PMC:7441788 / 35315-39123 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7441788","sourcedb":"PMC","sourceid":"7441788","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7441788","text":"6. Safety\nCQ/HCQ are basic medications for malaria with a long history of reliable safety records [3,62]. However, the therapeutic window of CQ is narrow, and the toxic dose is 3 times higher than the therapeutic dose [55,63]. The most common adverse effects of taking CQ are gastrointestinal discomforts, such as nausea, vomiting, diarrhea, and anorexia. These symptoms are mild and can be controlled by reducing the dose [3]. However, long-term and high-dose CQ intake can cause irreversible damage to the ear, cardiovascular system, and blood system, such as neurological deafness, conduction disorder cardiomyopathy, and leukopenia, though these adverse effects are very rare [3]. Compared to CQ, HCQ has fewer adverse effects, which may be related to its lower toxicity. In animal models, HCQ was about 40% less toxic than CQ [64]. Reportedly, only overdoses (average daily dose \u003e 5.0 mg/kg) and long-time (more than 5 years) ingestion of HCQ can cause retinopathy [65]. CQ/HCQ have similar pharmacokinetic characteristics, fast absorption in the gastrointestinal tract, fast excretion in liver and kidney, and a long half-life (40–50 days) [3,66]. Therefore, liver and kidney dysfunction may aggravate adverse effects. High-dose CQ (600 mg/2 times/day for 10 day) is associated with increased QTc interval prolongation in critically ill patients with COVID-19 [49] and should not be recommended. In the initial trial from France, of the 84 patients receiving HCQ treatment, 8 patients discontinued HCQ owing to ECG modifications within 4 days. Among them, 7 patients had a prolonged QTc interval more than 60 ms, and one patient developed a first-degree atrioventricular block within 2 days [53]. In a randomized clinical trial from Wuhan, 2 out of 31 patients receiving HCQ treatment had minor adverse effects (headache and rash) [50]. Prolonged QT interval after taking HCQ may also develop in ICU COVID-19 patients [67]. A recent observation showed that patients who received HCQ for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation (19%), and concurrent use of azithromycin was associated with greater changes in QTc (21%) [68]. Another observation in COVID-19 patients admitted to ICU showed that QTc intervals increased in 93% of patients receiving HCQ with or without azithromycin, prolonged QTc was observed in 36% of patients after a duration of the treatment for 2 to 5 days, and 6 of 18 (33%) patients treated with HCQ and azithromycin and 1 of 22 (5%) of those treated with HCQ alone developed an increase in QTc of 500 ms or greater [69]. The use of CQ, CQ with a macrolide, HCQ and HCQ with a macrolide were all found to be independently associated with increased risk for ventricular arrhythmia in hospitalized COVID-19 patients [61]. Therefore, clinicians should carefully weigh risks and benefits if considering CQ/HCQ with or without a macrolide. When CQ/HCQ are used, electrocardiogram examination should be routinely performed before taking the medicine, with close monitoring of QTc and concomitant medication usage. CQ/HCQ should be more cautiously used in patients with existing heart disease, and the use of QT interval prolonging drugs, such as antiarrhythmic drugs, antihistamines, and moxifloxacin should be avoided. In addition, close attention should be paid to symptoms after taking drugs and the drugs should be stopped in time if there are intolerable adverse reactions. In addition, CQ is extremely dangerous for patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency because of the possible induction of hemolytic anemia [70]. Therefore, more caution should be given for patients with G6PD deficiency when CQ is considered for the treatment and the best way should be to detect G6PD deficiency before the use of 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