Safety | Post-exposure Prophylaxis or Preemptive Treatment for Coronavirus

Folwell Components

Safety of Hydroxychloroquine

As you likely have heard, on 4/24/20 the FDA released a statement against the use of hydroxychloroquine for COVID-19 outside of clinical trials due to the risk of heart rhythm problems. We want you to know that this is related to increased use of this medication outside of clinical studies. The FDA found reports of high dose hydroxychloroquine use outside of a controlled setting and instances of prolonged QT and fatal arrhythmias have been reported.

The FDA is reminding people that hydroxychloroquine can cause abnormal heart rhythms, especially in combination with azithromycin. Patients with known heart arrhythmias or kidney disease may experience these side effects in greater frequency.

In our trial, we have excluded people with known heart arrhythmias or significant kidney disease. We are using standard dose hydroxychloroquine that has been used safely for malaria treatment or prophylaxis for decades. The FDA is aware of our trial and has approved it as safe to proceed. We have a Data Safety Monitoring Board that reviews all of the adverse events of the participants in both the placebo and hydroxychloroquine arms to ensure that participants are not at increased risk from participating in our study.

Several respected entities have contributed their perspective. The American Academy of Cardiology noted: “Chloroquine, and its more contemporary derivative hydroxychloroquine, have remained in clinical use for more than a half-century as an effective therapy for treatment of some malarias, lupus, and rheumatoid arthritis. Data show inhibition of iKr (potassium channels) and resultant mild QT prolongation associated with both agents. Despite these suggestive findings, several hundred million courses of chloroquine have been used worldwide making it one of the most widely used drugs in history, without reports of arrhythmic death under World Health Organization surveillance.” The WHO noted: “With enormous use of chloroquine in the second half of the 20^th century, there have been no reports of sudden unexplained death suggestive of cardiac arrhythmia at the doses used for malaria treatment.”

Relevant published data/studies include:

Azithromycin FDA Package Insert: Chloroquine phosphate 1g with azithromycin 500mg once resulted in an average QTc increase of 5ms.
NYU Retrospective Study – Hydroxychloroquine 400mg/day with azithromycin 500mg/day resulted in an average QTc increase of 28ms with 11% having QTc_B >500ms. (Chorin E, et al. Nature Medicine 2020)
Brazil Prospective Trial – Chloroquine phosphate 2g/day (1.2g chloroquine base) with azithromycin 500mg/day for 10 days resulted in 19% having a QTc >500ms and increased mortality compared to 1.5g chloroquine phosphate with azithromycin. (Silva Borba MG, et al JAMA 2020)
North Shore University Hospital Study - Hydroxychloroquine monotherapy (72 patients) was associated with QTc increase of 14ms. Hydroxychloroquine plus azithromycin (119 patients) was associated with QTc increase of 30ms. (Salah M, et al. Circulation: Arrhythmia and Electrophysiology 2020)

Relative to these studies, our study does not combine hydroxychloroquine with azithromycin, reducing the risk of QT prolongation. Additionally, the Brazil study used significantly higher dosing by giving ~4x more chloroquine base daily than our study.

If you have further questions, please feel free to email us. We are happy to answer your questions.