Hydroxychloroquine: Pharmacokinetics and Toxicity

Background/Purpose(s). We have extensively used HCQ at 200 mg three times a day (tid) to treat various infections such as Q fever and Whipple’s disease. Serum levels of between 1 μg/ml and 2 μg/ml serum level are recommended to achieve the safety and efficacy of these treatments. Our aim in this paper is to describe our experience regarding the pharmacokinetics and toxicity of HCQ in another infection caused by SARS-CoV-2. Methods. As recommended, we performed electrocardiograms before administering HCQ off-label. The HCQ concentration in the serum was monitored to ensure the effectiveness and safety of the treatment. We retrospectively analysed HCQ serum concentrations measured over time and toxicity data in patients with COVID-19 who were treated with HCQ at the IHU Marseille Infection. We did not treat patients with HCQ contraindications with this medication. Results. We measured HCQ concentrations in 1310 serum samples from 989 patients with COVID-19. The mean ± SD HCQ concentration increased in patients’ sera during treatment from day 1 (0.10 μg/ml ± 0.08) to day 11 (0.85 μg/ml ± 0.44), confirming that HCQ accumulates in the body during short-term therapy. However, the observed concentrations did not exceed the therapeutic range for other indications (0.80–1.20 μg/mL in Q fever patients treated for between 18 and 24 months). In patients treated with HCQ, major side effects included intestinal disorders (nausea, vomiting, and gastric pain) and QT prolongation. No conduction disorders (including torsades de pointes and ventricular arrhythmia), cardiomyopathy, retinopathy, or HCQ-related deaths were observed. Conclusions. In patients treated over a short time period with 200 mg tid of HCQ, therapeutic concentrations in serum were obtained in most patients without significant side effects or complications. Although patients must be carefully evaluated for HCQ contraindications, HCQ 200 mg tid for ten days can be considered an appropriate and safe dosage in patients with COVID-19.