- Hydroxychloroquine is typically used for treatment of malaria, SLE, or rheumatoid arthritis. It has anti-viral activity in vitro, as well as anti-inflammatory activities.
mechanism of action appears similar
- Multiple mechanisms of anti-viral activity, including:
- Interference with the cellular receptor ACE2 (potentially making it particularly effective against SARS and COVID-19).
- Impairment of acidification of endosomes, which interferes with virus trafficking within cells.
- Hydroxychloroquine also has immunosuppressive properties. Activity against many pro-inflammatory cytokines (e.g., IL-1 and IL-6) might be helpful in prevention or treatment of cytokine storm.
in vitro & animal data
- Yao et al. found that the hydroxychloroquine was much more potent than chloroquine at inhibition of COVID-19 in cell lines (EC50 of 0.7 uM vs. 5 uM, respectively). They recommended a regimen of 400 mg BID for the first day followed by 200 mg BID for the following four days.
- Gautret et al: Hydroxychloroquine and azithromycin (Marseille study)
- Non-randomized, open label study evaluating the use of chloroquine (200 mg TID) with or without azithromycin (500 mg once, followed by 250 mg daily for four days).
- The primary endpoint was reduction in viral load. This was achieved, especially by the combination of chloroquine plus azithromycin.
- Study limitations include withdrawal of some patients from the hydroxychloroquine group.
- Emerging reports from China suggest that chloroquine has been studied with favorable results, but data is currently not available (Gao 2020). An expert consensus group in China is recommending a treatment regimen of 500 mg PO twice daily for patients without contraindications (Zhi 2020). Hopefully, clinical data with chloroquine will be published shortly (it's still missing ?? where is this data ??).
dosing (Monograph from MedScape)
- Loading dose of 400 mg PO BID on day #1.
- Maintenance dose of 200 mg q12 hours for 5 days, preferably with food (Regimen used by U. Pennsylvania and Belgium Guidelines).
- No dosing adjustment for renal or hepatic dysfunction, or for obesity.
- Highly controversial with overall very weak evidentiary basis.
- Recommended in some guidelines (e.g. Belgian guidelines, ATS guidelines), but not other guidelines (e.g. IDSA guidelines, ANZICS guidelines).
- May be considered in hypoxemic patients who aren't candidates for RCTs (B&W guidelines).
contraindications/cautions for hydroxychloroquine
- QT prolongation (if baseline QTc 450-500 ms, consider daily EKG; maintain adequate Mg and K levels)
- Epilepsy (reduces seizure threshold)
- Myasthenia gravis
- Retinal pathology
- G6PD deficiency
- Serious adverse events generally result from prolonged use. Complications may include:
- Torsade de pointes
- Bone marrow suppression (thrombocytopenia, leukopenia)
- Hypoglycemia – use with caution in diabetic patients.
Thanks for these updates! Gao2020 referred to a number of ongoing trials, it’s quite likely that publications will be spread rather than consolidated (a pity). Among those published, you might include “Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial” https://doi.org/10.1101/2020.03.22.20040758 . Results are quite blurred so far, but isn’t it the usual case when small samples are used to assess efficacy levels that should *not* be high enough for small samples to work? *If* CQ/HCQ are useful as an early treatment, e.g. if they reduce the need of oxygen support / hospitalisation from, say, 10%… Read more »