Efficacy of Hydroxychloroquine in COVID-19
- Hydroxychloroquine is a more potent inhibitor of SARS-CoV-2 than chloroquine in vitro. It also has immunomodulating effects.
- Insufficient evidence to support widespread use [Evidence level C]
- Hydroxychloroquine 200 mg three times daily for ten days was used in a widely publicized open-label, randomized study in hospitalized patients testing positive for SARS-CoV-2. Six of 26 hydroxychloroquine patients were lost to follow-up: one due to death, three due to intensive care admission, one due to side effects (nausea), and one who left the hospital. Viral clearance at day six was 70% in the 20 remaining hydroxychloroquine patients vs 12.5% of the control patients (n = 16). Six treated patients also received azithromycin 500 mg on day one, then 250 mg on days two through five to prevent bacterial infection. In the combination group, viral clearance was 100% at day six vs 57.1% in the hydroxychloroquine-alone group.
- In a pilot study in China 30 patients were randomized to hydroxychloroquine 400 mg/day (it is unclear if this was divided) for five days, or usual care. There was no difference between groups in viral clearance at day seven, length of stay, or time to defervescence. In a study of 62 hospitalized patients with mild disease, 31 patients were randomized to hydroxychloroquine 200 mg twice daily. Time to recovery (defervescence and cough remission) was shortened by about one day in the treatment group. On day six, pneumonia was improved per CT in more patients in the treatment group. Four patients progressed to severe disease, all in the control group.
Other Dosing Regimens
- The FDA is suggesting, for hospitalized patients weighing ≥50 kg, a dose of 800 mg on day one, followed by 400 mg once daily for four to seven days. U.S. providers can request hydroxychloroquine through their local health department (EUA) for hospitalized patients unable to participate in a clinical trial.
- Some U.S. clinicians have reported anecdotally using 400 mg twice daily on day one, then 400 mg once daily for five days or 200 mg twice daily for four days; or 600 mg twice daily on day one, then 400 mg once daily on days two through five.
- An Italian guideline suggests 200 mg twice daily for ten days for patients with mild symptoms plus comorbidities, or more severe disease. The duration can be reduced to five days or extended to 20 days, depending on clinical severity.
- Other investigators are using a 14-day course, and at least one study is using a total daily dose of 800 mg.
- Clinical trials are planned on the use of hydroxychloroquine to prevent COVID-19 in healthcare workers.
- See www.clinicaltrials.gov for regimens being studied.
- Fewer adverse effects and drug interactions than chloroquine.
- A fact sheet on hydroxychloroquine for COVID-19 is available from the FDA (https://www.fda.gov/media/136537/download).
- Adverse effects are not well-characterized at the doses studied for COVID-19. In general, potential adverse effects include: gastrointestinal side effects (take with food or milk), headache, hypoglycemia, QT prolongation and other conduction disturbances (especially with hypokalemia, hypomagnesemia, or heart disease), cardiomyopathy, myopathy, movement disorders, neurotoxicity, ocular toxicity, ototoxicity, anemia, thrombocytopenia, neutropenia, bone marrow suppression, serious dermatologic reactions, and psoriasis flare. Monitor electrolytes, glucose, complete blood count, electrocardiogram, baseline renal and hepatic function, knee and ankle reflexes, vision, and mental status. When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.
A hydroxychloroquine suspension can be made by triturating 15 hydroxychloroquine sulfate 200 mg tablets to a fine power with a mortar and pestle. Levigate to a paste with a small amount of base (Oral Mix or Oral Mix SF). Add base by geometric dilution. Transfer to a graduated cylinder. Rinse mortar and pestle with base. QS with base to 120 mL. Transfer to an amber polyethylene terephthalate bottle. Shake well. Stable for 112 days at room temperature or under refrigeration.