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Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

Karatza et al., Xenobiotica
Sep 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects.
For instance, the dosing scheme proposed for a 70kg adult with moderate COVID-19 symptoms would be 600mg upon diagnosis, 400mg after 12h, 300mg after 24h, 200mg after 36h, followed by 200mg BID for 4 days, followed by 200mg OD for 5 days.
Suboptimal dosing regimens that do not fully account for the long half-life of HCQ or the patient characteristics are likely contribute to either limited efficacy where therapeutic levels take too long to reach, or significant adverse effects due to excessive dosage.
Karatza et al., 16 Sep 2020, peer-reviewed, 4 authors.
This PaperHCQAll
Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations
Eleni Karatza, George Ismailos, Markos Marangos, Vangelis Karalis
Xenobiotica, doi:10.1080/00498254.2020.1824301
1. During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. 2. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. 3. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. 4. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.
Disclosure statement No potential conflict of interest was reported by the author(s).
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