COVID-19. On March 28, 2020, the FDA issued an Emergency Use Authorization (EUA) that allows providers to request a supply of hydroxychloroquine or chloroquine for hospitalized patients with COVID-19 who are unable to join a clinical trial. The EUA does not mean that the FDA has approved these medications for the treatment of COVID-19. The intent of the EUA is to help increase access to these medications by allowing doctors to request a supply from the Strategic National Stockpile for these specific cases.
What do research studies say about hydroxychloroquine, chloroquine, and COVID-19?
Data is still extremely limited. We need more research to determine the best dose, when to give it and for how long, and how the risks and benefits of these medications stack up in the fight against COVID-19. Large, randomized, controlled trials (the gold standard for clinical trials) are needed to confirm many of the findings summarized below.
Several studies have gained a lot of attention in recent media reports. We break it down between those that suggest the medications work compared to those that did not see a benefit. (Please note that even though results are being shared, few have been accepted into peer-reviewed medical journals.)
Studies with positive results for hydroxychloroquine and chloroquine in COVID-19
Study 1 – March 16, 2020
Researchers from China reported in a letter that over 100 people with COVID-19 have been treated with chloroquine. These patients had less severe disease and a shorter illness duration compared to those who did not receive chloroquine. However, results from these studies are not yet available, nor do we have a lot of information about the type of people who received this drug, or what dose they took and for how long.
Study 2 – March 20, 2020
A small study in France reported that people who got 600 mg of hydroxychloroquine had a lower amount of the virus (viral load) in the body. The problem with this study is that comparisons were made between patients at different hospitals. This makes it difficult to know if improvements were because of hydroxychloroquine or other things. And, of the 26 people who initially got hydroxychloroquine, 6 people (23%) had to stop treatment because of nausea, worsening disease, leaving the hospital, or death.
Six people in this study also received azithromycin (a common antibiotic) with hydroxychloroquine. These individuals had even lower viral loads at the end of the study compared to those who only got hydroxychloroquine. This research group later released another article looking more into hydroxychloroquine and azithromycin in a study of 80 people (including the 6 above). They noted that 93% had cleared the virus after 8 days. Because this study did not have a control group, it is unclear whether people who did not receive these medications would have seen similar results. Research with more people is needed to help us understand whether improvements were because of the combination of medications or other factors.
More information on safety is also important because taking azithromycin and hydroxychloroquine together can increase the risk of serious side effects, particularly irregular heart rhythm.
Study 3 – March 31, 2020
A small, randomized study of 62 people in Wuhan, China looked at how well hydroxychloroquine worked for hospitalized patients with mild COVID-19. Cough and fever improved about 1 day earlier for those who got 400 mg of hydroxychloroquine for 5 days compared to those who did not get any. Additionally, pneumonia improved in 25 of 31 patients who received hydroxychloroquine (compared to 17 of 31 in the group who didn’t).
Studies with negative results for hydroxychloroquine and chloroquine in COVID-19
Study 4 – March 24, 2020
In a small Shanghai study of 30 people with COVID-19, half got 400 mg of hydroxychloroquine for 5 days while the other half did not. At the end of the study, 13 people (87%) who received hydroxychloroquine tested negative for COVID-19 compared to 14 people (93%) who also tested negative but did not receive the medication. This suggests that hydroxychloroquine did not make a difference in recovery.
Study 5 – March 30, 2020
Another small study in France wanted to verify the results of Study 2 above, so they gave 11 people the same combination of hydroxychloroquine and azithromycin. After 6 days, 8 of 10 patients were still positive for SARS-CoV-2 (1 person could not be tested due to death). In addition to the death, two people were transferred to the ICU and one had to stop treatment due to side effects. This study was short and, like another study above, did not have a control group to compare patients to.
Study 6 – April 14, 2020
In a study of patients hospitalized with COVID-19, 150 people were randomly assigned to either receive high doses of hydroxychloroquine (1,200 mg for 3 days, then 800 mg for 2-3 weeks) or not. At the end of the study, 85% of the patients who got hydroxychloroquine tested negative for the novel coronavirus compared to 81% who did not get the medication. The typical time it took for people to clear the virus and see improvements in symptoms was also similar between groups. About 30% reported side effects, though they were mostly mild.
Study 7 – April 21, 2020
A retrospective study looked at veterans affairs (VA) hospitals across the U.S. and identified 368 male veterans who were hospitalized with COVID-19. The veterans were grouped based on whether they had received (1) hydroxychloroquine, (2) hydroxychloroquine and azithromycin, or (3) no hydroxychloroquine.
Death rates were highest in the group that received hydroxychloroquine alone (28%), followed by the group that received hydroxychloroquine and azithromycin (22%). The group that did not receive hydroxychloroquine had the lowest death rate (11%).
One thing to note is that people who had more severe symptoms, which might partially explain the higher death rates, were also more likely to get medications. People in this study were over 65 years old (on average) and male, which makes it difficult to apply the results to everyone.
Study 8 – May 7, 2020
In a large observational study of 1,376 hospitalized patients with COVID-19 in New York City, 811 people (59%) received hydroxychloroquine. There was minimal difference in the risk of needing a breathing tube (intubation) or death between those who didn’t get hydroxychloroquine and those who did. Because this study was observational (meaning the researchers only looked at the end results and were not involved with treatment), it is possible that other factors (confounders) may have affected the findings. Regardless, the researchers concluded that their study does not support the use of hydroxychloroquine for COVID-19.
Study 9 – May 11, 2020
Another large observational study of 1,438 hospitalized patients with COVID-19 in New York state also did not see a difference in death rates between those who got hydroxychloroquine (with or without azithromycin) compared to those who did not. Again, because this was an observational study, other factors that were not measured could have also affected the results. Overall, hydroxychloroquine did not show a benefit in this study.
Are hydroxychloroquine and chloroquine safe?
Hydroxychloroquine and chloroquine are generally considered safe when taken for conditions that they have been approved for. If you currently take either of these for malaria or autoimmune conditions, you should continue taking them according to your doctor’s instructions. As with any medications, there are risks and benefits. Both hydroxychloroquine and chloroquine can cause side effects, but in these cases, the benefits outweigh the risk.
On April 24, 2020, the FDA issued a warning stating that using hydroxychloroquine or chloroquine for COVID-19 outside of a hospital setting can put people at risk of serious heart rhythm problems, particularly QT prolongation. This is a well-known side effect of these medications. Because there is still a lot we don’t know about COVID-19, it is unclear if COVID-19 itself increases this risk. Some hospitals in France, Brazil, and Sweden have had to stop using hydroxychloroquine and chloroquine for some coronavirus patients due to severe side effects.
Taking hydroxychloroquine or chloroquine with other medications, like azithromycin, that can also cause QT prolongation, can further increase this risk. Prior to the FDA’s warning, several cardiology groups, including the American Heart Association, had issued a joint statement cautioning about the risks of taking these medications together.
Can hydroxychloroquine or chloroquine prevent or cure COVID-19?
At the time of this writing, hydroxychloroquine and chloroquine are not FDA-approved for the prevention or treatment of COVID-19. Additional data is needed to better understand the efficacy and safety of hydroxychloroquine and chloroquine for COVID-19. This is particularly important because current reports are based on a small number of patients, some who received dosages that were typically higher than what has been approved for other conditions.
Hydroxychloroquine and chloroquine have not yet been shown to prevent COVID-19 either in a community or hospital setting. In the studies cited above, patients received these medications in the hospital only after they were confirmed to have COVID-19. Additionally, the FDA’s Emergency Use Authorization for hydroxychloroquine and chloroquine are only for hospitalized patients who are unable to participate in a clinical trial.
Many clinical studies are currently underway to find a treatment for COVID-19, and the FDA is working with various government agencies, academic centers, and biopharmaceutical companies to expedite the process.
How can I get hydroxychloroquine or chloroquine?
Hydroxychloroquine and chloroquine both require a prescription from your doctor. Due to the recent increase in demand as a result of the COVID-19 pandemic, both medications are currently in short supply. This has made it difficult for patients with rheumatoid arthritis or lupus to get hydroxychloroquine, putting them at increased risk of complications.
Many states have restricted pharmacists from dispensing certain medications unless it is specifically being prescribed for an FDA-approved use. Additionally, the American Medical Association, American Pharmacists Association, and American Society of Health-System Pharmacists issued a joint statement discouraging doctors and pharmacists from inappropriately prescribing medications such as hydroxychloroquine and chloroquine. This is to help prevent medication stockpiling and potential drug shortages.
What other medications are currently being used to treat COVID-19?
Researchers are studying many medications as potential treatments for COVID-19. Remdesivir, an investigational antiviral medication given via intravenous (IV) infusion, is one of these. Doctors are trying this medication on critically unwell patients in clinical trials across U.S. hospitals. It is also available through a compassionate use program for patients who do not qualify for the clinical trials. Access to remdesivir is temporarily paused due to overwhelming demand.