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All Studies   Meta Analysis    Recent:   

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 known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments. c19hcq.org
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).
References
Abdulaziz, Shah, Mccune, Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update, Curr Opin Rheumatol
Al-Rawi, Meggitt, Williams, Wahie, Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus, Lupus
Alpern, Gertner, Off-label therapies for COVID-19-are we all in this together?, Clin Pharmacol Ther
Arnold, Buckner, Hydroxychloroquine for treatment of SARS-CoV-2 infection? Improving our confidence in a model-based approach to dose selection, Clin Transl Sci
Arshad, Kilgore, Chaudhry, Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, Int J Infect Dis
Balevic, Green, Clowse, Pharmacokinetics of hydroxychloroquine in pregnancies with rheumatic diseases, Clin Pharmacokinet
Barbosa, Kaitis, Freedman, Le, Lin, Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasirandomized comparative study, New England Journal of Medicine
Briasoulis, Agarwal, Pierce, QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications, Cardiology
Carmichael, Charles, Tett, Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis, Ther Drug Monitor
Casadevall, Joyner, Pirofski, SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy, J Clin Invest, doi:10.1172/JCI139760
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate covid-19, N Engl J Med. Advance online publication, doi:10.1056/NEJMoa2019014
Chen, Hu, Zhang, Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial url: medRxiv preprint Posted, doi:10.1101/2020.03.22.20040758
Chen, Liu, Liu, A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19
Cheng, Luo, Wang, Kidney disease is associated with in-hospital death of patients with COVID-19, Kidney Int
Cortegiani, Ingoglia, Ippolito, A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19, J Crit Care
Da, Xue, Yi Xue, None, Ban
De Olano, Howland, Su, Toxicokinetics of hydroxychloroquine following a massive overdose, Am J Emerg Med
Dro_, Rosik, Lechowicz, FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy, Drug Resist Updat
Durcan, Magder, Petri, Hydroxychloroquine blood levels in systemic lupus erythematosus: clarifying dosing controversies and improving adherence, J Rheumatol
Elavarasi, Prasad, Seth, Chloroquine and hydroxychloroquine for the treatment of COVID-19: a systematic review and meta-analysis, J General Internal Med, doi:10.1007/s11606-020-06146-w
Fan, Zhang, Liu, Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID-19 patients, Clin Infect Dis, doi:10.1093/cid/ciaa623
Fda, Food and Drug Administration: memorandum explaining basis for revocation of emergency use authorization for emergency use of chloroquine phosphate and hydroxychloroquine sulfate
Food, answers (R3) guidance for industry
Furst, Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases, Lupus
Garcia-Cremades, Solans, Hughes, Optimizing hydroxychloroquine dosing for patients with COVID-19: an integrative modeling approach for effective drug repurposing, Clin Pharmacol Ther
Gautret, Lagier, Parola, Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study, Travel Med Infect Dis
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Haas, Appleman, Stein, Autophagy inhibition to augment mTOR inhibition: a phase I/II trial of everolimus and hydroxychloroquine in patients with previously treated renal cell carcinoma, Clin Cancer Res
Harapan, Itoh, Yufika, Coronavirus disease 2019 (COVID-19): a literature review, J Infect Public Health
Horby, Mafham, Linsell, Effect of hydroxychloroquine in hospitalized patients with COVID-19: preliminary results from a multi-centre, randomized, controlled trial
Jankelson, Karam, Becker, QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review, Heart Rhythm
Juurlink, Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection, Canad Med Assoc J
Karalis, Ismailos, Karatza, Chloroquine dosage regimens in patients with COVID-19: safety risks and optimization using simulations, Safety Sci
Label, Plaquenil V R Hydroxychloroquine Sulfate Tablets, USP, US Food and Drug Administration (USFDA) Label. Revised on
Lav E, Parrott, Grimm, Challenges and opportunities with modelling and simulation in drug discovery and drug development, Xenobiotica
Lavielle, mlxR: simulation of longitudinal data
Lee, Lee, Kwok, Factors related to blood hydroxychloroquine concentration in patients with systemic lupus erythematosus, Arthritis Care Res
Lee, Vinayagamoorthy, Han, Association of polymorphisms of cytochrome P450 2D6 with blood hydroxychloroquine levels in patients with systemic lupus erythematosus, Arthritis Rheumatol
Lim, Im, Cho, Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax, Antimicrob Agents Chemother
Liu, Cao, Xu, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Liu, Li, COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism
Liu, Yan, Wan, Viral dynamics in mild and severe cases of COVID-19, Lancet Infect Dis
Lowe, Hijazi, Luttringer, On the anticipation of the human dose in first-in-man trials from preclinical and prior clinical information in early drug development, Xenobiotica
Marmor, Kellner, Lai, Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision), Ophthalmology
Miller, Khalil, Nygard, Steady-state pharmacokinetics of hydroxychloroquine in rheumatoid arthritis patients, DICP
Molina, Delaugerre, Goff, No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection, Medecine et Maladies Infectieuses
Morita, Takahashi, Yoshida, Yokota, Population pharmacokinetics of hydroxychloroquine in Japanese patients with cutaneous or systemic lupus erythematosus, Ther Drug Monitor
Munster, Gibbs, Shen, Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis, Arthritis Rheum
Naicker, Yang, Hwang, The Novel Coronavirus 2019 epidemic and kidneys, Kidney Int
Perinel, Launay, Botelho-Nevers, Towards optimization of hydroxychloroquine dosing in intensive care unit COVID-19 patients, Clin Infect Dis, doi:10.1093/cid/ciaa394
Pujadas, Chaudhry, Mcbride, SARS-CoV-2 viral load predicts COVID-19 mortality, Lancet Respir Med
Qin, Zhou, Hu, Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China, Clin Infect Dis
Rangwala, Leone, Chang, Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma, Autophagy
Ronco, Reis, Kidney involvement in COVID-19 and rationale for extracorporeal therapies, Nat Rev Nephrol
Rosenfeld, Ye, Supko, A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme, Autophagy
Saleh, Gabriels, Chang, Effect of chloroquine, hydroxychloroquine, and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection, Circ Arrhythm Electrophysiol
Singh, Singh, Shaikh, Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: a systematic search and a narrative review with a special reference to India and other developing countries, Diabet Metabol Syndr
Singh-Uttam, Parida, Lingaraju, Drug repurposing approach to fight COVID-19, Pharmacol Rep, doi:10.1007/s43440-020-00155-6
Tang, Cao, Han, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Teng, Walter, Gaspar, Torsades de pointes and QT prolongation Associations with antibiotics: a pharmacovigilance study of the FDA adverse event reporting system, Int J Med Sci
Tukacs, Pharmacokinetics and extracorporeal membrane oxygenation in adults: a literature review, AACN Adv Crit Care
Vogl, Stadtmauer, Tan, Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma, Autophagy
Wang, Zhang, Sang, Kinetics of viral load and antibody response in relation to COVID-19 severity, Advance Online Publication, doi:10.1172/JCI13875
White, Watson, Hoglund, COVID-19 prevention and treatment: a critical analysis of chloroquine and hydroxychloroquine clinical pharmacology, PLoS Med
Who, Clinical management of COVID-19
Yang, Wu, Liu, Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model, doi:10.1101/2020.04.22.056762
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis
Yu, Wang, Li, Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19, medRxiv, doi:10.1101/2020.04.27.20073379v1
Zheng, Yu, Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January, BMJ
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