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2020 ; 129
(ä): 104842
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Chloroquine dosage regimens in patients with COVID-19: Safety risks and
optimization using simulations
#MMPMID32501367
Karalis V
; Ismailos G
; Karatza E
Saf Sci
2020[Sep]; 129
(ä): 104842
PMID32501367
show ga
Currently no specific medicinal treatment exists against the new SARS-CoV2 and
chloroquine is widely used, since it can decrease the length of hospital stay and
improve the evolution of the associated COVID-19 pneumonia. However, several
safety concerns have been raised from chloroquine use due to the lack of
essential information regarding its dosing. The aim of this study is to provide a
critical appraisal of the safety information regarding chloroquine treatment and
to apply simulation techniques to unveil relationships between the observed
serious adverse events and overdosing, as well as to propose optimized dosage
regimens. The dose related adverse events of chloroquine are unveiled and maximum
tolerated doses and concentration levels are quoted. Among others, treatment with
chloroquine can lead to severe adverse effects like prolongation of the QT
interval and cardiomyopathy. In case of chloroquine overdosing, conditions
similar to those produced by SARS-CoV2, such as pulmonary oedema with respiratory
insufficiency and circulatory collapse, can be observed. Co-administration of
chloroquine with other drugs for the treatment of COVID-19 patients, like
azithromycin, can further increase the risk of QT prolongation and
cardiomyopathy. For elder patients there is a high risk for toxicity and dose
reduction should be made. This study unveils the risks of some widely used dosing
regimens and binds the observed serious adverse events with dosing. Based on
simulations, safer alternative dosage regimens are proposed and recommendations
regarding chloroquine dosing are made.