COVID‐19 is a newly emerging human infectious disease of SARS‐CoV‐2 origin that has spread from China. The global COVID‐19 situation was described as a pandemic by the WHO on 11 March 2020. Several treatment strategies are being considered and evaluated in numerous clinical trials. Among several treatment strategies, hydroxychloroquine (HCQ) has been suggested as potential treatment option for COVID‐19. However, it has very long half‐life (5‐40 days) and large volume of distribution into blood and tissues which causes variability in treatment response. It is known that, the steady‐state concentration is reached within weeks and differs according to individual factors (eg, obesity, sepsis, burn, ascites, pregnancy, critical illness) even at the same dose regime especially in the treatment of rheumatic diseases.
Patients in intensive care unit (ICU) present certain characteristics such as presence of sepsis, obesity, extracorporeal membrane oxygenation that may cause an increase in the volume of distribution of drugs.
There is little information about the efficacy of HCQ and modalities of administration of this drug in ICU patients with COVID‐19. The therapeutic level of HCQ in patients with COVID‐19 has not yet been established. According to the studies, HCQ trough levels between 1‐2 mg/L were considered to be therapeutic.
In contrast, Perinel et al indicated that only 61% of patients reached the therapeutic level at 200 mg three times daily dosing regimen.
The most commonly seen adverse effect of HCQ in patients with COVID‐19 is cardiac toxicity. The relation between cardiac toxicity and HCQ concentration has not been determined; however, it is known that HCQ concentration should not exceed 2 mg/L in order to avoid ocular toxicity.
In addition, the day of HCQ initiation during the COVID‐19 infection was not indicated in the study by Perinel et al
Existence of high mortality rates in the ICU and uncertainty around reaching the therapeutic concentration, we suggest that individual dose modification by therapeutic drug monitoring for HCQ until its concentration reaches the therapeutic level (mean duration of 3‐4 days) in ICU patients with COVID‐19 can help to achieve optimal outcomes and reduce the risk of drug interactions. Further pharmacokinetic and pharmacodynamic (virological) studies are also warranted.
No conflict of interest was declared by the authors.
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