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

Abstract

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.

Population Pharmacokinetics of Hydroxychloroquine Sulfate in Healthcare Workers, Given for Prophylaxis Against Coronavirus Disease 2019 (COVID‐19) in India

“…The simulation‐based dosing recommendation using the final model is in agreement with the treatment suggested by Karataza et al, 29 who recommended a higher initial dose followed by lower sparse maintenance doses.…”

“…This is in accordance with the findings reported by Themans et al, 22 and by Morita et al 13 Thus, weight-based dosage regimens would help maintain blood concentrations within the desired range. In the published simulation-based studies, 29,30 the proposed dosing regimen for the prevention and treatment of COVID-19 was based on a previously developed model for HCQ in patients with malaria.…”

Antivirals and the Potential Benefits of Orally Inhaled Drug Administration in COVID-19 Treatment

“…Several reports for inhaled HCQ stated that doses ranging from 2 to 4 mg twice daily to 20 mg once daily can be effective in treating COVID-19 symptoms. 162−164 Oral dose of HCQ for COVID-19 ranging from 200 mg to 800 mg. 165 Considering that the dose of the drug is so low when administered as pulmonary, treatment can be achieved at very low doses with similar calculations for other antiviral agents.…”

Optimization in the Context of COVID-19 Prediction and Control: A Literature Review

“…With a plethora of papers published on various topics in relation to COVID-19, some literature reviews emerged that grouped similar papers and provided an overview of the current state-of-the-art in a particular topic and suggested future directions of research. Some of the most common literature review topics included: general overviews of the COVID-19 pandemic [56] – [58] , COVID-19 and its relation to or effect on other health issues [59] – [61] , diagnosis and treatment methods [62] – [66] , and effects of the pandemic on various areas of our life (e.g., supply chain [67] – [69] or the economy [70] , [71] ). However, there has yet to be a review of the literature which focuses on the optimization studies in relation to the COVID-19 pandemic, specifically pertaining to prediction and control – this paper closes that gap.…”