FDA Issues Safety Alert for Use of Hydroxychloroquine, Chloroquine for COVID-19

April 24, 2020

The FDA warned against the use of hydroxychloroquine and chloroquine outside of the hospital setting or clinical trials due to safety risks. 

Officials with the FDA have issued a safety alert regarding the use of hydroxychloroquine and chloroquine for coronavirus disease 2019 (COVID-19) treatment to warn against its use outside of certain closely supervised settings.1

In a drug safety communication, the agency cautioned against the use of these medications outside of the hospital setting or a clinical trial due to the risk of serious heart rhythm problems. According to the FDA, these risks may increase when these medications are combined with QT prolonging medications, such as azithromycin.1

“Patients who also have other health issues such as heart and kidney disease are likely to be at increased risk of these heart problems when receiving these medications,” the agency said.1

On March 30, the FDA authorized the emergency use of the investigational therapies in hospitalized patients with the virus when clinical trials are not available or participation is not feasible. The Emergency Use Authorization (EUA) was based upon limited evidence that the medicines may provide benefit, which is why it was only authorized for use in hospitalized patients under careful heart monitoring.

The FDA recommends initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.1

The FDA also stated that it is aware of increased use of these medications through outpatient prescriptions.1

Pharmacies have reported shortages of hydroxychloroquine, as well as other therapies that have seen spikes in demand since the outbreak began, such as azithromycin and albuterol inhalers.

Hydroxychloroquine and chloroquine are currently being studied in clinical studies, but there are not enough data to determine whether the therapies are safe and effective for use in treating COVID-19.1

Treatment guidelines recently released by the National Institutes of Health (NIH)did not establish definitive recommendations for the use of chloroquine, citing insufficient evidence to make a determination for or against its use. However, the expert panel did recommend against its use when combined with azithromycin for COVID-19.

Preliminary findings from the CloroCovid-19 study, published in JAMA Network Open, indicated that higher dosage of chloroquine should not be recommended for the treatment of severe COVID-19, especially among patients receiving azithromycin and oseltamivir. The phase 2b study highlighted safety concerns regarding QTc interval prolongation and increased lethality.2

Case series and other small randomized trials cited in the NIH treatment guidelines reported conflicting results. The combination of hydroxychloroquine plus azithromycin was associated with QTc prolongation in patients with COVID-19.3

References:

1. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problem. Drug Safety Communication. FDA; April 24, 2020. Accessed April 24, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or.

2. Silva Borba MG, Almeida Val FF, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Network Open. 2020. doi:10.1001/jamanetworkopen.2020.8857

3. COVID-19 Treatment Guidelines. National Institutes of Health; April 21, 2020. Accessed April 21, 2020. https://covid19treatmentguidelines.nih.gov/introduction/