Yin Kwan Wong, Jing Yang, Yingke He
Published: April 02, 2020
The lethal dose of chloroquine in adults is about 5 g. In the human body, chloroquine has a large volume of distribution with an elimination half-life of 20–60 days and a tendency to accumulate in metabolically active tissues at higher levels compared with the plasma concentration. In view of these properties, the recommended dose of 500 mg twice per day can quickly approach danger thresholds with sustained use. At the maximum course of 10 days, this regimen is substantially more aggressive than recommended regimens for the use of chloroquine as an antimalarial. The effects of chloroquine poisoning are well documented and include retinopathy and immunosuppression, with contraindications in several conditions including pregnancy.
On Feb 26, 2020, the treatment guidelines were revised, shortening the maximum course to 7 days while recommending a lower dose for patients weighing less than 50 kg and highlighting contraindications including pregnancy. It is encouraging that an appropriate adjustment with improved consideration for the toxicological properties of the drug was made so quickly given the urgency of the situation. However, we advise continued caution in bringing new treatments to clinical use in such a rapid manner. Recommended doses should be established with close reference to pharmacological profiles and side-effects must be closely monitored. The less toxic hydroxychloroquine should also be considered as an alternative. Finally, the potential toxicities of experimental treatments should be meticulously reported in peer-reviewed publications to avoid potentially misleading accounts and the risk of dangerous self-medication by the public. The rapid identification and development of such novel treatments is encouraging and will be instrumental in the battle against COVID-19, as long as prudence and rigour continue to be practised in both implementation and reporting.
The Lancet – DOI: https://doi.org/10.1016/S2665-9913(20)30093-X